Pharmacological effects of Chinese herb aconite (fuzi) on cardiovascular system.

PubMed

Zhao, Dandan; Wang, Jie; Cui, Yanjing; Wu, Xinfang

2012-09-01

Fuzi (aconite, Radix Aconiti praeparata), a widely used Chinese herb, plays a significant role in the cardiovascular system. This is mainly reflected by Fuzi's cardiotonic effect, its protective effect on myocardial cells, and its effect on heart rate and rhythm, blood pressure, and hemodynamics. In this article, the pharmacological effects and the corresponding mechanisms of Fuzi (aconite) and its active components on cardiovascular system are reviewed.

Applied modern biotechnology for cultivation of Ganoderma and development of their products.

PubMed

Zhou, Xuan-Wei; Su, Kai-Qi; Zhang, Yong-Ming

2012-02-01

A white-rot basidiomycete Ganoderma spp. has long been used as a medicinal mushroom in Asia, and it has an array of pharmacological properties for immunomodulatory activity. There have been many reports about the bioactive components and their pharmacological properties. In order to analyze the current status of Ganoderma products, the detailed process of cultivation of Ganoderma spp. and development of their products are restated in this review article. These include the breeding, cultivating, extracting bioactive component, and processing Ganoderma products, etc. This article will expand people's common knowledge on Ganoderma, and provide a beneficial reference for research and industrial production.

[Regularity of changes in main active components of Schisandra chinensis before and after being processed with vinegar].

PubMed

Li, Li; Xiao, Yong-Qing; Yu, Ding-Rong; Ma, Yin-Lian; Zhu, Ming-Gui; Chen, Liang

2012-12-01

To investigate the regularity of changes in the main active components of Schisandra chinensis preparations before and after being processed with vinegar. High performance liquid chromatography was used to analyze the changes in the content of lignans and organic acids in S. chinensis preparations before and after being processed with vinegar. After being processed with vinegar, the content of lignans in S. chinensis preparations significantly reduced, while that of organic acids significantly increased. The ratio between them reduced from 1:16 (raw product) to 1:21 (vinegar products). The changes in the main pharmacological effects of S. chinensis are related to not only the changes in the contents of lignan and organic acids, but also the significant changes in the ratio relations between the two components. This is of great significance to the correlation among the principle of S. chinensis processed with vinegar and material basis and the changes in pharmacological effects.

Studies on the muscle-paralyzing components of the juice of the banana plant.

PubMed

Singh, Y N; Inman, W D; Johnson, A; Linnell, E J

1993-01-01

The stem juice of the banana plant (Musa species) has been used as an arrow poison by African tribesmen. Lyophilized, partially purified extracts of the juice augment and then block both directly and indirectly evoked contractions of the mouse diaphragm. We have isolated, purified and determined the chemical composition of the active ingredients, and characterized their pharmacological activity. The lyophilized sample was extracted with a methanol-water (MeOH-H2O) (50/50) mixture and vacuum filtered. The filtrate was rotary evaporated and crystallized in a MeOH-H2O mixture to yield potassium nitrate crystals (melting point 332-334 degrees C). The filtrate was concentrated and chromatographed over Sephadex LH-20 gel using MeOH-H2O (40/60) as the eluent. The active component was found to be magnesium nitrate crystals (melting point 87-89 degrees C). In the mouse isolated phrenic nerve-hemidiaphragm preparation, the pharmacological profile of the first component was similar to that for authentic potassium nitrate which augments in low concentrations, and in higher concentrations augments, and then blocks both directly evoked muscle contraction the neuromuscular transmission. The second component had a profile of activity similar to that for authentic magnesium nitrate which only blocks neuromuscular transmission. It can be concluded that the two major active principles in the banana stem juice are potassium nitrate and magnesium nitrate.

Proteome analysis of snake venom toxins: pharmacological insights.

PubMed

Georgieva, Dessislava; Arni, Raghuvir K; Betzel, Christian

2008-12-01

Snake venoms are an extremely rich source of pharmacologically active proteins with a considerable clinical and medical potential. To date, this potential has not been fully explored, mainly because of our incomplete knowledge of the venom proteome and the pharmacological properties of its components, in particular those devoid of enzymatic activity. This review summarizes the latest achievements in the determination of snake venom proteome, based primarily on the development of new strategies and techniques. Detailed knowledge of the venom toxin composition and biological properties of the protein constituents should provide the scaffold for the design of new more effective drugs for the treatment of the hemostatic system and heart disorders, inflammation, cancer and consequences of snake bites, as well as new tools for clinical diagnostic and assays of hemostatic parameters.

Protonophore properties of hyperforin are essential for its pharmacological activity

PubMed Central

Sell, Thomas S.; Belkacemi, Thabet; Flockerzi, Veit; Beck, Andreas

2014-01-01

Hyperforin is a pharmacologically active component of the medicinal plant Hypericum perforatum (St. John's wort), recommended as a treatment for a range of ailments including mild to moderate depression. Part of its action has been attributed to TRPC6 channel activation. We found that hyperforin induces TRPC6-independent H+ currents in HEK-293 cells, cortical microglia, chromaffin cells and lipid bilayers. The latter demonstrates that hyperforin itself acts as a protonophore. The protonophore activity of hyperforin causes cytosolic acidification, which strongly depends on the holding potential, and which fuels the plasma membrane sodium-proton exchanger. Thereby the free intracellular sodium concentration increases and the neurotransmitter uptake by Na+ cotransport is inhibited. Additionally, hyperforin depletes and reduces loading of large dense core vesicles in chromaffin cells, which requires a pH gradient in order to accumulate monoamines. In summary the pharmacological actions of the “herbal Prozac” hyperforin are essentially determined by its protonophore properties shown here. PMID:25511254

[Study on the chemical components, antimicrobial and antitumor activities of the essential oil from the leaves of Zanthoxylum avicennae].

PubMed

Zhang, Da-Shuai; Zhong, Qiong-Xin; Song, Xin-Ming; Liu, Wen-Jie; Wang, Jing; Zhang, Qiong-Yu

2012-08-01

To study the chemical constituents, antimicrobial activity and antitumor activity of the essential oil from Zanthoxylum avicennae. The essential oil from the leaves of Zanthoxylum avicennae was extracted by steam distillation. The components of the essential oil were separated and identified by GC-MS. 72 components were identified and accounted for 98.15% of the all peak area. The essential oil exhibited strong antitumor activity against K-562 human tumor cell lines with IC50 of 1.76 microg/mL. It also exhibited moderate antimicrobial activity against three bacteria. The essential oil of Zanthoxylum avicennae contains various active constituents. This result provides scientific reference for the pharmacological further research of Zanthoxylum avicennae.

An integrated approach to uncover quality marker underlying the effects of Alisma orientale on lipid metabolism, using chemical analysis and network pharmacology.

PubMed

Liao, Maoliang; Shang, Haihua; Li, Yazhuo; Li, Tian; Wang, Miao; Zheng, Yanan; Hou, Wenbin; Liu, Changxiao

2018-06-01

Quality control of traditional Chinese medicines is currently a great concern, due to the correlation between the quality control indicators and clinic effect is often questionable. According to the "multi-components and multi-targets" property of TCMs, a new special quality and bioactivity evaluation system is urgently needed. Present study adopted an integrated approach to provide new insights relating to uncover quality marker underlying the effects of Alisma orientale (AO) on lipid metabolism. In this paper, guided by the concept of the quality marker (Q-marker), an integrated strategies "effect-compound-target-fingerprint" was established to discovery and screen the potential quality marker of AO based on network pharmacology and chemical analysis. Firstly, a bioactivity evaluation was performed to screen the main active fractions. Then the chemical compositions were rapidly identified by chemical analysis. Next, networks were constructed to illuminate the interactions between these component and their targets for lipid metabolism, and the potential Q-marker of AO was initially screened. Finally, the activity of the Q-markers was validated in vitro. 50% ethanol extract fraction was found to have the strongest lipid-lowering activity. Then, the network pharmacology was used to clarify the unique relationship between the Q-markers and their integral pharmacological action. Combined with the results obtained, five active ingredients in the 50% ethanol extract fraction were given special considerations to be representative Q-markers: Alisol A, Alisol B, Alisol A 23-acetate, Alisol B 23-acetate and Alisol A 24-acetate, respectively. The chromatographic fingerprints based Q-marker was establishment. The integrated Q-marker screen may offer an alternative quality assessment of herbal medicines. Copyright © 2018. Published by Elsevier GmbH.

Twin and Triplet Drugs in Opioid Research

NASA Astrophysics Data System (ADS)

Fujii, Hideaki

Twin and triplet drugs are defined as compounds that contain respectively two and three pharmacophore components exerting pharmacological effects in a molecule. The twin drug bearing the same pharmacophores is a "symmetrical twin drug", whereas that possessing different pharmacophores is a "nonsymmetrical twin drug." In general, the symmetrical twin drug is expected to produce more potent and/or selective pharmacological effects, whereas the nonsymmetrical twin drug is anticipated to show both pharmacological activities stemming from the individual pharmacophores (dual action). On the other hand, nonsymmetrical triplet drugs, which have two of the same pharmacophores and one different moiety, are expected to elicit both increased pharmacological action and dual action. The two identical portions could bind the same receptor sites simultaneously while the third portion could bind a different receptor site or enzyme. This review will mainly focus on the twin and triplet drugs with an evaluation of their in vivo pharmacological effects, and will also include a description of their pharmacology and synthesis.

Review of Ethnobotanical, Phytochemical, and Pharmacological Study of Thymus serpyllum L.

PubMed Central

Jarić, Snežana; Mitrović, Miroslava; Pavlović, Pavle

2015-01-01

Thymus serpyllum L. (wild thyme) is a perennial shrub, native to areas of northern and central Europe. Its aerial parts are most frequently used in ethnomedicine (mainly for treating illnesses and problems related to the respiratory and gastrointestinal systems), although recently its essential oils are becoming more popular as an important plant-derived product. The composition of these oils is affected by geographic region, the development stage of the plant, the harvest season, habitat, and climatic conditions. Wild thyme essential oil has an ever-growing number of uses in contemporary medicine due to its pharmacological properties: antioxidative, antimicrobial, and anticancerogenic activities. The antioxidative and antimicrobial properties of the essential oil are related to the synergistic and cumulative effect of its components. In terms of antitumor and cytotoxic activity, further research into the effects of essential oil is necessary, aimed at improving its cytotoxic effects, on the basis of which appropriate medicines can be formulated. Due to its pharmacological properties, the essential oil of wild thyme, a plant used in traditional medicine, represents an important natural resource for the pharmaceutical industry. In addition, it can be a source of natural antioxidants, nutritional supplements, or components of functional foods in the food industry. PMID:26265920

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke.

PubMed

Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

2010-07-08

Cannabis contains the psychoactive component delta⁸-tetrahydrocannabinol (delta⁸-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta⁸-THC and other cannabinoid CB₁ receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta⁸-THC also mediates psychological effects through the activation of the CB₁ receptor in the central nervous system. In addition to the CB₁ receptor agonists, cannabis also contains therapeutically active components which are CB₁ receptor independent. Of the CB₁ receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson's disease, Alzheimer's disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB₁ receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

PubMed Central

Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

2010-01-01

Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke. PMID:27713349

Uncovering the Mechanisms of Chinese Herbal Medicine (MaZiRenWan) for Functional Constipation by Focused Network Pharmacology Approach.

PubMed

Huang, Tao; Ning, Ziwan; Hu, Dongdong; Zhang, Man; Zhao, Ling; Lin, Chengyuan; Zhong, Linda L D; Yang, Zhijun; Xu, Hongxi; Bian, Zhaoxiang

2018-01-01

MaZiRenWan (MZRW, also known as Hemp Seed Pill) is a Chinese Herbal Medicine which has been demonstrated to safely and effectively alleviate functional constipation (FC) in a randomized, placebo-controlled clinical study with 120 subjects. However, the underlying pharmacological actions of MZRW for FC, are still largely unknown. We systematically analyzed the bioactive compounds of MZRW and mechanism-of-action biological targets through a novel approach called "focused network pharmacology." Among the 97 compounds identified by UPLC-QTOF-MS/MS in MZRW extract, 34 were found in rat plasma, while 10 were found in rat feces. Hierarchical clustering analysis suggest that these compounds can be classified into component groups, in which compounds are highly similar to each other and most of them are from the same herb. Emodin, amygdalin, albiflorin, honokiol, and naringin were selected as representative compounds of corresponding component groups. All of them were shown to induce spontaneous contractions of rat colonic smooth muscle in vitro . Network analysis revealed that biological targets in acetylcholine-, estrogen-, prostaglandin-, cannabinoid-, and purine signaling pathways are able to explain the prokinetic effects of representative compounds and corresponding component groups. In conclusion, MZRW active components enhance colonic motility, possibly by acting on multiple targets and pathways.

Uncovering the Mechanisms of Chinese Herbal Medicine (MaZiRenWan) for Functional Constipation by Focused Network Pharmacology Approach

PubMed Central

Huang, Tao; Ning, Ziwan; Hu, Dongdong; Zhang, Man; Zhao, Ling; Lin, Chengyuan; Zhong, Linda L. D.; Yang, Zhijun; Xu, Hongxi; Bian, Zhaoxiang

2018-01-01

MaZiRenWan (MZRW, also known as Hemp Seed Pill) is a Chinese Herbal Medicine which has been demonstrated to safely and effectively alleviate functional constipation (FC) in a randomized, placebo-controlled clinical study with 120 subjects. However, the underlying pharmacological actions of MZRW for FC, are still largely unknown. We systematically analyzed the bioactive compounds of MZRW and mechanism-of-action biological targets through a novel approach called “focused network pharmacology.” Among the 97 compounds identified by UPLC-QTOF-MS/MS in MZRW extract, 34 were found in rat plasma, while 10 were found in rat feces. Hierarchical clustering analysis suggest that these compounds can be classified into component groups, in which compounds are highly similar to each other and most of them are from the same herb. Emodin, amygdalin, albiflorin, honokiol, and naringin were selected as representative compounds of corresponding component groups. All of them were shown to induce spontaneous contractions of rat colonic smooth muscle in vitro. Network analysis revealed that biological targets in acetylcholine-, estrogen-, prostaglandin-, cannabinoid-, and purine signaling pathways are able to explain the prokinetic effects of representative compounds and corresponding component groups. In conclusion, MZRW active components enhance colonic motility, possibly by acting on multiple targets and pathways. PMID:29632490

Isolation and pharmacological characterization of fatty acids from saw palmetto extract.

PubMed

Abe, Masayuki; Ito, Yoshihiko; Suzuki, Asahi; Onoue, Satomi; Noguchi, Hiroshi; Yamada, Shizuo

2009-04-01

Saw palmetto extract (SPE) has been widely used for the treatment of lower urinary-tract symptoms secondary to benign prostatic hyperplasia. The mechanisms of pharmacological effects of SPE include the inhibition of 5alpha-reductase, anti-androgenic effects, anti-proliferative effects, and anti-inflammatory effects. Previously, we showed that SPE bound actively to alpha(1)-adrenergic, muscarinic and 1,4-dihydropyridine calcium channel (1,4-DHP) receptors in the prostate and bladder of rats, whereas its active constituents have not been fully clarified. The present investigation is aimed to identify the main active components contained in hexane and diethyl ether extracts of SPE with the use of column chromatography and preparative HPLC. Based on the binding activity with alpha(1)-adrenergic, muscarinic, and 1,4-DHP receptors, both isolated oleic and lauric acids were deduced to be active components. Authentic samples of oleic and lauric acids also exhibited similar binding activities to these receptors as the fatty acids isolated from SPE, consistent with our findings. In addition, oleic and lauric acids inhibited 5alpha-reductase, possibly leading to therapeutic effects against benign prostatic hyperplasia and related lower urinary-tract symptoms.

Azasugar inhibitors as pharmacological chaperones for Krabbe disease

DOE PAGES

Hill, Chris H.; Viuff, Agnete H.; Spratley, Samantha J.; ...

2015-03-23

Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe amore » new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.« less

Systems pharmacology-based drug discovery for marine resources: an example using sea cucumber (Holothurians).

PubMed

Guo, Yingying; Ding, Yan; Xu, Feifei; Liu, Baoyue; Kou, Zinong; Xiao, Wei; Zhu, Jingbo

2015-05-13

Sea cucumber, a kind of marine animal, have long been utilized as tonic and traditional remedies in the Middle East and Asia because of its effectiveness against hypertension, asthma, rheumatism, cuts and burns, impotence, and constipation. In this study, an overall study performed on sea cucumber was used as an example to show drug discovery from marine resource by using systems pharmacology model. The value of marine natural resources has been extensively considered because these resources can be potentially used to treat and prevent human diseases. However, the discovery of drugs from oceans is difficult, because of complex environments in terms of composition and active mechanisms. Thus, a comprehensive systems approach which could discover active constituents and their targets from marine resource, understand the biological basis for their pharmacological properties is necessary. In this study, a feasible pharmacological model based on systems pharmacology was established to investigate marine medicine by incorporating active compound screening, target identification, and network and pathway analysis. As a result, 106 candidate components of sea cucumber and 26 potential targets were identified. Furthermore, the functions of sea cucumber in health improvement and disease treatment were elucidated in a holistic way based on the established compound-target and target-disease networks, and incorporated pathways. This study established a novel strategy that could be used to explore specific active mechanisms and discover new drugs from marine sources. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The genus Pterocaulon (Asteraceae) - A review on traditional medicinal uses, chemical constituents and biological properties.

PubMed

Medeiros-Neves, Bruna; Teixeira, Helder Ferreira; von Poser, Gilsane Lino

2018-06-15

Species of the genus Pterocaulon (Asteraceae) are used in different parts of the world for mainly to treat skin and liver diseases, as well as disorders of the respiratory system, among others. This review aims to discuss the present state of the art concerning the ethnobotanical uses, secondary metabolites and biological effects of Pterocaulon species and their chemical components. The available information on the genus Pterocaulon was gathered from scientific databases (Web of Science, Pubmed, ScienceDirect, Scopus, ChemSpider, SciFinder ACS Publications, Wiley Online Library). Information was also obtained from local publications, M.Sc. and Ph.D. dissertations. All studies on the ethnobotany, phytochemistry, pharmacology and toxicology of the plants until December 2017 were included in this review. Approximately 40 coumarins and 30 flavonoids have been isolated from Pterocaulon species. Coumarins have been considered the chemotaxonomic markers in the genus and the most active components. Pharmacological studies carried out with extracts and isolated compounds revealed in vitro bioactivities that include antifungal, antiviral, and cytotoxicity. Most of the pharmacological investigations were not correlated with traditional uses of the plants. Pterocaulon species, a rich source of coumarins, have great ethnomedical potential. Nevertheless, further studies into the pharmacological activities are necessary since none of the purported effects of these plants was fully assessed. In-depth research regarding the toxicity are also required to ensure the safety of these medicinal plants. Copyright © 2018 Elsevier Ireland Ltd. All rights reserved.

Saffron: a natural product with potential pharmaceutical applications.

PubMed

Christodoulou, Eirini; Kadoglou, Nikolaos P E; Kostomitsopoulos, Nikolaos; Valsami, Georgia

2015-12-01

Recently, a great deal of interest has been developed to isolate and investigate novel bioactive components from natural resources with health beneficial effects. Saffron is the dried stigma of Crocus sativus L. and has been used for centuries in traditional medicine mainly for its healing properties, as well as for the treatment of various pathological conditions. Objectives of the present review are to unravel its therapeutic properties and investigate the potential applications of saffron in contemporary therapy of a wide spectrum of diseases and summarize previous and current evidence regarding the biological/pharmacological activities of saffron and its active ingredients and their possible therapeutic uses. Recent phytochemistry and pharmacological experiments have indicated that crocin and safranal, the major active ingredients of saffron, exert important actions, such as antioxidant, anti-tumor, anti-diabetic, anti-inflammatory and anti-atherosclerotic. Unfortunately, the vast majority of those data derive from in vitro studies, whereas a limited number of in vivo experiments support the aforementioned effects. In addition to studies with mechanistic implications, very few clinical trials provide preliminary evidence of saffron potentiality to alleviate depression and increase cognitive function in patients with Alzheimer's disease. The history and structural features of saffron constituents are given in the first part of the review, followed by a comprehensive and critical presentation of the published preclinical and clinical studies and review papers on the pharmacology and possible therapeutic uses of saffron and its main active components crocin and safranal. © 2015 Royal Pharmaceutical Society.

Physical-chemical properties and the reactivity of pyridoxine and pyrrolidone carboxylate and their protolytic forms.

PubMed

Golovenko, N Ya; Larionov, V B; Karpova, O V

2016-01-01

Preparation Methadoxine is equimolar salt, which cationic component (pyridoxine) is 3-oxypyridine derivative, possessing B6-vitamine like activity, while anionic component is the cyclic lactame of glutamic acid. Since biopharmaceutical and pharmacological properties of this drug depend on biochemical transformation its components, of the aim of this work was to determine the structure of possible ionized pyridoxine and pyrrolidone carboxylate forms and their reaction ability in biochemical processes. Physical-chemical properties of compounds (pKa, logP, logD, proton donor/acceptor quantity, solubility (g/l)) were calculated with ACD/pKaDB program or obtained from Pub-Med physical/chemical properties database. UV spectra of compounds were obtained after dissolution in different pH solutions (1.0, 4.5 and 6.8). It was found that at different pH values one can observe changes of the absorption spectra due to the presence of prevailing amount of the protonated form. An analysis of both pKa, logP and logD indicators and reactive functional groups of Methadoxine components has revealed that they can be protonated in different regions of gastro-intestinal tract, that influences their solubility in hydrophilic and lypophilic media. Pharmacological properties of pyridoxine and pyrrolidone carboxylate themselves are performed after their preliminary biotransformation to active metabolites. Only ionic interaction between Methadoxine components in the substance composition can appear, that provides its pharmaceutical stability and ensures its activity only in the organism conditions.

The International prevalence and variability of non-adherence to the non-pharmacologic treatment regimen after heart transplantation: Findings from the cross-sectional bright study.

PubMed

Helmy, Remon; Duerinckx, Nathalie; De Geest, Sabina; Denhaerynck, Kris; Berben, Lut; Russell, Cynthia L; Van Cleemput, Johan; Crespo-Leiro, Maria G; Dobbels, Fabienne

2018-05-13

Heart transplant (HTx) recipients need to follow a complex therapeutic regimen. We assessed the international prevalence and variability in non-adherence to six non-pharmacologic treatment components (physical activity, sun protection, diet, alcohol use, non-smoking, and outpatient follow-up visits). We used self-report data of 1397 adult HTx recipients from the 36-HTx-center, 11-country, 4-continent, cross-sectional BRIGHT study (ClinicalTrials. gov ID: NCT01608477). The non-adherence definitions used were: Physical activity: <3 times/week 20 minutes' vigorous activity, <5 times/week 30 minutes' moderate activity, or <5 times/week a combination of either intensity; Sun protection: not "always" applying any sun protection; Diet: not "often" or "always" following recommended diet(s); Alcohol use: > 1 alcoholic drink/day (women) or > 2 drinks/day (men); Smoking: current smokers or stopped <1 year before; Follow-up visits: missing ≥1 of the last 5 outpatient follow-up visits. Overall prevalence figures were adjusted to avoid over- or underrepresentation of countries. Between-country variability was assessed within each treatment component via chi-square testing. The adjusted study-wide non-adherence prevalence figures were: 47.8% for physical activity (95% CI [45.2-50.5%]), 39.9% for sun protection (95% CI [37.3-42.5%]), 38.2% for diet recommendations (95% CI [35.1-41.3%]), 22.9% for alcohol consumption (95% CI [20.8%-25.1%]), 7.4% for smoking cessation (95% CI [6.1%-8.7%]), and 5.7% for follow-up visits (95% CI [4.6-6.9%]). Significant variability was observed between countries in all treatment components except follow-up visits. Non-adherence to the post-HTx non-pharmacologic treatment regimen is prevalent and shows significant variability internationally, suggesting a need for tailored adherence-enhancing interventions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Hibiscus sabdariffa L., roselle calyx, from ethnobotany to pharmacology.

PubMed

Carvajal-Zarrabal, Octavio; Barradas-Dermitz, Dulce María; Orta-Flores, Zaida; Hayward-Jones, Patricia Margaret; Nolasco-Hipólito, Cirilo; Aguilar-Uscanga, M Guadalupe; Miranda-Medina, Anilú; Bujang, Kopli Bin

2012-01-01

Using MEDLINE and SCOPUS databases, a review of the literature from the pioneering study of 1991 until 2010 was performed on the effects on biological models of Hibiscus sabdariffa L. roselle calyx, its extracts mainly in polar solvents, or pure components found in extracts, as well as their possible relationship to these effects. Three relevant effects on lipid metabolism, antihypertensive activity, and apoptosis were observed. Our chronological review of the studies mentioned in the literature provides another opportunity to see how humans compile scientific knowledge of a chemical structure-physiological activity relationship starting from an ethnobotanical-ethnopharmagognosy contribution. The chemical components that are the main active principles in the physiological activities of Hibiscus sabdariffa L. calyx are anthocyanins and polyphenols (protocatechuic acid and quercetin). Advances have also been made in the elucidation of action mechanisms. Additionally, it has become clear that the lack of standardization in terms of chemical components of the material arising from Hibiscus sabdariffa L. used in testing on biological models imposes limits on the possibility of carrying out comparative analyses between studies. Fortunately, more recent studies are overcoming this obstacle by reporting component concentrations of assumed active principles; however, complete analysis of the extract, if this is to be considered as a therapeutic agent, is not commonly reported in the aforesaid studies. If one of the eventual scenarios for Hibiscus sabdariffa L. calyx is as a therapeutic agent in communities with economic limitations, then studies of a pharmacological nature should guarantee the effectiveness, safety, and tolerability of this material, which is widely accepted to be associated with chemical complexity, thus making this knowledge necessary.

Hibiscus sabdariffa L., roselle calyx, from ethnobotany to pharmacology

PubMed Central

Carvajal-Zarrabal, Octavio; Barradas-Dermitz, Dulce María; Orta-Flores, Zaida; Hayward-Jones, Patricia Margaret; Nolasco-Hipólito, Cirilo; Aguilar-Uscanga, M Guadalupe; Miranda-Medina, Anilú; Bujang, Kopli Bin

2012-01-01

Using MEDLINE and SCOPUS databases, a review of the literature from the pioneering study of 1991 until 2010 was performed on the effects on biological models of Hibiscus sabdariffa L. roselle calyx, its extracts mainly in polar solvents, or pure components found in extracts, as well as their possible relationship to these effects. Three relevant effects on lipid metabolism, antihypertensive activity, and apoptosis were observed. Our chronological review of the studies mentioned in the literature provides another opportunity to see how humans compile scientific knowledge of a chemical structure–physiological activity relationship starting from an ethnobotanical–ethnopharmagognosy contribution. The chemical components that are the main active principles in the physiological activities of Hibiscus sabdariffa L. calyx are anthocyanins and polyphenols (protocatechuic acid and quercetin). Advances have also been made in the elucidation of action mechanisms. Additionally, it has become clear that the lack of standardization in terms of chemical components of the material arising from Hibiscus sabdariffa L. used in testing on biological models imposes limits on the possibility of carrying out comparative analyses between studies. Fortunately, more recent studies are overcoming this obstacle by reporting component concentrations of assumed active principles; however, complete analysis of the extract, if this is to be considered as a therapeutic agent, is not commonly reported in the aforesaid studies. If one of the eventual scenarios for Hibiscus sabdariffa L. calyx is as a therapeutic agent in communities with economic limitations, then studies of a pharmacological nature should guarantee the effectiveness, safety, and tolerability of this material, which is widely accepted to be associated with chemical complexity, thus making this knowledge necessary. PMID:27186114

An overview of the pharmacological properties and potential applications of natural monoterpenes.

PubMed

Kozioł, Agata; Stryjewska, Agnieszka; Librowski, Tadeusz; Sałat, Kinga; Gaweł, Magdalena; Moniczewski, Andrzej; Lochyński, Stanisław

2014-01-01

Monoterpenes, the major components of essential oils, belong to the group of isoprenoids containing ten carbon atoms. Being widely distributed in the plant kingdom they are extensively used in cuisine and human health care products. Studies have shown that both natural monoterpenes and their synthetic derivatives are endowed with various pharmacological properties including antifungal, antibacterial, antioxidant, anticancer, antiarrhythmic, anti-aggregating, local anesthetic, antinociceptive, anti-inflammatory, antihistaminic and anti-spasmodic activities. Monoterpenes act also as regulators of growth, heat, transpiration, tumor inhibitors, inhibitors of oxidative phosphorylation, insect repellants, feline and canine attractants and antidiabetics. These interesting activities which might be potentially used not only in pharmaceutical, but also food and cosmetic industries are discussed below.

Pharmacological Effects of Active Components of Chinese Herbal Medicine in the Treatment of Alzheimer's Disease: A Review.

PubMed

Wang, Zhi-Yong; Liu, Jian-Gang; Li, Hao; Yang, Hui-Ming

2016-01-01

Alzheimer's disease (AD), the most common neurodegenerative disorder associated with dementia, not only severely decreases the quality of life for its victims, but also brings a heavy economic burden to the family and society. Unfortunately, few chemical drugs designed for clinical applications have reached the expected preventive or therapeutic effect so far, and combined with their significant side-effects, there is therefore an urgent need for new strategies to be developed for AD treatment. Traditional Chinese Medicine has accumulated many experiences in the treatment of dementia during thousands of years of practice; modern pharmacological studies have confirmed the therapeutic effects of many active components derived from Chinese herbal medicines (CHM). Ginsenoside Rg1, extracted from Radix Ginseng, exerts a [Formula: see text]-secretase inhibitor effect so as to decrease A[Formula: see text] aggregation. It can also inhibit the apoptosis of neuron cells. Tanshinone IIA, extracted from Radix Salviae miltiorrhizae, and baicalin, extracted from Radix Scutellariae[Formula: see text] can inhibit the oxidative stress injury in neuronal cells. Icariin, extracted from Epimedium brevicornum, can decrease A[Formula: see text] levels and the hyperphosphorylation of tau protein, and can also inhibit oxidative stress and apoptosis. Huperzine A, extracted from Huperzia serrata, exerts a cholinesterase inhibitor effect. Evodiamine, extracted from Fructus Evodiae, and curcumin, extracted from Rhizoma Curcumae Longae, exert anti-inflammatory actions. Curcumin can act on A[Formula: see text] and tau too. Due to the advantages of multi-target effects and fewer side effects, Chinese medicine is more appropriate for long-term use. In this present review, the pharmacological effects of commonly used active components derived from Chinese herbal medicines in the treatment of AD are discussed.

Zingiber zerumbet (L.) Smith: A Review of Its Ethnomedicinal, Chemical, and Pharmacological Uses

PubMed Central

Yob, N. J.; Jofrry, S. Mohd.; Affandi, M. M. R. Meor. Mohd.; Teh, L. K.; Salleh, M. Z.; Zakaria, Z. A.

2011-01-01

Zingiber zerumbet Sm., locally known to the Malay as “Lempoyang,” is a perennial herb found in many tropical countries, including Malaysia. The rhizomes of Z. zerumbet, particularly, have been regularly used as food flavouring and appetizer in various Malays' cuisines while the rhizomes extracts have been used in Malay traditional medicine to treat various types of ailments (e.g., inflammatory- and pain-mediated diseases, worm infestation and diarrhea). Research carried out using different in vitro and in vivo assays of biological evaluation support most of these claims. The active pharmacological component of Z. zerumbet rhizomes most widely studied is zerumbone. This paper presents the botany, traditional uses, chemistry, and pharmacology of this medicinal plant. PMID:21584247

Combination of HPLC chromatogram and hypoglycemic effect identifies isoflavones as the principal active fraction of Belamcanda chinensis leaf extract in diabetes treatment.

PubMed

Chen, Yan; Wu, Chong-Ming; Dai, Rong-Ji; Li, Liang; Yu, Yu-Hong; Li, Yan; Meng, Wei-Wei; Zhang, Liang; Zhang, Yongqian; Deng, Yu-Lin

2011-02-15

In previous study, we demonstrated the hypoglycemic effect of aqueous extract of Belamcanda chinensis leaves in rats. Here, we separated the aqueous extract of B. chinensis leaves and investigated the spectrum-effect relationships between HPLC chromatograms and hypoglycemic activities of different isolates from B. chinensis leaf extract. Sequential solvent extraction with petroleum ether, chloroform, acetic ester and n-butanol provided several isolates showing similar hypoglycemic activities, making it difficult to discriminate the active fractions. Stepwise elution through HP20 macroporous resin by water, 40% and 95% ethanol provided isolates with distinct hypoglycemic activities, representing a simple, rapid and efficient preparative separation method. Combination of HPLC chromatogram and pharmacological effect targeted a hypoglycemic activity-related region in HPLC chromatogram. Each peak in this region was analyzed by UV spectrum scan. Most of them were flavonoids in which tectoridin and swertisin were known flavonoids with anti-diabetic activities. In together, this work provides a general model of combination of HPLC chromatography and pharmacological effect to study the spectrum-effect relationships of aqueous extract from B. chinensis leaves, which can be used to find principle components of B. chinensis on pharmacological activity. Copyright © 2011 Elsevier B.V. All rights reserved.

The Effect of Temperature on Pressurised Hot Water Extraction of Pharmacologically Important Metabolites as Analysed by UPLC-qTOF-MS and PCA

PubMed Central

Khoza, B. S.; Chimuka, L.; Mukwevho, E.; Steenkamp, P. A.; Madala, N. E.

2014-01-01

Metabolite extraction methods have been shown to be a critical consideration for pharmacometabolomics studies and, as such, optimization and development of new extraction methods are crucial. In the current study, an organic solvent-free method, namely, pressurised hot water extraction (PHWE), was used to extract pharmacologically important metabolites from dried Moringa oleifera leaves. Here, the temperature of the extraction solvent (pure water) was altered while keeping other factors constant using a homemade PHWE system. Samples extracted at different temperatures (50, 100, and 150°C) were assayed for antioxidant activities and the effect of the temperature on the extraction process was evaluated. The samples were further analysed by mass spectrometry to elucidate their metabolite compositions. Principal component analysis (PCA) evaluation of the UPLC-MS data showed distinctive differential metabolite patterns. Here, temperature changes during PHWE were shown to affect the levels of metabolites with known pharmacological activities, such as chlorogenic acids and flavonoids. Our overall findings suggest that, if not well optimised, the extraction temperature could compromise the “pharmacological potency” of the extracts. The use of MS in combination with PCA was furthermore shown to be an excellent approach to evaluate the quality and content of pharmacologically important extracts. PMID:25371697

21 CFR 201.66 - Format and content requirements for over-the-counter (OTC) drug product labeling.

Code of Federal Regulations, 2013 CFR

2013-04-01

...: “[Bullet] side effects occur. You may report side effects to FDA at 1-800-FDA-1088.” The telephone number... means any component that is intended to furnish pharmacological activity or other direct effect in the... specified activity or effect. (3) Approved drug application means a new drug (NDA) or abbreviated new drug...

21 CFR 201.66 - Format and content requirements for over-the-counter (OTC) drug product labeling.

Code of Federal Regulations, 2012 CFR

2012-04-01

...: “[Bullet] side effects occur. You may report side effects to FDA at 1-800-FDA-1088.” The telephone number... means any component that is intended to furnish pharmacological activity or other direct effect in the... specified activity or effect. (3) Approved drug application means a new drug (NDA) or abbreviated new drug...

Dendrobium officinale Kimura et Migo: A Review on Its Ethnopharmacology, Phytochemistry, Pharmacology, and Industrialization

PubMed Central

Tang, Hanxiao; Zhao, Tianwen; Sheng, Yunjie; Zheng, Ting; Fu, Lingzhu

2017-01-01

Ethnopharmacological Relevance. Dendrobii Officinalis Caulis, the stems of Dendrobium officinale Kimura et Migo, as a tonic herb in Chinese materia medica and health food in folk, has been utilized for the treatment of yin-deficiency diseases for decades. Methods. Information for analysis of Dendrobium officinale Kimura et Migo was obtained from libraries and Internet scientific databases such as PubMed, Web of Science, Google Scholar, ScienceDirect, Wiley InterScience, Ingenta, Embase, CNKI, and PubChem. Results. Over the past decades, about 190 compounds have been isolated from Dendrobium officinale Kimura et Migo. Its wide modern pharmacological actions in hepatoprotective effect, anticancer effect, hypoglycemic effect, antifatigue effect, gastric ulcer protective effect, and so on were reported. This may mainly attribute to the major and bioactive components: polysaccharides. However, other small molecule components require further study. Conclusions. Due to the lack of systematic data of Dendrobium officinale, it is important to explore its ingredient-function relationships with modern pharmacology. Recently, studies on the chemical constituents of Dendrobium officinale concentrated in crude polysaccharides and its structure-activity relationships remain scant. Further research is required to determine the Dendrobium officinale toxicological action and pharmacological mechanisms of other pure ingredients and crude extracts. In addition, investigation is needed for better quality control and novel drug or product development. PMID:28386292

Imaging drugs with and without clinical analgesic efficacy.

PubMed

Upadhyay, Jaymin; Anderson, Julie; Schwarz, Adam J; Coimbra, Alexandre; Baumgartner, Richard; Pendse, G; George, Edward; Nutile, Lauren; Wallin, Diana; Bishop, James; Neni, Saujanya; Maier, Gary; Iyengar, Smriti; Evelhoch, Jeffery L; Bleakman, David; Hargreaves, Richard; Becerra, Lino; Borsook, David

2011-12-01

The behavioral response to pain is driven by sensory and affective components, each of which is mediated by the CNS. Subjective pain ratings are used as readouts when appraising potential analgesics; however, pain ratings alone cannot enable a characterization of CNS pain circuitry during pain processing or how this circuitry is modulated pharmacologically. Having a more objective readout of potential analgesic effects may allow improved understanding and detection of pharmacological efficacy for pain. The pharmacological/functional magnetic resonance imaging (phMRI/fMRI) methodology can be used to objectively evaluate drug action on the CNS. In this context, we aimed to evaluate two drugs that had been developed as analgesics: one that is efficacious for pain (buprenorphine (BUP)) and one that failed as an analgesic in clinical trials aprepitant (APREP). Using phMRI, we observed that activation induced solely by BUP was present in regions with μ-opioid receptors, whereas APREP-induced activation was seen in regions expressing NK(1) receptors. However, significant pharmacological modulation of functional connectivity in pain-processing pathways was only observed following BUP administration. By implementing an evoked pain fMRI paradigm, these drugs could also be differentiated by comparing the respective fMRI signals in CNS circuits mediating sensory and affective components of pain. We report a correlation of functional connectivity and evoked pain fMRI measures with pain ratings as well as peak drug concentration. This investigation demonstrates how CNS-acting drugs can be compared, and how the phMRI/fMRI methodology may be used with conventional measures to better evaluate candidate analgesics in small subject cohorts.

Imaging Drugs with and without Clinical Analgesic Efficacy

PubMed Central

Upadhyay, Jaymin; Anderson, Julie; Schwarz, Adam J; Coimbra, Alexandre; Baumgartner, Richard; Pendse, G; George, Edward; Nutile, Lauren; Wallin, Diana; Bishop, James; Neni, Saujanya; Maier, Gary; Iyengar, Smriti; Evelhoch, Jeffery L; Bleakman, David; Hargreaves, Richard; Becerra, Lino; Borsook, David

2011-01-01

The behavioral response to pain is driven by sensory and affective components, each of which is mediated by the CNS. Subjective pain ratings are used as readouts when appraising potential analgesics; however, pain ratings alone cannot enable a characterization of CNS pain circuitry during pain processing or how this circuitry is modulated pharmacologically. Having a more objective readout of potential analgesic effects may allow improved understanding and detection of pharmacological efficacy for pain. The pharmacological/functional magnetic resonance imaging (phMRI/fMRI) methodology can be used to objectively evaluate drug action on the CNS. In this context, we aimed to evaluate two drugs that had been developed as analgesics: one that is efficacious for pain (buprenorphine (BUP)) and one that failed as an analgesic in clinical trials aprepitant (APREP). Using phMRI, we observed that activation induced solely by BUP was present in regions with μ-opioid receptors, whereas APREP-induced activation was seen in regions expressing NK1 receptors. However, significant pharmacological modulation of functional connectivity in pain-processing pathways was only observed following BUP administration. By implementing an evoked pain fMRI paradigm, these drugs could also be differentiated by comparing the respective fMRI signals in CNS circuits mediating sensory and affective components of pain. We report a correlation of functional connectivity and evoked pain fMRI measures with pain ratings as well as peak drug concentration. This investigation demonstrates how CNS-acting drugs can be compared, and how the phMRI/fMRI methodology may be used with conventional measures to better evaluate candidate analgesics in small subject cohorts. PMID:21849979

Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells.

PubMed

Woollhead, A M; Sivagnanasundaram, J; Kalsi, K K; Pucovsky, V; Pellatt, L J; Scott, J W; Mustard, K J; Hardie, D G; Baines, D L

2007-08-01

AMP-activated protein kinase (AMPK) is activated by metformin, phenformin, and the AMP mimetic, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). We have completed an extensive study of the pharmacological effects of these drugs on AMPK activation, adenine nucleotide concentration, transepithelial amiloride-sensitive (I(amiloride)) and ouabain-sensitive basolateral (I(ouabain)) short circuit current in H441 lung epithelial cells. H441 cells were grown on permeable filters at air interface. I(amiloride), I(ouabain) and transepithelial resistance were measured in Ussing chambers. AMPK activity was measured as the amount of radiolabelled phosphate transferred to the SAMS peptide. Adenine nucleotide concentration was analysed by reverse phase HPLC and NAD(P)H autofluorescence was measured using confocal microscopy. Phenformin, AICAR and metformin increased AMPK (alpha1) activity and decreased I(amiloride). The AMPK inhibitor Compound C prevented the action of metformin and AICAR but not phenformin. Phenformin and AICAR decreased I(ouabain) across H441 monolayers and decreased monolayer resistance. The decrease in I(amiloride) was closely related to I(ouabain) with phenformin, but not in AICAR treated monolayers. Metformin and phenformin increased the cellular AMP:ATP ratio but only phenformin and AICAR decreased cellular ATP. Activation of alpha1-AMPK is associated with inhibition of apical amiloride-sensitive Na(+) channels (ENaC), which has important implications for the clinical use of metformin. Additional pharmacological effects evoked by AICAR and phenformin on I(ouabain), with potential secondary effects on apical Na+ conductance, ENaC activity and monolayer resistance, have important consequences for their use as pharmacological activators of AMPK in cell systems where Na+K+ATPase is an important component.

Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells

PubMed Central

Woollhead, A M; Sivagnanasundaram, J; Kalsi, K K; Pucovsky, V; Pellatt, L J; Scott, J W; Mustard, K J; Hardie, D G; Baines, D L

2007-01-01

Background and purpose: AMP-activated protein kinase (AMPK) is activated by metformin, phenformin, and the AMP mimetic, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). We have completed an extensive study of the pharmacological effects of these drugs on AMPK activation, adenine nucleotide concentration, transepithelial amiloride-sensitive (Iamiloride) and ouabain-sensitive basolateral (Iouabain) short circuit current in H441 lung epithelial cells. Experimental approach: H441 cells were grown on permeable filters at air interface. Iamiloride, Iouabain and transepithelial resistance were measured in Ussing chambers. AMPK activity was measured as the amount of radiolabelled phosphate transferred to the SAMS peptide. Adenine nucleotide concentration was analysed by reverse phase HPLC and NAD(P)H autofluorescence was measured using confocal microscopy. Key results: Phenformin, AICAR and metformin increased AMPK (α1) activity and decreased Iamiloride. The AMPK inhibitor Compound C prevented the action of metformin and AICAR but not phenformin. Phenformin and AICAR decreased Iouabain across H441 monolayers and decreased monolayer resistance. The decrease in Iamiloride was closely related to Iouabain with phenformin, but not in AICAR treated monolayers. Metformin and phenformin increased the cellular AMP:ATP ratio but only phenformin and AICAR decreased cellular ATP. Conclusions and implications: Activation of α1-AMPK is associated with inhibition of apical amiloride-sensitive Na+ channels (ENaC), which has important implications for the clinical use of metformin. Additional pharmacological effects evoked by AICAR and phenformin on Iouabain, with potential secondary effects on apical Na+ conductance, ENaC activity and monolayer resistance, have important consequences for their use as pharmacological activators of AMPK in cell systems where Na+K+ATPase is an important component. PMID:17603555

Constituents and biological activities of Schinus polygamus.

PubMed

Erazo, Silvia; Delporte, Carla; Negrete, Rosa; García, Rubén; Zaldívar, Mercedes; Iturra, Gladys; Caballero, Esther; López, José Luis; Backhouse, Nadine

2006-10-11

The folk medicine employs Schinus polygamus to treat arthritic pain and cleansing of wounds. As no reports of pharmacological studies supporting its anti-inflammatory and analgesic properties, extracts of increasing polarity were assayed on the base of fever, pain and inflammation, together with its antimicrobial activity. All the extracts showed pharmacological activities. From the most active extracts different metabolites were isolated that can in part explain the antipyretic, anti-inflammatory, and analgesic activity: beta-sitosterol, shikimic acid together with quercetin, previously reported. Also, the essential oil of leaves and fruits was obtained and compared with the oil obtained from Schinus polygamus collected in Argentine. Oils differed in composition and in antibacterial activity, where the Chilean species exhibited a wide spectrum of activity against Gram-positive and Gram-negative bacteria, and the most abundant compound found in leaves and fruits was beta-pinene, meanwhile the Argentine species showed high activity against Bacillus cereus, and the main components resulted to be alpha-phellandrene and limonene.

A Blended Learning Course Design in Clinical Pharmacology for Post-graduate Dental Students

PubMed Central

Rosenbaum, Paul-Erik Lillholm; Mikalsen, Øyvind; Lygre, Henning; Solheim, Einar; Schjøtt, Jan

2012-01-01

Postgraduate courses in clinical pharmacology are important for dentists to be updated on drug therapy and information related to their clinical practice, as well as knowledge of relevant adverse effects and interactions. A traditional approach with classroom delivery as the only method to teaching and learning has shortcomings regarding flexibility, individual learning preferences, and problem based learning (PBL) activities compared to online environments. This study examines a five week postgraduate course in clinical pharmacology with 15 hours of lectures and online learning activities, i.e. blended course design. Six postgraduate dental students participated and at the end of the course they were interviewed. Our findings emphasize that a blended learning course design can be successfully used in postgraduate dental education. Key matters for discussion were time flexibility and location convenience, change in teacher’s role, rein-forced learning strategies towards professional needs, scarcity in online communication, and proposed future utilization of e-learning components. PMID:23248716

Curcumin – Pharmacological Actions And its Role in Oral Submucous Fibrosis: A Review

PubMed Central

Singh, Indra Deo; Singh, Shivani; Kishore, Mallika; Jha, Prakash Chandra

2015-01-01

Turmeric has been in use for thousands of years as a dye, flavouring and a medicinal herb. Ancient Indian medicine has touted turmeric as an herb with the ability to provide glow and lustre to the skin as well as vigour and vitality to the entire body. Since curcumin has antimicrobial, antioxidant, astringents and other useful properties, it is quite useful in dentistry also. Curcumin, the most active polyphenolic constituent, is the active ingredient in the traditional herbal remedy and dietary spice turmeric. In gel form it is a component in local drugs delivery system. The objective of this article is to review the pharmacological action of turmeric and its use in treating oral submucous fibrosis. PMID:26557633

Cistanche deserticola Y. C. Ma, "Desert ginseng": a review.

PubMed

Wang, Tian; Zhang, Xiaoying; Xie, Wenyan

2012-01-01

Cistanche deserticola Y. C. Ma (C. deserticola, "Rou Cong Rong" in Chinese) is an officinal plant that grows in arid or semi-arid areas. The dried fleshy stem of C. deserticola has been generally used as a tonic in China and Japan for many years. Modern pharmacology studies have since demonstrated that C. deserticola possesses broad medicinal functions, especially for use in hormone regulation, aperient, immunomodulatory, neuroprotective, antioxidative, anti-apoptotic, anti-nociceptive, anti-inflammatory, anti-fatigue activities and the promotion of bone formation. The phenylethanoid glycosides (PhGs) presented in C. deserticola have been identified as the major active components. This review summarizes the up-to-date and comprehensive information on C. deserticola covering the aspects of the botany, traditional uses, phytochemistry, and pharmacology.

On the pharmacological properties of Delta9-tetrahydrocannabinol (THC).

PubMed

Costa, Barbara

2007-08-01

Cannabis is one of the first plants used as medicine, and the notion that it has potentially valuable therapeutic properties is a matter of current debate. The isolation of its main constituent, Delta9-tetrahydrocannabinol (THC), and the discovery of the endocannabinoid system (cannabinoid receptors CB1 and CB2 and their endogenous ligands) made possible studies concerning the pharmacological activity of cannabinoids. This paper reviews some of the most-important findings in the field of THC pharmacology. Clinical trials, anecdotal reports, and experiments employing animal models strongly support the idea that THC and its derivatives exhibit a wide variety of therapeutic applications. However, the psychotropic effects observed in laboratory animals and the adverse reactions reported during human trials, as well as the risk of tolerance development and potential dependence, limit the application of THC in therapy. Nowadays, researchers focus on other therapeutic strategies by which the endocannabinoid system might be modulated to clinical advantage (inhibitor or activator of endocannabinoid biosynthesis, cellular uptake, or metabolism). However, emerging evidence highlights the beneficial effects of the whole cannabis extract over those observed with single components, indicating cannabis-based medicines as new perspective to revisit the pharmacology of this plant.

Traditional Uses, Phytochemistry, and Pharmacology of Olea europaea (Olive)

PubMed Central

Hashmi, Muhammad Ali; Khan, Afsar; Hanif, Muhammad; Farooq, Umar; Perveen, Shagufta

2015-01-01

Aim of the Review. To grasp the fragmented information available on the botany, traditional uses, phytochemistry, pharmacology, and toxicology of Olea europaea to explore its therapeutic potential and future research opportunities. Material and Methods. All the available information on O. europaea was collected via electronic search (using Pubmed, Scirus, Google Scholar, and Web of Science) and a library search. Results. Ethnomedical uses of O. europaea are recorded throughout the world where it has been used to treat various ailments. Phytochemical research had led to the isolation of flavonoids, secoiridoids, iridoids, flavanones, biophenols, triterpenes, benzoic acid derivatives, isochromans, and other classes of secondary metabolites from O. europaea. The plant materials and isolated components have shown a wide spectrum of in vitro and in vivo pharmacological activities like antidiabetic, anticonvulsant, antioxidant, anti-inflammatory, immunomodulatory, analgesic, antimicrobial, antiviral, antihypertensive, anticancer, antihyperglycemic, antinociceptive, gastroprotective, and wound healing activities. Conclusions. O. europaea emerged as a good source of traditional medicine for the treatment of various ailments. The outcomes of phytochemical and pharmacological studies reported in this review will further expand its existing therapeutic potential and provide a convincing support to its future clinical use in modern medicine. PMID:25802541

Biological properties of 6-gingerol: a brief review.

PubMed

Wang, Shaopeng; Zhang, Caihua; Yang, Guang; Yang, Yanzong

2014-07-01

Numerous studies have revealed that regular consumption of certain fruits and vegetables can reduce the risk of many diseases. The rhizome of Zingiber officinale (ginger) is consumed worldwide as a spice and herbal medicine. It contains pungent phenolic substances collectively known as gingerols. 6-Gingerol is the major pharmacologically-active component of ginger. It is known to exhibit a variety of biological activities including anticancer, anti-inflammation, and anti-oxidation. 6-Gingerol has been found to possess anticancer activities via its effect on a variety of biological pathways involved in apoptosis, cell cycle regulation, cytotoxic activity, and inhibition of angiogenesis. Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, 6-gingerol has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various diseases. Taken together, this review summarizes the various in vitro and in vivo pharmacological aspects of 6-gingerol and the underlying mechanisms.

[Modern research progress of traditional Chinese medicine based on integrative pharmacology].

PubMed

Wang, Ping; Tang, Shi-Huan; Su, Jin; Zhang, Jia-Qi; Cui, Ru-Yi; Xu, Hai-Yu; Yang, Hong-Jun

2018-04-01

Integrative pharmacology (IP) is a discipline that studies the interaction, integration and principle of action of multiple components with the body, emphasizing the integrations of multi-level and multi-link, such as "whole and part", " in vivo and in vitro ", " in vivo process and activity evaluation". After four years of development and practice, the theory and method of IP has received extensive attention and application.In order to better promote the development of IP, this paper systematically reviews the concepts, research contents, research methods and application fields about IP. Copyright© by the Chinese Pharmaceutical Association.

Phytochemicals and bioactivities of Anemone raddeana Regel: a review.

PubMed

Sun, Yong-Xu; Liu, Ji-Cheng; Liu, Da-You

2011-11-01

Anemone raddeana, usually called as'"Toujian Liang" in China, is an Anemone herb belonging to the Ranunculaceae family. Until now there are in total 67 of chemical components identified including triterpenoids, steroids, lactones, fats and oils, saccharide and alkaloids. A broad spectrum of pharmacological activity of A. raddeana compounds have been reported, such as antitumor, antimicrobial, anti-inflammatory, sedative and analgesic activites, as well as anti-convulsant and anti-histamine effects. In view of this, we initiated this short review to present the phytochemical and pharmacological profile of A. raddeana to support future studies in this discipline.

Deconstructing the traditional Japanese medicine "Kampo": compounds, metabolites and pharmacological profile of maoto, a remedy for flu-like symptoms.

PubMed

Nishi, Akinori; Ohbuchi, Katsuya; Kushida, Hirotaka; Matsumoto, Takashi; Lee, Keiko; Kuroki, Haruo; Nabeshima, Shigeki; Shimobori, Chika; Komokata, Nagisa; Kanno, Hitomi; Tsuchiya, Naoko; Zushi, Makoto; Hattori, Tomohisa; Yamamoto, Masahiro; Kase, Yoshio; Matsuoka, Yukiko; Kitano, Hiroaki

2017-01-01

Pharmacological activities of the traditional Japanese herbal medicine (Kampo) are putatively mediated by complex interactions between multiple herbal compounds and host factors, which are difficult to characterize via the reductive approach of purifying major bioactive compounds and elucidating their mechanisms by conventional pharmacology. Here, we performed comprehensive compound, pharmacological and metabolomic analyses of maoto, a pharmaceutical-grade Kampo prescribed for flu-like symptoms, in normal and polyI:C-injected rats, the latter suffering from acute inflammation via Toll-like receptor 3 activation. In total, 352 chemical composition-determined compounds (CCDs) were detected in maoto extract by mass spectrometric analysis. After maoto treatment, 113 CCDs were newly detected in rat plasma. Of these CCDs, 19 were present in maoto extract, while 94 were presumed to be metabolites generated from maoto compounds or endogenous substances such as phospholipids. At the phenotypic level, maoto ameliorated the polyI:C-induced decrease in locomotor activity and body weight; however, body weight was not affected by individual maoto components in isolation. In accordance with symptom relief, maoto suppressed TNF-α and IL-1β, increased IL-10, and altered endogenous metabolites related to sympathetic activation and energy expenditure. Furthermore, maoto decreased inflammatory prostaglandins and leukotrienes, and increased anti-inflammatory eicosapentaenoic acid and hydroxyl-eicosapentaenoic acids, suggesting that it has differential effects on eicosanoid metabolic pathways involving cyclooxygenases, lipoxygenases and cytochrome P450s. Collectively, these data indicate that extensive profiling of compounds, metabolites and pharmacological phenotypes is essential for elucidating the mechanisms of herbal medicines, whose vast array of constituents induce a wide range of changes in xenobiotic and endogenous metabolism.

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

PubMed Central

Brinker, Anita M.; Ma, Jun; Lipsky, Peter E.; Raskin, Ilya

2013-01-01

Plants in the genus Tripterygium, such as Tripterygium wilfordii Hook. f., have a long history of use in traditional Chinese medicine. In recent years there has been considerable interest in the use of Tripterygium extracts and of the main bioactive constituent, the diterpene triepoxide triptolide (1), to treat a variety of autoimmune and inflammation-related conditions. The main mode of action of the Tripterygium extracts and triptolide (1) is the inhibition of expression of proinflammatory genes such as those for interleukin-2 (IL-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-γ). The efficacy and safety of certain types of Tripterygium extracts were confirmed in human clinical trials in the US and abroad. Over 300 compounds have been identified in the genus Tripterygium, and many of these have been evaluated for biological activity. The overall activity of the extract is based on the interaction between its components. Therefore, the safety and efficacy of the extract cannot be fully mimicked by any individual constituent. This review discusses the biochemical composition and biological and pharmacological activities of Tripterygium extracts, and their main bioactive components. PMID:17250858

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae).

PubMed

Brinker, Anita M; Ma, Jun; Lipsky, Peter E; Raskin, Ilya

2007-03-01

Plants in the genus Tripterygium, such as Tripterygium wilfordii Hook.f., have a long history of use in traditional Chinese medicine. In recent years there has been considerable interest in the use of Tripterygium extracts and of the main bioactive constituent, the diterpene triepoxide triptolide (1), to treat a variety of autoimmune and inflammation-related conditions. The main mode of action of the Tripterygium extracts and triptolide (1) is the inhibition of expression of proinflammatory genes such as those for interleukin-2 (IL-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-gamma). The efficacy and safety of certain types of Tripterygium extracts were confirmed in human clinical trials in the US and abroad. Over 300 compounds have been identified in the genus Tripterygium, and many of these have been evaluated for biological activity. The overall activity of the extract is based on the interaction between its components. Therefore, the safety and efficacy of the extract cannot be fully mimicked by any individual constituent. This review discusses the biochemical composition and biological and pharmacological activities of Tripterygium extracts, and their main bioactive components.

Systems biology impact on antiepileptic drug discovery.

PubMed

Margineanu, Doru Georg

2012-02-01

Systems biology (SB), a recent trend in bioscience research to consider the complex interactions in biological systems from a holistic perspective, sees the disease as a disturbed network of interactions, rather than alteration of single molecular component(s). SB-relying network pharmacology replaces the prevailing focus on specific drug-receptor interaction and the corollary of rational drug design of "magic bullets", by the search for multi-target drugs that would act on biological networks as "magic shotguns". Epilepsy being a multi-factorial, polygenic and dynamic pathology, SB approach appears particularly fit and promising for antiepileptic drug (AED) discovery. In fact, long before the advent of SB, AED discovery already involved some SB-like elements. A reported SB project aimed to find out new drug targets in epilepsy relies on a relational database that integrates clinical information, recordings from deep electrodes and 3D-brain imagery with histology and molecular biology data on modified expression of specific genes in the brain regions displaying spontaneous epileptic activity. Since hitting a single target does not treat complex diseases, a proper pharmacological promiscuity might impart on an AED the merit of being multi-potent. However, multi-target drug discovery entails the complicated task of optimizing multiple activities of compounds, while having to balance drug-like properties and to control unwanted effects. Specific design tools for this new approach in drug discovery barely emerge, but computational methods making reliable in silico predictions of poly-pharmacology did appear, and their progress might be quite rapid. The current move away from reductionism into network pharmacology allows expecting that a proper integration of the intrinsic complexity of epileptic pathology in AED discovery might result in literally anti-epileptic drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

Traditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.H. Chen: A review.

PubMed

Wang, Ting; Guo, Rixin; Zhou, Guohong; Zhou, Xidan; Kou, Zhenzhen; Sui, Feng; Li, Chun; Tang, Liying; Wang, Zhuju

2016-07-21

Panax notoginseng (Burk.) F.H. Chen is a widely used traditional Chinese medicine known as Sanqi or Tianqi in China. This plant, which is distributed primarily in the southwest of China, has wide-ranging pharmacological effects and can be used to treat cardiovascular diseases, pain, inflammation and trauma as well as internal and external bleeding due to injury. This paper provides up-to-date information on investigations of this plant, including its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology. The possible uses and perspectives for future investigation of this plant are also discussed. The relevant information on Panax notoginseng (Burk.) F.H. Chen was collected from numerous resources, including classic books about Chinese herbal medicine, and scientific databases, including Pubmed, SciFinder, ACS, Ebsco, Elsevier, Taylor, Wiley and CNKI. More than 200 chemical compounds have been isolated from Panax notoginseng (Burk.) F.H. Chen, including saponins, flavonoids and cyclopeptides. The plant has pharmacological effects on the cardiovascular system, immune system as well as anti-inflammatory, anti-atherosclerotic, haemostatic and anti-tumour activities, etc. Panax notoginseng is a valuable traditional Chinese medical herb with multiple pharmacological effects. This review summarizes the botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of P. notoginseng, and presents the constituents and their corresponding chemical structures found in P. notoginseng comprehensively for the first time. Future research into its phytochemistry of bio-active components should be performed by using bioactivity-guided isolation strategies. Further work on elucidation of the structure-function relationship among saponins, understanding of multi-target network pharmacology of P. notoginseng, as well as developing its new clinical usage and comprehensive utilize will enhance the therapeutic potentials of P. notoginseng. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pharmacological characterization and chemical fractionation of a liposterolic extract of saw palmetto (Serenoa repens): effects on rat prostate contractility.

PubMed

Chua, Thiam; Eise, Nicole T; Simpson, Jamie S; Ventura, Sabatino

2014-03-14

Saw palmetto (Serenoa repens) was first used medicinally by native American Indians to treat urological disorders. Nowadays, saw palmetto extracts are widely used in Europe and North America to treat the urinary symptoms associated with benign prostatic hyperplasia even though its mechanisms of action are poorly understood. This study aimed to characterize the bioactive constituents of a lipid extract of saw palmetto that are able to affect contractility of the rat prostate gland. The mechanism of action will also be investigated. A commercially available lipid extract of saw palmetto was subjected to fractionation using normal phase column chromatography. Composition of fractions was assessed by proton nuclear magnetic resonance spectroscopy ((1)H NMR) and mass spectrometry (MS). Contractile activities of these fractions were evaluated pharmacologically using isolated preparations of rat prostate gland and compared to the activity of the crude extract. Saw palmetto extract inhibited contractions of the rat prostate gland which were consistent with smooth muscle relaxant activity. Only the ethyl acetate fraction resulting from chromatography inhibited contractions of isolated rat prostates similarly to the inhibition produced by the crude lipid extract. Comparison with authentic samples and analysis of NMR data revealed that this bioactivity was due to the fatty acid components present in the ethyl acetate fraction. Bioassay using various pharmacological tools identified multiple contractile mechanisms which were affected by the bioactive constituents. A fatty acid component of saw palmetto extract causes inhibition of prostatic smooth muscle contractions via a non-specific mechanism. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Quercetin, kaempferol and isorhamnetin in Elaeagnus pungens Thunb. leaf: pharmacological activities and quantitative determination studies.

PubMed

Zhu, Ji-Xiao; Wen, Le; Zhong, Wei-Jin; Xiong, Li; Liang, Jian; Wang, Hong-Ling

2018-05-26

Elaeagnus pungens (E. pungens) leaf was documented to be very effective to treat asthma and chronic bronchitis both as traditional Chinese medicine and minority traditional medicine; yet the actual effective components still remain unknown. This work is to investigate the anti-inflammatory, antalgic and antitussive activities of E. pungens leaf, quercetin and kaempferol, and their contents in E. pungens leaf. Pharmacological experiments showed they could considerably reduce ear-swelling of mouse and relieve writhing reaction of mouse; they could also prevent mouse from coughing, significantly. These findings suggested quercetin and kaempferol are major effective components treating asthma and chronic bronchitis. Quantitative analysis results indicated the levels of quercetin, kaempferol and isorhamnetin varied greatly in different species of Elaeagnus and in different plant parts: E. pungens leaf is more similar to Elaeagnus umbellate leaf chemically; quercetin level is exceptionally high in Elaeagnus oldhami leaf; E. pungens leaf is a better medical part for treating asthma and chronic bronchitis in comparison with other parts. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effects of Insecticidal Ketones Present in Mint Plants on GABAA Receptor from Mammalian Neurons

PubMed Central

Sánchez-Borzone, Mariela Eugenia; Marin, Leticia Delgado; García, Daniel Asmed

2017-01-01

Background: The genus Mentha, an important member of the Lamiaceae family, is represented by many species commonly known as mint. The insecticidal activity of Mentha oil and its main components has been tested and established against various insects/pests. Among these, the ketone monoterpenes that are most common in different Mentha species demonstrated insect toxicity, with pulegone being the most active, followed by carvone and menthone. Considering that the GABAA receptor (GABAA-R) is one of the main insecticide targets on neurons, and that pulegone would modulate the insect GABA system, it may be expected that the insecticidal properties of Mentha ketones are mediated by their interaction with this receptor. Objective: In order to discern the pharmacological actions of these products when used as insecticides on mammalian organisms, we evaluated the pharmacologic activity of ketones, commonly present in Mentha plants, on native GABAA-R from rats. Materials and Methods: Determination of ketones effects on allosterically enhanced benzodiazepine binding, using primary cultures of cortical neurons, which express functional receptors and MTT assay to evaluate their cell toxicity. Results: Our results seem to indicate that ketone components of Mentha, with proven repellent or insecticide activity, were able to behave as GABAA-R negative allosteric modulators in murine cells and consequently could exhibit convulsant activity in mammalians. Only pulegone at the highest assayed concentration (2 mM) showed a significant reduction in cell viability after exposure for 24 hr. Conclusion: The present results strongly suggest that the ketone components of Mentha are able to exhibit convulsant activity in mammalian organisms, but functional assays and in vivo experiments would be necessary to corroborate this proposed action. SUMMARY The pharmacological activity of insecticide ketones, commonly present in Mentha plants, was evaluated on native GABAA receptor from mammalian neurons.All studied compounds: pulegone, menthone and dihydrocarvone, were able to behave as negative allosteric modulators and could exhibit convulsant activity in mammalian organisms.Citotoxicity assays demonstrated that only pulegone affected the cell viability. Abbreviations used: GABA: gamma aminobutyric acid, GABAA-R: GABAA receptor, MTT: 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazam, DMEM: Dulbecco's modified minimum essential mèdium, [3H]TBOB: [3H] t-Butylbicycloorthobenzoate PMID:28216893

Neuropharmacological effects of Nigella sativa

PubMed Central

Beheshti, Farimah; Khazaei, Majid; Hosseini, Mahmoud

2016-01-01

Nigella sativa (NS) (Ranunculaceae family) is generally utilized as a therapeutic plant all over the world. The seeds of the plant have a long history of use in different frameworks of medicines and food. In Islamic literature, it is considered as one of the greatest forms of therapeutics. It has been widely used to treat nervous system diseases such as memory impairment, epilepsy, neurotoxicity, pain, etc. Additionally, this is uncovered that the majority of therapeutic properties of this plant are due to the presence of thymoquinone (TQ) which is a major bioactive component of the essential oil. Pharmacological studies have been done to evaluate the effects of NS on the central nervous system (CNS). The present review is an effort to provide a detailed scientific literature survey about pharmacological activities of the plant on nervous system. Our literature review showed that NS and its components can be considered as promising agents in the treatment of nervous system disorders. PMID:27247928

The Neuroprotective Effects of Thymoquinone: A Review

PubMed Central

Farkhondeh, Tahereh; Samarghandian, Saeed; Samini, Fariborz

2018-01-01

Thymoquinone (TQ), one of the main components active of Nigella sativa, exhibited very useful biomedical effects such as anti-inflammatory, antioxidant, antimicrobial, antiparasitic, anticancer, hypoglycemic, antihypertensive, and antiasthmatic effects. There are several studies about pharmacological activities of TQ but its neuroprotection effects are not fully described. The literature search has indicated many studies pertaining to the effects of TQ in neurological problems such as epilepsy, parkinsonism, anxiety, and improvement of learning and memory, and so on. In addition, TQ protected brain cells from various injuries due to its antioxidant, anti-inflammatory, and apoptotic effects in cell line and experimental animal models. The present study has been designed to review the scientific literature about the pharmacological activities of TQ to the neurological diseases. This study purposed that although experimental studies indicated the beneficial effects of TQ against nervous system problems, better designed clinical trials in humans are needed to confirm these effects. PMID:29662431

Ligands for Ionotropic Glutamate Receptors

PubMed Central

Swanson, Geoffrey T.; Sakai, Ryuichi

2010-01-01

Marine-derived small molecules and peptides have played a central role in elaborating pharmacological specificities and neuronal functions of mammalian ionotropic glutamate receptors (iGluRs), the primary mediators of excitatory synaptic transmission in the central nervous system (CNS). As well, the pathological sequelae elicited by one class of compounds (the kainoids) constitute a widely-used animal model for human mesial temporal lobe epilepsy (mTLE). New and existing molecules could prove useful as lead compounds for the development of therapeutics for neuropathologies that have aberrant glutamatergic signaling as a central component. In this chapter we discuss natural source origins and pharmacological activities of those marine compounds that target ionotropic glutamate receptors. PMID:19184587

Ligands for Ionotropic Glutamate Receptors

NASA Astrophysics Data System (ADS)

Swanson, Geoffrey T.; Sakai, Ryuichi

Marine-derived small molecules and peptides have played a central role in elaborating pharmacological specificities and neuronal functions of mammalian ionotropic glutamate receptors (iGluRs), the primary mediators of excitatory syn-aptic transmission in the central nervous system (CNS). As well, the pathological sequelae elicited by one class of compounds (the kainoids) constitute a widely-used animal model for human mesial temporal lobe epilepsy (mTLE). New and existing molecules could prove useful as lead compounds for the development of therapeutics for neuropathologies that have aberrant glutamatergic signaling as a central component. In this chapter we discuss natural source origins and pharmacological activities of those marine compounds that target ionotropic glutamate receptors.

Pharmacology education for nurse prescribing students – a lesson in reusable learning objects

PubMed Central

Lymn, Joanne S; Bath-Hextall, Fiona; Wharrad, Heather J

2008-01-01

Background The shift away from a biological science to a social science model of nursing care has resulted in a reduction in pharmacology knowledge and understanding in pre-registration nursing students. This has a significant impact on nurse prescribing training where pharmacology is a critical component of the course from a patient safety perspective. Methods Reusable learning objects (RLOs) are electronic resources based on a single learning objective which use high quality graphics and audio to help engagement with the material and to facilitate learning. This study used questionnaire data from three successive cohorts of nurse prescribing students (n = 84) to evaluate the use of RLOs focussed around pharmacology concepts to promote the understanding of these concepts in students. A small number of students (n = 10) were followed up by telephone interview one year after qualification to gain further insight into students' perceptions of the value of RLOs as an educational tool. Results Students' perceptions of their own understanding of pharmacology concepts increased substantially following the introduction of RLOs to supplement the pharmacology component of the course. Student evaluation of the RLOs themselves was extremely positive with a number of students continuing to access these tools post-qualification. Conclusion The use of RLOs to support the pharmacology component of nurse prescribing courses successfully resulted in a perceived increase in pharmacology understanding, with some students directly implicating these educational tools in developing confidence in their own prescribing abilities. PMID:18215261

A Review of Botanical Characteristics, Traditional Usage, Chemical Components, Pharmacological Activities, and Safety of Pereskia bleo (Kunth) DC

PubMed Central

Tan, Chay-Hoon

2014-01-01

Pereskia bleo, a leafy cactus, is a medicinal plant native to West and South America and distributed in tropical and subtropical areas. It is traditionally used as a dietary vegetable, barrier hedge, water purifier, and insect repellant and for maintaining health, detoxification, prevention of cancer, and/or treatment of cancer, hypertension, diabetes, stomach ache, muscle pain, and inflammatory diseases such as dermatitis and rheumatism. The aim of this paper was to provide an up-to-date and comprehensive review of the botanical characteristics, traditional usage, phytochemistry, pharmacological activities, and safety of P. bleo. A literature search using MEDLINE (via PubMed), Science direct, Scopus and Google scholar and China Academic Journals Full-Text Database (CNKI) and available eBooks and books in the National University of Singapore libraries in English and Chinese was conducted. The following keywords were used: Pereskia bleo, Pereskia panamensis, Pereskia corrugata, Rhodocacus corrugatus, Rhodocacus bleo, Cactus panamensis, Cactus bleo, Spinach cactus, wax rose, Perescia, and Chinese rose. This review revealed the association between the traditional usage of P. bleo and reported pharmacological properties in the literature. Further investigation on the pharmacological properties and phytoconstituents of P. bleo is warranted to further exploit its potentials as a source of novel therapeutic agents or lead compounds. PMID:24987426

A Review of Botanical Characteristics, Traditional Usage, Chemical Components, Pharmacological Activities, and Safety of Pereskia bleo (Kunth) DC.

PubMed

Zareisedehizadeh, Sogand; Tan, Chay-Hoon; Koh, Hwee-Ling

2014-01-01

Pereskia bleo, a leafy cactus, is a medicinal plant native to West and South America and distributed in tropical and subtropical areas. It is traditionally used as a dietary vegetable, barrier hedge, water purifier, and insect repellant and for maintaining health, detoxification, prevention of cancer, and/or treatment of cancer, hypertension, diabetes, stomach ache, muscle pain, and inflammatory diseases such as dermatitis and rheumatism. The aim of this paper was to provide an up-to-date and comprehensive review of the botanical characteristics, traditional usage, phytochemistry, pharmacological activities, and safety of P. bleo. A literature search using MEDLINE (via PubMed), Science direct, Scopus and Google scholar and China Academic Journals Full-Text Database (CNKI) and available eBooks and books in the National University of Singapore libraries in English and Chinese was conducted. The following keywords were used: Pereskia bleo, Pereskia panamensis, Pereskia corrugata, Rhodocacus corrugatus, Rhodocacus bleo, Cactus panamensis, Cactus bleo, Spinach cactus, wax rose, Perescia, and Chinese rose. This review revealed the association between the traditional usage of P. bleo and reported pharmacological properties in the literature. Further investigation on the pharmacological properties and phytoconstituents of P. bleo is warranted to further exploit its potentials as a source of novel therapeutic agents or lead compounds.

Neural control of salivary glands in ixodid ticks.

PubMed

Šimo, Ladislav; Zitňan, Dušan; Park, Yoonseong

2012-04-01

Studies of tick salivary glands (SGs) and their components have produced a number of interesting discoveries over the last four decades. However, the precise neural and physiological mechanisms controlling SG secretion remain enigmatic. Major studies of SG control have identified and characterized many pharmacological and biological compounds that activate salivary secretion, including dopamine (DA), octopamine, γ-aminobutyric acid (GABA), ergot alkaloids, pilocarpine (PC), and their pharmacological relatives. Specifically, DA has shown the most robust activities in various tick species, and its effect on downstream actions in the SGs has been extensively studied. Our recent work on a SG dopamine receptor has aided new interpretations of previous pharmacological studies and provided new concepts for SG control mechanisms. Furthermore, our recent studies have suggested that multiple neuropeptides are involved in SG control. Myoinhibitory peptide (MIP) and SIFamide have been identified in the neural projections reaching the basal cells of acini types II and III. Pigment-dispersing factor (PDF)-immunoreactive neural projections reach type II acini, and RFamide- and tachykinin-immunoreactive projections reach the SG ducts, but the chemical nature of the latter three immunoreactive substances are unidentified yet. Here, we briefly review previous pharmacological studies and provide a revised summary of SG control mechanisms in ticks. Copyright © 2011 Elsevier Ltd. All rights reserved.

Relationship Between Emotional Behavior in Mice and the Concentration of (+)-α-Santalol in the Brain.

PubMed

Satou, Tadaaki; Ogawa, Yuko; Koike, Kazuo

2015-08-01

We previously reported finding anxiolytic-like activity for sandalwood oil after administration in mice. In this report, we further investigated the emotional behavior associated with inhaled or intraperitoneally administered (+)-α-santalol, the main component of sandalwood oil, in addition to examining whether pharmacological or neurological transfers are responsible for this behavior. After administration of (+)-α-santalol by inhalation or intraperitoneal injection, we assessed anxiolytic-like and locomotor activities using elevated-plus maze tests. We also examined the relationship between the emotional behavior and the (+)-α-santalol brain concentration. Anxiolytic-like activity was not observed immediately after administration or after water-immersion stress for 24 h for either the (+)-α-santalol 2 μL/L air inhalation or the (+)-α-santalol 0.03 mL/kg (i.p.) administration. However, mice administered (+)-α-santalol 0.03 mL/kg intraperitoneally exhibited a significant decrease in the locomotor activity after exposure to water-immersion stress for 24 h. The brain (+)-α-santalol concentration was 2.6 µg/g tissue after (+)-α-santalol 0.03 mL/kg (i.p.) administration. The observed shift of (+)-α-santalol to the brain suggests that this component acts via pharmacological transfer and is responsible for the sedative effect but not the anxiolytic-like activity. Copyright © 2015 John Wiley & Sons, Ltd.

Aloysia citrodora Paláu (Lemon verbena): A review of phytochemistry and pharmacology.

PubMed

Bahramsoltani, Roodabeh; Rostamiasrabadi, Pourouchista; Shahpiri, Zahra; Marques, André M; Rahimi, Roja; Farzaei, Mohammad Hosein

2018-08-10

Aloysia citrodora Paláu (Lippia citriodora Kunth), commonly known as "lemon verbena" is a medicinal plant native to South America, North Africa, and South of Europe which is used by native people for several indications such as diarrhea, flatulence, insomnia, and rheumatism. Despite the wide biological activities of lemon verbena, there is no current review summarizing medicinal properties of the plant; thus, this paper aims to discuss current state of the art regarding the phytochemistry, pharmacology, and therapeutic applications of A. citrodora considering in vitro, in vivo, and clinical studies. Electronic databases including PubMed, Scifinder, Cochrane library, Scopus, and Science direct were searched with the scientific name of the plant and its synonyms, as well as the common name. All studies on the ethnobotany, phytochemistry, pharmacology, and clinical application of the plant until October 2017 were included in this review. Despite the few number of studies on the ethnopharmacology of the plant, A. citrodora is widely assessed regarding its phytochemistry and biological activities. Neral and geranial are the main ingredients of the essential oil; whereas verbascoside is the most significant component of the extract. Biological activities such as antioxidant, anxiolytic, neuroprotective, anticancer, anesthetic, antimicrobial, and sedative effects are proved in cell cultures, as well as animal studies. Several pharmacological activities have been reported for A. citrodora; however, the plant is not fully assessed regarding its safety and efficacy in human. Future well-designed human studies are essential to confirm the therapeutic benefits of this plant in clinical settings. Copyright © 2018 Elsevier B.V. All rights reserved.

Berberis Vulgaris and Berberine: An Update Review.

PubMed

Imenshahidi, Mohsen; Hosseinzadeh, Hossein

2016-11-01

Berberine is an isoquinoline alkaloid present in several plants, including Coptis sp. and Berberis sp. Berberine is a customary component in Chinese medicine, and is characterized by a diversity of pharmacological effects. An extensive search in electronic databases (PubMed, Scopus, Ovid, Wiley, ProQuest, ISI, and Science Direct) were used to identify the pharmacological and clinical studies on Berberis vulgaris and berberine, during 2008 to 2015, using 'berberine' and 'Berberis vulgaris' as search words. We found more than 1200 new article studying the properties and clinical uses of berberine and B. vulgaris, for treating tumor, diabetes, cardiovascular disease, hyperlipidemia, inflammation, bacterial and viral infections, cerebral ischemia trauma, mental disease, Alzheimer disease, osteoporosis, and so on. In this article, we have updated the pharmacological effects of B. vulgaris and its active constituent, berberine. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Chemical and Biological Properties of S-1-Propenyl-l-Cysteine in Aged Garlic Extract.

PubMed

Kodera, Yukihioro; Ushijima, Mitsuyasu; Amano, Hirotaka; Suzuki, Jun-Ichiro; Matsutomo, Toshiaki

2017-03-31

S-1-Propenyl-l-cysteine (S1PC) is a stereoisomer of S-1-Propenyl-l-cysteine (SAC), an important sulfur-containing amino acid that plays a role for the beneficial pharmacological effects of aged garlic extract (AGE). The existence of S1PC in garlic preparations has been known since the 1960's. However, there was no report regarding the biological and/or pharmacological activity of S1PC until 2016. Recently, we performed a series of studies to examine the chemical, biological, pharmacological and pharmacokinetic properties of S1PC, and obtained some interesting results. S1PC existed only in trace amounts in raw garlic, but its concentration increased almost up to the level similar of SAC through aging process of AGE. S1PC showed immunomodulatory effects in vitro and in vivo, and reduced blood pressure in a hypertensive animal model. A pharmacokinetic study revealed that S1PC was readily absorbed after oral administration in rats and dogs with bioavailability of 88-100%. Additionally, S1PC had little inhibitory influence on human cytochrome P450 activities, even at a concentration of 1 mM. Based on these findings, S1PC was suggested to be another important, pharmacologically active and safe component of AGE similar to SAC. In this review, we highlight some results from recent studies on S1PC and discuss the potential medicinal value of S1PC.

Network pharmacology-based prediction of active compounds and molecular targets in Yijin-Tang acting on hyperlipidaemia and atherosclerosis.

PubMed

Lee, A Yeong; Park, Won; Kang, Tae-Wook; Cha, Min Ho; Chun, Jin Mi

2018-07-15

Yijin-Tang (YJT) is a traditional prescription for the treatment of hyperlipidaemia, atherosclerosis and other ailments related to dampness phlegm, a typical pathological symptom of abnormal body fluid metabolism in Traditional Korean Medicine. However, a holistic network pharmacology approach to understanding the therapeutic mechanisms underlying hyperlipidaemia and atherosclerosis has not been pursued. To examine the network pharmacological potential effects of YJT on hyperlipidaemia and atherosclerosis, we analysed components, performed target prediction and network analysis, and investigated interacting pathways using a network pharmacology approach. Information on compounds in herbal medicines was obtained from public databases, and oral bioavailability and drug-likeness was screened using absorption, distribution, metabolism, and excretion (ADME) criteria. Correlations between compounds and genes were linked using the STITCH database, and genes related to hyperlipidaemia and atherosclerosis were gathered using the GeneCards database. Human genes were identified and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Network analysis identified 447 compounds in five herbal medicines that were subjected to ADME screening, and 21 compounds and 57 genes formed the main pathways linked to hyperlipidaemia and atherosclerosis. Among them, 10 compounds (naringenin, nobiletin, hesperidin, galangin, glycyrrhizin, homogentisic acid, stigmasterol, 6-gingerol, quercetin and glabridin) were linked to more than four genes, and are bioactive compounds and key chemicals. Core genes in this network were CASP3, CYP1A1, CYP1A2, MMP2 and MMP9. The compound-target gene network revealed close interactions between multiple components and multiple targets, and facilitates a better understanding of the potential therapeutic effects of YJT. Pharmacological network analysis can help to explain the potential effects of YJT for treating dampness phlegm-related diseases such as hyperlipidaemia and atherosclerosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Linking quality of healthcare and health-related quality of life of patients with type 2 diabetes: an evaluative study in Mexican family practice.

PubMed

Doubova, Svetlana V; Mino-León, Dolores; Pérez-Cuevas, Ricardo

2013-12-01

To assess the association between quality of care and health-related quality of life among type 2 diabetes patients. A cross-sectional study assessing the association between quality of care and quality of life using multiple linear regression analysis. Family medicine clinics (FMC) (n = 39) of the Mexican Institute of Social Security (IMSS) in Mexico City. Type 2 diabetes patients (n = 312), older than 19 years. Health-related quality of life was measured using the MOS Short-Form-12 (SF-12); quality of healthcare was measured as the percentage of recommended care received under each of four domains: early detection of diabetes complications, non-pharmacological treatment, pharmacological treatment and health outcomes. The average quality of life score was 41.4 points on the physical component and 47.9 points on the mental component. Assessment of the quality of care revealed deficiencies. The average percentages of recommended care received were 21.9 for health outcomes and 56.6 for early detection of diabetes complications and pharmacological treatment; for every 10 percent additional points on the pharmacological treatment component, quality of life improved by 0.4 points on the physical component (coefficient 0.04, 95% confidence intervals 0.01-0.07). There was a positive association between the quality of pharmacological care and the physical component of quality of life. The quality of healthcare for type 2 diabetes patients in FMC of the IMSS in Mexico City is not optimal.

In Vivo Evaluation of the Antiasthmatic, Antitussive, and Expectorant Activities and Chemical Components of Three Elaeagnus Leaves

PubMed Central

Ge, Yuebin; Zhang, Fei; Qin, Qin; Shang, Yingying; Wan, Dingrong

2015-01-01

The leaf of Elaeagnus lanceolata and Elaeagnus henryi as well as Elaeagnus pungens has been documented as an effective herb for the treatment of asthma and chronic bronchitis in traditional clinical medicine. This study was aimed at evaluating the antiasthmatic, antitussive, and expectorant activities of the water extracts from the three plants in vivo and analyzing their chemical components by HPLC-DAD. At the medium and high doses, the water extracts of three Elaeagnus leaves significantly prolonged the preconvulsive time (P < 0.01) in guinea pigs, lengthened the latent period of cough (P < 0.01) and decreased the cough frequency caused by aqueous ammonia in mice (P < 0.01), and enhanced tracheal phenol red output in mice (P < 0.01). There were no significant differences in the pharmacological actions between the three Elaeagnus leaves. Moreover, there was more similarity on overlap peaks in the range of retention time from 10 to 40 min by HPLC and many peaks that belonged to flavonoids compounds. It suggested that the main constituents of the three Elaeagnus leaves were flavonoid for the pharmacological activities. These effects were the important evidence for the traditional use of E. henryi leaf and E. lanceolata leaf as well as E. pungens to treat asthma and chronic bronchitis. PMID:26576193

In Vivo Evaluation of the Antiasthmatic, Antitussive, and Expectorant Activities and Chemical Components of Three Elaeagnus Leaves.

PubMed

Ge, Yuebin; Zhang, Fei; Qin, Qin; Shang, Yingying; Wan, Dingrong

2015-01-01

The leaf of Elaeagnus lanceolata and Elaeagnus henryi as well as Elaeagnus pungens has been documented as an effective herb for the treatment of asthma and chronic bronchitis in traditional clinical medicine. This study was aimed at evaluating the antiasthmatic, antitussive, and expectorant activities of the water extracts from the three plants in vivo and analyzing their chemical components by HPLC-DAD. At the medium and high doses, the water extracts of three Elaeagnus leaves significantly prolonged the preconvulsive time (P < 0.01) in guinea pigs, lengthened the latent period of cough (P < 0.01) and decreased the cough frequency caused by aqueous ammonia in mice (P < 0.01), and enhanced tracheal phenol red output in mice (P < 0.01). There were no significant differences in the pharmacological actions between the three Elaeagnus leaves. Moreover, there was more similarity on overlap peaks in the range of retention time from 10 to 40 min by HPLC and many peaks that belonged to flavonoids compounds. It suggested that the main constituents of the three Elaeagnus leaves were flavonoid for the pharmacological activities. These effects were the important evidence for the traditional use of E. henryi leaf and E. lanceolata leaf as well as E. pungens to treat asthma and chronic bronchitis.

Titration-based screening for evaluation of natural product extracts: identification of an aspulvinone family of luciferase inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cruz, P.G.; Auld, D.S.; Schultz, P.J.

2011-11-28

The chemical diversity of nature has tremendous potential for the discovery of molecular probes and medicinal agents. However, sensitivity of HTS assays to interfering components of crude extracts derived from plants, and macro- and microorganisms has curtailed their use in lead discovery. Here, we describe a process for leveraging the concentration-response curves obtained from quantitative HTS to improve the initial selection of actives from a library of partially fractionated natural product extracts derived from marine actinomycetes and fungi. By using pharmacological activity, the first-pass CRC paradigm improves the probability that labor-intensive subsequent steps of reculturing, extraction, and bioassay-guided isolation ofmore » active component(s) target the most promising strains and growth conditions. We illustrate how this process identified a family of fungal metabolites as potent inhibitors of firefly luciferase, subsequently resolved in molecular detail by X-ray crystallography.« less

Comparison of Immunomodulatory Effects of Fresh Garlic and Black Garlic Polysaccharides on RAW 264.7 Macrophages.

PubMed

Li, Min; Yan, Yi-Xi; Yu, Qing-Tao; Deng, Yong; Wu, Ding-Tao; Wang, Ying; Ge, Ya-Zhong; Li, Shao-Ping; Zhao, Jing

2017-03-01

Garlic has a long history to be used for medicine and food purposes. Black garlic, the fermented product of fresh garlic, is considered with better biological activities, such as antioxidant activity, and is developed as an increasingly popular functional food. Polysaccharides are the major components of fresh and black garlic, and immunomodulatory activity is one major pharmacological effect of polysaccharides. Therefore, chemical characteristics and immunomodulatory effects of polysaccharides from fresh and black garlic are investigated and compared in vitro for the 1st time, in order to reveal their molecular and pharmacological differences. It is demonstrated that the molecular weights of polysaccharides from the 2 sources and molar ratios of monosaccharides after acid hydrolysis are greatly variant. The effects of polysaccharides from 2 sources on RAW 264.7 macrophages functions, including promotion of phagocytosis, release of NO, and expressions of several immune-related cytokines (including interleukin [IL]-6, IL-10, tumor necrosis factor alpha, and interferon gamma), were different from each other. The results indicated that fresh garlic polysaccharide exhibited stronger immunomodulatory activities than that of black garlic. Moreover, it is revealed that fructan might be the bioactive component in garlic and it is indicated that during the fermentation treatment, fructan constituents of garlic has degraded, and basically no immunomodulatory effect can be found in black garlic polysaccharides. © 2017 Institute of Food Technologists®.

Geraniol Induces Antinociceptive Effect in Mice Evaluated in Behavioural and Electrophysiological Models.

PubMed

La Rocca, Viviana; da Fonsêca, Diogo Vilar; Silva-Alves, Kerly Shamyra; Ferreira-da-Silva, Francisco Walber; de Sousa, Damião Pergentino; Santos, Priscila Laise; Quintans-Júnior, Lucindo José; Leal-Cardoso, José Henrique; de Almeida, Reinaldo Nóbrega

2017-01-01

Geraniol (GER) is a monoterpene alcohol with various biochemical and pharmacological properties present in the essential oil of more than 160 species of herbs (especially the Cymbopogon genus). In this study, we evaluated the antinociceptive activity of GER in behavioural and electrophysiological in vitro experimental models of nociception using male Swiss mice. GER (12.5, 25 or 50 mg/kg i.p. and 50 or 200 mg/kg p.o.) reduced the number of writhes induced by acetic acid. The opioid antagonist naloxone (5 mg/kg s.c.) administered in mice subsequently treated with GER (25 mg/kg i.p.) did not reverse such antinociceptive activity, suggesting a non-opioid pathway for the mechanism of action. GER (12.5, 25 and 50 mg/kg i.p.) reduced paw licking time in the second phase of the formalin test. Also, in the glutamate test, GER when administered 50 mg/kg i.p. reduced paw licking time, probably modulating glutamatergic neurotransmission. GER blocked reversibly components of the compound action potential (CAP) recorded in isolated sciatic nerve in a concentration- and drug exposure time-dependent manner: 1 mM to 120 min. for the first component and 0.6 mM to 90 min. for the second component. The IC 50 was calculated for the peak-to-peak amplitude (PPA) at 0.48 ± 0.04 mM. The conduction velocity was also reduced by exposure to GER starting from the concentration of 0.3 mM for both components of the CAP. In conclusion, it is suggested that GER has antinociceptive activity, especially in pain related to inflammation, and in part related to reduced peripheral nerve excitability. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Exploring the Therapeutic Mechanism of Desmodium styracifolium on Oxalate Crystal-Induced Kidney Injuries Using Comprehensive Approaches Based on Proteomics and Network Pharmacology.

PubMed

Hou, Jiebin; Chen, Wei; Lu, Hongtao; Zhao, Hongxia; Gao, Songyan; Liu, Wenrui; Dong, Xin; Guo, Zhiyong

2018-01-01

Purpose: As a Chinese medicinal herb, Desmodium styracifolium (Osb.) Merr (DS) has been applied clinically to alleviate crystal-induced kidney injuries, but its effective components and their specific mechanisms still need further exploration. This research first combined the methods of network pharmacology and proteomics to explore the therapeutic protein targets of DS on oxalate crystal-induced kidney injuries to provide a reference for relevant clinical use. Methods: Oxalate-induced kidney injury mouse, rat, and HK-2 cell models were established. Proteins differentially expressed between the oxalate and control groups were respectively screened using iTRAQ combined with MALDI-TOF-MS. The common differential proteins of the three models were further analyzed by molecular docking with DS compounds to acquire differential targets. The inverse docking targets of DS were predicted through the platform of PharmMapper. The protein-protein interaction (PPI) relationship between the inverse docking targets and the differential proteins was established by STRING. Potential targets were further validated by western blot based on a mouse model with DS treatment. The effects of constituent compounds, including luteolin, apigenin, and genistein, were investigated based on an oxalate-stimulated HK-2 cell model. Results: Thirty-six common differentially expressed proteins were identified by proteomic analysis. According to previous research, the 3D structures of 15 major constituents of DS were acquired. Nineteen differential targets, including cathepsin D (CTSD), were found using molecular docking, and the component-differential target network was established. Inverse-docking targets including p38 MAPK and CDK-2 were found, and the network of component-reverse docking target was established. Through PPI analysis, 17 inverse-docking targets were linked to differential proteins. The combined network of component-inverse docking target-differential proteins was then constructed. The expressions of CTSD, p-p38 MAPK, and p-CDK-2 were shown to be increased in the oxalate group and decreased in kidney tissue by the DS treatment. Luteolin, apigenin, and genistein could protect oxalate-stimulated tubular cells as active components of DS. Conclusion: The potential targets including the CTSD, p38 MAPK, and CDK2 of DS in oxalate-induced kidney injuries and the active components (luteolin, apigenin, and genistein) of DS were successfully identified in this study by combining proteomics analysis, network pharmacology prediction, and experimental validation.

The Multivariate Regression Statistics Strategy to Investigate Content-Effect Correlation of Multiple Components in Traditional Chinese Medicine Based on a Partial Least Squares Method.

PubMed

Peng, Ying; Li, Su-Ning; Pei, Xuexue; Hao, Kun

2018-03-01

Amultivariate regression statisticstrategy was developed to clarify multi-components content-effect correlation ofpanaxginseng saponins extract and predict the pharmacological effect by components content. In example 1, firstly, we compared pharmacological effects between panax ginseng saponins extract and individual saponin combinations. Secondly, we examined the anti-platelet aggregation effect in seven different saponin combinations of ginsenoside Rb1, Rg1, Rh, Rd, Ra3 and notoginsenoside R1. Finally, the correlation between anti-platelet aggregation and the content of multiple components was analyzed by a partial least squares algorithm. In example 2, firstly, 18 common peaks were identified in ten different batches of panax ginseng saponins extracts from different origins. Then, we investigated the anti-myocardial ischemia reperfusion injury effects of the ten different panax ginseng saponins extracts. Finally, the correlation between the fingerprints and the cardioprotective effects was analyzed by a partial least squares algorithm. Both in example 1 and 2, the relationship between the components content and pharmacological effect was modeled well by the partial least squares regression equations. Importantly, the predicted effect curve was close to the observed data of dot marked on the partial least squares regression model. This study has given evidences that themulti-component content is a promising information for predicting the pharmacological effects of traditional Chinese medicine.

Mango ginger (Curcuma amada Roxb.)--a promising spice for phytochemicals and biological activities.

PubMed

Policegoudra, R S; Aradhya, S M; Singh, L

2011-09-01

Mango ginger (Curcuma amada Roxb.) is a unique spice having morphological resemblance with ginger but imparts a raw mango flavour. The main use of mango ginger rhizome is in the manufacture of pickles and culinary preparations. Ayurveda and Unani medicinal systems have given much importance to mango ginger as an appetizer, alexteric, antipyretic, aphrodisiac, diuretic, emollient, expectorant and laxative and to cure biliousness, itching, skin diseases, bronchitis, asthma, hiccough and inflammation due to injuries. The biological activities of mango ginger include antioxidant activity, antibacterial activity, antifungal activity, anti-inflammatory activity, platelet aggregation inhibitory activity, cytotoxicity, antiallergic activity, hypotriglyceridemic activity, brine-shrimp lethal activity, enterokinase inhibitory activity, CNS depressant and analgesic activity. The major chemical components include starch, phenolic acids, volatile oils, curcuminoids and terpenoids like difurocumenonol, amadannulen and amadaldehyde. This article brings to light the major active components present in C. amada along with their biological activities that may be important from the pharmacological point of view.

Herb pair Danggui-Honghua: mechanisms underlying blood stasis syndrome by system pharmacology approach

NASA Astrophysics Data System (ADS)

Yue, Shi-Jun; Xin, Lan-Ting; Fan, Ya-Chu; Li, Shu-Jiao; Tang, Yu-Ping; Duan, Jin-Ao; Guan, Hua-Shi; Wang, Chang-Yun

2017-01-01

Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as HMOX1, NOS2, NOS3, HIF1A and PTGS2 were mainly involved in TNF signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway and neurotrophin signaling pathway. The contribution index of every active ingredient also indicated six compounds, including hydroxysafflor yellow A, safflor yellow A, safflor yellow B, Z-ligustilide, ferulic acid, and Z-butylidenephthalide, as the principal components of this herb pair. These results successfully explained the polypharmcological mechanisms underlying the efficiency of Danggui-Honghua for BSS treatment, and also probed into the potential novel therapeutic strategies for BSS in TCM.

Phytochemical and Pharmacological Profiles of Three Fagopyrum Buckwheats

PubMed Central

Jing, Rui; Li, Hua-Qiang; Hu, Chang-Ling; Jiang, Yi-Ping; Qin, Lu-Ping; Zheng, Cheng-Jian

2016-01-01

The genus Fagopyrum (Polygonaceae), currently comprising 15 species of plants, includes three important buckwheat species: Fagopyrum esculentum (F. esculentum) Moench. (common buckwheat), Fagopyrum tataricum (F. tataricum) (L.) Gaertn. (tartary buckwheat) and Fagopyrum dibotrys (F. dibotrys) (D. Don) Hara. (perennial buckwheat), which have been well explored due to their long tradition of both edible and medicinal use. This review aimed to present an up-to-date and comprehensive analysis of the phytochemistry and pharmacology of the three Fagopyrum buckwheats. In addition, the scope for future research was also discussed. All available references included in this paper were compiled from major databases, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. A total of 106 compounds isolated from three Fagopyrum buckwheats can be mainly divided into six classes: flavonoids, phenolics, fagopyritols, triterpenoids, steroids and fatty acids. Flavonoids and phenolic compounds were considered to be the major active components. Considerable pharmacological experiments both in vitro and in vivo have validated that Fagopyrum buckwheats possess antitumor, anti-oxidant, anti-inflammatory, hepatoprotective, anti-diabetic activities, etc. All reported data lead us to conclude that Fagopyrum buckwheats have convincing medicinal potential. However, further research is needed to explore its bioactive constituents, the relationship to their structural activities and the molecular mechanisms of action. PMID:27104519

Venoms of Heteropteran Insects: A Treasure Trove of Diverse Pharmacological Toolkits

PubMed Central

Walker, Andrew A.; Weirauch, Christiane; Fry, Bryan G.; King, Glenn F.

2016-01-01

The piercing-sucking mouthparts of the true bugs (Insecta: Hemiptera: Heteroptera) have allowed diversification from a plant-feeding ancestor into a wide range of trophic strategies that include predation and blood-feeding. Crucial to the success of each of these strategies is the injection of venom. Here we review the current state of knowledge with regard to heteropteran venoms. Predaceous species produce venoms that induce rapid paralysis and liquefaction. These venoms are powerfully insecticidal, and may cause paralysis or death when injected into vertebrates. Disulfide-rich peptides, bioactive phospholipids, small molecules such as N,N-dimethylaniline and 1,2,5-trithiepane, and toxic enzymes such as phospholipase A2, have been reported in predatory venoms. However, the detailed composition and molecular targets of predatory venoms are largely unknown. In contrast, recent research into blood-feeding heteropterans has revealed the structure and function of many protein and non-protein components that facilitate acquisition of blood meals. Blood-feeding venoms lack paralytic or liquefying activity but instead are cocktails of pharmacological modulators that disable the host haemostatic systems simultaneously at multiple points. The multiple ways venom is used by heteropterans suggests that further study will reveal heteropteran venom components with a wide range of bioactivities that may be recruited for use as bioinsecticides, human therapeutics, and pharmacological tools. PMID:26907342

Pharmacological and neuroprotective profile of an essential oil derived from leaves of Aloysia citrodora Palau.

PubMed

Abuhamdah, Sawsan; Abuhamdah, Rushdie; Howes, Melanie-Jayne R; Al-Olimat, Suleiman; Ennaceur, Abdel; Chazot, Paul L

2015-09-01

The Jordanian 'Melissa', (Aloysia citrodora) has been poorly studied both pharmacologically and in the clinic. Essential oils (EO) derived from leaves of A. citrodora were obtained by hydrodistillation, analysed by gas chromatography-mass spectrometry (GC-MS) and were investigated for a range of neurobiological and pharmacological properties, as a basis for potential future use in drug discovery. A selection of central nervous system (CNS) receptor-binding profiles was carried out. Antioxidant activity and ferrous iron-chelating assays were adopted, and the neuroprotective properties of A. citrodora EO assessed using hydrogen peroxide-induced and β-amyloid-induced neurotoxicity with the CAD (Cath.-a-differentiated) neuroblastoma cell line. The major chemical components detected in the A. citrodora EOs, derived from dried and fresh leaves, included limonene, geranial, neral, 1, 8-cineole, curcumene, spathulenol and caryophyllene oxide, respectively. A. citrodora leaf EO inhibited [(3) H] nicotine binding to well washed rat forebrain membranes, and increased iron-chelation in vitro. A. citrodora EO displays effective antioxidant, radical-scavenging activities and significant protective properties vs both hydrogen peroxide- and β-amyloid-induced neurotoxicity. A. citrodora EO displays a range of pharmacological properties worthy of further investigation to isolate the compounds responsible for the observed neuroactivities, to further analyse their mode of action and determine their clinical potential in neurodegenerative diseases. © 2015 Royal Pharmaceutical Society.

An Effective Quality Control of Pharmacologically Active Volatiles of Houttuynia cordata Thunb by Fast Gas Chromatography-Surface Acoustic Wave Sensor.

PubMed

Oh, Se Yeon

2015-06-03

Fast gas chromatography-surface acoustic wave sensor (GC/SAW) has been applied for the detection of the pharmacological volatiles emanated from Houttuynia cordata Thunb which is from South Korea. H. cordata Thunb with unpleasant and fishy odors shows a variety of pharmacological activities such as anti-microbial, anti-inflammatory, anti-cancer, and insect repellent. The aim of this study is to show a novel quality control by GC/SAW methodology for the discrimination of the three different parts of the plant such as leaves, aerial stems, and underground stems for H. cordata Thunb. Sixteen compounds were identified. β-Myrcene, cis-ocimene and decanal are the dominant volatiles for leaves (71.0%) and aerial stems (50.1%). While, monoterpenes (74.6%) are the dominant volatiles for underground stems. 2-Undecanone (1.3%) and lauraldehyde (3.5%) were found to be the characteristic components for leaves. Each part of the plant has its own characteristic fragrance pattern owing to its individual chemical compositions. Moreover, its individual characteristic fragrance patterns are conducive to discrimination of the three different parts of the plant. Consequently, fast GC/SAW can be a useful analytical method for quality control of the different parts of the plant with pharmacological volatiles as it provides second unit analysis, a simple and fragrant pattern recognition.

Anthocyanins in cardioprotection: A path through mitochondria.

PubMed

Liobikas, Julius; Skemiene, Kristina; Trumbeckaite, Sonata; Borutaite, Vilmante

2016-11-01

Constantly growing experimental data from in vitro, in vivo and epidemiological studies show the great potential of anthocyanin-containing fruit and berry extracts or pure individual anthocyanins as cardioprotective food components or pharmacological compounds. In general it is regarded that the cardioprotective activity of anthocyanins is related to their antioxidant properties. However there are recent reports that certain anthocyanins may protect the heart against ischemia/reperfusion-induced injury by activating signal transduction pathways and sustaining mitochondrial functions instead of acting solely as antioxidants. In this review, we summarize the proposed mechanisms of direct or indirect actions of anthocyanins within cardiac cells with the special emphasis on recently discovered their pharmacological effects on mitochondria in cardioprotection: reduction of cytosolic cytochrome c preventing apoptosis and sustainment of electron transfer between NADH dehydrogenase and cytochrome c supporting oxidative phosphorylation in ischemia-damaged mitochondria. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinacanthus nutans: A review of the medicinal uses, pharmacology and phytochemistry.

PubMed

Alam, Ariful; Ferdosh, Sahena; Ghafoor, Kashif; Hakim, Abdul; Juraimi, Abdul Shukor; Khatib, Alfi; Sarker, Zaidul I

2016-04-01

Clinacanthus nutans Lindau is known as snake grass belonging to the Acanthaceae family. This plant has diverse and potential medicinal uses in traditional herbal medicine for treating skin rashes, insects and snake bites, lesions caused by herpes simplex virus, diabetes, and gout in Malaysia, Indonesia, Thailand and China. Phytochemical investigations documented the varied contents of bioactive compounds from this plant namely flavonoids, glycosides, glycoglycerolipids, cerebrosides and monoacylmonogalatosylglycerol. The pharmacological experiment proved that various types of extracts and pure compounds from this species exhibited a broad range of biological properties such as anti-inflammatory, antiviral, antioxidant, and anti-diabetic activities. The findings of toxicity study showed that extracts from this plant did not show any toxicity thus it can be used as strong therapeutic agents for specific diseased conditions. However, further experiments on chemical components and their mode of action showing biological activities are required to elucidate the complete phytochemical profile and assess to confirm their suitability for future drugs. This review summarizes the medicinal uses, phytochemistry and pharmacology of this plant in order to explore its therapeutic potential and gaps necessitating for prospected research work. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Pharmacological and Toxicological Studies of Essential Oil of Lavandula stoechas subsp. luisieri.

PubMed

Arantes, Sílvia; Candeias, Fátima; Lopes, Orlando; Lima, Mónica; Pereira, Marízia; Tinoco, Teresa; Cruz-Morais, J; Martins, M Rosário

2016-09-01

The present study was carried out to evaluate the chemical and pharmacological properties of the essential oil of Lavandula stoechas subsp. luisieri, which is a spontaneous shrub widespread in Alentejo (Portugal). Oxygenated monoterpenes, such as 1,8-cineole, lavandulol, and necrodane derivatives, are the main components of essential oil. It revealed important antioxidant activity with a high ability to inhibit lipid peroxidation and showed an outstanding effect against a wide spectrum of microorganisms, such as gram-positive and gram-negative bacteria and pathogenic yeasts. The analgesic effect studied in rats was dose dependent, reaching a maximum of 67 % at 60 min with the dose of 200 mg/kg and the anti-inflammatory activity with this dose caused an inhibition in carrageenan-induced rat paw oedema (83 %) that is higher than dexamethasone 1 mg/Kg (69 %). Besides, animals exhibited normal behaviour after essential oil administration, revealing low toxicity. The essential oil of L. luisieri from Alentejo presents important pharmacological properties and low toxicity, and is a promised candidate to be used as a food supplement or in pharmaceutical applications. Georg Thieme Verlag KG Stuttgart · New York.

Botany, Phytochemistry, Pharmacology and Toxicity of Strychnos nux-vomica L.: A Review.

PubMed

Guo, Rixin; Wang, Ting; Zhou, Guohong; Xu, Mengying; Yu, Xiankuo; Zhang, Xiao; Sui, Feng; Li, Chun; Tang, Liying; Wang, Zhuju

2018-01-01

Strychnos nux-vomica L. belongs to the genus Strychnos of the family Loganiaceae and grows in Sri Lanka, India and Australia. The traditional medicinal component is its seed, called Nux vomica. This study provides a relevant and comprehensive review of S. nux-vomica L., including its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology, thus providing a foundation for future studies. Up to the present day, over 84 compounds, including alkaloids, iridoid glycosides, flavonoid glycosides, triterpenoids, steroids and organic acids, among others, have been isolated and identified from S. nux-vomica. These compounds possess an array of biological activities, including effects on the nervous system, analgesic and anti-inflammatory actions, antitumor effects, inhibition of the growth of pathogenic microorganisms and regulation of immune function. Furthermore, toxicity and detoxification methods are preliminarily discussed toward the end of this review. In further research on S. nux-vomica, bioactivity-guided isolation strategies should be emphasized. Its antitumor effects should be investigated further and in vivo animal experiments should be performed alongside in vitro testing. The pharmacological activity and toxicology of strychnine [Formula: see text]-oxide and brucine [Formula: see text]-oxide should be studied to explore the detoxification mechanism associated with processing more deeply.

Altered pharmacology of native rodent spinal cord TRPV1 after phosphorylation

PubMed Central

Mogg, AJ; Mill, CEJ; Folly, EA; Beattie, RE; Blanco, MJ; Beck, JP; Broad, LM

2013-01-01

Background and Purpose Evidence suggests that phosphorylation of TRPV1 is an important component underlying its aberrant activation in pathological pain states. To date, the detailed pharmacology of diverse TRPV1 receptor agonists and antagonists has yet to be reported for native TRPV1 under phosphorylating conditions. Our goal was to optimize a relatively high-throughput methodology to allow pharmacological characterization of the native TRPV1 receptor using a spinal cord neuropeptide release assay under naive and phosphorylating states. Experimental Approach Herein, we describe characterization of rodent TRPV1 by measurement of CGRP release from acutely isolated lumbar (L1-L6) spinal cord using a 96-well technique that combines use of native, adult tissue with quantitation of CGRP release by elisa. Key Results We have studied a diverse panel of TRPV1 agonists and antagonists under basal and phosphorylating conditions. We show that TRPV1-mediated CGRP release is evoked, in a temperature-dependent manner, by a PKC activator, phorbol 12,13-dibutyrate (PDBu); and that treatment with PDBu increases the potency and efficacy of known TRPV1 chemical agonists, in an agonist-specific manner. We also show that the pharmacological profile of diverse TRPV1 antagonists is dependent on whether the stimulus is PDBu or capsaicin. Of note, HPPB was identified as an antagonist of capsaicin-evoked, but a potentiator of PDBu-evoked, CGRP release. Conclusions and Implications Our findings indicate that both TRPV1 agonist and antagonist profiles can be differentially altered by PKC activation. These findings may offer new insights for targeting TRPV1 in pain states. PMID:23062150

Enhancing value of clinical pharmacodynamics in oncology drug development: An alliance between quantitative pharmacology and translational science.

PubMed

Venkatakrishnan, K; Ecsedy, J A

2017-01-01

Clinical pharmacodynamic evaluation is a key component of the "pharmacologic audit trail" in oncology drug development. We posit that its value can and should be greatly enhanced via application of a robust quantitative pharmacology framework informed by biologically mechanistic considerations. Herein, we illustrate examples of intersectional blindspots across the disciplines of quantitative pharmacology and translational science and offer a roadmap aimed at enhancing the caliber of clinical pharmacodynamic research in the development of oncology therapeutics. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases.

PubMed

Kumar, Hemant; Kim, In-Su; More, Sandeep Vasant; Kim, Byung-Wook; Choi, Dong-Kug

2014-01-01

Covering: 2000 to 2013. Oxidative stress is the central component of chronic diseases. The nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway is vital in the up-regulation of cytoprotective genes and enzymes in response to oxidative stress and treatment with certain dietary phytochemicals. Herein, we classify bioactive compounds derived from natural products that are Nrf2/ARE pathway activators and recapitulate the molecular mechanisms for inducing Nrf2 to provide favorable effects in experimental models of chronic diseases. Moreover, pharmacological inhibition of Nrf2 signalling has emerged as promising strategy against multi-drug resistance thereby improving the treatment efficacy. We have also enlisted natural product-derived inhibitors of Nrf2/ARE pathway.

A new and highly sensitive method of analyzing metabolic activity using FLIM (Conference Presentation)

NASA Astrophysics Data System (ADS)

Evers, Michael; Salma, Nunciada; Birngruber, Reginald; Evans, Conor L.; Manstein, Dieter

2017-02-01

Traditional assessments of cellular metabolism are often destructive, time consuming and without visual information. Fluorescence lifetime imaging microscopy (FLIM) provides a highly sensitive, non-invasive, and label-free alternative. This study uses FLIM in combination with two-photon microscopy to investigate pharmacological induced metabolic changes of adipocytes via changes in the fluorescence of the metabolic co-factors NADH and FAD. In agreement with recent publications NADH fluorescence suggests the presence of four distinct lifetimes in cell culture and tissue with two unbound and two protein bound states which show different responses to treatment with metabolic modifiers. We evaluated the effects on NADH fluorescence lifetime after systematic manipulations to change the balance between oxidative and glycolytic metabolism using five pharmacological reagents - Oligomycin, 2-DG, FCCP, Rotenone, and Glucose - which interact with different parts of the metabolic pathway. We established several ratios between the four distinct lifetimes of NADH after treatment and compared the results to oxygen consumption rate and extracellular acidification rate. We demonstrated, for the first time, a correlation between the two unbound fluorescence lifetimes components and glycolytic and oxidative metabolic activity with a significant higher sensitivity compared to the commonly used free-to-bound ratio of NADH. Analyzing all four lifetime components of NADH has the potential to become a powerful tool to evaluate metabolic activity of adipocytes with subcellular resolution.

Nursing students learning the pharmacology of diabetes mellitus with complexity-based computerized models: A quasi-experimental study.

PubMed

Dubovi, Ilana; Dagan, Efrat; Sader Mazbar, Ola; Nassar, Laila; Levy, Sharona T

2018-02-01

Pharmacology is a crucial component of medications administration in nursing, yet nursing students generally find it difficult and self-rate their pharmacology skills as low. To evaluate nursing students learning pharmacology with the Pharmacology Inter-Leaved Learning-Cells environment, a novel approach to modeling biochemical interactions using a multiscale, computer-based model with a complexity perspective based on a small set of entities and simple rules. This environment represents molecules, organelles and cells to enhance the understanding of cellular processes, and combines these cells at a higher scale to obtain whole-body interactions. Sophomore nursing students who learned the pharmacology of diabetes mellitus with the Pharmacology Inter-Leaved Learning-Cells environment (experimental group; n=94) or via a lecture-based curriculum (comparison group; n=54). A quasi-experimental pre- and post-test design was conducted. The Pharmacology-Diabetes-Mellitus questionnaire and the course's final exam were used to evaluate students' knowledge of the pharmacology of diabetes mellitus. Conceptual learning was significantly higher for the experimental than for the comparison group for the course final exam scores (unpaired t=-3.8, p<0.001) and for the Pharmacology-Diabetes-Mellitus questionnaire (U=942, p<0.001). The largest effect size for the Pharmacology-Diabetes-Mellitus questionnaire was for the medication action subscale. Analysis of complex-systems component reasoning revealed a significant difference for micro-macro transitions between the levels (F(1, 82)=6.9, p<0.05). Learning with complexity-based computerized models is highly effective and enhances the understanding of moving between micro and macro levels of the biochemical phenomena, this is then related to better understanding of medication actions. Moreover, the Pharmacology Inter-Leaved Learning-Cells approach provides a more general reasoning scheme for biochemical processes, which enhances pharmacology learning beyond the specific topic learned. The present study implies that deeper understanding of pharmacology will support nursing students' clinical decisions and empower their proficiency in medications administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anti-inflammatory and analgesic components from "hierba santa," a traditional medicine in Peru.

PubMed

Kawano, Marii; Otsuka, Mayumi; Umeyama, Kazuhiro; Yamazaki, Mikio; Shiota, Tetsuo; Satake, Motoyoshi; Okuyama, Emi

2009-04-01

"Hierba santa," a Peruvian herbal medicine, is used to alleviate many symptoms, including headache, hemorrhoids, fever, and rheumatism. Several Cestrum species are said to be the origin of hierba santa. Three lots of hierba santa: Cestrum auriculatum (herb 1 and herb 2) and C. hediundinum (herb 3), which were purchased from Peruvian markets at Cuzco (Andes area) and Equitos (Amazon area), respectively, were examined for their pharmacological activities and active components. Herbs 1-3 showed anti-inflammatory and analgesic activities in the in vivo writhing inhibition test in mouse and inhibited prostaglandin E(1)-, E(2)-, or ACh-induced contractions of guinea pig ileum in the Magnus method. Activity-based separation of each extract yielded cestrumines A and B, cestrusides A and B, a mixture of (+)- and (-)-pinoresinol glucosides, nicotiflorin, rutin, sinapoyl glucose, ursolic acid, beta-sitosteryl glucoside, and 2-sec-butyl-4,6-dihydroxyphenyl-beta-D: -glucopyranoside. Among them, cestrumine A and cestrusides A and B are new compounds. All three lots of hierba santa do not contain exactly the same active components.

Effects of Animal Venoms and Toxins on Hallmarks of Cancer

PubMed Central

Chaisakul, Janeyuth; Hodgson, Wayne C.; Kuruppu, Sanjaya; Prasongsook, Naiyarat

2016-01-01

Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components. PMID:27471574

Triphenylmethane dye activation of beta-arrestin.

PubMed

Barak, Larry S; Bai, Yushi; Snyder, Joshua C; Wang, Jiangbo; Chen, Wei; Caron, Marc G

2013-08-13

β-Arrestins regulate G protein-coupled receptor signaling as competitive inhibitors and protein adaptors. Low molecular weight biased ligands that bind receptors and discriminate between the G protein dependent arm and β-arrestin, clathrin-associated arm of receptor signaling are considered therapeutically valuable as a result of this distinctive pharmacological behavior. Other than receptor agonists, compounds that activate β-arrestins are not available. We show that within minutes of exposure to the cationic triphenylmethane dyes malachite green and brilliant green, tissue culture cells recruit β-arrestins to clathrin scaffolds in a receptor-activation independent manner. In the presence of these compounds, G protein signaling is inhibited, ERK and GSK3β signaling are preserved, and the recruitment of the beta2-adaptin, AP2 adaptor complex to clathrin as well as transferrin internalization is reduced. Moreover, malachite green binds β-arrestin2-GFP coated immunotrap beads relative to GFP only coated beads. Triphenylmethane dyes are FDA approved for topical use on newborns as components of triple-dye preparations and are not approved but used effectively as aqueous antibiotics in fish husbandry. As possible carcinogens, their chronic ingestion in food preparations, particularly through farmed fish, is discouraged in the U.S. and Europe. Our results indicate triphenylmethane dyes as a result of novel pharmacology may have additional roles as β-arrestin/clathrin pathway signaling modulators in both pharmacology research and clinical therapy.

Triphenylmethane Dye Activation of Beta-Arrestin

PubMed Central

2013-01-01

β-Arrestins regulate G protein-coupled receptor signaling as competitive inhibitors and protein adaptors. Low molecular weight biased ligands that bind receptors and discriminate between the G protein dependent arm and β-arrestin, clathrin-associated arm of receptor signaling are considered therapeutically valuable as a result of this distinctive pharmacological behavior. Other than receptor agonists, compounds that activate β-arrestins are not available. We show that within minutes of exposure to the cationic triphenylmethane dyes malachite green and brilliant green, tissue culture cells recruit β-arrestins to clathrin scaffolds in a receptor-activation independent manner. In the presence of these compounds, G protein signaling is inhibited, ERK and GSK3β signaling are preserved, and the recruitment of the beta2-adaptin, AP2 adaptor complex to clathrin as well as transferrin internalization is reduced. Moreover, malachite green binds β-arrestin2-GFP coated immunotrap beads relative to GFP only coated beads. Triphenylmethane dyes are FDA approved for topical use on newborns as components of triple-dye preparations and are not approved but used effectively as aqueous antibiotics in fish husbandry. As possible carcinogens, their chronic ingestion in food preparations, particularly through farmed fish, is discouraged in the U.S. and Europe. Our results indicate triphenylmethane dyes as a result of novel pharmacology may have additional roles as β-arrestin/clathrin pathway signaling modulators in both pharmacology research and clinical therapy. PMID:23865508

Titration-based screening for evaluation of natural product extracts: identification of an aspulvinone family of luciferase inhibitors

PubMed Central

Cruz, Patricia G.; Auld, Douglas S.; Schultz, Pamela J.; Lovell, Scott; Battaile, Kevin P.; MacArthur, Ryan; Shen, Min; Tamayo-Castillo, Giselle; Inglese, James; Sherman, David H.

2011-01-01

The chemical diversity of nature has tremendous potential for discovery of new molecular probes and medicinal agents. However, sensitivity of HTS assays to interfering components of crude extracts derived from plants, macro- and microorganisms has curtailed their use in lead discovery efforts. Here we describe a process for leveraging the concentration-response curves (CRCs) obtained from quantitative HTS to improve the initial selection of “actives” from a library of partially fractionated natural product extracts derived from marine actinomycetes and fungi. By using pharmacological activity, the first-pass CRC paradigm aims to improve the probability that labor-intensive subsequent steps of re-culturing, extraction and bioassay-guided isolation of active component(s) target the most promising strains and growth conditions. We illustrate how this process identified a family of fungal metabolites as potent inhibitors of firefly luciferase, subsequently resolved in molecular detail by x-ray crystallography. PMID:22118678

The hybrid modulatory/pattern generating N1L interneuron in the buccal feeding system of Lymnaea is cholinergic.

PubMed

Vehovszky, A; Elliott, C J

1995-01-01

This study examines neurotransmission between identified buccal interneurons in the feeding system of the snail Lymnaea stagnalis. We compare the pharmacology of the individual synaptic connections from a hybrid modulatory/pattern generating interneuron (N1L) to a pattern generating interneuron (N1M) with that from a modulatory interneuron (SO) to the same follower cell (N1M). The pharmacological properties of the N1L to N1M and the SO to N1M connections closely resemble each other. Both interneurons produce fast cholinergic EPSPs as judged by the blocking effects of cholinergic antagonists hexamethonium, d-tubocurarine and the cholinergic neurotoxin AF-64A. A slower, more complex but non-cholinergic component of the synaptic response is also present after stimulating either the presynaptic N1L or SO interneurons. This second component of the postsynaptic response is not dopaminergic, on the basis of its persistence in the presence of dopaminergic antagonists ergometrine and fluphenazine and the dopaminergic neurotoxin MPP+. We conclude that, although there has been an evolutionary divergence in function, the modulatory SO and the hybrid modulatory/pattern generating N1L are pharmacologically similar. Neither of them contributes directly to dopaminergic modulation of the feeding activity. These neurons also resemble the N1M protraction phase pattern generating neurons which are cholinergic (Elliott and Kemenes, 1992).

Discovery of potent and selective small-molecule PAR-2 agonists.

PubMed

Seitzberg, Jimmi Gerner; Knapp, Anne Eeg; Lund, Birgitte Winther; Mandrup Bertozzi, Sine; Currier, Erika A; Ma, Jian-Nong; Sherbukhin, Vladimir; Burstein, Ethan S; Olsson, Roger

2008-09-25

Proteinase activated receptor-2 plays a crucial role in a wide variety of conditions with a strong inflammatory component. We present the discovery and characterization of two structurally different, potent, selective, and metabolically stable small-molecule PAR-2 agonists. These ligands may be useful as pharmacological tools for elucidating the complex physiological role of the PAR-2 receptors as well as for the development of PAR-2 antagonists.

Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arctigenin and arctiin from Arctium lappa L.

PubMed

Gao, Qiong; Yang, Mengbi; Zuo, Zhong

2018-05-01

Arctigenin (AR) and its glycoside, arctiin, are two major active ingredients of Arctium lappa L (A lappa), a popular medicinal herb and health supplement frequently used in Asia. In the past several decades, bioactive components from A lappa have attracted the attention of researchers due to their promising therapeutic effects. In the current article, we aimed to provide an overview of the pharmacology of AR and arctiin, focusing on their anti-inflammatory effects, pharmacokinetics properties and clinical efficacies. Compared to acrtiin, AR was reported as the most potent bioactive component of A lappa in the majority of studies. AR exhibits potent anti-inflammatory activities by inhibiting inducible nitric oxide synthase (iNOS) via modulation of several cytokines. Due to its potent anti-inflammatory effects, AR may serve as a potential therapeutic compound against both acute inflammation and various chronic diseases. However, pharmacokinetic studies demonstrated the extensive glucuronidation and hydrolysis of AR in liver, intestine and plasma, which might hinder its in vivo and clinical efficacy after oral administration. Based on the reviewed pharmacological and pharmacokinetic characteristics of AR, further pharmacokinetic and pharmacodynamic studies of AR via alternative administration routes are suggested to promote its ability to serve as a therapeutic agent as well as an ideal bioactive marker for A lappa.

Nociception-specific blink reflex: pharmacology in healthy volunteers.

PubMed

Marin, J C A; Gantenbein, A R; Paemeleire, K; Kaube, H; Goadsby, P J

2015-01-01

The physiology and pharmacology of activation or perception of activation of pain-coding trigeminovascular afferents in humans is fundamental to understanding the biology of headache and developing new treatments. The blink reflex was elicited using a concentric electrode and recorded in four separate sessions, at baseline and two minutes after administration of ramped doses of diazepam (final dose 0.07 mg/kg), fentanyl (final dose 1.11 μg/kg), ketamine (final dose 0.084 mg/kg) and 0.9 % saline solution. The AUC (area under the curve, μV*ms) and the latency (ms) of the ipsi- and contralateral R2 component of the blink reflex were calculated by PC-based offline analysis. Immediately after each block of blink reflex recordings certain psychometric parameters were assessed. There was an effect due to DRUG on the ipsilateral (F 3,60 = 7.3, P < 0.001) AUC as well as on the contralateral (F 3,60 = 6.02, P < 0.001) AUC across the study. A significant decrement in comparison to placebo was observed only for diazepam, affecting the ipsilateral AUC. The scores of alertness, calmness, contentedness, reaction time and precision were not affected by the DRUG across the sessions. Previous studies suggest central, rather than peripheral changes in nociceptive trigeminal transmission in migraine. This study demonstrates a robust effect of benzodiazepine receptor modulation of the nociception specific blink reflex (nBR) without any μ-opiate or glutamate NMDA receptor component. The nociception specific blink reflex offers a reproducible, quantifiable method of assessment of trigeminal nociceptive system in humans that can be used to dissect pharmacology relevant to primary headache disorders.

Diacylglycerol kinase α inactivation is an integral component of the costimulatory pathway that amplifies TCR signals.

PubMed

Arranz-Nicolás, Javier; Ogando, Jesús; Soutar, Denise; Arcos-Pérez, Raquel; Meraviglia-Crivelli, Daniel; Mañes, Santos; Mérida, Isabel; Ávila-Flores, Antonia

2018-06-01

The arsenal of cancer therapies has evolved to target T lymphocytes and restore their capacity to destroy tumor cells. T cells rely on diacylglycerol (DAG) to carry out their functions. DAG availability and signaling are regulated by the enzymes diacylglycerol kinase (DGK) α and ζ, whose excess function drives T cells into hyporesponsive states. Targeting DGKα is a promising strategy for coping with cancer; its blockade could reinstate T-cell attack on tumors while limiting tumor growth, due to positive DGKα functions in several oncogenic pathways. Here, we made a side-by-side comparison of the effects of commercial pharmacological DGK inhibitors on T-cell responses with those promoted by DGKα and DGKζ genetic deletion or silencing. We show the specificity for DGKα of DGK inhibitors I and II and the structurally similar compound ritanserin. Inhibitor treatment promoted Ras/ERK (extracellular signal-regulated kinase) signaling and AP-1 (Activator protein-1) transcription, facilitated DGKα membrane localization, reduced the requirement for costimulation, and cooperated with enhanced activation following DGKζ silencing/deletion. DGKiII and ritanserin had similar effects on TCR proximal signaling, but ritanserin counteracted long-term T-cell activation, an effect that was potentiated in DGKα -/- cells. In contrast with enhanced activation triggered by pharmacological inhibition, DGKα silencing/genetic deletion led to impaired Lck (lymphocyte-specific protein tyrosine kinase) activation and limited costimulation responses. Our results demonstrate that pharmacological inhibition of DGKα downstream of the TCR provides a gain-of-function effect that amplifies the DAG-dependent signaling cascade, an ability that could be exploited therapeutically to reinvigorate T cells to attack tumors.

Improving cancer treatment with cyclotron produced radionuclides. Progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1993-11-01

This report describes our continuing long term goal of promoting nuclear medicine applications by improving the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The program includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. An essential strategy is as follows: novel radionuclides and radiotracers developed in the Radiochemistry/Cyclotron section will be employed in the Pharmacology and Immunology sections during the next year. The development of novel radionuclides and tracers is of course useful in and of itself, but their utility is greatly enhanced by the interaction with the immunologymore » and pharmacology components of the program.« less

A Network Pharmacology Approach to Understanding the Mechanisms of Action of Traditional Medicine: Bushenhuoxue Formula for Treatment of Chronic Kidney Disease

PubMed Central

Zheng, Xiao-yong; Cao, Dong-sheng; Ye, Fa-qing; Xiang, Zheng

2014-01-01

Traditional Chinese medicine (TCM) has unique therapeutic effects for complex chronic diseases. However, for the lack of an effective systematic approach, the research progress on the effective substances and pharmacological mechanism of action has been very slow. In this paper, by incorporating network biology, bioinformatics and chemoinformatics methods, an integrated approach was proposed to systematically investigate and explain the pharmacological mechanism of action and effective substances of TCM. This approach includes the following main steps: First, based on the known drug targets, network biology was used to screen out putative drug targets; Second, the molecular docking method was used to calculate whether the molecules from TCM and drug targets related to chronic kidney diseases (CKD) interact or not; Third, according to the result of molecular docking, natural product-target network, main component-target network and compound-target network were constructed; Finally, through analysis of network characteristics and literature mining, potential effective multi-components and their synergistic mechanism were putatively identified and uncovered. Bu-shen-Huo-xue formula (BSHX) which was frequently used for treating CKD, was used as the case to demonstrate reliability of our proposed approach. The results show that BSHX has the therapeutic effect by using multi-channel network regulation, such as regulating the coagulation and fibrinolytic balance, and the expression of inflammatory factors, inhibiting abnormal ECM accumulation. Tanshinone IIA, rhein, curcumin, calycosin and quercetin may be potential effective ingredients of BSHX. This research shows that the integration approach can be an effective means for discovering active substances and revealing their pharmacological mechanisms of TCM. PMID:24598793

Synchronized and sustained release of multiple components in silymarin from erodible glyceryl monostearate matrix system.

PubMed

Lu, Cheng; Lu, Yi; Chen, Jian; Zhang, Wentong; Wu, Wei

2007-05-01

Development of sustained delivery systems for herbal medicines was very difficult because of their complexity in composition. The concept of synchronized release from sustained release systems, which is characterized by release of multiple components in their original ratio that defines a herbal medicine, served as the basis for keeping the original pharmacological activity. In this study, erodible matrix systems based on glyceryl monostearate and polyethylene glycol 6000 or poloxamer 188 were prepared to perform strict control on synchronized release of the five active components of silymarin, i.e. taxifolin, silychrystin, silydianin, isosilybin and silybin. The matrix system was prepared by a melt fusion method. Synchronized release was achieved with high similarity factor f(2) values between each two of the five components. Erosion profiles of the matrix were in good correlation with release profiles of the five components, showing erosion-controlled release mechanisms. Through tuning some of the formulation variables, the system can be adjusted for synchronized and sustained release of silymarin for oral administration. In vitro hemolysis study indicated that the synchronized release samples showed a much better stabilizing effect on erythrocyte membrane.

Discharges of aortic and carotid sinus baroreceptors during spontaneous motor activity and pharmacologically evoked pressor interventions.

PubMed

Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Ishida, Tomoko; Idesako, Mitsuhiro; Liang, Nan

2014-07-01

Our laboratory has demonstrated that the cardiomotor component of aortic baroreflex is temporarily inhibited at the onset of spontaneous motor activity in decerebrate cats, without altering carotid sinus baroreflex. A reason for this dissociation may be attributed to a difference in the responses between aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity. The stimulus-response curves of AoNA and CsNA against mean arterial blood pressure (MAP) were compared between the pressor interventions evoked by spontaneous motor activity and by intravenous administration of phenylephrine or norepinephrine, in which the responses in heart rate (HR) were opposite (i.e., tachycardia vs. baroreflex bradycardia), despite the identical increase in MAP of 34-40 mmHg. In parallel to the pressor response, mean AoNA and CsNA increased similarly by 78-81 and by 88 % of the baseline control, respectively, irrespective of whether the pressor response was evoked by spontaneous motor activity or by a pharmacological intervention. The slope of the stimulus-response curve of the mean AoNA became greater (P < 0.05) during spontaneous motor activity as compared to the pharmacological intervention. On the other hand, the stimulus-response curve of the mean CsNA and its slope were equal (P > 0.05) between the two pressor interventions. Furthermore, the slopes of the stimulus-response curves of both diastolic AoNA and CsNA (defined as the minimal value within a beat) exhibited a greater increase during spontaneous motor activity. All differences in the slopes of the stimulus-response curves were abolished by restraining HR at the intrinsic cardiac frequency. In conclusion, mean mass activities of both aortic and carotid sinus baroreceptors are able to encode the beat-by-beat changes in MAP not only at rest but also during spontaneous motor activity and spontaneous motor activity-related reduction of aortic baroreceptor activity is denied accordingly.

The impact of nicotine lozenges and stimulus expectancies on cigarette craving.

PubMed

Schlagintweit, Hera E; Good, Kimberley P; Barrett, Sean P

2014-08-01

Reduced craving associated with nicotine replacement therapy use is frequently attributed to the effects of nicotine pharmacology, however non-pharmacological factors may also play a role. This study examined the impact of nicotine pharmacology and non-pharmacological components of an acute nicotine lozenge (4 mg) on cigarette craving, mood and heart rate in 70 daily smokers (36 male). Smoking-related stimuli were used to assess cue-induced craving. Participants were randomly assigned to one of four conditions in a balanced placebo design where half the participants were provided deceptive information regarding the nicotine content of a lozenge. Subjective ratings of craving and mood were collected and heart rate was assessed before and after neutral and smoking cues. Nicotine expectancy reduced withdrawal-related craving (p = 0.006) regardless of actual nicotine administration while combined nicotine expectancy and administration reduced intentions to smoke (p = 0.046) relative to each of the other conditions. Exposure to smoking-related stimuli increased cigarette craving (p ≤ 0.001) and negative affect (p ≤ 0.001) regardless of expectancy or pharmacology. Following the smoking cue, women reported a greater increase in withdrawal-related craving than men (p = 0.027). Findings suggest that both pharmacological and non-pharmacological components of nicotine lozenge administration contribute to its acute effects on craving, yet neither appears effective in preventing craving triggered by exposure to environmental smoking stimuli. © The Author(s) 2014.

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons

PubMed Central

Guan, Dongxu; Horton, Leslie R.; Armstrong, William E.

2011-01-01

Potassium channels regulate numerous aspects of neuronal excitability, and several voltage-gated K+ channel subunits have been identified in pyramidal neurons of rat neocortex. Previous studies have either considered the development of outward current as a whole or divided currents into transient, A-type and persistent, delayed rectifier components but did not differentiate between current components defined by α-subunit type. To facilitate comparisons of studies reporting K+ currents from animals of different ages and to understand the functional roles of specific current components, we characterized the postnatal development of identified Kv channel-mediated currents in pyramidal neurons from layers II/III from rat somatosensory cortex. Both the persistent/slowly inactivating and transient components of the total K+ current increased in density with postnatal age. We used specific pharmacological agents to test the relative contributions of putative Kv1- and Kv2-mediated currents (100 nM α-dendrotoxin and 600 nM stromatoxin, respectively). A combination of voltage protocol, pharmacology, and curve fitting was used to isolate the rapidly inactivating A-type current. We found that the density of all identified current components increased with postnatal age, approaching a plateau at 3–5 wk. We found no significant changes in the relative proportions or kinetics of any component between postnatal weeks 1 and 5, except that the activation time constant for A-type current was longer at 1 wk. The putative Kv2-mediated component was the largest at all ages. Immunocytochemistry indicated that protein expression for Kv4.2, Kv4.3, Kv1.4, and Kv2.1 increased between 1 wk and 4–5 wk of age. PMID:21451062

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons.

PubMed

Guan, Dongxu; Horton, Leslie R; Armstrong, William E; Foehring, Robert C

2011-06-01

Potassium channels regulate numerous aspects of neuronal excitability, and several voltage-gated K(+) channel subunits have been identified in pyramidal neurons of rat neocortex. Previous studies have either considered the development of outward current as a whole or divided currents into transient, A-type and persistent, delayed rectifier components but did not differentiate between current components defined by α-subunit type. To facilitate comparisons of studies reporting K(+) currents from animals of different ages and to understand the functional roles of specific current components, we characterized the postnatal development of identified Kv channel-mediated currents in pyramidal neurons from layers II/III from rat somatosensory cortex. Both the persistent/slowly inactivating and transient components of the total K(+) current increased in density with postnatal age. We used specific pharmacological agents to test the relative contributions of putative Kv1- and Kv2-mediated currents (100 nM α-dendrotoxin and 600 nM stromatoxin, respectively). A combination of voltage protocol, pharmacology, and curve fitting was used to isolate the rapidly inactivating A-type current. We found that the density of all identified current components increased with postnatal age, approaching a plateau at 3-5 wk. We found no significant changes in the relative proportions or kinetics of any component between postnatal weeks 1 and 5, except that the activation time constant for A-type current was longer at 1 wk. The putative Kv2-mediated component was the largest at all ages. Immunocytochemistry indicated that protein expression for Kv4.2, Kv4.3, Kv1.4, and Kv2.1 increased between 1 wk and 4-5 wk of age.

Extraction, Characterization, Stability and Biological Activity of Flavonoids Isolated from Chamomile Flowers

PubMed Central

Srivastava, Janmejai K; Gupta, Sanjay

2009-01-01

Dried flowers of Chamomile (Matricaria chamomilla) are largely used for their medicinal properties. In the present study, we examined the pharmacological properties of aqueous and methanolic fraction isolated from two varieties of German chamomile. HPLC-MS analysis of chamomile extract confirmed apigenin-7-O-glucoside as the major constituent of chamomile; some minor glycoside components were observed along with essential oils. These glucosides are highly stable in solution at different temperature range and their degradation occurs after long-term storage and extraction conditions at different pH and solvent. Methanolic fraction isolated from chamomile flowers demonstrated higher biologic response in inhibiting cell growth and causing induction of apoptosis in various human cancer cell lines compared to aqueous chamomile fraction. Apigenin glucosides inhibited cancer cell growth through deconjugation of glycosides that occurs in the cellular compartment to produce aglycone, apigenin. Taken together, the pharmacological profile of chamomile extract was dependent upon extraction process, storage conditions which affected the biological activity. PMID:20098626

Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis.

PubMed

Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L; Zhang, Yuxi; Chen, Li; Postert, Benno; Parsons, Stuart; Ditzel, Nicholas; Khosla, Sundeep; Johansen, Harald Thidemann; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie; Abdallah, Basem M; Hesselson, Daniel; Solberg, Rigmor; Kassem, Moustapha

2017-02-14

Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Phytochemistry and biological activities of Phlomis species.

PubMed

Limem-Ben Amor, Ilef; Boubaker, Jihed; Ben Sgaier, Mohamed; Skandrani, Ines; Bhouri, Wissem; Neffati, Aicha; Kilani, Soumaya; Bouhlel, Ines; Ghedira, Kamel; Chekir-Ghedira, Leila

2009-09-07

The genus Phlomis L. belongs to the Lamiaceae family and encompasses 100 species native to Turkey, North Africa, Europe and Asia. It is a popular herbal tea enjoyed for its taste and aroma. Phlomis species are used to treat various conditions such as diabetes, gastric ulcer, hemorrhoids, inflammation, and wounds. This review aims to summarize recent research on the phytochemistry and pharmacological properties of the genus Phlomis, with particular emphasis on its ethnobotanical uses. The essential oil of Phomis is composed of four chemotypes dominated by monoterpenes (alpha-pinene, limonene and linalool), sesquiterpenes (germacrene D and beta-caryophyllene), aliphalic compounds (9,12,15-octadecatrienoic acid methyl ester), fatty acids (hexadecanoic acid) and other components (trans-phytol, 9,12,15-octadecatrien-1-ol). Flavonoids, iridoids and phenylethyl alcohol constitute the main compounds isolated from Phlomis extracts. The pharmacological activities of some Phlomis species have been investigated. They are described according to antidiabetic, antinociceptive, antiulcerogenic, protection of the vascular system, anti-inflammatory, antiallergic, anticancer, antimicrobial and antioxidant properties.

Predictors of adherence to pharmacological and behavioral treatment in a cessation trial among smokers in Aleppo, Syria

PubMed Central

Ben Taleb, Ziyad; Ward, Kenneth D; Asfar, Taghrid; Bahelah, Raed; Maziak, Wasim

2015-01-01

Introduction The development of evidence-based smoking cessation programs is in its infancy in developing countries, which continue to bear the main brunt of the tobacco epidemic. Adherence to treatment recommendations is an important determinant of the success of smoking cessation programs, but little is known about factors influencing adherence to either pharmacological or behavioral treatment in developing countries settings. Our study represents the first attempt to examine the predictors of adherence to cessation treatment in a low-income developing country. Methods Predictors of adherence to pharmacological and behavioral treatment were identified by analyzing data from a multi-site, two-group, parallel-arm, double-blind, randomized, placebo-controlled smoking cessation trial in primary care clinics in Aleppo, Syria. Participants received 3 in-person behavioral counseling sessions plus 5 brief follow-up phone counseling sessions, and were randomized to either 6 weeks of nicotine or placebo patch. Results Of the 269 participants, 68% adhered to pharmacological treatment, while 70% adhered to behavioral counseling. In logistic regression modeling, lower adherence to pharmacological and behavioral treatment was associated with higher daily smoking at baseline, greater withdrawal symptoms, and perception of receiving placebo instead of active nicotine patch. Women showed lower adherence than men to behavioral treatment, while being assigned to placebo condition and baseline waterpipe use were associated with lower adherence to pharmacological treatment. Conclusion Adherence to cessation treatment for cigarette smokers in low-income countries such as Syria may benefit from integrated cessation components that provide intensive treatment for subjects with higher nicotine dependence, and address concurrent waterpipe use at all stages. PMID:26077603

Mass spectrometry in life science research.

PubMed

Lehr, Stefan; Markgraf, Daniel

2016-12-01

Investigating complex signatures of biomolecules by mass spectrometry approaches has become indispensable in molecular life science research. Nowadays, various mass spectrometry-based omics technologies are available to monitor qualitative and quantitative changes within hundreds or thousands of biological active components, including proteins/peptides, lipids and metabolites. These comprehensive investigations have the potential to decipher the pathophysiology of disease development at a molecular level and to monitor the individual response of pharmacological treatment or lifestyle intervention.

[Medicinal chemistry and pharmacology focused on cannabidiol, a major component of the fiber-type cannabis].

PubMed

Takeda, Shuso

2013-01-01

Considerable attention has focused on cannabidiol (CBD), a major non-psychotropic constituent of fiber-type cannabis plant, and it has been reported to possess diverse biological activities. Although CBD is obtained from non-enzymatic decarboxylation of its parent molecule, cannabidiolic acid (CBDA), several studies have investigated whether CBDA itself is biologically active. In the present report, the author summarizes findings indicating that; 1) CBDA is a selective cyclooxygenase-2 (COX-2) inhibitor, and ii) CBDA possesses an anti-migrative potential for highly invasive cancer cells, apparently through a mechanism involving inhibition of cAMP-dependent protein kinase A, coupled with an activation of the small GTPase, RhoA. Further, the author introduces recent findings on the medicinal chemistry and pharmacology of the CBD derivative, CBD-2',6'-dimethyl ether (CBDD), that exhibits inhibitory activity toward 15-lipoxygenase (15-LOX), an enzyme responsible for the production of oxidized low-density lipoprotein (LDL). These studies establish CBD as both an important experimental tool and as a lead compound for pharmaceutical development. In this review, the author further discusses the potential uses of CBD and its derivatives in future medicines.

Marine Pharmacology in 2012-2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

PubMed

Mayer, Alejandro M S; Rodríguez, Abimael D; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

2017-08-29

The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998-2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012-2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories.

Different accumulation profiles of multiple components between pericarp and seed of Alpinia oxyphylla capsular fruit as determined by UFLC-MS/MS.

PubMed

Chen, Feng; Li, Hai-Long; Tan, Yin-Feng; Guan, Wei-Wei; Zhang, Jun-Qing; Li, Yong-Hui; Zhao, Yuan-Sheng; Qin, Zhen-Miao

2014-04-10

Plant secondary metabolites are known to not only play a key role in the adaptation of plants to their environment, but also represent an important source of active pharmaceuticals. Alpinia oxyphylla capsular fruits, made up of seeds and pericarps, are commonly used in traditional East Asian medicines. In clinical utilization of these capsular fruits, inconsistent processing approaches (i.e., hulling pericarps or not) are employed, with the potential of leading to differential pharmacological effects. Therefore, an important question arises whether the content levels of pharmacologically active chemicals between the seeds and pericarps of A. oxyphylla are comparable. Nine secondary metabolites present in A. oxyphylla capsular fruits, including flavonoids (e.g., tectochrysin, izalpinin, chrysin, apigenin-4',7-dimethylether and kaempferide), diarylheptanoids (e.g., yakuchinone A and B and oxyphyllacinol) and sesquiterpenes (e.g., nootkatone), were regarded as representative constituents with putative pharmacological activities. This work aimed to investigate the abundance of the nine constituents in the seeds and pericarps of A. oxyphylla. Thirteen batches of A. oxyphylla capsular fruits were gathered from different production regions. Accordingly, an ultra-fast high performance liquid chromatography/quadrupole tandem mass spectrometry (UFLC-MS/MS) method was developed and validated. We found that: (1) the nine secondary metabolites were differentially concentrated in seeds and fruit capsules; (2) nootkatone is predominantly distributed in the seeds; in contrast, the flavonoids and diarylheptanoids are mainly deposited in the capsules; and (3) the content levels of the nine secondary metabolites occurring in the capsules varied greatly among different production regions, although the nootkatone levels in the seeds were comparable among production regions. These results are helpful to evaluating and elucidating pharmacological activities of A. oxyphylla capsular fruits. Additionally, it may be of interest to elucidate the mechanisms involved in the distinct accumulation profiles of these secondary metabolites between seeds and pericarps.

A review on phytochemistry and pharmacological activities of the processed lateral root of Aconitum carmichaelii Debeaux.

PubMed

Zhou, Guohong; Tang, Liying; Zhou, Xidan; Wang, Ting; Kou, Zhenzhen; Wang, Zhuju

2015-02-03

The processed lateral root of Aconitum carmichaelii Debeaux (Ranunculaceae), an extensively used traditional Chinese medicine, is known as Fuzi in China (Chinese: ), "bushi" in Japan, "Kyeong-Po Buja" in Korea, Chinese aconite, monkshood or Chinese wolfsbane. It has been used to treat shock resulting from acute myocardial infarction, low blood pressure, coronary heart disease, chronic heart failure, etc. The present paper aims to provide an up-to-date review at the advancements of the investigations on the ethnopharmacology, phytochemistry, pharmacological effect and toxicity of Fuzi. Besides, the possible tendency and perspective for future research of this plant are discussed, as well. All available information on Fuzi was collected via electronic search (using Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, and Web of Science), books and classic works about Chinese herb. 122 chemical constituents, among which C19-diterpenoid alkaloids and C20-diterpenoid alkaloids are the predominant groups, have been isolated and identified from Fuzi. Fuzi with its active compounds is possessed of wide-reaching biological activities, including effects on cardiovascular system, anti-inflammation and analgesic action, anti-tumor activity, effect on the immune system, hypoglycemic and hypolipidemic effects, anti-aging effect, effect of protecting kidney and effect on energy metabolism. Nearly all of compounds were found from the roots of the plant, so further phytochemical studies should focus more on the other parts of the plant, such as the leaves, flowers or stems. Besides, a majority of the pharmacological studies were carried out using crude and poorly characterized extracts. Thus, more bioactive components particularly cardiotonic and analgesic compounds should be identified through bioactivity-guided isolation strategies. Moreover, investigations on how to develop Fuzi׳s new clinical usage on the basis of its pharmacological effects are in requirement. Copyright © 2014. Published by Elsevier Ireland Ltd.

Incorporating Team-Based Learning Into a Physician Assistant Clinical Pharmacology Course.

PubMed

Nguyen, Timothy; Wong, Elaine; Pham, Antony

2016-03-01

To obtain student perceptions of team-based learning and compare the effectiveness of team-based learning and traditional lecture formats in a clinical pharmacology course for physician assistant (PA) students. Clinical pharmacology is a course offered to PA students in their first year of training at LIU Brooklyn, Brooklyn, NY. In spring 2014, half of the course was offered in a traditional lecture format and the remaining half was offered in a team-based learning format. The team-based learning format had 3 components: (1) prereading assignments, (2) individual readiness assessment tests, and (3) team readiness assessment tests. So that student perceptions of the integration of team-based learning activities into the course could be evaluated, presurveys and postsurveys were administered. The effectiveness of team-based learning was evaluated by comparing overall student performance with student performance in the preceding year. Thirty-three students were enrolled in the course and completed the presurveys and postsurveys. The survey results are presented in Table 1. Comparison of student performance on examinations with performance from the previous year showed similar outcomes. Incorporating a team-based learning pedagogical approach in the PA pharmacology course yielded similar examination results to those of traditional lecture formats. Presurvey and postsurvey questionnaires yielded various student perceptions of team-based learning.

David Triggle: Research collaborations and scientific exchanges with the China Pharmaceutical University, Nanjing, China.

PubMed

Dai, De-Zai

2015-11-15

Over the period 1995-2012, David Triggle was a frequent visitor to the China Pharmaceutical University in Nanjing, China making many important contributions that enhanced the activities of the Research Division of Pharmacology at the University. In addition to providing collegial advice and facilitating interactions with the international pharmacological community, Professor Triggle's international reputation as a thought leader in the field of ion channel research and drug discovery provided important insights into the potential pathophysiological and therapeutic effects of targeting ion channels. This included the L-type calcium channel and the outward delayed rectified potassium currents of rapid (IKr) and slow (IKs) components in the myocardium. The Nanjing research team had been particularly interested in ion channel dysfunction in the context of cardiac arrhythmias, remodeling and drug discovery. With Professor Triggle's assistance, the relationship between an increase in ICa.L and other biological events including an enhancement of IKr and IKr currents, NADPH oxidase and endothelin receptor activation, down regulation of calcium modulating protein FKBP12.6, sarco/endoplasmic reticulum Ca(2+)ATPse (SERCA2A) and calsequens 2 (CASQ2), calcium leak at the diastole and endoplasmic reticulum stress, were evaluated and are discussed. Additionally, the organization of several international symposia was greatly enhanced by input from Professor Triggle as were the published research manuscripts in international pharmacology journals. During his association with the China Pharmaceutical University, Professor Triggle aided in enhancing the scientific standing of the Pharmacology department and was a highly effective ambassador for international research cooperation. Copyright © 2015. Published by Elsevier Inc.

Baicalin and its metabolites suppresses gluconeogenesis through activation of AMPK or AKT in insulin resistant HepG-2 cells.

PubMed

Wang, Tao; Jiang, Hongmei; Cao, Shijie; Chen, Qian; Cui, Mingyuan; Wang, Zhijie; Li, Dandan; Zhou, Jing; Wang, Tao; Qiu, Feng; Kang, Ning

2017-12-01

Scutellaria baicalensis Georgi (S. baicalensis), as a traditional Chinese herbal medicine, is an important component of several famous Chinese medicinal formulas for treating patients with diabetes mellitus. Baicalin (BG), a main bioactive component of S. baicalensis, has been reported to have antidiabetic effects. However, pharmacokinetic studies have indicated that BG has poor oral bioavailability. Therefore, it is hard to explain the pharmacological effects of BG in vivo. Interestingly, several reports show that BG is extensively metabolized in rats and humans. Therefore, we speculate that the BG metabolites might be responsible for the pharmacological effects. In this study, BG and its three metabolites (M1-M3) were examined their effects on glucose consumption in insulin resistant HepG-2 cells with a commercial glucose assay kit. Real-time PCR and western blot assay were used to confirm genes and proteins of interest, respectively. The results demonstrate that BG and its metabolites (except for M3) enhanced the glucose consumption which might be associated with inhibiting the expression of the key gluconeogenic genes, including glucose-6-phosphatase (G6Pase), phosphoenolypyruvate carboxykinase (PEPCK) and glucose transporter 2 (GLUT2). Further study found that BG and M1 could suppress hepatic gluconeogenesis via activation of the AMPK pathway, while M2 could suppress hepatic gluconeogenesis via activation of the PI3K/AKT signaling pathway. Taken together, our findings suggest that both BG and its metabolites have antihyperglycemic activities, and might be the active forms of oral doses of BG in vivo. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Pharmacological versus sensory factors in the satiation of chocolate craving.

PubMed

Michener, W; Rozin, P

1994-09-01

This is the first experimental study directed at differentiating between physiological or sensory accounts of the satiation of nondrug cravings, using chocolate craving, the most common craving in North America. At the onset of craving, chocolate cravers consumed a chocolate bar, the caloric equivalent in "white chocolate" (containing none of the pharmacological components of chocolate), the pharmacological equivalent in cocoa capsules, placebo, and no treatment conditions had virtually no effect. White chocolate produced partial abatement, unchanged by the addition of all the pharmacological factors in cocoa. This result indicates no role for pharmacological effects in the satisfaction of chocolate craving. It also suggests a role for aroma independent of sweetness, texture, and calories.

Fuzzy pharmacology: theory and applications.

PubMed

Sproule, Beth A; Naranjo, Claudio A; Türksen, I Burhan

2002-09-01

Fuzzy pharmacology is a term coined to represent the application of fuzzy logic and fuzzy set theory to pharmacological problems. Fuzzy logic is the science of reasoning, thinking and inference that recognizes and uses the real world phenomenon that everything is a matter of degree. It is an extension of binary logic that is able to deal with complex systems because it does not require crisp definitions and distinctions for the system components. In pharmacology, fuzzy modeling has been used for the mechanical control of drug delivery in surgical settings, and work has begun evaluating its use in other pharmacokinetic and pharmacodynamic applications. Fuzzy pharmacology is an emerging field that, based on these initial explorations, warrants further investigation.

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

PubMed

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Augmentation of Creatine in the Heart.

PubMed

Zervou, Sevasti; Whittington, Hannah J; Russell, Angela J; Lygate, Craig A

2016-01-01

Creatine is a principle component of the creatine kinase (CK) phosphagen system common to all vertebrates. It is found in excitable cells, such as cardiomyocytes, where it plays an important role in the buffering and transport of chemical energy to ensure that supply meets the dynamic demands of the heart. Multiple components of the CK system, including intracellular creatine levels, are reduced in heart failure, while ischaemia and hypoxia represent acute crises of energy provision. Elevation of myocardial creatine levels has therefore been suggested as potentially beneficial, however, achieving this goal is not trivial. This mini-review outlines the evidence in support of creatine elevation and critically examines the pharmacological approaches that are currently available. In particular, dietary creatine-supplementation does not sufficiently elevate creatine levels in the heart due to subsequent down-regulation of the plasma membrane creatine transporter (CrT). Attempts to increase passive diffusion and bypass the CrT, e.g. via creatine esters, have yet to be tested in the heart. However, studies in mice with genetic overexpression of the CrT demonstrate proof-of-principle that elevated creatine protects the heart from ischaemia-reperfusion injury. This suggests activation of the CrT as a major unmet pharmacological target. However, translation of this finding to the clinic will require a greater understanding of CrT regulation in health and disease and the development of small molecule activators.

Augmentation of Creatine in the Heart

PubMed Central

Zervou, Sevasti; Whittington, Hannah J.; Russell, Angela J.; Lygate, Craig A.

2016-01-01

Creatine is a principle component of the creatine kinase (CK) phosphagen system common to all vertebrates. It is found in excitable cells, such as cardiomyocytes, where it plays an important role in the buffering and transport of chemical energy to ensure that supply meets the dynamic demands of the heart. Multiple components of the CK system, including intracellular creatine levels, are reduced in heart failure, while ischaemia and hypoxia represent acute crises of energy provision. Elevation of myocardial creatine levels has therefore been suggested as potentially beneficial, however, achieving this goal is not trivial. This mini-review outlines the evidence in support of creatine elevation and critically examines the pharmacological approaches that are currently available. In particular, dietary creatine-supplementation does not sufficiently elevate creatine levels in the heart due to subsequent down-regulation of the plasma membrane creatine transporter (CrT). Attempts to increase passive diffusion and bypass the CrT, e.g. via creatine esters, have yet to be tested in the heart. However, studies in mice with genetic overexpression of the CrT demonstrate proof-of-principle that elevated creatine protects the heart from ischaemia-reperfusion injury. This suggests activation of the CrT as a major unmet pharmacological target. However, translation of this finding to the clinic will require a greater understanding of CrT regulation in health and disease and the development of small molecule activators. PMID:26202199

Pharmacological evaluation of Pachyrrhizus erosus (L) seeds for central nervous system depressant activity.

PubMed

Abid, Mohd; Hrishikeshavan, H J; Asad, Mohammed

2006-01-01

The research work deals with the screening of ethanol and chloroform extracts of Pachyrrhizus erosus seeds for central nervous system (CNS) depressant activity. The Pachyrrhizus erosus seed is known to contain rotinoids, flavonoids and phenylfuranocoumarin derivatives as chemical components and is reported to have antifungal, antisecretory, insecticides, antibacterial and spasmolytic activity. Since seeds of Pachyrrhizus erosus is used as folk medicine in treatment of insomnia, we made an attempt to study its CNS depressant effect. The different activities studied were potentiation of pentobarbitone-induced sleep, test for locomotor activity, effect on muscle co-ordination, antiaggressive and antianxiety activities. The result of the study reflected that ethanol extract of the seeds (150 mg/kg, p.o) decreased locomotor activity, produced muscle relaxation and showed antianxiety and antiaggressive activity.

Competency-based medical education: An overview and application in pharmacology

PubMed Central

Shah, Nilima; Desai, Chetna; Jorwekar, Gokul; Badyal, Dinesh; Singh, Tejinder

2016-01-01

Competency-based medical education (CBME) is gaining momentum across the globe. The Medical Council of India has described the basic competencies required of an Indian Medical Graduate and designed a competency-based module on attitudes and communication. Widespread adoption of a competency-based approach would mean a paradigm shift in the current approach to medical education. CBME, hence, needs to be reviewed for its usefulness and limitations in the Indian context. This article describes the rationale of CBME and provides an overview of its components, i.e., competency, entrustable professional activity, and milestones. It elaborates how CBME could be implemented in an institute, in the context of basic sciences in general and pharmacology in particular. The promises and perils of CBME that need to be kept in mind to maximize its gains are described. PMID:28031599

Safranal: From an Aromatic Natural Product to a Rewarding Pharmacological Agent

PubMed Central

Rezaee, Ramin; Hosseinzadeh, Hossein

2013-01-01

Safranal, the main component of Crocus sativus essential oil, is thought to be the main cause of saffron unique odor. It is now about eighty years that this compound has been discovered and since then different scientific experiments have been done investigating its biological-pharmacological activities. Safranal effects in CNS have been more attractive to scientists and an escalating number of papers have been published regarding its neuropsychological effects. These promising properties of safranal propose its presence as a therapeutic agent in future, although there is a great need for further clinical trials and toxicological studies. In this review article, according to Scopus ®, Thomson Reuters Web of Knowledge®, Scientific Information Database (SID) ® and Pubmed ® all papers published until July 2012 were thoroughly discussed and a brief note of each study was prepared. PMID:23638289

Bioactive polyphenols and cardiovascular disease: chemical antagonists, pharmacological agents or xenobiotics that drive an adaptive response?

PubMed Central

Goszcz, Katarzyna; Duthie, Garry G; Stewart, Derek; Leslie, Stephen J

2017-01-01

Polyphenols are widely regarded to have a wide range of health‐promoting qualities, including beneficial effects on cardiovascular disease. Historically, the benefits have been linked to their well‐recognized powerful antioxidant activity. However, the concept that the beneficial effects are attributable to direct antioxidant activity in vivo does not pay sufficient heed to the fact that polyphenols degrade rapidly, are poorly absorbed and rapidly metabolized, resulting in very low bioavailability. This review explores alternative mechanisms by which polyphenols, or their metabolites, exert biological activity via mechanisms that can be activated by physiologically relevant concentrations. Evidence is presented to support the action of phenolic derivatives on receptors and signalling pathways to induce adaptive responses that drive changes in endogenous antioxidant, antiplatelet, vasodilatory and anti‐inflammatory effects. The implications are that in vitro antioxidant measures as predictors of polyphenol protective activity in vivo hold little relevance and that closer attention needs to be paid to bioavailable metabolites to understand the mode of action of these diet‐derived components. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc PMID:28071785

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action †

PubMed Central

Mayer, Alejandro M. S.; Rodríguez, Abimael D.; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

2017-01-01

The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998–2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012–2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories. PMID:28850074

Improving cancer treatment with cyclotron produced radionuclides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M. Finn, R.D.

1992-08-04

This report describes the author's continuing long term goal of promoting nuclear medicine applications by improving the scientific basis for tumor diagnosis treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The program has 3 interactive components: Radiochemistry /Cyclotron; Pharmacology; and Immunology. An essential strategy is as follows: novel radionuclides and radiotracers developed in the Radiochemistry/Cyclotron section under the DOE grant during the 1989--1992 grant period, will be employed in the Pharmacology and Immunology sections of the DOE grant during the 1992--1995 grant period. The development of novel radionuclides and tracers is of course usefulmore » in and of itself, but their utility is greatly enhanced by the interaction with the immunology and pharmacology components of the program.« less

Could Notch signaling pathway be a potential therapeutic option in renal diseases?

PubMed

Marquez-Exposito, Laura; Cantero-Navarro, Elena; Lavoz, Carolina; Fierro-Fernández, Marta; Poveda, Jonay; Rayego-Mateos, Sandra; Rodrigues-Diez, Raúl R; Morgado-Pascual, José Luis; Orejudo, Macarena; Mezzano, Sergio; Ruiz-Ortega, Marta

2018-02-10

Notch pathway regulates key processes in the kidney, involved in embryonic development and tissue damage. In many human chronic renal diseases a local activation of Notch pathway has been described, suggesting that several components of Notch pathway could be considered as biomarkers of renal damage. Experimental studies by genetic modulation of Notch components or pharmacological approaches by γ-secretase inhibitors have demonstrated the role of this pathway in renal regeneration renal, podocyte apoptosis, proliferation and fibroblasts activation, and induction of epithelial to mesenchymal transition of tubular epithelial cells. Recent studies suggest an interaction between Notch and NF-κB pathway involved in the regulation of renal inflammatory process. On the other hand, there are some miRNAs that could regulate Notch components and down-stream responses. All these data suggest that Notch blockade could be a novel therapeutic option for renal diseases. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Bioactivity-guided isolation of spasmolytic components of Pycnocycla spinosa Decne ex Boiss.

PubMed

Sadraei, H; Asghari, G; Behzad, S

2011-07-01

Hydroalcoholic extract of Pycnocycla spinosa has spasmolytic effect in vitro and antidiarrhoeal action in vivo. The aim of this research was to separate fractions of total hydroalcoholic extract of P. spinosa guided by their spasmolytic activity. Aerial parts of P. spinosa were extracted with ethanol. The concentrated extract was subjected to column chromatography and thin layer chromatography. Initially four fractions were obtained (F1, F2, F3, and F4) and their spasmolytic activities were determined on ileum contraction induced by KCl (80 mM). The more active fraction was subjected to further isolation and tested to find its most active components. The active component was phytochemically characterized using phytochemical methods including ultraviolet and infrared spectroscopy. Hydroalcoholic extract of P. spinosa (10-320 μg/ml) in a concentration dependent manner inhibited ileum contraction with the IC(50) value of 47 ± 8.1 μg/ml (mean ± S.E.M., n=6). Fraction F2 was the most potent inhibitor of ileum contraction (IC(50)= 3.4 ± 0.33 μg/ml). From five sub-fractions separated from fraction F2 (F2a, F2b, F2c, F2d, and F2e, respectively), F2c was a more active component with the IC(50) value of 2.6 ± 0.27 μg/ml. The primary results of target fraction (F2c) showed sugar moiety in its structure or in one of its components. In this research we have isolated pharmacological active fraction which is most likely responsible for antispasmodic action of P. spinosa hydroalcoholic extract.

Pharmacological activity and toxicity of some neurotropic agents under conditions of experimental hypodynamia

NASA Technical Reports Server (NTRS)

Kirichek, L. T.

1980-01-01

The indices of pharmacological range, risk coefficients, ED50, LD50, the size of the area of toxic activity, and maximal tolerated and absolute lethal doses were compared in hypodynamic mice. The pharmacological activity of the test neurotropic agents exhibiting a central action underwent change, but their toxicity remained unchanged.

Predictors of adherence to pharmacological and behavioral treatment in a cessation trial among smokers in Aleppo, Syria.

PubMed

Ben Taleb, Ziyad; Ward, Kenneth D; Asfar, Taghrid; Bahelah, Raed; Maziak, Wasim

2015-08-01

The development of evidence-based smoking cessation programs is in its infancy in developing countries, which continue to bear the main brunt of the tobacco epidemic. Adherence to treatment recommendations is an important determinant of the success of smoking cessation programs, but little is known about factors influencing adherence to either pharmacological or behavioral treatment in developing countries settings. Our study represents the first attempt to examine the predictors of adherence to cessation treatment in a low-income developing country. Predictors of adherence to pharmacological and behavioral treatment were identified by analyzing data from a multi-site, two-group, parallel-arm, double-blind, randomized, placebo-controlled smoking cessation trial in primary care clinics in Aleppo, Syria. Participants received 3 in-person behavioral counseling sessions plus 5 brief follow-up phone counseling sessions, and were randomized to either 6 weeks of nicotine or placebo patch. Of the 269 participants, 68% adhered to pharmacological treatment, while 70% adhered to behavioral counseling. In logistic regression modeling, lower adherence to pharmacological and behavioral treatment was associated with higher daily smoking at baseline, greater withdrawal symptoms, and perception of receiving placebo instead of active nicotine patch. Women showed lower adherence than men to behavioral treatment, while being assigned to placebo condition and baseline waterpipe use were associated with lower adherence to pharmacological treatment. Adherence to cessation treatment for cigarette smokers in low-income countries such as Syria may benefit from integrated cessation components that provide intensive treatment for subjects with higher nicotine dependence, and address concurrent waterpipe use at all stages. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Opinion of stakeholders on existing curriculum for postgraduate (MD) course in Pharmacology: A survey.

PubMed

Badyal, Dinesh K; Daniel, Sujit R

2016-10-01

To survey the opinion about various curricular components of Doctor of Medicine (MD) pharmacology curriculum in India by stakeholders, including faculty and students. An online survey was done to evaluate the various curricular components of MD pharmacology curriculum being used in India. A total of 393 respondents including faculty, MD students, and other stakeholders completed the survey. The survey was developed using SurveyMonkey platform and link to survey was E-mailed to stakeholders. The results were expressed as percentages. There was a balanced representation of respondents from various designations, teaching experience, regions, and age groups. Most of the respondents (83%) were aware of the MD pharmacology curriculum. However, they reported that it is more inclined to knowledge domain. About half of respondents (53%) said that animal experiments are being used. The most common teaching methods mentioned are seminars (98.5%), journal clubs (95%), and practical exercises by postgraduates (73%), but there is less use of newer methods (25%) in theory and less of clinical pharmacology exercise (39%) in practical classes. The log books are maintained but not assessed regularly. Internal assessment is sparingly used. The MD pharmacology curriculum needs to be made uniform at the national level and updated to include the newer methods in teaching-learning and assessment. There should be sharing of newer methods at a common platform implemented at the national level.

Calcium channels in solitary retinal ganglion cells from post-natal rat.

PubMed Central

Karschin, A; Lipton, S A

1989-01-01

1. Calcium currents from identified, post-natal retinal ganglion cell neurones from rat were studied with whole-cell and single-channel patch-clamp techniques. Na+ and K+ currents were suppressed with pharmacological agents, allowing isolation of current carried by either 10 mM-Ca2+ or Ba2- during whole-cell recordings. For cell-attached patch recordings, the recording pipette contained 96-110 mM-BaCl2 while the bath solution consisted of isotonic potassium aspartate in order to zero the neuronal membrane potential. 2. A transient component, present in approximately one-third of the whole-cell recordings resembles closely the T-type calcium current observed previously in other tissues. This component activates at low voltages (-40 to -50 mV from holding potentials negative to -80 mV), inactivates with a time constant of 10-30 ms at 35 degrees C, and is carried equally well by Ba2+ or Ca2+. In single-channel recordings small (8 pS) channels are observed whose aggregate microscopic kinetics correspond well to the macroscopic current obtained during whole-cell measurements. 3. During whole-cell recordings, a more prolonged component activates in all retinal ganglion cells at -40 to -20 mV from a holding potential of -90 mV. This component is substantially larger when equimolar Ba2+ replaces Ca2+ as the charge carrier, and is sensitive to the dihydropyridine agonist Bay K8644 (5 microM) and antagonists nifedipine (1-10 microM) and nimodipine (1-10 microM). Thus, the dihydropyridine pharmacology of this prolonged component resembles that of the L-type calcium current found in dorsal root ganglion neurones and in heart cells. Also reminiscent of the L-current, the prolonged component in this preparation is less inactivated at depolarized holding potentials (-60 to -40 mV) than the transient component. In cell-attached recordings, large (20 pS) channels are observed with activation properties similar to those of the prolonged portion of the whole-cell current. 4. omega-Conotoxin fraction GVIA (omega-CgTX VIA), a peptide from the venom of the snail Conus geographus, produces a readily reversible blockade of all components of the calcium current in these central mammalian neurones. This finding is in contrast to that of other preparations in which this toxin is responsible for an ephemeral block of T-current but a long-lasting block of other components of calcium current. 5. In summary, at least two components of calcium current with discrete underlying unitary events are present in post-natal retinal ganglion cells from rat. One component closely resembles the T or transient current observed in other cell types.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2559971

AMPK Re-Activation Suppresses Hepatic Steatosis but its Downregulation Does Not Promote Fatty Liver Development.

PubMed

Boudaba, Nadia; Marion, Allison; Huet, Camille; Pierre, Rémi; Viollet, Benoit; Foretz, Marc

2018-02-01

Nonalcoholic fatty liver disease is a highly prevalent component of disorders associated with disrupted energy homeostasis. Although dysregulation of the energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic factor in the development of fatty liver its role has not been directly demonstrated. Unexpectedly, we show here that liver-specific AMPK KO mice display normal hepatic lipid homeostasis and are not prone to fatty liver development, indicating that the decreases in AMPK activity associated with hepatic steatosis may be a consequence, rather than a cause, of changes in hepatic metabolism. In contrast, we found that pharmacological re-activation of downregulated AMPK in fatty liver is sufficient to normalize hepatic lipid content. Mechanistically, AMPK activation reduces hepatic triglyceride content both by inhibiting lipid synthesis and by stimulating fatty acid oxidation in an LKB1-dependent manner, through a transcription-independent mechanism. Furthermore, the effect of the antidiabetic drug metformin on lipogenesis inhibition and fatty acid oxidation stimulation was enhanced by combination treatment with small-molecule AMPK activators in primary hepatocytes from mice and humans. Overall, these results demonstrate that AMPK downregulation is not a triggering factor in fatty liver development but in contrast, establish the therapeutic impact of pharmacological AMPK re-activation in the treatment of fatty liver disease. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Audience response technology: engaging and empowering non-medical prescribing students in pharmacology learning.

PubMed

Lymn, Joanne S; Mostyn, Alison

2010-10-27

Non-medical prescribing (NMP) is a six month course for nurses and certain allied health professionals. It is critical that these students develop a good understanding of pharmacology; however, many students are mature learners with little or no formal biological science knowledge and struggle with the pharmacology component. The implications for patient safety are profound, therefore we encourage students not just to memorise enough pharmacology to pass the exam but to be able to integrate it into clinical practice. Audience response technology (ART), such as the KeePad system (KS) has been shown to promote an active approach to learning and provide instant formative feedback. The aim of this project, therefore, was to incorporate and evaluate the use the KS in promoting pharmacology understanding in NMP students. Questions were incorporated into eight pharmacology lectures, comprising a mix of basic and clinical pharmacology, using TurningPoint software. Student (n = 33) responses to questions were recorded using the KS software and the percentage of students getting the question incorrect and correct was made immediately available in the lecture in graphical form. Survey data collected from these students investigated student perceptions on the use of the system generally and specifically as a learning tool. More in depth discussion of the usefulness of the KS was derived from a focus group comprising 5 students. 100% of students enjoyed using the KS and felt it promoted their understanding of key concepts; 92% stated that it helped identify their learning needs and 87% agreed that the technology was useful in promoting integration of concepts. The most prevalent theme within feedback was that of identifying their own learning needs. Analysis of data from the focus group generated similar themes, with the addition of improving teaching. Repeated questioning produced a significant increase (p < 0.05) in student knowledge of specific pharmacological concepts. The use of ART enhanced non-medical prescribing students' experience of pharmacology teaching. Student perceptions were that this system increased their ability to identify learning needs and promoted understanding and integration of concepts. Students also reported that the technology aided exam revision and reduced associated anxiety.

Audience response technology: Engaging and empowering non-medical prescribing students in pharmacology learning

PubMed Central

2010-01-01

Background Non-medical prescribing (NMP) is a six month course for nurses and certain allied health professionals. It is critical that these students develop a good understanding of pharmacology; however, many students are mature learners with little or no formal biological science knowledge and struggle with the pharmacology component. The implications for patient safety are profound, therefore we encourage students not just to memorise enough pharmacology to pass the exam but to be able to integrate it into clinical practice. Audience response technology (ART), such as the KeePad system (KS) has been shown to promote an active approach to learning and provide instant formative feedback. The aim of this project, therefore, was to incorporate and evaluate the use the KS in promoting pharmacology understanding in NMP students. Methods Questions were incorporated into eight pharmacology lectures, comprising a mix of basic and clinical pharmacology, using TurningPoint software. Student (n = 33) responses to questions were recorded using the KS software and the percentage of students getting the question incorrect and correct was made immediately available in the lecture in graphical form. Survey data collected from these students investigated student perceptions on the use of the system generally and specifically as a learning tool. More in depth discussion of the usefulness of the KS was derived from a focus group comprising 5 students. Results 100% of students enjoyed using the KS and felt it promoted their understanding of key concepts; 92% stated that it helped identify their learning needs and 87% agreed that the technology was useful in promoting integration of concepts. The most prevalent theme within feedback was that of identifying their own learning needs. Analysis of data from the focus group generated similar themes, with the addition of improving teaching. Repeated questioning produced a significant increase (p < 0.05) in student knowledge of specific pharmacological concepts. Conclusions The use of ART enhanced non-medical prescribing students' experience of pharmacology teaching. Student perceptions were that this system increased their ability to identify learning needs and promoted understanding and integration of concepts. Students also reported that the technology aided exam revision and reduced associated anxiety. PMID:20979620

Development of a Clinical Pharmacology Graduate Program at the University of Kentucky.

ERIC Educational Resources Information Center

Blouin, Robert A.; And Others

1994-01-01

The structure, components, and anticipated outcomes of a University of Kentucky doctoral program in pharmacology are described. The program is designed to develop pharmacy-trained specialists who are interested in rigorous, intensive clinical experience, state-of-the-art coursework, and integrated laboratory-based and clinical dissertation…

Curcumin and its promise as an anticancer drug: An analysis of its anticancer and antifungal effects in cancer and associated complications from invasive fungal infections.

PubMed

Chen, Jin; He, Zheng-Min; Wang, Feng-Ling; Zhang, Zheng-Sheng; Liu, Xiu-zhen; Zhai, Dan-Dan; Chen, Wei-Dong

2016-02-05

Invasive fungal infections (IFI) are important complications of cancer, and they have become a major cause of morbidity and mortality in cancer patients. Effective anti-infection therapy is necessary to inhibit significant deterioration from these infections. However, they are difficult to treat, and increasing antifungal drug resistance often leads to a relapse. Curcumin, a natural component that is isolated from the rhizome of Curcuma longa plants, has attracted great interest among many scientists studying solid cancers over the last half century. Interestingly, curcumin provides an ideal alternative to current therapies because of its relatively safe profile, even at high doses. To date, curcumin's potent antifungal activity against different strains of Candida, Cryptococcus, Aspergillus, Trichosporon and Paracoccidioides have been reported, indicating that curcumin anticancer drugs may also possess an antifungal role, helping cancer patients to resist IFI complications. The aim of this review is to discuss curcumin's dual pharmacological activities regarding its applications as a natural anticancer and antifungal agent. These dual pharmacological activities are expected to lead to clinical trials and to improve infection survival among cancer patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Modelling the interactions between animal venom peptides and membrane proteins.

PubMed

Hung, Andrew; Kuyucak, Serdar; Schroeder, Christina I; Kaas, Quentin

2017-12-01

The active components of animal venoms are mostly peptide toxins, which typically target ion channels and receptors of both the central and peripheral nervous system, interfering with action potential conduction and/or synaptic transmission. The high degree of sequence conservation of their molecular targets makes a range of these toxins active at human receptors. The high selectivity and potency displayed by some of these toxins have prompted their use as pharmacological tools as well as drugs or drug leads. Molecular modelling has played an essential role in increasing our molecular-level understanding of the activity and specificity of animal toxins, as well as engineering them for biotechnological and pharmaceutical applications. This review focuses on the biological insights gained from computational and experimental studies of animal venom toxins interacting with membranes and ion channels. A host of recent X-ray crystallography and electron-microscopy structures of the toxin targets has contributed to a dramatic increase in the accuracy of the molecular models of toxin binding modes greatly advancing this exciting field of study. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

Marijuana-based drugs: innovative therapeutics or designer drugs of abuse?

PubMed

Seely, Kathryn A; Prather, Paul L; James, Laura P; Moran, Jeffery H

2011-02-01

The principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), activates CB1 cannabinoid receptors (CB1Rs). Unfortunately, pharmacological research into the design of effective THC analogs has been hampered by psychiatric side effects. THC-based drug design of a less academic nature, however, has led to the marketing of "synthetic marijuana," labeled as K2 or "Spice," among other terms, which elicits psychotropic actions via CB1R activation. Because of structural dissimilarity to THC, the active ingredients of K2/Spice preparations are widely unregulated. The K2/Spice "phenomenon" provides a context for considering whether marijuana-based drugs will truly provide innovative therapeutics or merely perpetuate drug abuse.

[Advances in studies on bear bile powder].

PubMed

Zhou, Chao-fan; Gao, Guo-jian; Liu, Ying

2015-04-01

In this paper, a detailed analysis was made on relevant literatures about bear bile powder in terms of chemical component, pharmacological effect and clinical efficacy, indicating bear bile powder's significant pharmacological effects and clinical application in treating various diseases. Due to the complex composition, bear bile powder is relatively toxic. Therefore, efforts shall be made to study bear bile powder's pharmacological effects, clinical application, chemical composition and toxic side-effects, with the aim to provide a scientific basis for widespread reasonable clinical application of bear bile powder.

The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions

PubMed Central

Diogo, Lucilia N.; Monteiro, Emília C.

2014-01-01

Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CPAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT. PMID:25295010

Nuclear factor κB–inducing kinase activation as a mechanism of pancreatic β cell failure in obesity

PubMed Central

Malle, Elisabeth K.; Zammit, Nathan W.; Walters, Stacey N.; Koay, Yen Chin; Wu, Jianmin; Tan, Bernice M.; Villanueva, Jeanette E.; Brink, Robert; Loudovaris, Tom; Cantley, James; McAlpine, Shelli R.; Hesselson, Daniel

2015-01-01

The nuclear factor κB (NF-κB) pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic β cell dysfunction in the metabolic syndrome. Whereas canonical NF-κB signaling is well studied, there is little information on the divergent noncanonical NF-κB pathway in the context of pancreatic islet dysfunction. Here, we demonstrate that pharmacological activation of the noncanonical NF-κB–inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. We identify NIK as a critical negative regulator of β cell function, as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of noncanonical NF-κB components p100 to p52, and accumulation of RelB. TNF and receptor activator of NF-κB ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive β cell–intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the noncanonical NF-κB transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to β cell failure. These studies reveal that NIK contributes a central mechanism for β cell failure in diet-induced obesity. PMID:26122662

Gymnadenia conopsea (L.) R. Br.: A Systemic Review of the Ethnobotany, Phytochemistry, and Pharmacology of an Important Asian Folk Medicine

PubMed Central

Shang, Xiaofei; Guo, Xiao; Liu, Yu; Pan, Hu; Miao, Xiaolou; Zhang, Jiyu

2017-01-01

Gymnadenia conopsea (L.) R. Br. (Orchidaceae) is a perennial herbaceous orchid plant that grows widely throughout Europe and in temperate and subtropical zones of Asia. In China, its tuber has been used in traditional Chinese medicines, Tibetan medicines, Mongolian medicines and other ethnic medicines, and taken to treat numerous health conditions. The present paper provides a review of the traditional uses, phytochemistry, biological activities, and toxicology to highlight the future prospects of the plant. More than 120 chemical compounds have been isolated, and the primary components are glucosides, dihydrostilbenes, phenanthrenes, aromatic compounds, and other compounds. G. conopsea and its active constituents possess broad pharmacological properties, such as the tonifying effect, anti-oxidative activity, anti-viral activity, immunoregulatory, antianaphylaxis, antigastric ulcer, sedative, and hypnotic activities, etc. However, overexploitation combined with the habitat destruction has resulted in the rapid decrease of the resources of this plant, and the sustainable use of G. conopsea is necessary to study. Meanwhile, the toxicity of this plant had not been comprehensively studied, and the active constituents and the mechanisms of action of the tuber were still unclear. Further, studies on G. conopsea should lead to the development of scientific quality control and new drugs and therapies for various diseases; thus, its use and development require additional investigation. PMID:28217096

Improving cancer treatment with cyclotron produced radionuclides. Comprehensive progress report, February 1, 1990--January 31, 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M. Finn, R.D.

1992-08-04

This report describes the author`s continuing long term goal of promoting nuclear medicine applications by improving the scientific basis for tumor diagnosis treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The program has 3 interactive components: Radiochemistry /Cyclotron; Pharmacology; and Immunology. An essential strategy is as follows: novel radionuclides and radiotracers developed in the Radiochemistry/Cyclotron section under the DOE grant during the 1989--1992 grant period, will be employed in the Pharmacology and Immunology sections of the DOE grant during the 1992--1995 grant period. The development of novel radionuclides and tracers is of course usefulmore » in and of itself, but their utility is greatly enhanced by the interaction with the immunology and pharmacology components of the program.« less

Recent advances in herbal medicines treating Parkinson's disease.

PubMed

Li, Xu-Zhao; Zhang, Shuai-Nan; Liu, Shu-Min; Lu, Fang

2013-01-01

Herbal medicines have attracted considerable attention in recent years, which are used to treat Parkinson's disease (PD) in China based on traditional Chinese medicine or modern pharmacological theories. We summarized and analyzed the anti-Parkinsonian activities of herbal medicines and herbal formulations investigated in PD models and provide future references for basic and clinical investigations. All the herbal medicines and herbal formulations were tested on PD models in vitro and in vivo. The relevant compounds and herbal extracts with anti-Parkinsonian activities were included and analyzed according to their genera or pharmacological activities. A total of 38 herbal medicines and 11 herbal formulations were analyzed. The relevant compounds, herbal extracts and formulations were reported to be effective on PD models by modulating multiple key events or signaling pathways implicated in the pathogenesis of PD. The plant species of these herbal medicines belong to 24 genera and 18 families, such as Acanthopanax, Alpinia and Astragalus, etc. These herbal medicines can be an alternative and valuable source for anti-Parkinsonian drug discovery. The plant species in these genera and families may be the most promising candidates for further investigation and deserve further consideration in clinical trials. Active components in some of the herbal extracts and the compatibility law of herbal formulations remain to be further investigated. Copyright © 2012 Elsevier B.V. All rights reserved.

Heterologous expression of the plant cysteine protease bromelain and its inhibitor in Pichia pastoris.

PubMed

Luniak, Nora; Meiser, Peter; Burkart, Sonja; Müller, Rolf

2017-01-01

Expression of proteases in heterologous hosts remains an ambitious challenge due to severe problems associated with digestion of host proteins. On the other hand, proteases are broadly used in industrial applications and resemble promising drug candidates. Bromelain is an herbal drug that is medicinally used for treatment of oedematous swellings and inflammatory conditions and consists in large part of proteolytic enzymes. Even though various experiments underline the requirement of active cysteine proteases for biological activity, so far no investigation succeeded to clearly clarify the pharmacological mode of action of bromelain. The potential role of proteases themselves and other molecules of this multi-component extract currently remain largely unknown or ill defined. Here, we set out to express several bromelain cysteine proteases as well as a bromelain inhibitor molecule in order to gain defined molecular entities for subsequent studies. After cloning the genes from its natural source Ananas comosus (pineapple plant) into Pichia pastoris and subsequent fermentation and purification, we obtained active protease and inhibitor molecules which were subsequently biochemically characterized. Employing purified bromelain fractions paves the way for further elucidation of pharmacological activities of this natural product. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:54-65, 2017. © 2016 American Institute of Chemical Engineers.

In vitro evidence of a tissue factor-independent mode of action of recombinant factor VIIa in hemophilia.

PubMed

Augustsson, Cecilia; Persson, Egon

2014-11-13

Successful competition of activated factor VII (FVIIa) with zymogen factor VII (FVII) for tissue factor (TF) and loading of the platelet surface with FVIIa are plausible driving forces behind the pharmacological effect of recombinant FVIIa (rFVIIa) in hemophilia patients. Thrombin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which potentially could reduce the effective (r)FVIIa:TF complex concentration and thereby attenuate factor Xa production. However, (auto)activation of FVII apparently counteracted the negative effect of zymogen binding; a small impact was observed at endogenous concentrations of FVII and FVIIa but was virtually absent at pharmacological amounts of rFVIIa. Moreover, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the range where a physiological level of FVII was capable to downregulate thrombin generation. These data strongly suggest that rFVIIa acts independently of TF in hemophilia therapy and that FVII displacement by rFVIIa is a negligible mechanistic component. © 2014 by The American Society of Hematology.

Multiscale Modeling of Drug-induced Effects of ReDuNing Injection on Human Disease: From Drug Molecules to Clinical Symptoms of Disease

NASA Astrophysics Data System (ADS)

Luo, Fang; Gu, Jiangyong; Zhang, Xinzhuang; Chen, Lirong; Cao, Liang; Li, Na; Wang, Zhenzhong; Xiao, Wei; Xu, Xiaojie

2015-05-01

ReDuNing injection (RDN) is a patented traditional Chinese medicine, and the components of it were proven to have antiviral and important anti-inflammatory activities. Several reports showed that RDN had potential effects in the treatment of influenza and pneumonia. Though there were several experimental reports about RDN, the experimental results were not enough and complete due to that it was difficult to predict and verify the effect of RDN for a large number of human diseases. Here we employed multiscale model by integrating molecular docking, network pharmacology and the clinical symptoms information of diseases and explored the interaction mechanism of RDN on human diseases. Meanwhile, we analyzed the relation among the drug molecules, target proteins, biological pathways, human diseases and the clinical symptoms about it. Then we predicted potential active ingredients of RDN, the potential target proteins, the key pathways and related diseases. These attempts may offer several new insights to understand the pharmacological properties of RDN and provide benefit for its new clinical applications and research.

Effects of processing adjuvants on traditional Chinese herbs.

PubMed

Chen, Lin-Lin; Verpoorte, Robert; Yen, Hung-Rong; Peng, Wen-Huang; Cheng, Yung-Chi; Chao, Jung; Pao, Li-Heng

2018-04-01

Processing of Chinese medicines is a pharmaceutical technique that transforms medicinal raw materials into decoction pieces for use in different therapies. Various adjuvants, such as vinegar, wine, honey, and brine, are used in the processing to enhance the efficacy and reduce the toxicity of crude drugs. Proper processing is essential to ensure the quality and safety of traditional Chinese medicines (TCMs). Therefore, sound knowledge of processing principles is crucial to the standardized use of these processing adjuvants and to facilitate the production and clinical use of decoction pieces. Many scientific reports have indicated the synergistic effects of processing mechanisms on the chemistry, pharmacology, and pharmacokinetics of the active ingredients in TCMs. Under certain conditions, adjuvants change the content of active or toxic components in drugs by chemical or physical transformation, increase or decrease drug dissolution, exert their own pharmacological effects, or alter drug pharmacokinetics. This review summarizes various processing methods adopted in the last two decades, and highlights current approaches to identify the effects of processing parameters on TCMs. Copyright © 2018. Published by Elsevier B.V.

Antimicrobial, antibiofilm and antitumor activities of essential oil of Agastache rugosa from Xinjiang, China.

PubMed

Haiyan, Gong; Lijuan, He; Shaoyu, Li; Chen, Zhang; Ashraf, Muhammad Aqeel

2016-07-01

In the study, we evaluated chemical composition and antimicrobial, antibiofilm, and antitumor activities of essential oils from dried leaf essential oil of leaf and flower of Agastache rugosa for the first time. Essential oil of leaf and flower was evaluated with GC and GC-MS methods, and the essential oil of flower revealed the presence of 21 components, whose major compounds were pulegone (34.1%), estragole (29.5%), and p-Menthan-3-one (19.2%). 26 components from essential oil of leaf were identified, the major compounds were p-Menthan-3-one (48.8%) and estragole (20.8%). At the same time, essential oil of leaf, there is a very effective antimicrobial activity with MIC ranging from 9.4 to 42 μg ml(-1) and potential antibiofilm, antitumor activities for essential oils of flower and leaf essential oil of leaf. The study highlighted the diversity in two different parts of A. rugosa grown in Xinjiang region and other places, which have different active constituents. Our results showed that this native plant may be a good candidate for further biological and pharmacological investigations.

[Research progress of chemical constituents and pharmacological activities of essential oil of Ligusticum chuanxiong].

PubMed

Du, Jing-Chang; Xie, Xiao-Fang; Xiong, Liang; Sun, Chen; Peng, Cheng

2016-12-01

Essential oil is the low polar and volatile components distilled or extracted from Ligusticum chuanxiong, the dry root of perennial herb L. chuanxiong, which has proven to be one of the main biological active ingredients of L. chuanxiong. Studies suggested that essential oil of L. chuanxiong mainly contains phthalide, terpene alcohols and fatty acids compounds. Different regions or varied extraction technology had influences on the type and contents of compound in essential oil of L. chuanxiong and the total yield efficiency of essential oil, while the differences among the distribution of compounds leads to the variant pharmacological function of essential oil of L. chuanxiong. Researches confirmed that essential oil of L. chuanxiong has kinds of pharmacological activities such as sedation, analgesia, improve function of blood vessels, protected nerve cells and fever-reducing, all these benefits were verified by experiment studies in vivo and some of which were used as therapies in treating migraine, the underlining mechanisms include anti-inflammation, apoptosis pathway and studies found that essential oil of L. chuanxiong possessed very low acute and chronic toxicity at the same time, revealed its great value of development and utilization in clinical applications. Recent studies light some problems such as lack of quality standards and the research of relationship between efficacy and material. The key to apply the usage of essential oil of L. chuanxiong locate in its substantial basis research, the establishment of the quality standards and the joint research institute, more study should work on these fields. Copyright© by the Chinese Pharmaceutical Association.

The Physiological Effects of Dandelion (Taraxacum Officinale) in Type 2 Diabetes.

PubMed

Wirngo, Fonyuy E; Lambert, Max N; Jeppesen, Per B

2016-01-01

The tremendous rise in the economic burden of type 2 diabetes (T2D) has prompted a search for alternative and less expensive medicines. Dandelion offers a compelling profile of bioactive components with potential anti-diabetic properties. The Taraxacum genus from the Asteraceae family is found in the temperate zone of the Northern hemisphere. It is available in several areas around the world. In many countries, it is used as food and in some countries as therapeutics for the control and treatment of T2D. The anti-diabetic properties of dandelion are attributed to bioactive chemical components; these include chicoric acid, taraxasterol (TS), chlorogenic acid, and sesquiterpene lactones. Studies have outlined the useful pharmacological profile of dandelion for the treatment of an array of diseases, although little attention has been paid to the effects of its bioactive components on T2D to date. This review recapitulates previous work on dandelion and its potential for the treatment and prevention of T2D, highlighting its anti-diabetic properties, the structures of its chemical components, and their potential mechanisms of action in T2D. Although initial research appears promising, data on the cellular impact of dandelion are limited, necessitating further work on clonal β-cell lines (INS-1E), α-cell lines, and human skeletal cell lines for better identification of the active components that could be of use in the control and treatment of T2D. In fact, extensive in-vitro, in-vivo, and clinical research is required to investigate further the pharmacological, physiological, and biochemical mechanisms underlying the effects of dandelion-derived compounds on T2D.

The Physiological Effects of Dandelion (Taraxacum Officinale) in Type 2 Diabetes

PubMed Central

Wirngo, Fonyuy E.; Lambert, Max N.; Jeppesen, Per B.

2016-01-01

The tremendous rise in the economic burden of type 2 diabetes (T2D) has prompted a search for alternative and less expensive medicines. Dandelion offers a compelling profile of bioactive components with potential anti-diabetic properties. The Taraxacum genus from the Asteraceae family is found in the temperate zone of the Northern hemisphere. It is available in several areas around the world. In many countries, it is used as food and in some countries as therapeutics for the control and treatment of T2D. The anti-diabetic properties of dandelion are attributed to bioactive chemical components; these include chicoric acid, taraxasterol (TS), chlorogenic acid, and sesquiterpene lactones. Studies have outlined the useful pharmacological profile of dandelion for the treatment of an array of diseases, although little attention has been paid to the effects of its bioactive components on T2D to date. This review recapitulates previous work on dandelion and its potential for the treatment and prevention of T2D, highlighting its anti-diabetic properties, the structures of its chemical components, and their potential mechanisms of action in T2D. Although initial research appears promising, data on the cellular impact of dandelion are limited, necessitating further work on clonal β-cell lines (INS-1E), α-cell lines, and human skeletal cell lines for better identification of the active components that could be of use in the control and treatment of T2D. In fact, extensive in-vitro, in-vivo, and clinical research is required to investigate further the pharmacological, physiological, and biochemical mechanisms underlying the effects of dandelion-derived compounds on T2D. PMID:28012278

Efficacy of Neurofeedback Versus Pharmacological Support in Subjects with ADHD.

PubMed

González-Castro, Paloma; Cueli, Marisol; Rodríguez, Celestino; García, Trinidad; Álvarez, Luis

2016-03-01

Behavioral training in neurofeedback has proven to be an essential complement to generalize the effects of pharmacological support in subjects who have attention deficit with hyperactivity disorder (ADHD). Therefore, this investigation attempts to analyze the efficacy of neurofeedback compared with pharmacological support and the combination of both. Participants were 131 students, classified into four groups: control (did not receive neurofeedback or pharmacological support), neurofeedback group, pharmacological support group, and combined group (neurofeedback + pharmacological support). Participants' executive control and cortical activation were assessed before and after treatment. Results indicate that the combined group obtained more benefits and that the neurofeedback group improved to a greater extent in executive control than the pharmacological support group. It is concluded that this kind of training may be an alternative to stimulate activation in subjects with ADHD.

Pharmacological properties of Datura stramonium L. as a potential medicinal tree: An overview

PubMed Central

Soni, Priyanka; Siddiqui, Anees Ahmad; Dwivedi, Jaya; Soni, Vishal

2012-01-01

India has a great wealth of various naturally occurring plant drugs which have great potential pharmacological activities. Datura stramonium (D. stramonium) is one of the widely well known folklore medicinal herbs. The troublesome weed, D. stramonium is a plant with both poisonous and medicinal properties and has been proven to have great pharmacological potential with a great utility and usage in folklore medicine. D. stromonium has been scientifically proven to contain alkaloids, tannins, carbohydrates and proteins. This plant has contributed various pharmacological actions in the scientific field of Indian systems of medicines like analgesic and antiasthmatic activities. The present paper presents an exclusive review work on the ethnomedical, phytochemical, pharmacological activities of this plant. PMID:23593583

Lycium Barbarum: A Traditional Chinese Herb and A Promising Anti-Aging Agent

PubMed Central

Gao, Yanjie; Wei, Yifo; Wang, Yuqing; Gao, Fang; Chen, Zhigang

2017-01-01

Lycium barbarum has been used in China for more than 2,000 years as a traditional medicinal herb and food supplement. Lycium barbarum contains abundant Lycium barbarum polysaccharides (LBPs), betaine, phenolics, carotenoids (zeaxanthin and β-carotene), cerebroside, 2-O-β-d-glucopyranosyl-l-ascorbic acid (AA-2βG), β-sitosterol, flavonoids and vitamins (in particular, riboflavin, thiamine, and ascorbic acid). LBPs are the primary active components of Lycium barbarum. In this review, we discuss the pharmacological activities of LBPs and other major components. They have been reported to mediate significant anti-aging effects, through antioxidant, immunoregulative, anti-apoptotic activities and reducing DNA damage. Thus, the basic scientific evidence for anti-aging effects of LBPs is already available. However, additional studies are needed to understand mechanisms by which LBPs mediate anti-aging properties. Novel findings from such studies would likely pave the way for the clinical application of traditional chinese medicine Lycium barbarum in modern evidence-based medicine. PMID:29344416

Drug selection in French university hospitals: analysis of formularies for nine competitive pharmacological classes.

PubMed

Gallini, Adeline; Juillard-Condat, Blandine; Saux, Marie-Claude; Taboulet, Florence

2011-11-01

To give a panorama of the selectivity and agreement of French university hospitals' drug formularies (HDF) for nine competitive classes. All university hospitals were asked to send their HDF and selection criteria as of January 2009 for nine competitive pharmacological classes (proton pump inhibitors, serotonin antagonists, low molecular weight heparins, erythropoietins, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, statins, α-adrenoreceptor antagonists and selective serotonin re-uptake inhibitors). Selectivity of HDF was estimated by the percentage of drug entities selected by the hospital within the pharmacological class. Agreement between hospitals was assessed with modified kappa coefficients for multi-raters. Twenty-one out of the 29 hospitals agreed to participate. These hospitals selected between 34% and 63% of the drug entities available for the nine classes, which represented 18 to 35 agents. Regarding the nature of chosen drug entities, the overall level of agreement was 'fair' and varied with pharmacological classes. Selection criteria were sent by only 12 hospitals. The technical component was the most important element in all hospitals. The weight of the economic component varied between 20% and 40% in the tender's grade. Large variations were seen in the number and nature of drugs selected by university hospitals which can be attributable to two successive decision-making processes (evaluation by the Drug and Therapeutics Committee followed by the purchasing process). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Blue-Print Autophagy: Potential for Cancer Treatment

PubMed Central

Ruocco, Nadia; Costantini, Susan; Costantini, Maria

2016-01-01

The marine environment represents a very rich source of biologically active compounds with pharmacological applications. This is due to its chemical richness, which is claiming considerable attention from the health science communities. In this review we give a general overview on the marine natural products involved in stimulation and inhibition of autophagy (a type of programmed cell death) linked to pharmacological and pathological conditions. Autophagy represents a complex multistep cellular process, wherein a double membrane vesicle (the autophagosome) captures organelles and proteins and delivers them to the lysosome. This natural and destructive mechanism allows the cells to degrade and recycle its cellular components, such as amino acids, monosaccharides, and lipids. Autophagy is an important mechanism used by cells to clear pathogenic organism and deal with stresses. Therefore, it has also been implicated in several diseases, predominantly in cancer. In fact, pharmacological stimulation or inhibition of autophagy have been proposed as approaches to develop new therapeutic treatments of cancers. In conclusion, this blue-print autophagy (so defined because it is induced and/or inhibited by marine natural products) represents a new strategy for the future of biomedicine and of biotechnology in cancer treatment. PMID:27455284

Digitalis metabolism and human liver alcohol dehydrogenase.

PubMed Central

Frey, W A; Vallee, B L

1980-01-01

Human liver alcohol dehydrogenase (alcohol: NAD" oxidoreductase, EC 1.1.1.1) catalyzes the oxidation of the 3 beta-OH group of digitoxigenin, digoxigenin, and gitoxigenin to their 3-keto derivatives, which have been characterized by high performance liquid chromatography and mass spectrometry. These studies have identified human liver alcohol dehydrogenase as the unknown NAD(H)-dependent liver enzyme specific for the free hydroxyl group at C3 of the cardiac genins; this hydroxyl is the critical site of the genins' enzymatic oxidation and concomitant pharmacological inactivation in humans. Several kinetic approaches have demonstrated that ethanol and the pharmacologically active components of the digitalis glycosides are oxidized with closely similar kcat/Km values at the same site on human liver alcohol dehydrogenase, for which they compete. Human liver alcohol dehydrogenase thereby becomes an important biochemical link in the metabolism, pharmacology, and toxicology of ethanol and these glycosides, structurally unrelated agents that are both used widely. Both the competition of ethanol with these cardiac sterols and the narrow margin of safety in the therapeutic use of digitalis derivatives would seem to place at increased risk those individuals who receive digitalis and simultaneously consume large amounts of ethanol or whose alcohol dehydrogenase function is impaired. PMID:6987673

A Quantitative Systems Pharmacology Approach to Infer Pathways Involved in Complex Disease Phenotypes.

PubMed

Schurdak, Mark E; Pei, Fen; Lezon, Timothy R; Carlisle, Diane; Friedlander, Robert; Taylor, D Lansing; Stern, Andrew M

2018-01-01

Designing effective therapeutic strategies for complex diseases such as cancer and neurodegeneration that involve tissue context-specific interactions among multiple gene products presents a major challenge for precision medicine. Safe and selective pharmacological modulation of individual molecular entities associated with a disease often fails to provide efficacy in the clinic. Thus, development of optimized therapeutic strategies for individual patients with complex diseases requires a more comprehensive, systems-level understanding of disease progression. Quantitative systems pharmacology (QSP) is an approach to drug discovery that integrates computational and experimental methods to understand the molecular pathogenesis of a disease at the systems level more completely. Described here is the chemogenomic component of QSP for the inference of biological pathways involved in the modulation of the disease phenotype. The approach involves testing sets of compounds of diverse mechanisms of action in a disease-relevant phenotypic assay, and using the mechanistic information known for the active compounds, to infer pathways and networks associated with the phenotype. The example used here is for monogenic Huntington's disease (HD), which due to the pleiotropic nature of the mutant phenotype has a complex pathogenesis. The overall approach, however, is applicable to any complex disease.

A Comprehensive Review of Punica granatum (Pomegranate) Properties in Toxicological, Pharmacological, Cellular and Molecular Biology Researches

PubMed Central

Rahimi, Hamid Reza; Arastoo, Mohammad; Ostad, Seyed Nasser

2012-01-01

Punica granatum (Pg), commonly known as pomegranate (Pg), is a member of the monogeneric family, Punicaceae, and is mainly found in Iran which is considered to be its primary centre of origin. Pg and its chemical components possess various pharmacological and toxicological properties including antioxidant, anti-inflammatory (by inhibiting pro-inflammatory cytokines), anti-cancer and anti-angiogenesis activities. They also show inhibitory effects on invasion/motility, cell cycle, apoptosis, and vital enzymes such as cyclooxygenase (COX), lipooxygenase (LOX), cytochrome P450 (CYP450), phospholipase A2 (PLA2), ornithine decarboxylase (ODC), carbonic anhydrase (CA), 17beta-hydroxysteroid dehydrogenase (17β-HSDs) and serine protease (SP). Furthermore, they can stimulate cell differentiation and possess anti-mutagenic effects. Pg can also interfere with several signaling pathways including PI3K/AKT, mTOR, PI3K, Bcl-X, Bax, Bad, MAPK, ERK1/2, P38, JNK, and caspase. However, the exact mechanisms for its pharmacological and toxicological properties remain to be unclear and need further evaluation. These properties strongly suggest a wide range use of Pg for clinical applications. This review will discuss the areas for which Pg has shown therapeutic properties in different mechanisms. PMID:24250463

Diospyros, an under-utilized, multi-purpose plant genus: A review.

PubMed

Rauf, Abdur; Uddin, Ghias; Patel, Seema; Khan, Ajmal; Halim, Sobia Ahsan; Bawazeer, Saud; Ahmad, Khalid; Muhammad, Naveed; Mubarak, Mohammad S

2017-07-01

The genus Diospyros from family Ebenaceae has versatile uses including edible fruits, valuable timber, and ornamental uses. The plant parts of numerous species have been in use as remedies in various folk healing practices, which include therapy for hemorrhage, incontinence, insomnia, hiccough, diarrhea etc. Phytochemical constituents such as terpenoids, ursanes, lupanes, polyphenols, tannins, hydrocarbons, and lipids, benzopyrones, naphthoquinones, oleananes, and taraxeranes have been isolated from different species of this genus. The biological activities of these plants such as antioxidant, anti-inflammatory, analgesic, antipyretic, anti-diabetic, antibacterial, anthelmintic, antihypertensive, cosmeceutical, enzyme-inhibitory etc. have been validated by means of an in vitro, in vivo, and clinical tests. As a rich reserve of pharmacologically important components, this genus can accelerate the pace of drug discovery. Accordingly, the aim of the present review is to survey and summarize the recent literature pertaining to the medicinal and pharmacological uses of Diospyros, and to select experimental evidence on the pharmacological properties of this genus. In addition, the review also aims at identifying areas that need development to make use of this genus, especially its fruit and phytochemicals as means for economic development and for drug discovery. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Acetylcholine-activated ionic currents in parasympathetic neurons of bullfrog heart.

PubMed

Tateishi, N; Kim, D K; Akaike, N

1990-05-01

1. The electrical and pharmacologic properties of acetylcholine (ACh)-induced current (IACh) were studied in the parasympathetic neurons isolated from bullfrog heart with the use of the concentration-clamp technique, which allows intracellular perfusion and rapid change of external solution within 2 ms under the single-electrode voltage-clamp condition. 2. The IACh consisted of an initial transient peak component and a successive steady-state plateau component. Both currents increased in a sigmoidal fashion with increasing ACh concentration. The dissociation constant (Kd value) and the Hill coefficient for each component were 2.2 X 10(-5) M and 1.6, respectively. 3. In the K(+)-free solution, the reversal potential (EACh) of IACh was close to the Na+ equilibrium potential (ENa). The current-voltage (I-V) relation showed inward rectification at positive potentials. 4. Nicotine mimicked only the peak component of IACh. However both peak and steady-state components were blocked nonselectively by the nicotinic blockers d-tubocurarine and hexamethonium. 5. Carbamylcholine (CCh) mimicked the steady-state component of IACh. The steady-state component was selectively inhibited by atropine at concentrations 1,000 times lower than that required for inhibition of the peak component. The steady state was blocked equally by either pirenzepine (M1 blocker) or AF-DX-116 (M2 blocker). 6. It was concluded that the IACh consisted of a peak component having double exponential activation and inactivation, mediated through the nicotinic actions, and a steady-state component having no inactivation, mediated through the muscarinic action.

Insights into Supplements with Tribulus Terrestris used by Athletes

PubMed Central

Pokrywka, Andrzej; Obmiński, Zbigniew; Malczewska-Lenczowska, Jadwiga; Fijałek, Zbigniew; Turek-Lepa, Ewa; Grucza, Ryszard

2014-01-01

Herbal and nutritional supplements are more and more popular in the western population. One of them is an extract of an exotic plant, named Tribulus terrestris (TT). TT is a component of several supplements that are available over-the-counter and widely recommended, generally as enhancers of human vitality. TT is touted as a testosterone booster and remedy for impaired erectile function; therefore, it is targeted at physically active men, including male athletes. Based on the scientific literature describing the results of clinical trials, this review attempted to verify information on marketing TT with particular reference to the needs of athletes. It was found that there are few reliable data on the usefulness of TT in competitive sport. In humans, a TT extract used alone without additional components does not improve androgenic status or physical performance among athletes. The results of a few studies have showed that the combination of TT with other pharmacological components increases testosterone levels, but it was not discovered which components of the mixture contributed to that effect. TT contains several organic compounds including alkaloids and steroidal glycosides, of which pharmacological action in humans is not completely explained. One anti-doping study reported an incident with a TT supplement contaminated by a banned steroid. Toxicological studies regarding TT have been carried out on animals only, however, one accidental poisoning of a man was described. The Australian Institute of Sport does not recommend athletes’ usage of TT. So far, the published data concerning TT do not provide strong evidence for either usefulness or safe usage in sport. PMID:25114736

The metabolism of berberine and its contribution to the pharmacological effects.

PubMed

Wang, Kun; Feng, Xinchi; Chai, Liwei; Cao, Shijie; Qiu, Feng

2017-05-01

Berberine, a bioactive alkaloid isolated from several herbal substances, possesses multiple pharmacological effects, including antimicrobial, antidiabetic, anticancer activities. Meanwhile, berberine undergoes extensive metabolism after oral administration which results in its extremely low plasma exposure. Therefore, it is believed that the metabolites of berberine also contribute a lot to its pharmacological effects. Along these lines, this review covers the metabolism studies of berberine in terms of its metabolic pathways and metabolic organs based on the identified metabolites, and it also covers the pharmacological activities of its active metabolites. In brief, the predominant metabolic pathways of berberine are demethylation, demethylenation, reduction, hydroxylation and subsequent conjugation in vivo. Active metabolites such as columbamine, berberrubine and demethyleneberberine also exhibit similar pharmacological effects by comparison with berberine, such as antioxidant, anti-inflammatory, antitumor, antimicrobial, hepatoprotective, neuroprotective, hypolipidemic and hypoglycemic effects. Overall, berberine together with its metabolites formed the material basis of berberine in vivo.

[Study on composition, antibiotic activity and antioxidant activity of volatile oils from uyghur medicine Althaea rosea].

PubMed

Munira, Abudukeremu; Muheta'er, Tu'erhong; Resalat, Yimin; Xia, Na

2015-04-01

Althaea rosea is a type of mallow plant. Its dry flowers are one of common herb in Uyghur medicines and recorded to have several efficacies such as external application for detumescence, moistening lung and arresting cough, sweating and relieving asthma, diminishing swelling and promoting eruption, soothing the nerves and strengthening heart. However, there are only fewer studies on effective components of A. rosea and no literature about its volatile oil and pharmacological activity. In this paper, the volatile oil of A. rosea was obtained by using the chemical distillation and extraction method. The individual chemical components were separated from the volatile oil and identified by the Gas Chromatograph-Mass Spectrometer technique (GC-MS). The antioxidant activity against free radicals was detected by the'ultraviolet and visible spectrophotometer method. The antibiotic activity was detected by the filter paper diffusion method. The experimental results showed nearly 70 compounds in the volatile oil, with complex chemical components. With a low content, most of the compounds were aromatic and aliphatic compounds and their derivatives. A. rosea had a better antibiotic activity for common microorganisms, with a wide antibacterial spectrum. According to the results, the volatile oil of A. rosea will have a good application value in medicine, food and cosmetic industries, which provided a scientific basis for the development of natural A. rosea resources.

Application of multi-target phytotherapeutic concept in malaria drug discovery: a systems biology approach in biomarker identification.

PubMed

Tarkang, Protus Arrey; Appiah-Opong, Regina; Ofori, Michael F; Ayong, Lawrence S; Nyarko, Alexander K

2016-01-01

There is an urgent need for new anti-malaria drugs with broad therapeutic potential and novel mode of action, for effective treatment and to overcome emerging drug resistance. Plant-derived anti-malarials remain a significant source of bioactive molecules in this regard. The multicomponent formulation forms the basis of phytotherapy. Mechanistic reasons for the poly-pharmacological effects of plants constitute increased bioavailability, interference with cellular transport processes, activation of pro-drugs/deactivation of active compounds to inactive metabolites and action of synergistic partners at different points of the same signaling cascade. These effects are known as the multi-target concept. However, due to the intrinsic complexity of natural products-based drug discovery, there is need to rethink the approaches toward understanding their therapeutic effect. This review discusses the multi-target phytotherapeutic concept and its application in biomarker identification using the modified reverse pharmacology - systems biology approach. Considerations include the generation of a product library, high throughput screening (HTS) techniques for efficacy and interaction assessment, High Performance Liquid Chromatography (HPLC)-based anti-malarial profiling and animal pharmacology. This approach is an integrated interdisciplinary implementation of tailored technology platforms coupled to miniaturized biological assays, to track and characterize the multi-target bioactive components of botanicals as well as identify potential biomarkers. While preserving biodiversity, this will serve as a primary step towards the development of standardized phytomedicines, as well as facilitate lead discovery for chemical prioritization and downstream clinical development.

Differences in direct pharmacologic effects and antioxidative properties of mature breast milk and infant formulas.

PubMed

Lugonja, Nikoleta; Spasić, Snežana D; Laugier, Olga; Nikolić-Kokić, Aleksandra; Spasojević, Ivan; Oreščanin-Dušić, Zorana; Vrvić, Miroslav M

2013-02-01

Early-onset and exclusive breast-feeding provides a significant health benefit to infants compared with infant formulas. The aim of this study was to compare mature breast milk with standard infant formulas by examining their effects on non-vascular smooth muscle contraction and their antioxidative properties. The pharmacologic effects of breast milk and formulas were examined using a model system of the rat uterine smooth muscle contraction. Electron paramagnetic resonance spin-trapping spectroscopy was used to compare the antioxidative capacities of breast milk (obtained in the ninth week of lactation) with commercial infant formulas against hydroxyl radical production in the Fenton reaction. The activities of superoxide dismutase, glutathione peroxidase, and the sulfhydryl group were determined in the breast milk and infant formulas. In contrast to the infant formulas, breast milk exerted a relaxing effect on isolated non-vascular smooth muscle. In general, breast milk showed higher antioxidative activity compared with the infant formulas. In all samples, the generation of hydroxyl radicals led to the formation of carbon-centered and ascorbyl radicals. Human milk exerts direct pharmacologic relaxation effects and provides better antioxidant protection compared with infant formulas because of the presence of specific enzymatic components, such as human superoxide dismutase. We propose that these effects should be advantageous to an infant's gastrointestinal tract by supporting the normal work of the smooth musculature and maintaining redox homeostasis and may represent one of the mechanisms by which breast-feeding benefits health. Copyright © 2013 Elsevier Inc. All rights reserved.

Downregulation of LRRC8A protects human ovarian and alveolar carcinoma cells against Cisplatin-induced expression of p53, MDM2, p21Waf1/Cip1, and Caspase-9/-3 activation

PubMed Central

Sørensen, Belinda Halling; Nielsen, Dorthe; Thorsteinsdottir, Unnur Arna; Hoffmann, Else Kay

2016-01-01

The leucine-rich repeat containing 8A (LRRC8A) protein is an essential component of the volume-sensitive organic anion channel (VSOAC), and using pharmacological anion channel inhibitors (NS3728, DIDS) and LRRC8A siRNA we have investigated its role in development of Cisplatin resistance in human ovarian (A2780) and alveolar (A549) carcinoma cells. In Cisplatin-sensitive cells Cisplatin treatment increases p53-protein level as well as downstream signaling, e.g., expression of p21Waf1/Cip1, Bax, Noxa, MDM2, and activation of Caspase-9/-3. In contrast, Cisplatin-resistant cells do not enter apoptosis, i.e., their p53 and downstream signaling are reduced and caspase activity unaltered following Cisplatin exposure. Reduced LRRC8A expression and VSOAC activity are previously shown to correlate with Cisplatin resistance, and here we demonstrate that pharmacological inhibition and transient knockdown of LRRC8A reduce the protein level of p53, MDM2, and p21Waf1/Cip1 as well as Caspase-9/-3 activation in Cisplatin-sensitive cells. Cisplatin resistance is accompanied by reduction in total LRRC8A expression (A2780) or LRRC8A expression in the plasma membrane (A549). Activation of Caspase-3 dependent apoptosis by TNFα-exposure or hyperosmotic cell shrinkage is almost unaffected by pharmacological anion channel inhibition. Our data indicate 1) that expression/activity of LRRC8A is essential for Cisplatin-induced increase in p53 protein level and its downstream signaling, i.e., Caspase-9/-3 activation, expression of p21Waf1/Cip1 and MDM2; and 2) that downregulation of LRRC8A-dependent osmolyte transporters contributes to acquirement of Cisplatin resistance in ovarian and lung carcinoma cells. Activation of LRRC8A-containing channels is upstream to apoptotic volume decrease as hypertonic cell shrinkage induces apoptosis independent of the presence of LRRC8A. PMID:26984736

Anti-Gastric Ulcer Activity of Polysaccharide Fraction Isolated from Mycelium Culture of Lion's Mane Medicinal Mushroom, Hericium erinaceus (Higher Basidiomycetes).

PubMed

Wang, Mingxing; Konishi, Tetsuya; Gao, Yang; Xu, Duoduo; Gao, Qipin

2015-01-01

Hericium erinaceus is a culinary-medicinal mushroom that is used in traditional medicine, in folk medicine, and as medicinal cuisine in Asian countries such as China, Japan, and Korea. H. erinaceus exhibits various pharmacological properties, such as anti-cancer, immunomodulation, anti-dementia, and anti-gastric ulcer effects. The extracts of the fruiting body of H. erinaceus demonstrate anti-gastritis activity. However, the active principle in the extract, as well as the mechanism to treat gastric ulcers, remains uncertain. The current study aims to identify the active component, with anti-gastric ulcer function, from the extracts of the H. erinaceus mycelium culture. In the experiment, anti-gastric ulcer activity was evaluated using an ethanol-induced ulcer model in mice and with an 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay using MC cell lines. The results suggest that the polysaccharide fraction can significantly decrease the ulcerated area compared with the control group and the effect is fairly dose dependent, irrespective of animal or cell experiments. These results indicate that the polysaccharide fraction is the active component of the H. erinaceus mycelium culture, which protects against gastric ulcers.

[Psychosocial interventions in dementia].

PubMed

Kurz, A

2013-01-01

Psychosocial interventions improve cognitive abilities (cognitive stimulation, cognitive training), enhance emotional well-being (activity planning, reminiscence), reduce behavioral symptoms (aromatherapy, music therapy) and promote everyday functioning (occupational therapy). Through these effects they reinforce and augment pharmacological treatments for dementia. In addition, psychosocial interventions complement the treatment of patients by supporting family caregivers (educational groups, support programs). The potential of psychosocial interventions in dementia needs to be explored further in studies using improved methodology to determine effective components, clinical relevance and duration of effects, predictors of individual treatment response and health-economic implications.

Efficacy of Daphne oleoides subsp. kurdica used for wound healing: identification of active compounds through bioassay guided isolation technique.

PubMed

Süntar, Ipek; Küpeli Akkol, Esra; Keles, Hikmet; Yesilada, Erdem; Sarker, Satyajit D; Arroo, Randolph; Baykal, Turhan

2012-06-14

In Turkish traditional medicine, the aerial parts of Daphne oleoides Schreber subsp. kurdica (DOK) have been used to treat malaria, rheumatism and for wound healing. The aim was to evaluate the ethnopharmacological usage of the plant using in vivo and in vitro pharmacological experimental models, and to perform bioassay-guided fractionation of the 85% methanolic extract of DOK for the isolation and identification of active wound-healing component(s) and to elucidate possible mechanism of the wound-healing activity. In vivo wound-healing activity was evaluated by the linear incision and the circular excision wound models. Anti-inflammatory and antioxidant activities, which are known to support the wound healing process, were also assessed by the Whittle method and the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging assays, respectively. The total phenolic content of the extract and subextracts was estimated to establish any correlation between the phenolic content and the antioxidant activity. The methanolic extract of DOK was subjected to various chromatographic separation techniques leading to the isolation and identification of the active component(s). Furthermore, in vitro hyaluronidase, collagenase and elastase enzymes inhibitory activity assays were conducted on the active components to explore the activity pathways of the remedy. After confirmation of the wound-healing activity, the methanolic extract was subjected to successive solvent partitioning using solvents of increasing polarity creating five subextracts. Each subextract was tested on the same biological activity model and the ethyl acetate (EtOAc) subextract had the highest activity. The EtOAc subextract was subjected to further chromatographic separation for the isolation of components 1, 2 and 3. The structures of these compounds were elucidated as daphnetin (1), demethyldaphnoretin 7-O-glucoside (2) and luteolin-7-O-glucoside (3). Further in vivo testing revealed that luteolin-7-O-glucoside was responsible for the wound-healing activity of the aerial parts. It was also found to exert significant anti-inflammatory, antioxidant, anti-hyaluronidase and anti-collagenase activities. The present study explored the wound-healing potential of Daphne oleoides subsp. kurdica. Through bioassay-guided fractionation and isolation techniques, luteolin-7-O-glucoside was determined as the main active component of the aerial parts. This compound exerts its activity through inhibition of hyaluronidase and collagenase enzymes activity as well as interfering with the inflammatory stage. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A review on the ethnomedicinal uses, phytochemistry and pharmacology of Alpinia officinarum Hance.

PubMed

Abubakar, Ibrahim Babangida; Malami, Ibrahim; Yahaya, Yakubu; Sule, Sahabi Manga

2018-05-25

Alpinia officinarum Hance is a perennial plant that has been traditionally used for many decades to treat several ailments including inflammation, pain, stomach-ache, cold, amongst others. Pharmacological studies over the years have demonstrated remarkable bioactivities that could be further explored for development of new therapeutic agents against various ailments. The paper critically reviewed the ethno-medicinal uses, pharmacology, and phytochemistry of A. officinarum. Keywords including A. officinarum and its synonyms were searched using electronic databases including ISI web of knowledge, Science direct, Scopus, PubMed, Google scholar and relevant database for Masters and Doctoral theses. A. officinarum is prepared in Asia, Turkey, Morocco and Iran as a decoction, infusion or juice as a single preparation or in combination with other herbs, food or drinks for the treatment of general health problems including cold, inflammation, digestive disorders, etc. Pharmacological studies revealed the potent in vitro and in vivo bioactivities of various parts of A. officinarum that include anti-inflammatory, cytotoxicity, homeostasis, lipid regulation, antioxidant, antiviral, antimicrobial, antiosteoporosis, etc. Over 90 phytochemical constituents have been identified and isolated from A. officinarum comprising vastly of phenolic compounds especially diarylheptanoids isolated from the rhizome and considered the most active bioactive components. In vitro and in vivo studies have confirmed the potency of A. officinarum. However, further studies are required to establish the mechanisms mediating its bioactivities in relation to the medicinal uses as well as investigating any potential toxicity for future clinical studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Ethnobotanical study of Loloh: Traditional herbal drinks from Bali (Indonesia).

PubMed

Sujarwo, Wawan; Keim, Ary Prihardhyanto; Savo, Valentina; Guarrera, Paolo Maria; Caneva, Giulia

2015-07-01

Loloh are herbal drinks produced and consumed exclusively in Bali (Indonesia) to prevent and treat different ailments. This is the first study to document plants species used as Loloh, reporting the phytochemical components and pharmacological properties of the most cited plants. Documenting the plants used in herbal drinks in Bali by local communities to treat various ailments (providing some information on phytochemistry and pharmacology of the most interesting plants). Ethnobotanical data were obtained through semi-structured interviews (individual and group discussions) and questionnaires. Plant specimens were collected, identified and made into herbarium vouchers. A total of 51 plants species (belonging to 32 families) have been documented for their use in the various preparation of Loloh. Different plants and plant parts are used to prepare Loloh to treat heartburn, fever, diarrhea, hypertension, aphthous stomatitis (canker sores), and other minor health problems. These plants are mainly prepared as decoctions, are juiced or simply added to the preparation. The most cited plants (>30 informants) are Alstonia scholaris (L.) R. Br., Blumea balsamifera (L.) DC., Cinnamomum burmanni Nees ex Bl., and Piper betle L. These plants are well studied with multiple demonstrated pharmacological activities (e.g., antimicrobial, anticancer, antidiabetic). The Balinese communities still preserve a rich ethnobotanical knowledge. Several species are well known for their pharmacological properties, but some [such as Pneumatopteris callosa (Blume) Nakai and Dendrocnide stimulans (L. f.) Chew] are understudied and could be promising candidates for further research. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells*

PubMed Central

Lam, Vincent M.; Salahpour, Ali

2016-01-01

A number of pathological conditions have been linked to mutations in the dopamine transporter gene, including hereditary dopamine transporter deficiency syndrome (DTDS). DTDS is a rare condition that is caused by autosomal recessive loss-of-function mutations in the dopamine transporter (DAT), which often affects transporter trafficking and folding. We examined the possibility of using pharmacological chaperones of DAT to rescue DTDS mutations. After screening a set of known DAT ligands for their ability to increase DAT surface expression, we found that bupropion and ibogaine increased DAT surface expression, whereas others, including cocaine and methylphenidate, had no effect. Bupropion and ibogaine increased wild type DAT protein levels and also promoted maturation of the endoplasmic reticulum (ER)-retained DAT mutant K590A. Rescue of K590A could be blocked by inhibiting ER to Golgi transport using brefeldin A. Furthermore, knockdown of coat protein complex II (COPII) component SEC24D, which is important in the ER export of wild type DAT, also blocked the rescue effects of bupropion and ibogaine. These data suggest that bupropion and ibogaine promote maturation of DAT by acting as pharmacological chaperones in the ER. Importantly, both drugs rescue DAT maturation and functional activity of the DTDS-associated mutations A314V and R445C. Together, these results are the first demonstration of pharmacological chaperoning of DAT and suggest this may be a viable approach to increase DAT levels in DTDS and other conditions associated with reduced DAT function. PMID:27555326

Essential Oil Composition, Antimicrobial and Pharmacological Activities of Lippia sidoides Cham. (Verbenaceae) From São Gonçalo do Abaeté, Minas Gerais, Brazil.

PubMed

de Morais, Sandra Ribeiro; Oliveira, Thiago Levi Silva; de Oliveira, Lanussy Porfiro; Tresvenzol, Leonice Manrique Faustino; da Conceição, Edemilson Cardoso; Rezende, Maria Helena; Fiuza, Tatiana de Sousa; Costa, Elson Alves; Ferri, Pedro Henrique; de Paula, José Realino

2016-01-01

Lippia sidoides (Verbenaceae) is used in Brazilian folk medicine as an antiseptic, and it is usually applied topically on skin, mucous membranes, mouth, and throat, or used for vaginal washings. To analyze the chemical composition of the essential oil from L. sidoides collected in São Gonçalo do Abaeté, Minas Gerais and grown in Hidrolândia, Goiás; to evaluate the antimicrobial activity of the essential oil, crude ethanol extract, and hexane, dichloromethane, ethyl-acetate, and aqueous fractions (AFs); to study the antinociceptive, anti-inflammatory, and central nervous system activities of the crude ethanol extract. The essential oils were obtained by hydro-distillation using a Clevenger-type apparatus and analyzed by GC/MS. The antimicrobial activity in vitro was performed by broth microdilution method. The pharmacological tests were performed using female Swiss albino mice. The major components of the essential oil were isoborneol (14.66%), bornyl acetate (11.86%), α -humulene (11.23%), α -fenchene (9.32%), and 1.8-cineole (7.05%), supporting the existence of two chemotypes of this species. The hexane fraction (HF) had good antifungal activity against Cryptococcus sp. ATCC D (MIC = 31.25 μg/mL) and Cryptococcus gatti L48 (MIC = 62.5 μg/mL). In the pharmacological tests, the crude ethanol extract presented antinociceptive and anti-inflammatory activities. Given that the ethanol extract of L. sidoides is included in the Formulary of Phytotherapeutic Agents of the Brazilian Pharmacopeia as an anti-inflammatory for oral cavities, the present work provides scientific evidence to back this use and highlight the importance of selecting the appropriate chemotype on the basis of the expected biological response. The major components of the essential oil of L. sidoides were isoborneol bornyl acetate, α -humulene, α -fenchene, and 1.8-cineole. The HF had good antifungal activity against Cryptococcus sp. ATCC D and C. gatti L4.The crude ethanol extract of L. sidoides presented antinociceptive and anti-inflammatory activities.The present work provides scientific evidence of the importance of selecting the appropriate chemotype on the basis of the expected biological response. Abbreviations used: UFG: Universidade Federal de Goiás; HF: hexane fraction; DF: dichloromethane fraction; EAF: ethyl acetate fraction; AF: aqueous fraction; MeOH: methanol; MIC: minimum inhibitory concentration; ATCC: American Type Culture Collection; MH: Müller Hinton; DMSO: dimethyl sulfoxide; RPMI: Roswell Park Memorial Institute; NaCl: sodium chloride; μL: microliters; mL: milliliters; μg: microgram; kg: kilogram; h: hour; min: minute; cm: centimeter; COBEA: Brazilian College of Animal Experiments; p.o.:, oral; i.p.: intraperitoneal; s.c.: subcutaneous; SEM: standard error of the mean; RI: retention indices.

Preparation of Clinically Useful Sennoside-reduced Rhubarb.

PubMed

Arai, Makoto; Nakada, Yoshinobu; Kajiwara, Kagemasa; Kimura, Minoru; Ishii, Naoaki

2016-03-20

The aim of this study was to develop a method of removing sennoside to reduce the cathartic effect of rhubarb while conserving its other pharmacological activities. Rhubarb powder was steam autoclaved at 121°C and 0.14 MPa for 20, 60, or 120 minutes, and HPLC analysis was conducted to determine levels of rhubarb components. Mice were fed non-autoclaved or 20-minute-autoclaved rhubarb extracts. Feces were collected and weighed over a 24-hour period. India ink was orally administered to determine the distance of fecal migration through the intestinal tract. Autoclaving 20, 60, and 120 minutes decreased sennoside A and B to trace levels but only autoclaving 20 minutes conserved most of the (+)-catechin, (-)-epicatechin, and (-)-epicatechin gallate contents (i.e., 69%, 90%, 88%, respectively). Therefore only rhubarb autoclaved for 20 minutes was used in subsequent experiments. Fecal output (in g) in mice treated with water (control), autoclaved rhubarb, and non-autoclaved rhubarb was 2.78 ± 0.07, 3.30 ± 0.13 (p = 0.348), and 3.81 ± 0.07 (p = 0.005). India ink migration was far less in mice treated with autoclaved rhubarb vs non-autoclaved rhubarb. Steam autoclaving the rhubarb for 20 minutes reduces sennoside levels and its cathartic activity while conserving its other pharmacological activities.

The Hippo pathway in disease and therapy: cancer and beyond

PubMed Central

2014-01-01

The Hippo tumour suppressor pathway co-ordinates cell proliferation, cell death and cell differentiation to regulate tissue growth control. In mammals, a conserved core Hippo signalling module receives signal inputs on different levels to ensure the proper regulation of YAP/TAZ activities as transcriptional co-activators. While the core module members MST1/2, Salvador, LATS1/2 and MOB1 have been attributed tumour suppressive functions, YAP/TAZ have been mainly described to have oncogenic roles, although some reports provided evidence supporting growth suppressive roles of YAP/TAZ in certain cancer settings. Intriguingly, mammalian Hippo signalling is also implicated in non-cancer diseases and plays a role in tissue regeneration following injury. Cumulatively, these findings indicate that the pharmacological inhibition or activation of the Hippo pathway could be desirable depending on the disease context. In this review, we first summarise the functions of the mammalian Hippo pathway in tumour formation, and then discuss non-cancer diseases involving Hippo signalling core components with a specific focus on our current understanding of the non-cancer roles of MST1/2 and YAP/TAZ. In addition, the pros and cons of possible pharmacological interventions with Hippo signalling will be reviewed, with particular emphasis on anti-cancer drug development and regenerative medicine. PMID:25097725

Can Phlorotannins Purified Extracts Constitute a Novel Pharmacological Alternative for Microbial Infections with Associated Inflammatory Conditions?

PubMed Central

Lopes, Graciliana; Sousa, Carla; Silva, Luís R.; Pinto, Eugénia; Andrade, Paula B.; Bernardo, João; Mouga, Teresa; Valentão, Patrícia

2012-01-01

Bacterial and fungal infections and the emerging multidrug resistance are driving interest in fighting these microorganisms with natural products, which have generally been considered complementary to pharmacological therapies. Phlorotannins are polyphenols restricted to brown seaweeds, recognized for their biological capacity. This study represents the first research on the antibacterial, antifungal, anti-inflammatory and antioxidant activity of phlorotannins purified extracts, which were obtained from ten dominant brown seaweeds of the occidental Portuguese coast. Phlorotannins content was determined by the specific dimethoxybenzaldehyde (DMBA) method and a yield between 75 and 969 mg/Kg phloroglucinol units (dry matter) was obtained. Fucus spiralis ranked first, followed by three Cystoseira species. The anti-inflammatory potential of the purified extracts was assessed via inhibitory effect on nitric oxide (NO) production by lipopolysaccharide-stimulated RAW 264.7 macrophage cells, Cystoseira tamariscifolia being the one showing promising activity for the treatment of inflammation. NO scavenging ability was also addressed in cell free systems, F. spiralis being the species with highest capacity. The antimicrobial potential of the extracts was checked against five Gram-positive and four Gram-negative bacteria and three fungi strains, that commonly colonize skin and mucosa and are responsible for food contamination. The different extracts were more effective against Gram-positive bacteria, Staphylococcus epidermidis being the most susceptible species. Concerning antifungal activity, Trichophyton rubrum was the most sensitive species. Although the molecular mechanisms underlying these properties remain poorly understood, the results obtained turn phlorotannins purified extracts a novel and potent pharmacological alternative for the treatment of a wide range of microbial infections, which usually also present an inflammatory component. In addition to the biological properties demonstrated herein, phlorotannins extracts may also be preferred, in order to avoid side effects and allergic reactions commonly associated with synthetic drugs. PMID:22319609

Role of hyperforin in the pharmacological activities of St. John's Wort.

PubMed

Zanoli, Paola

2004-01-01

The phloroglucinol derivative hyperforin has been recently shown to be a major antidepressant component in the extract of Hypericum perforatum. Experimental studies clearly demonstrated its activity in different behavioral models of depression. Moreover clinical studies linked the therapeutic efficacy of Hypericum extracts to their hyperforin content, in a dose-dependent manner. The molecular mechanism of action of hyperforin is still under investigation. Hyperforin has been shown to inhibit, like conventional antidepressants, the neuronal uptake of serotonin, norepinephrine and dopamine. However, hyperforin inhibits also the uptake of gamma-aminobutyric acid (GABA) and L-glutamate. The uptake inhibition by hyperforin does not involve specific binding sites at the transporter molecules; its mechanism of action seems to be related to sodium conductive pathways, leading to an elevation in intracellular Na(+) concentration. Other additional mechanisms of action of hyperforin, involving ionic conductances as well synaptosomal and vesicular function, have been suggested. In addition to its antidepressant activity, hyperforin has many other pharmacological effects in vivo (anxiolytic-like, cognition-enhancing effects) and in vitro (antioxidant, anticyclooxygenase-1, and anticarcinogenic effects). These effects could be of clinical importance. On the other hand, the role of hyperforin in the pharmacological interactions occurring during Hypericum extract therapy must be fully investigated. Hyperforin seems to be responsible for the induction of liver cytochrome oxidase enzymes and intestinal P-glycoprotein. Several pharmacokinetic studies performed in rats and humans demonstrated oral bioavailability of hyperforin from Hypericum extract. Only recently a new chromatographic method for detection of hyperforin in the brain tissue has been developed and validated. Taking into account the chemical instability of hyperforin, current efforts are directed to the synthesis of new neuroactive derivatives.

Endothelin@25 - new agonists, antagonists, inhibitors and emerging research frontiers: IUPHAR Review 12.

PubMed

Maguire, J J; Davenport, A P

2014-12-01

Since the discovery of endothelin (ET)-1 in 1988, the main components of the signalling pathway have become established, comprising three structurally similar endogenous 21-amino acid peptides, ET-1, ET-2 and ET-3, that activate two GPCRs, ETA and ETB . Our aim in this review is to highlight the recent progress in ET research. The ET-like domain peptide, corresponding to prepro-ET-193-166 , has been proposed to be co-synthesized and released with ET-1, to modulate the actions of the peptide. ET-1 remains the most potent vasoconstrictor in the human cardiovascular system with a particularly long-lasting action. To date, the major therapeutic strategy to block the unwanted actions of ET in disease, principally in pulmonary arterial hypertension, has been to use antagonists that are selective for the ETA receptor (ambrisentan) or that block both receptor subtypes (bosentan). Macitentan represents the next generation of antagonists, being more potent than bosentan, with longer receptor occupancy and it is converted to an active metabolite; properties contributing to greater pharmacodynamic and pharmacokinetic efficacy. A second strategy is now being more widely tested in clinical trials and uses combined inhibitors of ET-converting enzyme and neutral endopeptidase such as SLV306 (daglutril). A third strategy based on activating the ETB receptor, has led to the renaissance of the modified peptide agonist IRL1620 as a clinical candidate in delivering anti-tumour drugs and as a pharmacological tool to investigate experimental pathophysiological conditions. Finally, we discuss biased signalling, epigenetic regulation and targeting with monoclonal antibodies as prospective new areas for ET research. © 2014 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Prostaglandins, steroids and reception (an attempt to model the structure of the active centers of adrenoreception).

PubMed

Podymov, V K; Piruzyan, L A; Gladkikh, S P; Kats, M M; Nizhnii, S V

1980-01-01

On the basis of numerous results of investigations on adrenergic systems, an orientational model of the adrenoreceptor (AR) is postulated. Its active center includes low-molecular-weight components--prostaglandins (PGE, PGF), steroids (cortisone, hydrocortisone), S+-adenosylmethionine, Ca, Mg, and Mn ions. Appraisal of the stereospecific characteristics of such a functional unit of AR explains the difference in the nature and magnitude of the effects of interaction of the catecholamines, their agonists and antagonists will the so-called alpha- and beta-AR. Depending on the organ or tissue in which the AR is located, its protein subunits comprise adenylcyclase (beta-AR) or Na,K-ATPase (alpha-AR). An obligatory component of the AR is catechol-O-methyltransferase. The model elaborated describes satisfactorily the molecular mechanisms of action of many pharmacological agents, explains why attempts to isolate and reconstruct the AR have proved fruitless, and gives grounds for rejecting the hypothesis that there exist steroid, prostaglandin, and purinergic receptors, linking the exceptionally high and diverse activity of these biologically active substances with their participation in adrenoreception among other reasons. A conception of the active centers of the AR as low-molecular-weight entities permits the explanation of such phenomena as the desensitization of the AR, the "interconversion" of beta-AR into alpha-AR with a change in the parameters of the medium, and certain components of the pathogenesis of bronchial asthma, etc.

Anticancer and antimetastatic effects of cordycepin, an active component of Cordyceps sinensis.

PubMed

Nakamura, Kazuki; Shinozuka, Kazumasa; Yoshikawa, Noriko

2015-01-01

Cordyceps sinensis, a fungus that parasitizes on the larva of Lepidoptera, has been used as a valued traditional Chinese medicine. We investigated the effects of water extracts of Cordyceps sinensis (WECS), and particularly focused on its anticancer and antimetastatic actions. Based on in vitro studies, we report that WECS showed an anticancer action, and this action was antagonized by an adenosine A3 receptor antagonist. Moreover, this anticancer action of WECS was promoted by an adenosine deaminase inhibitor. These results suggest that one of the components of WECS with an anticancer action might be an adenosine or its derivatives. Therefore, we focused on cordycepin (3'-deoxyadenosine) as one of the active ingredients of WECS. According to our experiments, cordycepin showed an anticancer effect through the stimulation of adenosine A3 receptor, followed by glycogen synthase kinase (GSK)-3β activation and cyclin D1 suppression. Cordycepin also showed an antimetastatic action through inhibiting platelet aggregation induced by cancer cells and suppressing the invasiveness of cancer cells via inhibiting the activity of matrix metalloproteinase (MMP)-2 and MMP-9, and accelerating the secretion of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 from cancer cells. In conclusion, cordycepin, an active component of WECS, might be a candidate anticancer and antimetastatic agent. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Interprofessional education in pharmacology using high-fidelity simulation.

PubMed

Meyer, Brittney A; Seefeldt, Teresa M; Ngorsuraches, Surachat; Hendrickx, Lori D; Lubeck, Paula M; Farver, Debra K; Heins, Jodi R

2017-11-01

This study examined the feasibility of an interprofessional high-fidelity pharmacology simulation and its impact on pharmacy and nursing students' perceptions of interprofessionalism and pharmacology knowledge. Pharmacy and nursing students participated in a pharmacology simulation using a high-fidelity patient simulator. Faculty-facilitated debriefing included discussion of the case and collaboration. To determine the impact of the activity on students' perceptions of interprofessionalism and their ability to apply pharmacology knowledge, surveys were administered to students before and after the simulation. Attitudes Toward Health Care Teams scale (ATHCT) scores improved from 4.55 to 4.72 on a scale of 1-6 (p = 0.005). Almost all (over 90%) of the students stated their pharmacology knowledge and their ability to apply that knowledge improved following the simulation. A simulation in pharmacology is feasible and favorably affected students' interprofessionalism and pharmacology knowledge perceptions. Pharmacology is a core science course required by multiple health professions in early program curricula, making it favorable for incorporation of interprofessional learning experiences. However, reports of high-fidelity interprofessional simulation in pharmacology courses are limited. This manuscript contributes to the literature in the field of interprofessional education by demonstrating that an interprofessional simulation in pharmacology is feasible and can favorably affect students' perceptions of interprofessionalism. This manuscript provides an example of a pharmacology interprofessional simulation that faculty in other programs can use to build similar educational activities. Copyright © 2017 Elsevier Inc. All rights reserved.

Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones.

PubMed Central

Fox, A P; Nowycky, M C; Tsien, R W

1987-01-01

1. Calcium currents in cultured dorsal root ganglion (d.r.g.) cells were studied with the whole-cell patch-clamp technique. Using experimental conditions that suppressed Na+ and K+ currents, and 3-10 mM-external Ca2+ or Ba2+, we distinguished three distinct types of calcium currents (L, T and N) on the basis of voltage-dependent kinetics and pharmacology. 2. Component L activates at relatively positive test potentials (t.p. greater than -10 mV) and shows little inactivation during a 200 ms depolarization. It is completely reprimed at a holding potential (h.p.) of -60 mV, and can be isolated by using a more depolarized h.p. (-40 mV) to inactivate the other two types of calcium currents. 3. Component T can be seen in isolation with weak test pulses. It begins activating at potentials more positive than -70 mV and inactivates quickly and completely during a maintained depolarization (time constant, tau approximately 20-50 ms). The current amplitude and the rate of decay increase with stronger depolarizations until both reach a maximum at approximately -40 mV. Inactivation is complete at h.p. greater than -60 mV and is progressively removed between -60 and -95 mV. 4. Component N activates at relatively strong depolarizations (t.p. greater than -20 mV) and decays with time constants ranging from 50 to 110 ms. Inactivation is removed over a very broad range of holding potentials (h.p. between -40 and -110 mV). 5. With 10 mM-EGTA in the pipette solution, substitution of Ba2+ for Ca2+ as the charge carrier does not alter the rates of activation or relaxation of any component. However, T-type channels are approximately equally permeable to Ca2+ and Ba2+, while L-type and N-type channels are both much more permeable to Ba2+. 6. Component N cannot be explained by current-dependent inactivation of L current resulting from recruitment of extra L-type channels at negative holding potentials: raising the external Ba2+ concentration to 110 mM greatly increases the amplitude of L current evoked from h.p. = -30 mV but produces little inactivation. 7. Cadmium ions (20-50 microM) virtually eliminate both N and L currents (greater than 90% block) but leave T relatively unaffected (less than 50% block). 200 microM-Cd2+ blocks all three components. 8. Nickel ions (100 microM) strongly reduce T current but leave N and L current little changed. 9. The dihydropyridine antagonist nifedipine (10 microM) inhibits L current (approximately 60% block) at a holding potential that inactivates half the L-type channels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2451016

[An Occupational Therapy Intervention for People With Dementia].

PubMed

Ke, Hung-Hsun

2018-02-01

The percentage of individuals with dementia worldwide is increasing with the continued trend toward global trend overall. As options for the medical treatment of dementia remain limited, combined, non-pharmacological interventions are necessary to maintain and slow the degeneration of functional capabilities. Additionally, there is a need to help caregivers develop better patterns of care and methods to reduce the burden of care. Therefore, occupational therapists play an important role in the dementia care team. This article introduces how occupational therapists help dementia patient maintain their functional capabilities and delay degeneration and help caregivers reduce their burden of care. Both activities are based on the concept of occupational therapy, which includes three important components: people, activities, and the environment.

Identification and comparative quantification of bio-active phthalides in essential oils from si-wu-tang, fo-shou-san, radix angelica and rhizoma chuanxiong.

PubMed

Tang, Yuping; Zhu, Min; Yu, Sheng; Hua, Yongqing; Duan, Jin-Ao; Su, Shulan; Zhang, Xu; Lu, Yin; Ding, Anwei

2010-01-15

Phthalides are important bio-active constituents in Si-Wu-Tang and Fo-Shou-San, two commonly used Traditional Chinese Medicine (TCM) combined prescriptions mainly derived from Radix Angelica and Rhizoma Chuanxiong. In this paper, the contents of eight phthalides, including Z-ligustilide, E-ligustilide, Z-butylenephthalide, E-butylene-phthalide, 3-butylphthalide, neocnidilide and senkyunolide A were determined or estimated by gas chromatography-mass spectrometry (GC-MS). The results showed GC-MS was a simple, rapid, and high sensitive method for analyzing phthalides in Si-Wu-Tang, Fo-Shou-San, Radix Angelica and Rhizoma Chuanxiong, and the extractable contents of each phthalides including Z-ligustilide, E-ligustilide, Z-butylenephthalide, etc. varied after Radix Angelica, Rhizoma Chuanxiong were combined into a formulation, such as Si-Wu-Tang and Fo-Shou-San. Furthermore, inhibition activity of essential oils from Si-Wu-Tang, Fo-Shou-San, Radix Angelica and Rhizoma Chuanxiong on uterine contraction was tested in an in vitro assay, and the results showed that the activity of the essential oil is higher as the content of the phthalides increase, which demonstrated that phthalides are possibly main active components inhibiting mice uterine contraction in vitro. All of the results suggested that comparative analysis of chemical components and pharmacological activities of each herb and formula is possibly helpful to elucidate the active components in traditional Chinese medicine, and to reveal the compatibility mechanism of TCM formulae.

Ginsenoside Re: pharmacological effects on cardiovascular system.

PubMed

Peng, Lu; Sun, Shi; Xie, Lai-Hua; Wicks, Sheila M; Xie, Jing-Tian

2012-08-01

Ginsenosides are the bioactive constituents of ginseng, a key herb in traditional Chinese medicine. As a single component of ginseng, ginsenoside Re (G-Re) belongs to the panaxatriol group. Many reports demonstrated that G-Re possesses the multifaceted beneficial pharmacological effects on cardiovascular system. G-Re has negative effect on cardiac contractility and autorhythmicity. It causes alternations in cardiac electrophysiological properties, which may account for its antiarrhythmic effect. In addition, G-Re also exerts antiischemic effect and induces angiogenic regeneration. In this review, we first outline the chemistry and the pharmacological effects of G-Re on the cardiovascular system. © 2011 Blackwell Publishing Ltd.

Can active components of licorice, glycyrrhizin and glycyrrhetinic acid, lick rheumatoid arthritis?

PubMed

Huang, Qing-Chun; Wang, Mao-Jie; Chen, Xiu-Min; Yu, Wan-Lin; Chu, Yong-Liang; He, Xiao-Hong; Huang, Run-Yue

2016-01-12

This review stated the possible application of the active components of licorice, glycyrrhizin (GL) and glycyrrhetinic acid (GA), in rheumatoid arthritis (RA) treatment based on the cyclooxygenase (COX)-2/thromboxane A2 (TxA2) pathway. The extensive literature from inception to July 2015 was searched in PubMed central, and relevant reports were identified according to the purpose of this study. The active components of licorice GL and GA exert the potential anti-inflammatory effects through, at least in part, suppressing COX-2 and its downstream product TxA2. Additionally, the COX-2/TxA2 pathway, an auto-regulatory feedback loop, has been recently found to be a crucial mechanism underlying the pathogenesis of RA. However, TxA2 is neither the pharmacological target of non-steroidal anti-inflammatory drugs (NSAIDs) nor the target of disease modifying anti-rheumatic drugs (DMARDs), and the limitations and side effects of those drugs may be, at least in part, attributable to lack of the effects on the COX-2/TxA2 pathway. Therefore, GL and GA capable of targeting this pathway hold the potential as a novel add-on therapy in therapeutic strategy, which is supported by several bench experiments. The active components of licorice, GL and GA, could not only potentiate the therapeutic effects but also decrease the adverse effects of NSAIDs or DMARDs through suppressing the COX-2/TxA2 pathway during treatment course of RA.

Can active components of licorice, glycyrrhizin and glycyrrhetinic acid, lick rheumatoid arthritis?

PubMed Central

Huang, Qing-Chun; Wang, Mao-Jie; Chen, Xiu-Min; Yu, Wan-Lin; Chu, Yong-Liang; He, Xiao-Hong; Huang, Run-Yue

2016-01-01

OBJECTIVES This review stated the possible application of the active components of licorice, glycyrrhizin (GL) and glycyrrhetinic acid (GA), in rheumatoid arthritis (RA) treatment based on the cyclooxygenase (COX)-2/thromboxane A2 (TxA2) pathway. METHODS The extensive literature from inception to July 2015 was searched in PubMed central, and relevant reports were identified according to the purpose of this study. RESULTS The active components of licorice GL and GA exert the potential anti-inflammatory effects through, at least in part, suppressing COX-2 and its downstream product TxA2. Additionally, the COX-2/TxA2 pathway, an auto-regulatory feedback loop, has been recently found to be a crucial mechanism underlying the pathogenesis of RA. However, TxA2 is neither the pharmacological target of non-steroidal anti-inflammatory drugs (NSAIDs) nor the target of disease modifying anti-rheumatic drugs (DMARDs), and the limitations and side effects of those drugs may be, at least in part, attributable to lack of the effects on the COX-2/TxA2 pathway. Therefore, GL and GA capable of targeting this pathway hold the potential as a novel add-on therapy in therapeutic strategy, which is supported by several bench experiments. CONCLUSIONS The active components of licorice, GL and GA, could not only potentiate the therapeutic effects but also decrease the adverse effects of NSAIDs or DMARDs through suppressing the COX-2/TxA2 pathway during treatment course of RA. PMID:26498361

Sustained and Transient Contributions to the Rat Dark-Adapted Electroretinogram b-Wave

PubMed Central

Dang, Trung M.; Vingrys, Algis J.; Bui, Bang V.

2013-01-01

The most dominant feature of the electroretinogram, the b-wave, is thought to reflect ON-bipolar cell responses. However, a number of studies suggest that the b-wave is made up of several components. We consider the composition of the rat b-wave by subtracting corneal negative components obtained using intravitreal application of pharmacological agents to remove postreceptoral responses. By analyzing the intensity-response characteristic of the PII across a range of fixed times during and after a light step, we find that the rat isolated PII has 2 components. The first has fast rise and decay characteristics with a low sensitivity to light. GABAc-mediated inhibitory pathways enhance this transient-ON component to manifest increased and deceased sensitivity to light at shorter (<160 ms) and longer times, respectively. The second component has slower temporal characteristics but is more sensitive to light. GABAc-mediated inhibition enhances this sustained-ON component but has little effect on its sensitivity to light. After stimulus offset, both transient and sustained components return to baseline, and a long latency sustained positive component becomes apparent. The light sensitivities of transient-ON and sustained-OFF components are consistent with activity arising from cone ON- and OFF-bipolar cells, whereas the sustained-ON component is likely to arise from rod bipolar cells. PMID:23533706

Internet discussion forums as part of a student-centred teaching concept of pharmacology.

PubMed

Sucha, Michael; Engelhardt, Stefan; Sarikas, Antonio

2013-01-01

The world wide web opens up new opportunities to interconnect electronic and classroom teaching and to promote active student participation. In this project article we describe the use of internet discussion forums as part of a student-centred teaching concept of pharmacology and discuss its advantages and disadvantages based on evaluation data and current literature. Final year medical students at the Technische Universität München (Munich, Germany) with the elective pharmacology moderated an internet forum that allowed all students to discuss pharmacology-related questions. Evaluation results of forum participants and elective students demonstrated a learning benefit of internet forums in pharmacology teaching. Internet discussion forums offer an easy-to-implement and effective way to actively engage students and increase the learning benefit of electronic and classroom teaching in pharmacology.

Exercise and Sarcopenia.

PubMed

Phu, Steven; Boersma, Derek; Duque, Gustavo

2015-01-01

Sarcopenia is a major component of the frailty syndrome and is also a strong predictor of disability, morbidity, and mortality in older persons. Without any available pharmacological intervention to sarcopenia, non-pharmacological interventions are the only option to prevent these poor outcomes in sarcopenic patients. Among those interventions, physical activity with or without protein supplementation has demonstrated to be effective in improving muscle mass and function and in preventing disability and frailty in older persons. Additionally, to the beneficial effect of physical activity on metabolic and cardiovascular diseases, a regular exercise program (3 times/wk) that includes resistance and endurance exercise training would have a major positive effect on sarcopenic muscle through improving muscle mass, strength, and function. In this review, we looked at the effect of exercise on sarcopenic frail older persons from the biological aspects of the response of the muscle to exercise to some practical aspects of exercise prescription in this high-risk population. We conclude that, although challenging, older persons should be encouraged to participate in this type of programs, which would improve not only their function and independence but also their quality of life. Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Cerebroprotective functions of HO-2.

PubMed

Parfenova, Helena; Leffler, Charles W

2008-01-01

The constitutive isoform of heme oxygenase, HO-2, is highly expressed in the brain and in cerebral vessels. HO-2 functions in the brain have been evaluated using pharmacological inhibitors of the enzyme and HO-2 gene deletion in in vivo animal models and in cultured cells (neurons, astrocytes, cerebral vascular endothelial cells). Rapid activation of HO-2 via post-translational modifications without upregulation of HO-2 expression or HO-1 induction coincides with the increase in cerebral blood flow aimed at maintaining brain homeostasis and neuronal survival during seizures, hypoxia, and hypotension. Pharmacological inhibition or gene deletion of brain HO-2 exacerbates oxidative stress induced by seizures, glutamate, and inflammatory cytokines, and causes cerebral vascular injury. Carbon monoxide (CO) and bilirubin, the end products of HO-catalyzed heme degradation, have distinct cytoprotective functions. CO, by binding to a heme prosthetic group, regulates the key components of cell signaling, including BK(Ca) channels, guanylyl cyclase, NADPH oxidase, and the mitochondria respiratory chain. Cerebral vasodilator effects of CO are mediated via activation of BK(Ca) channels and guanylyl cyclase. CO, by inhibiting the major components of endogenous oxidant-generating machinery, NADPH oxidase and the cytochrome C oxidase of the mitochondrial respiratory chain, blocks formation of reactive oxygen species. Bilirubin, via redox cycling with biliverdin, is a potent oxidant scavenger that removes preformed oxidants. Overall, HO-2 has dual housekeeping cerebroprotective functions by maintaining autoregulation of cerebral blood flow aimed at improving neuronal survival in a changing environment, and by providing an effective defense mechanism that blocks oxidant formation and prevents cell death caused by oxidative stress.

Anti-inflammatory activity of essential oils from Syzygium cumini and Psidium guajava.

PubMed

Siani, Antonio C; Souza, Mariana C; Henriques, Maria G M O; Ramos, Mônica F S

2013-07-01

Despite the many biological activities reported for essential oils, their anti-inflammatory ability is relatively underexplored considering the wide variation in plant sources and in their volatile composition. Oils from Syzygium cumini Skells (SC) and Psidium guajava L. (PG) (Myrtaceae) have been described as having diverse pharmacological activities. The current study seeks to evaluate the anti-inflammatory activity of the essential oils from the leaves of SC and PG, as well as some of their terpene-enriched fractions (+V = more volatile and -V = less volatile) obtained by vacuum distillation. Both the pharmacological responses and chemical compositions were correlated. The relative contents of the oils and their fractions were evaluated by gas chromatography. Individual constituents in the oils were characterized by gas chromatography coupled to mass spectrometry. Anti-inflammatory activity was accessed in the lipopolysaccharide-induced pleurisy model, by measuring the inhibition of total leukocyte, neutrophil and eosinophil migration in the mice pleural lavage, after oil treatment with the oils at 100 mg/kg. Eosinophil migration was inhibited by SC (67%), SC (+V) (63%), PG (76%), PG (+V) (67%) and PG (-V) (74%). This efficacy was correlated with the presence of β-pinene and β-caryophyllene in the oils, a result that was reinforced by evaluating both these pure components (38 and 50% inhibition, respectively). Synergistic effects associated with the presence of α-pinene were speculated. Essential oils from SC and PG may be useful to treat inflammatory diseases by mechanisms that include the inhibition of eosinophil migration.

[Renin-angiotensin-aldosteron system: evolution of views from renin discovery to nowadays. Perspectives of therapeutic block].

PubMed

Shestakova, M V

2011-01-01

Recent revolution in the knowledge about structure, physiological and pathophysiological effects of renin-angiotensin-aldosteron system (RAAS) took place recently when it was discovered that local synthesis of all the RAAS components occurs in target organs and their tissues (the heart, kidneys, vessels, brain tissues). It was found that besides classic RAAS acting via activation of angiotensin II (Ang-II) and its receptors, there is an alternative RAAS opposed to atherogenic potential of Ang-II. Renin and prorenin are shown to have both enzymatic and hormonal activities. Wider understanding appeared of extrarenal effects of aldosteron, its non-genomic activity. The above discoveries open new opportunities for pharmacological regulation of RAAS activity, which enables more effectively correct overactivity of this system in organs at risk of negativeAng-II impact.

Polysaccharides from the Marine Environment with Pharmacological, Cosmeceutical and Nutraceutical Potential.

PubMed

Ruocco, Nadia; Costantini, Susan; Guariniello, Stefano; Costantini, Maria

2016-04-27

Carbohydrates, also called saccharides, are molecules composed of carbon, hydrogen, and oxygen. They are the most abundant biomolecules and essential components of many natural products and have attracted the attention of researchers because of their numerous human health benefits. Among carbohydrates the polysaccharides represent some of the most abundant bioactive substances in marine organisms. In fact, many marine macro- and microorganisms are good resources of carbohydrates with diverse applications due to their biofunctional properties. By acting on cell proliferation and cycle, and by modulating different metabolic pathways, marine polysaccharides (including mainly chitin, chitosan, fucoidan, carrageenan and alginate) also have numerous pharmaceutical activities, such as antioxidative, antibacterial, antiviral, immuno-stimulatory, anticoagulant and anticancer effects. Moreover, these polysaccharides have many general beneficial effects for human health, and have therefore been developed into potential cosmeceuticals and nutraceuticals. In this review we describe current advances in the development of marine polysaccharides for nutraceutical, cosmeceutical and pharmacological applications. Research in this field is opening new doors for harnessing the potential of marine natural products.

Microwave-assisted extraction, HPLC analysis, and inhibitory effects on carbonic anhydrase I, II, VA, and VII isoforms of 14 blueberry Italian cultivars.

PubMed

Mollica, Adriano; Locatelli, Marcello; Macedonio, Giorgia; Carradori, Simone; Sobolev, Anatoly P; De Salvador, Roberto F; Monti, Simona M; Buonanno, Martina; Zengin, Gokhan; Angeli, Andrea; Supuran, Claudiu T

2016-01-01

The multi-component fingerprint and the biological evaluation of plant-derived material are indispensable for the pharmaceutical field, in food quality control procedures, and in all plant-based products. We investigated the quantitative content of biologically active compounds (anthocyanins and chlorogenic acid) of microwave-assisted blueberry extracts from 14 different Italian cultivars, using validated high-performance liquid chromatography-photodiode array detector (HPLC-PDA) method and routinely instrument configuration. The carbonic anhydrase (CA, EC 4.2.1.1) inhibition profiles against several pharmacologically relevant CA isoforms of blueberry extracts and some bioactive compounds were also investigated. The various cultivars showed a highly variable content in anthocyanins and chlorogenic acid, and their CA inhibitory effects were also highly variable. Overall these data prove that antioxidant natural products found in blueberries may be useful for designing pharmacological agents in which various CAs are involved, e.g., antiobesity, antitumor, or anticonvulsants agents.

Brain mast cells link the immune system to anxiety-like behavior

PubMed Central

Nautiyal, Katherine M.; Ribeiro, Ana C.; Pfaff, Donald W.; Silver, Rae

2008-01-01

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links. PMID:19004805

Brain mast cells link the immune system to anxiety-like behavior.

PubMed

Nautiyal, Katherine M; Ribeiro, Ana C; Pfaff, Donald W; Silver, Rae

2008-11-18

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient Kit(W-sh/W-sh) (sash(-/-)) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links.

Pharmacological Potential of Sea Cucumbers

PubMed Central

Khotimchenko, Yuri

2018-01-01

This review presents a detailed analysis of published research data focused on the pharmacological activity exerted by biologically active compounds isolated from sea cucumbers belonging to the class of Holothuroidea, phylum Echinodermata. The review contains descriptions of the structure, physico-chemical properties and pharmacological effects of these active substances. Particular attention is given to compounds with anticoagulant, antithrombotic, antioxidant, anticancer, anti-infectious, immune-stimulating and anti-ACE (angiotensin converting enzyme) activities as well as to the substances exerting a regulating influence on lipid and carbohydrate metabolism. All these compounds may be considered as prototypes for development of new pharmaceutical substances and medicines. PMID:29724051

The Effects of Chlordiazepoxide and d-Amphetamine during a Three-Component Multiple Schedule

PubMed Central

Romanowich, Paul; Lamb, R. J.

2013-01-01

Multiple schedules have been used in behavioral pharmacology research to show that a drug’s effect on behavior can be a function of the schedule of reinforcement that supports that behavior. However, less research has examined whether the context of the schedule of reinforcement in a multiple schedule can change the drug’s effect on behavior. We examined the effects of acute chlordiazepoxide and d-amphetamine injections on the behavior of two groups of pigeons trained on a three-component multiple schedule with identical schedules of reinforcement in the first and last components. For one group of pigeons reinforcement was unavailable during the middle component (decreased-middle-component). For the second group reinforcement rate was higher during the middle component than during the first or third components (increased-middle-component). In the decreased-middle-component group, chlordiazepoxide (3.2-32 mg/kg) decreased third-component response rates less than it decreased responding in the first component. Conversely, in the increased-middle-component group, chlordiazepoxide (3.2-10 mg/kg) decreased third-component response rates more than in the first component. In both groups, d-amphetamine did not differentially affect response rates across components. These results are consistent with previous research showing that drugs can differentially affect responding to two different schedules of reinforcement during the same session, and suggest that pharmacological preparations may be helpful in elucidating the mechanisms that control multiple schedule interactions. PMID:23633164

[Mechanism of Tongsaimai tablet for atherosclerosis based on network pharmacology].

PubMed

Li, Na; Zhang, Xin-Zhuang; Wang, Yan-Ru; Cao, Liang; Ding, Gang; Wang, Zhen-Zhong; Xiao, Wei; Xu, Xiao-Jie

2016-05-01

Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Tongsaimai tablets for atherosclerosis. In molecular docking and molecular-target protein network analysis, 97 molecules in Tongsaimai tablets showed good interaction with the atherosclerosis-related target protein (docking score ≥ 7), and 37 molecules of them could act on more than 2 targets (≥ 2) with higher betweenness, suggesting that these 37 molecules might be the main active compounds group in Tongsaimai tablets for atherosclerosis treatment. Furthermore, the predicted active compounds contained more flavonoids and saponins, reminding more attention should be paid on flavonoids and saponins in study of effective compounds and quality standards of Tongsaimai tablets. Targets network analysis showed that, the active compounds of Tongsaimai tablets could regulate inflammation, stabilize plaque, protect vascular endothelial cell, regulate blood lipid and inhibit blood coagulation through acting on the main 22 target proteins, such as Toll-like receptors (TLR1, TLR2), matrix metalloproteinase (MMP1, MMP2, MMP3, MMP9), angiotensin converting enzyme (ACE), leukotriene A4 hydrolase (LTA4-H), 5-lipoxidase (5-LOX), peroxisome proliferators-activated receptors (PPARα, PPARγ). These active compounds can participate in regulating different pathologic stages of atherosclerosis and thus treat atherosclerosis finally. This study revealed the main active compounds and possible mechanism of Tongsaimai tablets for treatment of atherosclerosis and meanwhile, verified the characteristics of multi-components, multi-targets and integral regulation for Tongsaimai tablets, providing theoretical references for the following systematic laboratory experiments on effective compounds and action mechanism of Tongsaimai Tablet. Copyright© by the Chinese Pharmaceutical Association.

Is psychological treatment efficacious for attention deficit hyperactivity disorder (ADHD)? Review of non-pharmacological treatments in children and adolescents with ADHD.

PubMed

Serrano-Troncoso, Eduardo; Guidi, Monica; Alda-Díez, José Ángel

2013-01-01

Attention deficit hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in children and adolescents, and has a great impact on the psychological development of affected patients. Even though its efficacy is proven, the use of medication for ADHD has several limitations, and non-pharmacological interventions are considered a necessary component of treatment. This work is a review of evidence-based non-pharmacological treatments with demonstrated efficacy for ADHD in children and adolescents, analyzed by age groups. Non-pharmacological treatments that have shown scientific evidence of efficacy are psychological and psychoeducational interventions. Psychological interventions include behavioral therapy, parent training (PT) and social skills training. Psychoeducational interventions include a set of practices to improve learning and are carried out in the school setting. Scientific evidence of efficacy in preschool children is limited to PT, while different psychological and psychoeducational interventions have been shown to be beneficial in school-age children. The available evidence for non-pharmacological treatment in adolescence is so far insufficient. Though more randomized controlled trials are necessary for non-pharmacological interventions to become established practices, there are clear indications of their efficacy. For more severe cases of ADHD, a combination of non-pharmacological and pharmacological treatment is recommended.

The genus Caesalpinia L. (Caesalpiniaceae): phytochemical and pharmacological characteristics.

PubMed

Zanin, João L Baldim; de Carvalho, Bianca A; Martineli, Paloma Salles; dos Santos, Marcelo Henrique; Lago, João Henrique G; Sartorelli, Patrícia; Viegas, Cláudio; Soares, Marisi G

2012-06-29

The genus Caesalpinia (Caesalpiniaceae) has more than 500 species, many of which have not yet been investigated for potential pharmacological activity. Several classes of chemical compounds, such as flavonoids, diterpenes, and steroids, have been isolated from various species of the genus Caesalpinia. It has been reported in the literature that these species exhibit a wide range of pharmacological properties, including antiulcer, anticancer, antidiabetic, anti-inflammatory, antimicrobial, and antirheumatic activities that have proven to be efficacious in ethnomedicinal practices. In this review we present chemical and pharmacological data from recent phytochemical studies on various plants of the genus Caesalpinia.

A review on ethno-medicinal uses and pharmacology of Vernonia cinerea Less.

PubMed

Dogra, Nittya K; Kumar, Suresh

2015-01-01

Vernonia cinerea Less. (ash-coloured fleabane; Asteraceae) is a widely distributed plant throughout India. The plant has reputation as folklore medicine in various traditional systems of medicine. The plant has been evaluated for varied pharmacological activities to validate its traditional claims, and has been scientifically reported to possess anti-inflammatory, antidiabetic, renoprotective, anticancer, antiviral, antimicrobial activities, etc. This review emphasises on ethnopharmacology and pharmacology of V. cinerea.

Recent Advances in Momordica charantia: Functional Components and Biological Activities.

PubMed

Jia, Shuo; Shen, Mingyue; Zhang, Fan; Xie, Jianhua

2017-11-28

Momordica charantia L. ( M. charantia ), a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia .

Recent Advances in Momordica charantia: Functional Components and Biological Activities

PubMed Central

Jia, Shuo; Shen, Mingyue; Zhang, Fan; Xie, Jianhua

2017-01-01

Momordica charantia L. (M. charantia), a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia. PMID:29182587

Enhancement of carer skills and patient function in the non-pharmacological management of frontotemporal dementia (FTD): A call for randomised controlled studies

PubMed Central

O'Connor, Claire M.; Clemson, Lindy; da Silva, Thaís Bento Lima; Piguet, Olivier; Hodges, John R.; Mioshi, Eneida

2013-01-01

FTD is a unique condition which manifests with a range of behavioural symptoms, marked dysfunction in activities of daily living (ADL) and increased levels of carer burden as compared to carers of other dementias. No efficacious pharmacological interventions to treat FTD currently exist, and research on pharmacological symptom management is variable. The few studies on non-pharmacological interventions in FTD focus on either the carer or the patients' symptoms, and lack methodological rigour. This paper reviews and discusses current studies utilising non-pharmacological approaches, exposing the clear need for more rigorous methodologies to be applied in this field. Finally, a successful randomised controlled trial helped reduce behaviours of concern in dementia, and through implementing participation in tailored activities, the FTD-specific Tailored Activities Program (TAP) is presented. Crucially, this protocol has scope to target both the person with FTD and their carer. This paper highlights that studies in this area would help to elucidate the potential for using activities to reduce characteristic behaviours in FTD, improving quality of life and the caregiving experience in FTD. PMID:29213832

Screening of immunomodulatory components in Yu-ping-feng-san using splenocyte binding and HPLC.

PubMed

Hong, Min; Wang, Xin-zhi; Wang, Liang; Hua, Yong-qing; Wen, Hong-mei; Duan, Jin-ao

2011-01-05

Yu-ping-feng-san (YPFS) is a widely used immunomodulatory herbal medication used in traditional Chinese medicine, but the active molecules remain obscure. To screen for bioactive components we combined splenocyte binding with high performance liquid chromatography (SB-HPLC). After enrichment by splenocyte binding, two YPFS components (C1 and C2) were analyzed by HPLC. Compound C2 was identified as linoleic acid (LA) based on UV absorption and mass spectrometry. Silica gel chromatography was used to purify compound C1 from Radix Saposhnikoviae, a major constituent of YPFS. This allowed identification of the molecule as panaxynol (PAN) based on EI-MS and NMR spectrometry. Bioassay in vitro demonstrated that PAN significantly inhibited splenocyte proliferation induced by concanavalin A (ConA) in a concentration-dependent manner, whereas LA had no significant effect on splenocyte proliferation. In vivo, PAN was found to attenuate allergic contact dermatitis in a mouse model of delayed-type hypersensitivity (DTH), a pharmacological activity not previously reported for this molecule. It is suggested that PAN contributes to the anti-DTH effects of YPFS. SB-HPLC provides a rapid and efficient method for the identification of potential immunomodulatory components in traditional Chinese medicines. Copyright © 2010 Elsevier B.V. All rights reserved.

Influence of pharmacological experiments of chemicals and other factors in diets of laboratory animals.

PubMed

Newberne, P M

1975-02-01

Results derived from animal experimentation depend to a considerable degree on the health and welfare of the animal from which the results are obtained. This, in turn, reflects the quality of housing, care, and nutrition provided the animal. Most diets designed for a particular species provide a reasonable balance of nutrients in quantities sufficient for normal growth and maintenance and reproduction of that species. Under usual conditions of animal feed manufacture, however, concentrations of essential ingredients may vary appreciably in different batches of a formulation made with different lots of natural ingredients, even though the guaranteed analysis shown on the label remains correct. A feed may also contain intentional or unintentional additives and other biologically active components. Variations in the concentrations of essential dietary components, as well as the presence of extraneous materials, can significantly influence the performance of an experimental animal consuming the diet and can thus lead to a biased interpretation of esperimental results. Investigators must consider factors which can result in efficient or inefficient utilization of energy, the variation in prepared diets whether from natural or purified products, and how these can modify the animal and change the response to a given experimental regimen. Proteins, fat, carbohydrates, vitamins, and minerals can all have pharmacological as well as physiological effects on a biological system. The control of vitamin D metabolism and calcium, parathormone, calcitonin among others are important factors subject to dietary modification. A conditioned marginal or frank deficiency of folic acid can result from oral contraceptives and administration of anticonvulsants; if studies are done in animals using these types of chemicals, dietary folate will be highly significant. Newer information about the role of ascorbic acid in activation of lipase and lipid mobilization is of direct concern to those using research animals requiring a source of dietary ascorbic acid. Trace elements, some amino acids, natural enzyme inducers, and toxic contaminants, all of which can affect the response of experimental animals, are highly important to the quality of animal research in pharmacologic investigations.

The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis

PubMed Central

Liu, Yi; Wang, Jihui; Wang, Wei; Zhang, Hanyue; Zhang, Xuelan; Han, Chunchao

2015-01-01

Cordyceps sinensis, also called DongChongXiaCao (winter worm, summer grass) in Chinese, is becoming increasingly popular and important in the public and scientific communities. This study summarizes the chemical constituents and their corresponding pharmacological actions of Cordyceps sinensis. Many bioactive components of Cordyceps sinensis have been extracted including nucleoside, polysaccharide, sterol, protein, amino acid, and polypeptide. In addition, these constituents' corresponding pharmacological actions were also shown in the study such as anti-inflammatory, antioxidant, antitumour, antiapoptosis, and immunomodulatory actions. Therefore can use different effects of C. sinensis against different diseases and provide reference for the study of Cordyceps sinensis in the future. PMID:25960753

An Effective Solution to Discover Synergistic Drugs for Anti-Cerebral Ischemia from Traditional Chinese Medicinal Formulae

PubMed Central

Lu, Peng; Chen, Chang; Fu, Meihong; Fang, Jing; Gao, Jian; Zhu, Li; Liang, Rixin; Shen, Xin; Yang, Hongjun

2013-01-01

Recently, the pharmaceutical industry has shifted to pursuing combination therapies that comprise more than one active ingredient. Interestingly, combination therapies have been used for more than 2500 years in traditional Chinese medicine (TCM). Understanding optimal proportions and synergistic mechanisms of multi-component drugs are critical for developing novel strategies to combat complex diseases. A new multi-objective optimization algorithm based on least angle regression-partial least squares was proposed to construct the predictive model to evaluate the synergistic effect of the three components of a novel combination drug Yi-qi-jie-du formula (YJ), which came from clinical TCM prescription for the treatment of encephalopathy. Optimal proportion of the three components, ginsenosides (G), berberine (B) and jasminoidin (J) was determined via particle swarm optimum. Furthermore, the combination mechanisms were interpreted using PLS VIP and principal components analysis. The results showed that YJ had optimal proportion 3(G): 2(B): 0.5(J), and it yielded synergy in the treatment of rats impaired by middle cerebral artery occlusion induced focal cerebral ischemia. YJ with optimal proportion had good pharmacological effects on acute ischemic stroke. The mechanisms study demonstrated that the combination of G, B and J could exhibit the strongest synergistic effect. J might play an indispensable role in the formula, especially when combined with B for the acute stage of stroke. All these data in this study suggested that in the treatment of acute ischemic stroke, besides restoring blood supply and protecting easily damaged cells in the area of the ischemic penumbra as early as possible, we should pay more attention to the removal of the toxic metabolites at the same time. Mathematical system modeling may be an essential tool for the analysis of the complex pharmacological effects of multi-component drug. The powerful mathematical analysis method could greatly improve the efficiency in finding new combination drug from TCM. PMID:24236065

[Ginseng prescription rules and molecular mechanism in treating coronary heart disease based on data mining and integrative pharmacology].

PubMed

Li, Sen; Tang, Shi-Huan; Liu, Jin-Ling; Su, Jin; He, Fu-Yuan

2018-04-01

The ancient dragon Materia Medica, Compendium of Materia Medica and other works recorded that the main effect of ginseng is tonifying qi. It is reported that the main active ingredient of ginseng is ginsenoside. Modern studies have found that ginseng mono saponins are effective for cardiovascular related diseases. This paper preliminary clarified the efficacy of traditional ginseng-nourishing qi and cardiovascular disease through the traditional Chinese medicine (TCM) inheritance auxiliary platform and integration platform of association of pharmacology. With the help of TCM inheritance auxiliary platform-analysis of "Chinese medicine database", Chinese medicine treatment of modern diseases that ginseng rules, so the traditional effect associated with modern medicine and pharmacology; application integration platform enrichment analysis on the target of drug and gene function, metabolic pathway, to further explore the molecular mechanism of ginseng in the treatment of coronary heart disease, aimed at mining the molecular mechanism of ginseng in the treatment of coronary heart disease. Chinese medicine containing ginseng 307 prescriptions, 87 kinds of disease indications, western medicine disease Chinese medicine therapy for ginseng main coronary heart disease; analysis of molecular mechanism of ginseng pharmacology integration platform for the treatment of coronary heart disease. Ginsenosides（Ra₁, Ra₂, Rb₁, Rb₂, Rg₁, Ro) bind these targets, PRKAA1, PRKAA2, NDUFA4, COX5B, UQCRC1, affect chemokines, non-alcoholic fatty liver, gonadotropin, carbon metabolism, glucose metabolism and other pathways to treat coronary heart disease indirectly. The molecular mechanism of Panax ginseng's multi-component, multi-target and synergistic action is preliminarily elucidated in this paper. Copyright© by the Chinese Pharmaceutical Association.

Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells.

PubMed

Beerepoot, Pieter; Lam, Vincent M; Salahpour, Ali

2016-10-14

A number of pathological conditions have been linked to mutations in the dopamine transporter gene, including hereditary dopamine transporter deficiency syndrome (DTDS). DTDS is a rare condition that is caused by autosomal recessive loss-of-function mutations in the dopamine transporter (DAT), which often affects transporter trafficking and folding. We examined the possibility of using pharmacological chaperones of DAT to rescue DTDS mutations. After screening a set of known DAT ligands for their ability to increase DAT surface expression, we found that bupropion and ibogaine increased DAT surface expression, whereas others, including cocaine and methylphenidate, had no effect. Bupropion and ibogaine increased wild type DAT protein levels and also promoted maturation of the endoplasmic reticulum (ER)-retained DAT mutant K590A. Rescue of K590A could be blocked by inhibiting ER to Golgi transport using brefeldin A. Furthermore, knockdown of coat protein complex II (COPII) component SEC24D, which is important in the ER export of wild type DAT, also blocked the rescue effects of bupropion and ibogaine. These data suggest that bupropion and ibogaine promote maturation of DAT by acting as pharmacological chaperones in the ER. Importantly, both drugs rescue DAT maturation and functional activity of the DTDS-associated mutations A314V and R445C. Together, these results are the first demonstration of pharmacological chaperoning of DAT and suggest this may be a viable approach to increase DAT levels in DTDS and other conditions associated with reduced DAT function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Metabolomic and elemental analysis of camel and bovine urine by GC-MS and ICP-MS.

PubMed

Ahamad, Syed Rizwan; Alhaider, Abdul Qader; Raish, Mohammad; Shakeel, Faiyaz

2017-01-01

Recent studies from the author's laboratory indicated that camel urine possesses antiplatelet activity and anti-cancer activity which is not present in bovine urine. The objective of this study is to compare the volatile and elemental components of bovine and camel urine using GC-MS and ICP-MS analysis. We are interested to know the component that performs these biological activities. The freeze dried urine was dissolved in dichloromethane and then derivatization process followed by using BSTFA for GC-MS analysis. Thirty different compounds were analyzed by the derivatization process in full scan mode. For ICP-MS analysis twenty eight important elements were analyzed in both bovine and camel urine. The results of GC-MS and ICP-MS analysis showed marked difference in the urinary metabolites. GC-MS evaluation of camel urine finds a lot of products of metabolism like benzene propanoic acid derivatives, fatty acid derivatives, amino acid derivatives, sugars, prostaglandins and canavanine. Several research reports reveal the metabolomics studies on camel urine but none of them completely reported the pharmacology related metabolomics. The present data of GC-MS suggest and support the previous studies and activities related to camel urine.

Glucose Transporter 1–Dependent Glycolysis Is Increased during Aging-Related Lung Fibrosis, and Phloretin Inhibits Lung Fibrosis

PubMed Central

Cho, Soo Jung; Moon, Jong-Seok; Lee, Chang-Min; Choi, Augustine M. K.

2017-01-01

Aging is associated with metabolic diseases such as type 2 diabetes mellitus, cardiovascular disease, cancer, and neurodegeneration. Aging contributes to common processes including metabolic dysfunction, DNA damage, and reactive oxygen species generation. Although glycolysis has been linked to cell growth and proliferation, the mechanisms by which the activation of glycolysis by aging regulates fibrogenesis in the lung remain unclear. The objective of this study was to determine if glucose transporter 1 (GLUT1)–induced glycolysis regulates age-dependent fibrogenesis of the lung. Mouse and human lung tissues were analyzed for GLUT1 and glycolytic markers using immunoblotting. Glycolytic function was measured using a Seahorse apparatus. To study the effect of GLUT1, genetic inhibition of GLUT1 was performed by short hairpin RNA transduction, and phloretin was used for pharmacologic inhibition of GLUT1. GLUT1-dependent glycolysis is activated in aged lung. Genetic and pharmacologic inhibition of GLUT1 suppressed the protein expression of α-smooth muscle actin, a key cytoskeletal component of activated fibroblasts, in mouse primary lung fibroblast cells. Moreover, we demonstrated that the activation of AMP-activated protein kinase, which is regulated by GLUT1-dependent glycolysis, represents a critical metabolic pathway for fibroblast activation. Furthermore, we demonstrated that phloretin, a potent inhibitor of GLUT1, significantly inhibited bleomycin-induced lung fibrosis in vivo. These results suggest that GLUT1-dependent glycolysis regulates fibrogenesis in aged lung and that inhibition of GLUT1 provides a potential target of therapy of age-related lung fibrosis. PMID:27997810

Glucose Transporter 1-Dependent Glycolysis Is Increased during Aging-Related Lung Fibrosis, and Phloretin Inhibits Lung Fibrosis.

PubMed

Cho, Soo Jung; Moon, Jong-Seok; Lee, Chang-Min; Choi, Augustine M K; Stout-Delgado, Heather W

2017-04-01

Aging is associated with metabolic diseases such as type 2 diabetes mellitus, cardiovascular disease, cancer, and neurodegeneration. Aging contributes to common processes including metabolic dysfunction, DNA damage, and reactive oxygen species generation. Although glycolysis has been linked to cell growth and proliferation, the mechanisms by which the activation of glycolysis by aging regulates fibrogenesis in the lung remain unclear. The objective of this study was to determine if glucose transporter 1 (GLUT1)-induced glycolysis regulates age-dependent fibrogenesis of the lung. Mouse and human lung tissues were analyzed for GLUT1 and glycolytic markers using immunoblotting. Glycolytic function was measured using a Seahorse apparatus. To study the effect of GLUT1, genetic inhibition of GLUT1 was performed by short hairpin RNA transduction, and phloretin was used for pharmacologic inhibition of GLUT1. GLUT1-dependent glycolysis is activated in aged lung. Genetic and pharmacologic inhibition of GLUT1 suppressed the protein expression of α-smooth muscle actin, a key cytoskeletal component of activated fibroblasts, in mouse primary lung fibroblast cells. Moreover, we demonstrated that the activation of AMP-activated protein kinase, which is regulated by GLUT1-dependent glycolysis, represents a critical metabolic pathway for fibroblast activation. Furthermore, we demonstrated that phloretin, a potent inhibitor of GLUT1, significantly inhibited bleomycin-induced lung fibrosis in vivo. These results suggest that GLUT1-dependent glycolysis regulates fibrogenesis in aged lung and that inhibition of GLUT1 provides a potential target of therapy of age-related lung fibrosis.

Importance of the pharmacological profile of the bound ligand in enrichment on nuclear receptors: toward the use of experimentally validated decoy ligands.

PubMed

Lagarde, Nathalie; Zagury, Jean-François; Montes, Matthieu

2014-10-27

The evaluation of virtual ligand screening methods is of major importance to ensure their reliability. Taking into account the agonist/antagonist pharmacological profile should improve the quality of the benchmarking data sets since ligand binding can induce conformational changes in the nuclear receptor structure and such changes may vary according to the agonist/antagonist ligand profile. We indeed found that splitting the agonist and antagonist ligands into two separate data sets for a given nuclear receptor target significantly enhances the quality of the evaluation. The pharmacological profile of the ligand bound in the binding site of the target structure was also found to be an additional critical parameter. We also illustrate that active compound data sets for a given pharmacological activity can be used as a set of experimentally validated decoy ligands for another pharmacological activity to ensure a reliable and challenging evaluation of virtual screening methods.

Neurotoxicity and other pharmacological activities of the snake venom phospholipase A2 OS2: The N-terminal region is more important than enzymatic activity

PubMed Central

Rouault, Morgane; Rash, Lachlan D.; Escoubas, Pierre; Boilard, Eric; Bollinger, James; Lomonte, Bruno; Maurin, Thomas; Guillaume, Carole; Canaan, Stéphane; Deregnaucourt, Christiane; Schrével, Joseph; Doglio, Alain; Gutiérrez, José María; Lazdunski, Michel; Gelb, Michael H.; Lambeau, Gérard

2009-01-01

Several snake venom secreted phospholipases A2 (sPLA2s) including OS2 exert a variety of pharmacological effects ranging from central neurotoxicity to anti-HIV activity by mechanisms that are not yet fully understood. To conclusively address the role of enzymatic activity and map the key structural elements of OS2 responsible for its pharmacological properties, we have prepared single point OS2 mutants at the catalytic site and large chimeras between OS2 and OS1, an homologous but non toxic sPLA2. Most importantly, we found that the enzymatic activity of the active site mutant H48Q is 500-fold lower than that of the wild-type protein, while central neurotoxicity is only 16-fold lower, providing convincing evidence that catalytic activity is at most a minor factor that determines central neurotoxicity. The chimera approach has identified the N-terminal region (residues 1–22) of OS2, but not the central one (residues 58–89), as crucial for both enzymatic activity and pharmacological effects. The C-terminal region of OS2 (residues 102–119) was found to be critical for enzymatic activity, but not for central neurotoxicity and anti-HIV activity, allowing us to further dissociate enzymatic activity and pharmacological effects. Finally, direct binding studies with the C-terminal chimera which poorly binds to phospholipids while it is still neurotoxic, led to the identification of a subset of brain N-type receptors which may be directly involved in central neurotoxicity. PMID:16669624

Bioactive Components in Fish Venoms

PubMed Central

Ziegman, Rebekah; Alewood, Paul

2015-01-01

Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

A review of traditional pharmacological uses, phytochemistry, and pharmacological activities of Tribulus terrestris.

PubMed

Zhu, Wenyi; Du, Yijie; Meng, Hong; Dong, Yinmao; Li, Li

2017-07-11

Tribulus terrestris L. (TT) is an annual plant of the family Zygophyllaceae that has been used for generations to energize, vitalize, and improve sexual function and physical performance in men. The fruits and roots of TT have been used as a folk medicine for thousands of years in China, India, Sudan, and Pakistan. Numerous bioactive phytochemicals, such as saponins and flavonoids, have been isolated and identified from TT that are responsible alone or in combination for various pharmacological activities. This review provides a comprehensive overview of the traditional applications, phytochemistry, pharmacology and overuse of TT and provides evidence for better medicinal usage of TT.

Marine pharmacology in 2005–6: Marine Compounds with Anthelmintic, Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiprotozoal, Antituberculosis, and Antiviral Activities; affecting the Cardiovascular, Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

PubMed Central

Mayer, Alejandro M. S.; Rodriguez, Abimael D.; Berlinck, Roberto G. S.; Hamann, Mark T.

2009-01-01

BACKGROUND The review presents the 2005–2006 peer-reviewed marine pharmacology literature, and follows a similar format to the authors’ 1998–2004 reviews. The preclinical pharmacology of chemically characterized marine compounds isolated from marine animals, algae, fungi and bacteria is systematically presented. RESULTS Anthelminthic, antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis and antiviral activities were reported for 78 marine chemicals. Additionally 47 marine compounds were reported to affect the cardiovascular, immune and nervous system as well as possess anti-inflammatory effects. Finally, 58 marine compounds were shown to bind to a variety of molecular targets, and thus could potentially contribute to several pharmacological classes. CONCLUSIONS Marine pharmacology research during 2005–2006 was truly global in nature, involving investigators from 32 countries, and the United States, and contributed 183 marine chemical leads to the research pipeline aimed at the discovery of novel therapeutic agents. SIGNIFICANCE Continued preclinical and clinical research with marine natural products demonstrating a broad spectrum of pharmacological activity and will probably result in novel therapeutic agents for the treatment of multiple disease categories. PMID:19303911

Pinocembrin: A Novel Natural Compound with Versatile Pharmacological and Biological Activities

PubMed Central

Rasul, Azhar; Millimouno, Faya Martin; Ali Eltayb, Wafa; Ali, Muhammad; Li, Jiang; Li, Xiaomeng

2013-01-01

Pinocembrin (5,7-dihydroxyflavanone) is one of the primary flavonoids isolated from the variety of plants, mainly from Pinus heartwood, Eucalyptus, Populus, Euphorbia, and Sparattosperma leucanthum, in the diverse flora and purified by various chromatographic techniques. Pinocembrin is a major flavonoid molecule incorporated as multifunctional in the pharmaceutical industry. Its vast range of pharmacological activities has been well researched including antimicrobial, anti-inflammatory, antioxidant, and anticancer activities. In addition, pinocembrin can be used as neuroprotective against cerebral ischemic injury with a wide therapeutic time window, which may be attributed to its antiexcitotoxic effects. Pinocembrin exhibits pharmacological effects on almost all systems, and our aim is to review the pharmacological and therapeutic applications of pinocembrin with specific emphasis on mechanisms of actions. The design of new drugs based on the pharmacological effects of pinocembrin could be beneficial. This review suggests that pinocembrin is a potentially promising pharmacological candidate, but additional studies and clinical trials are required to determine its specific intracellular sites of action and derivative targets in order to fully understand the mechanism of its anti-inflammatory, anticancer, and apoptotic effects to further validate its medical applications. PMID:23984355

Microglial activation and the nitric oxide/cGMP/PKG pathway underlie enhanced neuronal vulnerability to mitochondrial dysfunction in experimental multiple sclerosis.

PubMed

Mancini, Andrea; Tantucci, Michela; Mazzocchetti, Petra; de Iure, Antonio; Durante, Valentina; Macchioni, Lara; Giampà, Carmela; Alvino, Alessandra; Gaetani, Lorenzo; Costa, Cinzia; Tozzi, Alessandro; Calabresi, Paolo; Di Filippo, Massimiliano

2018-05-01

During multiple sclerosis (MS), a close link has been demonstrated to occur between inflammation and neuro-axonal degeneration, leading to the hypothesis that immune mechanisms may promote neurodegeneration, leading to irreversible disease progression. Energy deficits and inflammation-driven mitochondrial dysfunction seem to be involved in this process. In this work we investigated, by the use of striatal electrophysiological field-potential recordings, if the inflammatory process associated with experimental autoimmune encephalomyelitis (EAE) is able to influence neuronal vulnerability to the blockade of mitochondrial complex IV, a crucial component for mitochondrial activity responsible of about 90% of total cellular oxygen consumption. We showed that during the acute relapsing phase of EAE, neuronal susceptibility to mitochondrial complex IV inhibition is markedly enhanced. This detrimental effect was counteracted by the pharmacological inhibition of microglia, of nitric oxide (NO) synthesis and its intracellular pathway (involving soluble guanylyl cyclase, sGC, and protein kinase G, PKG). The obtained results suggest that mitochondrial complex IV exerts an important role in maintaining neuronal energetic homeostasis during EAE. The pathological processes associated with experimental MS, and in particular the activation of microglia and of the NO pathway, lead to an increased neuronal vulnerability to mitochondrial complex IV inhibition, representing promising pharmacological targets. Copyright © 2018 Elsevier Inc. All rights reserved.

Gas chromatographic mass analysis and further pharmacological actions of Cymbopogon proximus essential oil.

PubMed

Al-Taweel, A M; Fawzy, G A; Perveen, S; El Tahir, K E H

2013-09-01

The present study reports Gas chromatographic mass analysis (GC-MS) as well as important biological activities of Cymbopogon proximus essential oil. The chemical composition of the essential oil of Cymbopogon proximus was investigated by GC-MS. Furthermore, the effects of Cymbopogon proximus essential oil on the cardiac parasympathetic ganglia in rats, the intra-tracheal pressure in guinea-pigs and on carrageenan-induced inflammation in the rats paw, were studied. The GC-MS study led to the identification of 22 components with Piperitone representing (73.81%), Elemol (9.32%), alpha-Eudesmol (5.21%) and alpha-Terpineol (3.01%) of the oils composition. The percentage protective effect of the oil on the vagus-induced bradycardia in rats was 90.1±3.1%, which represents a significant protection. As for the effect of Cymbopogon oil on bronchoconstrictors-induced increase in intra-tracheal pressure in guinea-pigs, the oil antagonized the actions of 5-HT and histamine by 80±3.7 and 93±8.3%, respectively. Pharmacological investigations using Cymbopogon oil revealed its inherent ability to possess a bronchodilator activity mediated via blockade of both histamine and serotonin receptors. It possessed a significant ganglionic blocking action and a limited anti-inflammatory activity that seemed to involve blockade of histamine and serotonin receptors in the rats' paws. © Georg Thieme Verlag KG Stuttgart · New York.

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology.

PubMed

Layé, Sophie; Nadjar, Agnès; Joffre, Corinne; Bazinet, Richard P

2018-01-01

Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Studies in neuroendocrine pharmacology

NASA Technical Reports Server (NTRS)

Maickel, R. P.

1976-01-01

The expertise and facilities available within the Medical Sciences Program section on Pharmacology were used along with informational input from various NASA sources to study areas relevant to the manned space effort. Topics discussed include effects of drugs on deprivation-induced fluid consumption, brain biogenic amines, biochemical responses to stressful stimuli, biochemical and behavioral pharmacology of amphetamines, biochemical and pharmacological studies of analogues to biologically active indole compounds, chemical pharmacology: drug metabolism and disposition, toxicology, and chemical methodology. Appendices include a bibliography, and papers submitted for publication or already published.

Pharmacological Modulation of Diacylglycerol-Sensitive TRPC3/6/7 Channels

PubMed Central

Harteneck, Christian; Gollasch, Maik

2011-01-01

Members of the classic type of transient receptor potential channels (TRPC) represent important molecules involved in hormonal signal transduction. TRPC3/6/7 channels are of particular interest as they are components of phospholipase C driven signalling pathways. Upon receptor-activation, G-protein-mediated stimulation of phospholipase C results in breakdown of phosphatidylinositides leading to increased intracellular diacylglycerol and inositol-trisphosphate levels. Diacylglycerol activates protein kinase C, but more interestingly diacylglycerol directly activates TRPC2/3/6/7 channels. Molecular cloning, expression and characterization of TRP channels enabled reassignment of traditional inhibitors of receptor-dependent calcium entry such as SKF-96365 and 2-APB as blockers of TRPC3/6/7 and several members of non-classic TRP channels. Furthermore, several enzyme inhibitors have also been identified as TRP channel blockers, such as ACA, a phospholipase A2 inhibitor, and W-7, a calmodulin antagonist. Finally, the naturally occurring secondary plant compound hyperforin has been identified as TRPC6-selective drug, providing an exciting proof of concept that it is possible to generate TRPC-selective channel modulators. The description of Pyr3 as the first TRPC3-selective inhibitor shows that not only nature but also man is able to generate TRP-selective modulators. The review sheds lights on the current knowledge and historical development of pharmacological modulators of TRPC3/6/7. Our analysis indicates that Pyr3 and hyperforin provide promising core structures for the development of new, selective and more potent modulators of TRPC3/6/7 activity. PMID:20932261

Essential Oil Composition, Antimicrobial and Pharmacological Activities of Lippia sidoides Cham. (Verbenaceae) From São Gonçalo do Abaeté, Minas Gerais, Brazil

PubMed Central

de Morais, Sandra Ribeiro; Oliveira, Thiago Levi Silva; de Oliveira, Lanussy Porfiro; Tresvenzol, Leonice Manrique Faustino; da Conceição, Edemilson Cardoso; Rezende, Maria Helena; Fiuza, Tatiana de Sousa; Costa, Elson Alves; Ferri, Pedro Henrique; de Paula, José Realino

2016-01-01

Background: Lippia sidoides (Verbenaceae) is used in Brazilian folk medicine as an antiseptic, and it is usually applied topically on skin, mucous membranes, mouth, and throat, or used for vaginal washings. Objectives: To analyze the chemical composition of the essential oil from L. sidoides collected in São Gonçalo do Abaeté, Minas Gerais and grown in Hidrolândia, Goiás; to evaluate the antimicrobial activity of the essential oil, crude ethanol extract, and hexane, dichloromethane, ethyl-acetate, and aqueous fractions (AFs); to study the antinociceptive, anti-inflammatory, and central nervous system activities of the crude ethanol extract. Materials and methods: The essential oils were obtained by hydro-distillation using a Clevenger-type apparatus and analyzed by GC/MS. The antimicrobial activity in vitro was performed by broth microdilution method. The pharmacological tests were performed using female Swiss albino mice. Results: The major components of the essential oil were isoborneol (14.66%), bornyl acetate (11.86%), α-humulene (11.23%), α-fenchene (9.32%), and 1.8-cineole (7.05%), supporting the existence of two chemotypes of this species. The hexane fraction (HF) had good antifungal activity against Cryptococcus sp. ATCC D (MIC = 31.25 μg/mL) and Cryptococcus gatti L48 (MIC = 62.5 μg/mL). In the pharmacological tests, the crude ethanol extract presented antinociceptive and anti-inflammatory activities. Conclusion: Given that the ethanol extract of L. sidoides is included in the Formulary of Phytotherapeutic Agents of the Brazilian Pharmacopeia as an anti-inflammatory for oral cavities, the present work provides scientific evidence to back this use and highlight the importance of selecting the appropriate chemotype on the basis of the expected biological response. SUMMARY The major components of the essential oil of L. sidoides were isoborneol bornyl acetate, α-humulene, α-fenchene, and 1.8-cineole. The HF had good antifungal activity against Cryptococcus sp. ATCC D and C. gatti L4.The crude ethanol extract of L. sidoides presented antinociceptive and anti-inflammatory activities.The present work provides scientific evidence of the importance of selecting the appropriate chemotype on the basis of the expected biological response. Abbreviations used: UFG: Universidade Federal de Goiás; HF: hexane fraction; DF: dichloromethane fraction; EAF: ethyl acetate fraction; AF: aqueous fraction; MeOH: methanol; MIC: minimum inhibitory concentration; ATCC: American Type Culture Collection; MH: Müller Hinton; DMSO: dimethyl sulfoxide; RPMI: Roswell Park Memorial Institute; NaCl: sodium chloride; μL: microliters; mL: milliliters; μg: microgram; kg: kilogram; h: hour; min: minute; cm: centimeter; COBEA: Brazilian College of Animal Experiments; p.o.:, oral; i.p.: intraperitoneal; s.c.: subcutaneous; SEM: standard error of the mean; RI: retention indices. PMID:27867267

Alimentary regimen in non-alcoholic fatty liver disease: Mediterranean diet

PubMed Central

Abenavoli, Ludovico; Milic, Natasa; Peta, Valentina; Alfieri, Francesco; De Lorenzo, Antonino; Bellentani, Stefano

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The mechanisms of the underlying disease development and progression are awaiting clarification. Insulin resistance and obesity-related inflammation status, among other possible genetic, dietary, and lifestyle factors, are thought to play the key role. There is no consensus concerning the pharmacological treatment. However, the dietary nutritional management to achieve weight loss is an essential component of any treatment strategy. On the basis of its components, the literature reports on the effectiveness of the Mediterranean diet in reducing cardiovascular risk and in preventing major chronic diseases, including obesity and diabetes. New evidence supports the idea that the Mediterranean diet, associated with physical activity and cognitive behaviour therapy, may have an important role in the prevention and the treatment of NAFLD. PMID:25492997

Polymeric drugs: Advances in the development of pharmacologically active polymers

PubMed Central

Li, Jing; Yu, Fei; Chen, Yi; Oupický, David

2015-01-01

Synthetic polymers play a critical role in pharmaceutical discovery and development. Current research and applications of pharmaceutical polymers are mainly focused on their functions as excipients and inert carriers of other pharmacologically active agents. This review article surveys recent advances in alternative pharmaceutical use of polymers as pharmacologically active agents known as polymeric drugs. Emphasis is placed on the benefits of polymeric drugs that are associated with their macromolecular character and their ability to explore biologically relevant multivalency processes. We discuss the main therapeutic uses of polymeric drugs as sequestrants, antimicrobials, antivirals, and anticancer and anti-inflammatory agents. PMID:26410809

Metabolism of hyperforin, the active constituent of St. John's wort, in human liver microsomes.

PubMed

Hokkanen, Juho; Tolonen, Ari; Mattila, Sampo; Turpeinen, Miia

2011-02-14

The metabolism of hyperforin, one of the pharmacologically most active components of St. John's wort (Hypericum perforatum), was characterized in vitro using human liver microsomes and recombinant heterologously expressed P450 enzymes. A total of 57 hyperforin metabolites were detected. Of those, six were identified as monohydroxylations (M1-M6), while the others were formed via two or more hydroxylation reactions, via dehydrogenation, or by combinations of these reactions. A combined approach of cDNA-expressed recombinant CYPs, CYP-selective chemical inhibitors and correlation with CYP-specific marker activities indicated a central role of the CYP2C and CYP3A families in the metabolism of hyperforin. In addition, hyperforin was found to inhibit CYP2D6 and CYP3A4 model activities quite potently. Copyright © 2010 Elsevier B.V. All rights reserved.

Ginseng leaf-stem: bioactive constituents and pharmacological functions

PubMed Central

Wang, Hongwei; Peng, Dacheng; Xie, Jingtian

2009-01-01

Ginseng root is used more often than other parts such as leaf stem although extracts from ginseng leaf-stem also contain similar active ingredients with pharmacological functions. Ginseng's leaf-stems are more readily available at a lower cost than its root. This article reviews the pharmacological effects of ginseng leaf-stem on some diseases and adverse effects due to excessive consumption. Ginseng leaf-stem extract contains numerous active ingredients, such as ginsenosides, polysaccharides, triterpenoids, flavonoids, volatile oils, polyacetylenic alcohols, peptides, amino acids and fatty acids. The extract contains larger amounts of the same active ingredients than the root. These active ingredients produce multifaceted pharmacological effects on the central nervous system, as well as on the cardiovascular, reproductive and metabolic systems. Ginseng leaf-stem extract also has anti-fatigue, anti-hyperglycemic, anti-obesity, anti-cancer, anti-oxidant and anti-aging properties. In normal use, ginseng leaf-stem extract is quite safe; adverse effects occur only when it is over dosed or is of poor quality. Extracts from ginseng root and leaf-stem have similar multifaceted pharmacological activities (for example central nervous and cardiovascular systems). In terms of costs and source availability, however, ginseng leaf-stem has advantages over its root. Further research will facilitate a wider use of ginseng leaf-stem. PMID:19849852

Identification and Quantification of Alkaloid in KHR98 and Fragmentation Pathways in HPLC-Q-TOF-MS.

PubMed

Long, Jiakun; Wang, Yang; Xu, Chen; Liu, Tingting; Duan, Gengli; Yu, Yingjia

2018-05-01

Uncaria rhynchophylla is woody climber plant distributed mainly in China and Japan, the stems and hooks of which can be collected as "Gou-Teng" for the treatment of hyperpyrexia, epilepsy and preeclampsia. Fudan University first manufactured KHR98, the extract of Uncaria rhynchophylla. In order to study the active components and structural information of KHR98, we established a HPLC coupled with quadrupole time-of-flight (Q-TOF)-MS method for rapid analysis of alkaloids. In qualitative analysis, a total of eight compounds, including four known alkaloids and four unknown components, were detected and identified. The fragmentation behaviors, such as the fragment ion information and the fragmentation pathways of the eight components were summarized simultaneously, and the concentration of the above components was determined by HPLC-MS method. The quantitative method was proved to be reproducible, precise and accurate. This study shed light on the standardization and quality control of the KHR98 and provided a foundation for the further research on pharmacology, follow-up clinical research and New Drug Applications.

Experiences of nurses as postgraduate students of pharmacology and therapeutics: a multiple case narrative study.

PubMed

Lim, Anecita Gigi; North, Nicola; Shaw, John

2014-06-01

Pharmacology and therapeutics are essential components of educational programmes in prescribing, yet little is known about students' experiences in studying these subjects for a prescribing role. To investigate the views and experiences of nurses as postgraduate students who were studying pharmacology and therapeutics in preparation for a prescribing role. Qualitative study using a multiple case narrative approach. The participants were undertaking or had recently completed a Master's degree programme; they worked in a range of clinical areas and services in the Auckland region. Twenty nurses, with advanced clinical backgrounds and experience engaged in postgraduate studies in pharmacology and therapeutics. A semi-structured interview of approximately 1h was undertaken with each participant. Transcripts were analysed within and across cases using Narralizer software to support thematic analysis. There were four broad thematic areas. In the first, 'prescribing in the context of advanced nursing practice', participants reflected on why prescribing authority was important to them. In the second theme, 'adequacy of prior pharmacology knowledge' they discussed the relative lack of pharmacology in their undergraduate programmes and in nursing practice. In the third, 'drawing on clinical experience in acquiring pharmacology knowledge', participants discussed how, as they grappled with new pharmacological science, they drew on clinical experience which facilitated their learning. In the fourth theme, 'benefits of increased pharmacology knowledge' they discussed how their studies improved their interactions with patients, medical colleagues and as members of multi-disciplinary teams. All nurses viewed their studies in pharmacology as fundamental to their roles as prescribers, through knowledge development and an increase in confidence. Although pharmacology theory was new to many participants, their learning was facilitated because they were able to reflect on previous clinical experience and apply this to theory. Copyright © 2014 Elsevier Ltd. All rights reserved.

The N2-P3 complex of the evoked potential and human performance

NASA Technical Reports Server (NTRS)

Odonnell, Brian F.; Cohen, Ronald A.

1988-01-01

The N2-P3 complex and other endogenous components of human evoked potential provide a set of tools for the investigation of human perceptual and cognitive processes. These multidimensional measures of central nervous system bioelectrical activity respond to a variety of environmental and internal factors which have been experimentally characterized. Their application to the analysis of human performance in naturalistic task environments is just beginning. Converging evidence suggests that the N2-P3 complex reflects processes of stimulus evaluation, perceptual resource allocation, and decision making that proceed in parallel, rather than in series, with response generation. Utilization of these EP components may provide insights into the central nervous system mechanisms modulating task performance unavailable from behavioral measures alone. The sensitivity of the N2-P3 complex to neuropathology, psychopathology, and pharmacological manipulation suggests that these components might provide sensitive markers for the effects of environmental stressors on the human central nervous system.

Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation

PubMed Central

den Brok, Martijn H.; Büll, Christian; Wassink, Melissa; de Graaf, Annemarie M.; Wagenaars, Jori A.; Minderman, Marthe; Thakur, Mayank; Amigorena, Sebastian; Rijke, Eric O.; Schrier, Carla C.; Adema, Gosse J.

2016-01-01

Saponin-based adjuvants (SBAs) are being used in animal and human (cancer) vaccines, as they induce protective cellular immunity. Their adjuvant potency is a factor of inflammasome activation and enhanced antigen cross-presentation by dendritic cells (DCs), but how antigen cross-presentation is induced is not clear. Here we show that SBAs uniquely induce intracellular lipid bodies (LBs) in the CD11b+ DC subset in vitro and in vivo. Using genetic and pharmacological interference in models for vaccination and in situ tumour ablation, we demonstrate that LB induction is causally related to the saponin-dependent increase in cross-presentation and T-cell activation. These findings link adjuvant activity to LB formation, aid the application of SBAs as a cancer vaccine component, and will stimulate development of new adjuvants enhancing T-cell-mediated immunity. PMID:27819292

Unique Medicinal Properties of Withania somnifera: Phytochemical Constituents and Protein Component.

PubMed

Dar, Parvaiz A; Singh, Laishram R; Kamal, Mohammad A; Dar, Tanveer A

2016-01-01

Withania somnifera is an important medicinal herb that has been widely used for the treatment of different clinical conditions. The overall medicinal properties of Withania somnifera make it a viable therapeutic agent for addressing anxiety, cancer, microbial infection, immunomodulation, and neurodegenerative disorders. Biochemical constituents of Withania somnifera like withanolideA, withanolide D, withaferin A and withaniamides play an important role in its pharmacological properties. Proteins like Withania somnifera glycoprotein and withania lectin like-protein possess potent therapeutic properties like antimicrobial, anti-snake venom poison and antimicrobial. In this review, we have tried to present different pharmacological properties associated with different extract preparations, phytochemical constituents and protein component of Withania somnifera. Future insights in this direction have also been highlighted.

Rehmannia glutinosa: review of botany, chemistry and pharmacology.

PubMed

Zhang, Ru-Xue; Li, Mao-Xing; Jia, Zheng-Ping

2008-05-08

Rehmannia glutinosa, a widely used traditional Chinese herb, belongs to the family of Scrophulariaceae, and is taken to nourish Yin and invigorate the kidney in traditional Chinese medicine (TCM) and has a very high medicinal value. In recent decades, a great number of chemical and pharmacological studies have been done on Rehmannia glutinosa. More than 70 compounds including iridoids, saccharides, amino acid, inorganic ions, as well as other trace elements have been found in the herb. Studies show that Rehmannia glutinosa and its active principles possess wide pharmacological actions on the blood system, immune system, endocrine system, cardiovascular system and the nervous system. Currently, the effective monomeric compounds or active parts have been screened for the pharmacological activity of Rehmannia glutinosa and the highest quality scientific data is delivered to support the further application and exploitation for new drug development.

Comparative analysis of pharmacological treatments with N-acetyl-DL-leucine (Tanganil) and its two isomers (N-acetyl-L-leucine and N-acetyl-D-leucine) on vestibular compensation: Behavioral investigation in the cat.

PubMed

Tighilet, Brahim; Leonard, Jacques; Bernard-Demanze, Laurence; Lacour, Michel

2015-12-15

Head roll tilt, postural imbalance and spontaneous nystagmus are the main static vestibular deficits observed after an acute unilateral vestibular loss (UVL). In the UVL cat model, these deficits are fully compensated over 6 weeks as the result of central vestibular compensation. N-Acetyl-dl-leucine is a drug prescribed in clinical practice for the symptomatic treatment of acute UVL patients. The present study investigated the effects of N-acetyl-dl-leucine on the behavioral recovery after unilateral vestibular neurectomy (UVN) in the cat, and compared the effects of each of its two isomers N-acetyl-L-leucine and N-acetyl-D-leucine. Efficacy of these three drug treatments has been evaluated with respect to a placebo group (UVN+saline water) on the global sensorimotor activity (observation grids), the posture control (support surface measurement), the locomotor balance (maximum performance at the rotating beam test), and the spontaneous vestibular nystagmus (recorded in the light). Whatever the parameters tested, the behavioral recovery was strongly and significantly accelerated under pharmacological treatments with N-acetyl-dl-leucine and N-acetyl-L-leucine. In contrast, the N-acetyl-D-leucine isomer had no effect at all on the behavioral recovery, and animals of this group showed the same recovery profile as those receiving a placebo. It is concluded that the N-acetyl-L-leucine isomer is the active part of the racemate component since it induces a significant acceleration of the vestibular compensation process similar (and even better) to that observed under treatment with the racemate component only. Copyright © 2015 Elsevier B.V. All rights reserved.

Simultaneous quantitative determination of multiple bioactive markers in Ocimum sanctum obtained from different locations and its marketed herbal formulations using UPLC-ESI-MS/MS combined with principal component analysis.

PubMed

Pandey, Renu; Chandra, Preeti; Srivastava, Mukesh; Mishra, D K; Kumar, Brijesh

2015-01-01

Ocimum sanctum L., with phenolic acids, flavonoids, propenyl phenols and terpenoids as active pharmacological constituents, is a popular medicinal herb and is present as an ingredient in many herbal formulations. Therefore, development of a reliable analytical method for simultaneous determination of the pharmacologically active constituents of O. sanctum is of high importance. To develop and validate a new, rapid, sensitive and selective UPLC-ESI/MS/MS method for simultaneous determination of 23 bioactive markers including phenolic acids, flavonoids, propenyl phenol and terpenoid in the leaf extract and marketed herbal formulations of O. sanctum. An UPLC-ESI/MS/MS method using negative electrospray ionisation (ESI) in multiple-reaction-monitoring (MRM) mode was used for simultaneous determination. Chromatographic separation was achieved on an Acquity UPLC BEH C18 -column using a gradient elution with 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Principal component analysis (PCA) was applied to correlate and discriminate eight geographical collections of O. sanctum based on quantitative data of the analytes. The developed method was validated as per International Conference on Harmonization guidelines and found to be accurate, with overall recovery in the range 95.09-104.84% (RSD ≤ 1.85%), precise (RSD ≤ 1.98%) and linear (r(2)  ≥ 0.9971) over the concentration range of 0.5-1000 ng/mL. Ursolic acid was found to be the most abundant marker in all the samples investigated, except for the marketed tablet. The method established is simple, rapid and sensitive, hence it can be reliably utilised for the quality control of O. sanctum and derived herbal formulations. Copyright © 2015 John Wiley & Sons, Ltd.

Dietary Strategies and Novel Pharmaceutical Approaches Targeting Serum ApoA-I Metabolism: A Systematic Overview

PubMed Central

Smolders, Lotte; Plat, Jogchum

2017-01-01

The incidence of CHD is still increasing, which underscores the need for new preventive and therapeutic approaches to decrease CHD risk. In this respect, increasing apoA-I concentrations may be a promising approach, especially through increasing apoA-I synthesis. This review first provides insight into current knowledge on apoA-I production, clearance, and degradation, followed by a systematic review of dietary and novel pharmacological approaches to target apoA-I metabolism. For this, a systematic search was performed to identify randomized controlled intervention studies that examined effects of whole foods and (non)nutrients on apoA-I metabolism. In addition, novel pharmacological approaches were searched for, which were specifically developed to target apoA-I metabolism. We conclude that both dietary components and pharmacological approaches can be used to increase apoA-I concentrations or functionality. For the dietary components in particular, more knowledge about the underlying mechanisms is necessary, as increasing apoA-I per se does not necessarily translate into a reduced CHD risk. PMID:28695008

[Evaluation of autonomic nervous system function with heart rate variability analysis in patients with hyperthyroidism and during euthyroidism after pharmacologic and surgical treatment].

PubMed

Barczyński, M; Tabor, S; Thor, P

1997-01-01

The aim of the present study was both to estimate autonomic nervous system (ANS) function in patients with hyperthyroidism by the heart rate variability (HRV) analysis and to evaluate the impact of pharmacological and surgical treatment on the ANS function. Analysis of the HRV underwent 10 female patients in course of thyreotoxicosis and after reaching full clinical and biochemical euthyroidism, after pharmacological therapy and in month after surgical treatment. The 10 minutes records at rest, in horizontal position were evaluated. The HRV parameters like mean of the heart rate, mean of RR intervals, standard deviation of all normal RR intervals (SDNN), range of the heart rate variability, low frequency (LF), high frequency (HF) components of the heart rate power spectral density and LF/HF ratio were assessed. The results were compared to those obtained from 10 age-, sex-, and body mass index-matched control subjects. The statistical significance (p < 0.05) was found in reduction of range of RR intervals, in increase of LF/HF ratio and in decrease of SDNN in hyperthyroidism in comparison to the control group (151.6/346.8 ms; 2.4/0.74; 24.4/57.2 ms2). In course of pharmacological euthyroidism there were statistically significant (p < 0.05) increase of range of RR intervals, reduction of LF/HF ratio and increase of SDNN in comparison to hyperthyroidism (270/151.6 ms; 0.995/2.4; 39/24.4 ms2). In euthyroidism after surgical treatment all the above parameters kept the similar levels as in pharmacological euthyroidism (no statistical significance for p < 0.05). On the base of the outcomes it was considered that in hyperthyroid patients there is advantage of sympathetic part of ANS over parasympathetic one which is due to sharp reduction of parasympathetic system activity. Pharmacological therapy with thyreostatics normalises balance of ANS to the level of the control group and after surgical treatment the balance keeps the same. Moreover, in the estimation of ANS as important as LF/HF ratio is the mean range of RR intervals.

Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action †

PubMed Central

Mayer, Alejandro M. S.; Rodríguez, Abimael D.; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

2013-01-01

The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories. PMID:23880931

Determining the pharmacological activity of Physalis peruviana fruit juice on rabbit eyes and fibroblast primary cultures.

PubMed

Pardo, Juan Manuel; Fontanilla, Marta Raquel; Ospina, Luis Fernando; Espinosa, Lady

2008-07-01

The pharmacologic activity of compounds isolated from Physalis peruviana has been demonstrated. The use of this fruit juice for treating pterygium has been reported in Colombian traditional medicine. However, studies demonstrating the fruit juice's pharmacologic activity when used in this disease have not been published to date. In the present study the anti-inflammatory and cytostatic activities of P. peruviana fruit juice in a rabbit eye inflammatory model were investigated. A novel rabbit eye inflammation model was developed for studying the juice's anti-inflammatory activity (based on an adaptation of the Draize test). Cytostatic activity was evaluated by measuring and comparing growth rates of cultured fibroblasts exposed and not exposed to various fruit juice concentrations. P. peruviana fruit juice exhibited a mild anti-inflammatory activity compared with methylprednisolone, a known anti-inflammatory drug. An interesting dose-dependent cytostatic effect on cultured fibroblasts was also established. The data found suggest that the P. peruviana fruit juice anti-pterygium effect described in traditional medicine may be related to its inhibiting fibroblast growth. The present study contributes to the pharmacologic knowledge regarding a remedy commonly used in Colombian traditional medicine.

Stem cell derived phenotypic human neuromuscular junction model for dose response evaluation of therapeutics.

PubMed

Santhanam, Navaneetha; Kumanchik, Lee; Guo, Xiufang; Sommerhage, Frank; Cai, Yunqing; Jackson, Max; Martin, Candace; Saad, George; McAleer, Christopher W; Wang, Ying; Lavado, Andrea; Long, Christopher J; Hickman, James J

2018-06-01

There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units. A system was developed in which human myotubes and motoneurons derived from stem cells were cultured in a serum-free medium in a BioMEMS construct. The system is composed of two chambers linked by microtunnels to enable axonal outgrowth to the muscle chamber that allows separate stimulation of each component and physiological NMJ function and MN stimulated tetanus. The muscle's contractions, induced by motoneuron activation or direct electrical stimulation, were monitored by image subtraction video recording for both frequency and amplitude. Bungarotoxin, BOTOX ® and curare dose response curves were generated to demonstrate pharmacological relevance of the phenotypic screening device. This quantifiable functional hNMJ system establishes a platform for generating patient-specific NMJ models by including patient-derived iPSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pharmacological inhibition of fatty-acid oxidation synergistically enhances the effect of l-asparaginase in childhood ALL cells.

PubMed

Hermanova, I; Arruabarrena-Aristorena, A; Valis, K; Nuskova, H; Alberich-Jorda, M; Fiser, K; Fernandez-Ruiz, S; Kavan, D; Pecinova, A; Niso-Santano, M; Zaliova, M; Novak, P; Houstek, J; Mracek, T; Kroemer, G; Carracedo, A; Trka, J; Starkova, J

2016-01-01

l-asparaginase (ASNase), a key component in the treatment of childhood acute lymphoblastic leukemia (ALL), hydrolyzes plasma asparagine and glutamine and thereby disturbs metabolic homeostasis of leukemic cells. The efficacy of such therapeutic strategy will depend on the capacity of cancer cells to adapt to the metabolic challenge, which could relate to the activation of compensatory metabolic routes. Therefore, we studied the impact of ASNase on the main metabolic pathways in leukemic cells. Treating leukemic cells with ASNase increased fatty-acid oxidation (FAO) and cell respiration and inhibited glycolysis. FAO, together with the decrease in protein translation and pyrimidine synthesis, was positively regulated through inhibition of the RagB-mTORC1 pathway, whereas the effect on glycolysis was RagB-mTORC1 independent. As FAO has been suggested to have a pro-survival function in leukemic cells, we tested its contribution to cell survival following ASNase treatment. Pharmacological inhibition of FAO significantly increased the sensitivity of ALL cells to ASNase. Moreover, constitutive activation of the mammalian target of rapamycin pathway increased apoptosis in leukemic cells treated with ASNase, but did not increase FAO. Our study uncovers a novel therapeutic option based on the combination of ASNase and FAO inhibitors.

A Web-based e-learning course: integration of pathophysiology into pharmacology.

PubMed

Tse, Mimi M Y; Lo, Lisa W L

2008-11-01

The Internet is becoming the preferred place to find information. Millions of people go online in search of health and medical information. Likewise, the demand for Web-based courses is growing. This paper presents the development, utilization, and evaluation of a Web-based e-learning course for nursing students, entitled Integration of Pathophysiology into Pharmacology. The pathophysiology component included cardiovascular, respiratory, central nervous and immune system diseases, while the pharmacology component was developed based on 150 commonly used drugs. One hundred and nineteen Year 1 nursing students took part in the course. The Web-based e-learning course materials were uploaded to a WebCT for students' self-directed learning and attempts to pass two scheduled online quizzes. At the end of the semester, students were given a questionnaire to measure the e-learning experience. Their experience in the e-learning course was a positive one. Students stated that they were able to understand rather than memorize the subject content, and develop their problem solving and critical thinking abilities. Online quizzes yielded satisfactory results. In the focus group interview, students indicated that they appreciated the time flexibility and convenience associated with Web-based learning, and also made good suggestions for enhancing Web-based learning. The Web-based approach is promising for teaching and learning pathophysiology and pharmacology for nurses and other healthcare professionals.

The Pharmacological Potential of Mushrooms

PubMed Central

2005-01-01

This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial, antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory, antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature. The production of mushrooms or mushroom compounds is discussed briefly. PMID:16136207

Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway

PubMed Central

Mao, Mao; Sudhahar, Varadarajan; Ansenberger-Fricano, Kristine; Fernandes, Denise C.; Tanaka, Leonardo Y.; Fukai, Tohru; Laurindo, Francisco R.M.; Mason, Ronald P.; Vasquez-Vivar, Jeannette; Minshall, Richard D.; Stadler, Krisztian; Bonini, Marcelo G.

2012-01-01

Nitroglycerin (GTN) has been clinically used to treat angina pectoris and acute heart episodes for over 100 years. The effects of GTN have long been recognized and active research has contributed to the unraveling of numerous metabolic routes capable of converting GTN to the potent vasoactive messenger nitric oxide. Recently, the mechanism by which minute doses of GTN elicit robust pharmacological responses was revisited and eNOS activation was implicated as an important route mediating vasodilation induced by low GTN doses (1–50 nM). Here, we demonstrate that at such concentrations the pharmacologic effects of nitroglycerin are largely dependent on the phosphatidylinositol 3-kinase, Akt/PKB, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signal transduction axis. Furthermore, we demonstrate that nitroglycerin-dependent accumulation of 3,4,5-InsP3, probably because of inhibition of PTEN, is important for eNOS activation, conferring a mechanistic basis for GTN pharmacological action at pharmacologically relevant doses. PMID:22037515

A new cross-correlation algorithm for the analysis of "in vitro" neuronal network activity aimed at pharmacological studies.

PubMed

Biffi, E; Menegon, A; Regalia, G; Maida, S; Ferrigno, G; Pedrocchi, A

2011-08-15

Modern drug discovery for Central Nervous System pathologies has recently focused its attention to in vitro neuronal networks as models for the study of neuronal activities. Micro Electrode Arrays (MEAs), a widely recognized tool for pharmacological investigations, enable the simultaneous study of the spiking activity of discrete regions of a neuronal culture, providing an insight into the dynamics of networks. Taking advantage of MEAs features and making the most of the cross-correlation analysis to assess internal parameters of a neuronal system, we provide an efficient method for the evaluation of comprehensive neuronal network activity. We developed an intra network burst correlation algorithm, we evaluated its sensitivity and we explored its potential use in pharmacological studies. Our results demonstrate the high sensitivity of this algorithm and the efficacy of this methodology in pharmacological dose-response studies, with the advantage of analyzing the effect of drugs on the comprehensive correlative properties of integrated neuronal networks. Copyright © 2011 Elsevier B.V. All rights reserved.

The endocannabinoid system as a target for the treatment of cannabis dependence.

PubMed

Clapper, Jason R; Mangieri, Regina A; Piomelli, Daniele

2009-01-01

The endocannabinoid system modulates neurotransmission at inhibitory and excitatory synapses in brain regions relevant to the regulation of pain, emotion, motivation, and cognition. This signaling system is engaged by the active component of cannabis, Delta9-tetrahydrocannabinol (Delta9-THC), which exerts its pharmacological effects by activation of G protein-coupled type-1 (CB1) and type-2 (CB2) cannabinoid receptors. During frequent cannabis use a series of poorly understood neuroplastic changes occur, which lead to the development of dependence. Abstinence in cannabinoid-dependent individuals elicits withdrawal symptoms that promote relapse into drug use, suggesting that pharmacological strategies aimed at alleviating cannabis withdrawal might prevent relapse and reduce dependence. Cannabinoid replacement therapy and CB1 receptor antagonism are two potential treatments for cannabis dependence that are currently under investigation. However, abuse liability and adverse side-effects may limit the scope of each of these approaches. A potential alternative stems from the recognition that (i) frequent cannabis use may cause an adaptive down-regulation of brain endocannabinoid signaling, and (ii) that genetic traits that favor hyperactivity of the endocannabinoid system in humans may decrease susceptibility to cannabis dependence. These findings suggest in turn that pharmacological agents that elevate brain levels of the endocannabinoid neurotransmitters, anandamide and 2-arachidonoylglycerol (2-AG), might alleviate cannabis withdrawal and dependence. One such agent, the fatty-acid amide hydrolase (FAAH) inhibitor URB597, selectively increases anandamide levels in the brain of rodents and primates. Preclinical studies show that URB597 produces analgesic, anxiolytic-like and antidepressant-like effects in rodents, which are not accompanied by overt signs of abuse liability. In this article, we review evidence suggesting that (i) cannabis influences brain endocannabinoid signaling and (ii) FAAH inhibitors such as URB597 might offer a possible therapeutic avenue for the treatment of cannabis withdrawal.

A role for synaptic and network plasticity in controlling epileptiform activity in CA1 in the kainic acid-lesioned rat hippocampus in vitro.

PubMed Central

Bernard, C; Wheal, H V

1996-01-01

1. Stimulation of the surviving afferents in the stratum radiatum of the CA1 area in kainic acid-lesioned hippocampal slices produced graded epileptiform activity, part of which (> 20%) involved the activation of N-methyl-D-aspartate (NMDA) receptors. There was also a failure of synaptic inhibition in this region. In this preparation, we have tested the effects of low-frequency stimulation (LFS; 1 Hz for 15 min) on synaptic responses and epileptiform activity. 2. LFS resulted in long-term depression (LTD) of excitatory synaptic potentials (EPSPs), long-term decrease of population spike amplitudes (PSAs) and EPSP-spike (E-S) potentiation. Evoked epileptiform activity was reduced but neurons had a higher probability of discharge. LTD could be reversed by subsequent tetanic stimulation whereas E-S dissociation remained unchanged. Synaptic and network responses could be saturated towards either potentiation or depression. However, E-S potentiation was maximal following the first conditioning stimulus. 3. NMDA receptor-mediated responses were pharmacologically isolated. LFS resulted in LTD of synaptic responses, long-term decrease of PSAs and E-S depression. These depressions could not be reversed by subsequent tetanic stimulation. alpha-Amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and NMDA receptor-mediated responses were then measured in isolation before and following conditioning stimuli. LFS was shown to simultaneously produce LTD of AMPA and NMDA receptor-mediated responses. E-S potentiation of the AMPA component and E-S depression of the NMDA component occurred coincidentally. 4. LTD of AMPA and NMDA receptor-mediated responses were shown to be NMDA dependent. In contrast, E-S potentiation and depression occurred even when NMDA receptors were pharmacologically blocked. 5. These findings indicate that synaptic responses could be modified bidirectionally in the CA1 area of kainic acid-lesioned rat hippocampus in an NMDA receptor-dependent manner. However, E-S dissociations were independent of the activation of NMDA receptors, hinting at mechanisms different from those of synaptic LTD. We suggest that changes in E-S coupling were caused by a modification of the firing threshold of the CA1 pyramidal neurons. Furthermore, the firing mechanisms controlling NMDA and AMPA receptor-mediated network activity appeared to be different. The possible use of LFS applied to the hippocampus as a clinical intervention to suppress epileptiform activity is discussed. PMID:8866357

Interprofessional pharmacy observation activity for third-year dental students.

PubMed

Conway, Susan E; Smith, Winter J; Truong, Teresa H; Shadid, Jill

2014-09-01

Interprofessional learning is a key component of today's health sciences education. Within a two-course series in dental pharmacology and therapeutics, a dental curriculum was revised to provide an interprofessional activity to expose dental students to a community pharmacy setting. The objectives of this activity were to augment students' learning about drug laws and prescription writing, as well as to foster interprofessional relationships and collaboration between pharmacists and dentists. Dental students were scheduled for one-hour observations at community pharmacies on campus. Learning objectives to guide this activity focused on demonstrating community pharmacy operating procedures, identifying ways to minimize prescribing and dosing errors, and understanding how pharmacists can assist dentists in prescribing. Following the observation, students were required to submit a written assignment, which accounted for 14 percent of their course grade. All 119 dental students (100 percent) enrolled in the course for the summers of 2012 and 2013 completed the activity. The average grade on the written assignment was 96.2 out of 100. At the end of the course, students were asked to participate in an online course evaluation survey, for which response rates were 37 percent and 43 percent for 2012 and 2013, respectively. The students rated the pharmacy observation activity favorably on this course evaluation. The pharmacy observation activity provided a successful interprofessional component to the didactic pharmacy course and was well received by the dental students as well as the community pharmacists.

Overview of non-pharmacological intervention for dementia and principles of brain-activating rehabilitation.

PubMed

Yamaguchi, Haruyasu; Maki, Yohko; Yamagami, Tetsuya

2010-12-01

Non-pharmacological interventions for dementia are likely to have an important role in delaying disease progression and functional decline. Research into non-pharmacological interventions has focused on the differentiation of each approach and a comparison of their effects. However, Cochrane Reviews on non-pharmacological interventions have noted the paucity of evidence regarding the effects of these interventions. The essence of non-pharmacological intervention is dependent of the patients, families, and therapists involved, with each situation inevitably being different. To obtain good results with non-pharmacological therapy, the core is not 'what' approach is taken but 'how' the therapists communicate with their patients. Here, we propose a new type of rehabilitation for dementia, namely brain-activating rehabilitation, that consists of five principles: (i) enjoyable and comfortable activities in an accepting atmosphere; (ii) activities associated with empathetic two-way communication between the therapist and patient, as well as between patients; (iii) therapists should praise patients to enhance motivation; (iv) therapists should try to offer each patient some social role that takes advantage of his/her remaining abilities; and (v) the activities should be based on errorless learning to ensure a pleasant atmosphere and to maintain a patient's dignity. The behavioral and cognitive status is not necessarily a reflection of pathological lesions in the brain; there is cognitive reserve for improvement. The aim of brain-activating rehabilitation is to enhance patients' motivation and maximize the use of their remaining function, recruiting a compensatory network, and preventing the disuse of brain function. The primary expected effect is that patients recover a desire for life, as well as their self-respect. Enhanced motivation can lead to improvements in cognitive function. Amelioration of the behavioral and psychological symptoms of dementia and improvements in activities of daily living can also be expected due to the renewed positive attitude towards life. In addition, improvements in the quality of life for both patients and caregivers is an expected outcome. To establish evidence for non-pharmacological interventions, research protocols and outcome measures should be standardized to facilitate comparison among studies, as well as meta-analysis. © 2010 The Authors. Journal compilation © 2010 Japanese Psychogeriatric Society.

Osthole: A Review on Its Bioactivities, Pharmacological Properties, and Potential as Alternative Medicine

PubMed Central

Zhang, Zhong-Rong; Leung, Wing Nang; Cheung, Ho Yee; Chan, Chun Wai

2015-01-01

This paper reviews the latest understanding of biological and pharmacological properties of osthole (7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one), a natural product found in several medicinal plants such as Cnidium monnieri and Angelica pubescens. In vitro and in vivo experimental results have revealed that osthole demonstrates multiple pharmacological actions including neuroprotective, osteogenic, immunomodulatory, anticancer, hepatoprotective, cardiovascular protective, and antimicrobial activities. In addition, pharmacokinetic studies showed osthole uptake and utilization are fast and efficient in body. Moreover, the mechanisms of multiple pharmacological activities of osthole are very likely related to the modulatory effect on cyclic adenosine monophosphate (cAMP) and cyclic adenosine monophosphate (cGMP) level, though some mechanisms remain unclear. This review aims to summarize the pharmacological properties of osthole and give an overview of the underlying mechanisms, which showcase its potential as a multitarget alternative medicine. PMID:26246843

A review on indole alkaloids isolated from Uncaria rhynchophylla and their pharmacological studies.

PubMed

Ndagijimana, Andre; Wang, Xiaoming; Pan, Guixiang; Zhang, Fan; Feng, Hong; Olaleye, Olajide

2013-04-01

Uncaria rhynchophylla (Miq.) Jacks, Rubiaceae, is one of the original plants of the important Chinese crude drug, Gou-teng, mainly used for the treatment of convulsion, hypertension, epilepsy, eclampsia, and cerebral diseases. The pharmacological activities of this plant are related to the presence of active compounds predominantly indole alkaloids. In this article, we have reviewed some reports about the pharmacological activities of the main indole alkaloids isolated from U. rhynchophylla. This review paper will contribute to the studies on the chemistry, safety and quality control of medicinal preparations containing Uncaria species. Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical constituents and bioactivities of the plants of genus Flemingia Roxb. et Ait. (Leguminosae).

PubMed

Li, Hua; Zhai, Fengyan; Liu, Zhongdong

2012-09-01

The genus Flemingia Roxb. et Ait. (Leguminosae) has been used for disease prevention and therapy in China since ancient times. So the material basis of the pharmacological activity in the genus Flemingia should be clear for how to use this kind of traditional Chinese medicines more reasonably in pharmacology. Therefore, this review gives an account of the current knowledge on the chemical constituents, biological activities and pharmacological properties of the plants of the genus. Several different classes of compounds were previously isolated, which the main groups are flavones, particularly prenylated flavones, and triterpenes accompanied with sterols, anthraquinones, and others. The names and structures of the chemical constituents are given in this review. In addition, the pharmacological effects of the extracts and individual compounds (mainly for flavones) derived from the genus plants have been found, including neuroprotection, anti-inflammation, anti-oxidation, cytotoxicity, hormone-like effects, antimicrobial activities, and so on.

Memory Enhancing Effect of Black Pepper in the AlCl3 Induced Neurotoxicity Mouse Model is Mediated Through Its Active Component Chavicine.

PubMed

Iqbal, Ghazala; Iqbal, Anila; Mahboob, Aamra; Farhat, Syeda M; Ahmed, Touqeer

Black pepper (Piper nigrum Linn.) has vital pharmacological properties with profound effects on central nervous system. Neurotoxic agents like Aluminum Chloride (AlCl3) cause the oxidative stress and result in improper processing of amyloid proteins leading to accumulation of amyloid β plaques. The study aimed to explore the neuroprotective potential of black pepper (BP) extract (12.5mg/kg/day) on memory enhancement and its effect on expression of amyloid precursor protein (APP) isoforms (APP770 and APP695) in AlCl3 induced neurotoxicity (250mg/kg) mouse model. The study included the isolation and identification of pure compound from BP (chavicine) which was found pharmacologically active. Morris water maze test, elevated plus maze, fear conditioning, context and cue dependent test and social preference tests were performed to investigate the learning and memory. Gene expression (APP isoforms) and in-vitro and ex-vivo DPPH free radical scavenging activity were performed to evaluate the role of BP. BP significantly improved memory in AlCl3 induced neurotoxicity mouse model along with effectively decreasing the expression of APP770 (amyloidogenic) isoform and improved level of APP695 (non-amyloidogenic) in hippocampus, amygdala and cortex. Fear extinction learning was considerably improved in BP treated group (7.83±2.03) than AlCl3 induced neurotoxicity group (39.75±4.25). In the hippocampus, BP significantly reduced the expression of APP770 (0.37±0.05) as compared to AlCl3 induced neurotoxicity group (0.72±0.06), and effectively increased (34.80±1.39) the percentage inhibition of DPPH free radicals as compared to AlCl3 induced neurotoxicity group (14±2.68). The study revealed that BP improves memory and chavicine is a lead compound producing pharmacological effects of BP.

Effectiveness of modified seminars as a teaching-learning method in pharmacology

PubMed Central

Palappallil, Dhanya Sasidharan; Sushama, Jitha; Ramnath, Sai Nathan

2016-01-01

Context: Student-led seminars (SLS) are adopted as a teaching-learning (T-L) method in pharmacology. Previous studies assessing the feedback on T-L methods in pharmacology points out that the traditional seminars consistently received poor feedbacks as they were not favorite among the students. Aims: This study aimed to obtain feedback on traditional SLS, introduce modified SLS and compare the modified seminars with the traditional ones. Settings and Design: This was a prospective interventional study done for 2 months in medical undergraduates of fifth semester attending Pharmacology seminars at a Government Medical College in South India. Subjects and Methods: Structured questionnaire was used to elicit feedback from participants. The responses were coded on 5-point Likert scale. Modifications in seminar sessions such as role plays, quiz, tests, group discussion, and patient-oriented problem-solving exercises were introduced along with SLS. Statistical Analysis Used: The data were analyzed using SPSS version 16. The descriptive data were expressed using frequencies and percentages. Wilcoxon signed rank test, and Friedman tests were used to compare traditional with modified seminars. Results: The participants identified interaction as the most important component of a seminar. Majority opined that the teacher should summarize at the end of SLS. Student feedback shows that modified seminars created more interest, enthusiasm, and inspiration to learn the topic when compared to traditional SLS. They also increased peer coordination and group dynamics. Students opined that communication skills and teacher-student interactions were not improved with modified seminars. Conclusions: Interventions in the form of modified SLS may be adopted to break the monotony of traditional seminars through active participation, peer interaction, and teamwork. PMID:27563587

Development of a rat model of sexual performance anxiety: effect of behavioural and pharmacological hyperadrenergic stimulation on APO-induced erections.

PubMed

Brien, S E; Smallegange, C; Gofton, W T; Heaton, J P W; Adams, M A

2002-04-01

As part of the multifactorial nature of erectile dysfunction, anxiety associated with sexual performance (SPA) remains a major contributing factor to its progression. In fact, the heightened sympathetic activity associated with sexual performance anxiety may be a key early component of this disruption of normal erectile responses. We are not aware that any animal models have been developed to assess this phenomenon. Using apomorphine (APO, 80 microg/kg s.c.)-induced erections in rats we characterised the effects of behavioural or pharmacological hyperadrenergic stimulation (that is, anxiety) on erections and hemodynamics. We developed an experimental SPA paradigm by exposing male rats to the stress of being observed by a larger, older male rat placed in close proximity to test rats during APO testing. In a separate group, adrenergic stress was simulated using a sympathomimetic, methoxamine (MXA) given prior to APO testing. In a third group, the changes in circulatory parameters (mean arterial pressure, heart rate) were determined following instrumentation with radiotelemetric transducers for each scenario. APO-induced erections were significantly lower in both the behavioural (1.25+/-0.8) and pharmacological (0.33+/-0.5) stressor paradigms compared to controls (2.81+/-0.9). Further, erections in MXA-treated rats were significantly lower than in the observed scenario. Despite the differences in erections hemodynamic assessments showed no differences in MAP or HR changes between the different experimental conditions. Thus, both the behavioural and pharmacological paradigms of SPA decreased erections, but did not affect the circulation. This suggests that the level of hyperadrenergic input required to induce erectile dysfunction can be subtle, and target only erectogenic pathways.

Committee Opinion No. 702 Summary: Female Athlete Triad.

PubMed

2017-06-01

The female athlete triad is a medical condition observed in physically active females involving three components: 1) low energy availability with or without disordered eating, 2) menstrual dysfunction, and 3) low bone density. An individual does not need to show clinical manifestations of all three components of the female athlete triad simultaneously to be affected by the condition. Consequences of these clinical conditions may not be completely reversible, so prevention, early diagnosis, and intervention are critical. All athletes are at risk of the female athlete triad, regardless of body build or sport. All active females should be assessed for components of the triad and further evaluation should be performed if one or more components are identified. The obstetrician-gynecologist has the opportunity to screen athletes for components of the female athlete triad at comprehensive visits for preventive care. Using the menstrual cycle as a vital sign is a useful tool for identifying athletes at risk of female athlete triad and should be an integral part of the preparticipatory sports physical. The goal of treatment for those diagnosed with female athlete triad is restoration of regular menses as a clinical marker of reestablishment of energy balance and enhancement of bone mineral density. The female athlete triad is a result of energy imbalance; thus, adjusting the energy expenditure and energy availability is the main intervention. Pharmacologic treat-ment may be considered when nonpharmacologic treatment has failed. A team approach involving the patient, obstetrician-gynecologist, sports nutritionist, coaches, parents, and mental health care provider, if indicated, is optimal.

Committee Opinion No.702: Female Athlete Triad.

PubMed

2017-06-01

The female athlete triad is a medical condition observed in physically active females involving three components: 1) low energy availability with or without disordered eating, 2) menstrual dysfunction, and 3) low bone density. An individual does not need to show clinical manifestations of all three components of the female athlete triad simultaneously to be affected by the condition. Consequences of these clinical conditions may not be completely reversible, so prevention, early diagnosis, and intervention are critical. All athletes are at risk of the female athlete triad, regardless of body build or sport. All active females should be assessed for components of the triad and further evaluation should be performed if one or more components are identified. The obstetrician-gynecologist has the opportunity to screen athletes for components of the female athlete triad at comprehensive visits for preventive care. Using the menstrual cycle as a vital sign is a useful tool for identifying athletes at risk of female athlete triad and should be an integral part of the preparticipatory sports physical. The goal of treatment for those diagnosed with female athlete triad is restoration of regular menses as a clinical marker of reestablishment of energy balance and enhancement of bone mineral density. The female athlete triad is a result of energy imbalance; thus, adjusting the energy expenditure and energy availability is the main intervention. Pharmacologic treat-ment may be considered when nonpharmacologic treatment has failed. A team approach involving the patient, obstetrician-gynecologist, sports nutritionist, coaches, parents, and mental health care provider, if indicated, is optimal.

Activated release of membrane-anchored TGF-alpha in the absence of cytosol

PubMed Central

1993-01-01

The ectodomain of proTGF-alpha, a membrane-anchored growth factor, is converted into soluble TGF-alpha by a regulated cellular proteolytic system that recognizes proTGF-alpha via the C-terminal valine of its cytoplasmic tail. In order to define the biochemical components involved in proTGF-alpha cleavage, we have used cells permeabilized with streptolysin O (SLO) that have been extensively washed to remove cytosol. PMA, acting through a Ca(2+)-independent protein kinase C, activates cleavage as efficiently in permeabilized cells as it does in intact cells. ProTGF-alpha cleavage is also stimulated by GTP gamma S through a mechanism whose pharmacological properties suggest the involvement of a heterotrimeric G protein acting upstream of the PMA- sensitive Ca(2+)-independent protein kinase C. Activated proTGF-alpha cleavage is dependent on ATP hydrolysis, appears not to require vesicular traffic, and acts specifically on proTGF-alpha that has reached the cell surface. These results indicate that proTGF-alpha is cleaved from the cell surface by a regulated system whose signaling, recognition, and proteolytic components are retained in cells devoid of cytosol. PMID:8314849

[Hypoxia and memory. Specific features of nootropic agents effects and their use].

PubMed

Voronina, T A

2000-01-01

Hypoxia and hypoxic adaptation are powerful factors of controlling memory and behavior processes. Acute hypoxia exerts a differential impact on different deficits of mnestic and cognitive functions. Instrumental reflexes of active and passive avoidance, negative learning, behavior with a change in the stereotype of learning are more greatly damaged. Memory with spatial and visual differentiation and their rearrangement change to a lesser extent and conditional reflexes are not deranged. In this contract, altitude hypoxic adaptation enhances information fixation and increases the degree and duration of retention of temporary relations. Nootropic agents with an antihypoxic action exert a marked effect on hypoxia-induced cognitive and memory disorders and the magnitude of this effect depends on the ration of proper nootropic to antihypoxic components in the spectrum of the drugs' pharmacological activity. The agents that combine a prevailing antiamnestic effect and a marked and moderate antihypoxic action (mexidole, nooglutil, pyracetam, beglymin, etc.) are most effective in eliminating different hypoxia-induced cognitive and memory disorders, nootropic drugs that have a pronounced antiamnestic activity (centrophenoxine, etc.) and no antihypoxic component also restore the main types of mnestic disorders after hypoxia, but to a lesser extent.

Studies on antioxidant activity, volatile compound and fatty acid composition of different parts of Glycyrrhiza echinata L.

PubMed Central

Çakmak, Yavuz Selim; Aktumsek, Abdurrahman; Duran, Ahmet

2012-01-01

The essential oil compound, fatty acid composition and the in vitro antioxidant activity of the root and aerial of Glycyrrhiza echinata L., a medicinal plant growing in Turkey, have been studied. The antioxidant capacity tests were designed to evaluate the antioxidant activities of methanol extracts. Total phenolic and flavonoid concentrations of each extract were also determined by using both Folin-Ciocalteu reagent and aluminum chloride. The aerial part was found to possess the highest total phenolic content (146.30 ± 4.58 mg GAE/g) and total antioxidant capacity (175.33 ± 3.98 mg AE/g). The essential oil from root and aerial parts was analyzed by gas chromatography mass spectroscopy (GC-MS) systems. The major components identified were n-hexadecanoic acid, hexahydro farnesyl acetone, α-caryophyllen, hexanal and phytol. In fatty acid profiles of plant, palmitic, stearic, oleic and linoleic acid were detected as the main components. The results of this study have shown that the extracts G. echinata are suitable as a natural antioxidant and food supplement source for pharmacological and food industries due to their beneficial chemical composition and antioxidant capacity. PMID:27418901

Rosa damascena as holy ancient herb with novel applications

PubMed Central

Mahboubi, Mohaddese

2015-01-01

Rosa damascena as an ornamental plant is commonly known as “Gole Mohammadi” in Iran. Iranian people have been called this plant, the flower of Prophet “Mohammad”. R. damascena is traditionally used for treatment of abdominal and chest pains, strengthening the heart, menstrual bleeding, digestive problems and constipation. This paper reviews the ethnopharmacology, phytochemistry and pharmaceutical investigations on R. damascena. All relevant databases and local books on ethnopharmacology of R. damascena were probed without limitation up to 31st March 2015 and the results of these studies were collected and reviewed. R. damascena has an important position in Iranian traditional medicine. It is economically a valuable plant with therapeutic applications in modern medicine. The antimicrobial, antioxidant, analgesic, anti-inflammatory, anti-diabetic and anti-depressant properties of R. damascena have been confirmed. Citronellol and geraniol as the main components of R. damascena essential oil are responsible for pharmacological activities. Overall, R. damascena as holy ancient plant with modern pharmacological investigations should be more investigated as traditional uses in large preclinical and clinical studies. PMID:26870673

Molecular Analysis of Chinese Celastrus and Tripterygium and Implications in Medicinal and Pharmacological Studies

PubMed Central

Zhao, Liang-Cheng; Zhang, Zhi-Xiang

2017-01-01

Celastrus and Tripterygium species, which are used in traditional Chinese medicine, have attracted much attention due to their anti-tumor promoting and neuroprotective activities, in addition to their applications in autoimmune disorders. However, systematic relationships between them and among species are unclear, and it may disturb their further medicinal utilization. In the present study, the molecular analysis of combined chloroplast and nuclear markers of all Chinese Celastrus and Tripterygium was performed, and clear inter- and intra-genus relationships were presented. The result suggests that Tripterygium constitute a natural monophyletic clade within Celastrus with strong support value. Fruit and seed type are better than inflorescence in subgeneric classification. Chinese Celastrus are classified for three sections: Sect. Sempervirentes (Maxim.) CY Cheng & TC Kao, Sect. Lunatus XY Mu & ZX Zhang, sect. nov., and Sect. Ellipticus XY Mu & ZX Zhang, sect. nov. The phylogenetic data was consistent with their chemical components reported previously. Owing to the close relationship, several evergreen Celastrus species are recommended for chemical and pharmacological studies. Our results also provide reference for molecular identification of Chinese Celastrus and Tripterygium. PMID:28081198

Pharmacological modulation in mesial temporal lobe epilepsy: Current status and future perspectives.

PubMed

Gambardella, Antonio; Labate, Angelo; Cifelli, Pierangelo; Ruffolo, Gabriele; Mumoli, Laura; Aronica, Eleonora; Palma, Eleonora

2016-11-01

Mesial temporal lobe epilepsy (MTLE) is frequently associated with hippocampal sclerosis (Hs), possibly caused by a primary brain injury that occurs a long time before the appearance of neurological symptoms. MTLE-Hs is, however, a heterogeneous condition that evolves with time, involving both environmental and genetic components. Recent experimental studies emphasize that drugs or drug combinations that target modulation and circuitry reorganization of the epileptogenic networks favorably modify the complex molecular and cellular alterations underlying MTLE. In particular, the link between neuroinflammation, GABA A R and epilepsy has been extensively studied mainly because of the relevant therapeutic implications that the pharmacological modulation of these phenomena would have in the clinical practice. In this review, we briefly summarize the studies that could pave the road to develop new disease-modifying therapeutic strategies for pharmacoresistant MTLE patients. Both clinical observations in human MTLE and experimental findings will be discussed, highlighting the potential modulatory crosstalk between the deregulation of the inhibitory (GABAergic) transmission and the sustained activation of the innate immune response. Copyright © 2016 Elsevier Ltd. All rights reserved.

Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies.

PubMed

Szopa, Agnieszka; Ekiert, Radosław; Ekiert, Halina

2017-01-01

Schisandra chinensis Turcz. (Baill.) is a plant species whose fruits have been well known in Far Eastern medicine for a long time. However, schisandra seems to be a plant still underestimated in contemporary therapy still in the countries of East Asia. The article presents latest available information on the chemical composition of this plant species. Special attention is given to dibenzo cyclooctadiene lignans. In addition, recent studies of the biological activity of dibenzocyclooctadiene lignans and schisandra fruit extracts are recapitulated. The paper gives a short resume of their beneficial effects in biological systems in vitro, in animals, and in humans, thus underlining their medicinal potential. The cosmetic properties are depicted, too. The analytical methods used for assaying schisandra lignans in the scientific studies and also in industry are also presented. Moreover, special attention is given to the information on the latest biotechnological studies of this plant species. The intention of this review is to contribute to a better understanding of the huge potential of the pharmacological relevance of S. chinensis.

Toxic fungi.

PubMed

Lampe, K F

1979-01-01

Much progress in the areas of identification of active components and elucidation of the toxic mechanisms for the principal poisonous mushrooms has been made in the past decade. This affords a more rational approach to therapeutic management which has consequently resulted in a decrease in the morbidity and mortality associated with these species. However, the effectiveness of a large number of adjuvants for Amanita phalloides poisoning still needs critical laboratory evaluation. The current status of knowledge concerning the toxic potential and contituents of many mushroom species, including the gastroenteric irritants, is inadequate. The problem of geographic variation or genetic strain in the concentration of toxins of many species also requires further investigation. The recent awareness and interest in the pharmacology and toxicology of uncultivated mushrooms in North America and Great Britain should encourage continued active research.

Protein-Based Therapeutic Killing for Cancer Therapies.

PubMed

Serna, Naroa; Sánchez-García, Laura; Unzueta, Ugutz; Díaz, Raquel; Vázquez, Esther; Mangues, Ramón; Villaverde, Antonio

2018-03-01

The treatment of some high-incidence human diseases is based on therapeutic cell killing. In cancer this is mainly achieved by chemical drugs that are systemically administered to reach effective toxic doses. As an innovative alternative, cytotoxic proteins identified in nature can be adapted as precise therapeutic agents. For example, individual toxins and venom components, proapoptotic factors, and antimicrobial peptides from bacteria, animals, plants, and humans have been engineered as highly potent drugs. In addition to the intrinsic cytotoxic activities of these constructs, their biological fabrication by DNA recombination allows the recruitment, in single pharmacological entities, of diverse functions of clinical interest such as specific cell-surface receptor binding, self-activation, and self-assembling as nanoparticulate materials, with wide applicability in cell-targeted oncotherapy and theragnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Advance in flavonoids biosynthetic pathway and synthetic biology].

PubMed

Zou, Li-Qiu; Wang, Cai-Xia; Kuang, Xue-Jun; Li, Ying; Sun, Chao

2016-11-01

Flavonoids are the valuable components in medicinal plants, which possess a variety of pharmacological activities, including anti-tumor, antioxidant and anti-inflammatory activities. There is an unambiguous understanding about flavonoids biosynthetic pathway, that is,2S-flavanones including naringenin and pinocembrin are the skeleton of other flavonoids and they can transform to other flavonoids through branched metabolic pathway. Elucidation of the flavonoids biosynthetic pathway lays a solid foundation for their synthetic biology. A few flavonoids have been produced in Escherichia coli or yeast with synthetic biological technologies, such as naringenin, pinocembrin and fisetin. Synthetic biology will provide a new way to get valuable flavonoids and promote the research and development of flavonoid drugs and health products, making flavonoids play more important roles in human diet and health. Copyright© by the Chinese Pharmaceutical Association.

Traditional Chinese medicines and Alzheimer's disease.

PubMed

Wu, Tzong-Yuan; Chen, Chih-Ping; Chen, Chip-Ping; Jinn, Tzyy-Rong

2011-06-01

Traditional Chinese medicines have been widely investigated for the treatment of Alzheimer's disease (AD) because none of the current therapies-either the cholinesterase inhibitors or antagonist of N-methyl-d-aspartate receptors-has profound effects on halting the progression of AD. In recent years, scientists have isolated many active compounds from herbs, which can alleviate dementia and neurodegenerative syndrome with fewer side effects than conventional drugs and, thus, are regarded as promising drug candidates for AD therapy. In this review, we summarize the latest research progress on six herbs for AD therapy-Huperzia serrata, Amaryllidaceae family, Ginkgo biloba, Uncaria rhynchophylla, Polygala tenuifolia, and Salvia officinalis-and focus on the analysis of their active components and possible mechanisms of pharmacological actions on AD. Copyright © 2011. Published by Elsevier B.V.

Differentiation of essential oils in Atractylodes lancea and Atractylodes koreana by gas chromatography with mass spectrometry.

PubMed

Liu, Qiutao; Zhang, Shanshan; Yang, Xihui; Wang, Ruilin; Guo, Weiying; Kong, Weijun; Yang, Meihua

2016-12-01

Atractylodes rhizome is a valuable traditional Chinese medicinal herb that comprises complex several species whose essential oils are the primary pharmacologically active component. Essential oils of Atractylodes lancea and Atractylodes koreana were extracted by hydrodistillation, and the yield was determined. The average yield of essential oil obtained from A. lancea (2.91%) was higher than that from A. koreana (2.42%). The volatile components of the essential oils were then identified by a gas chromatography with mass spectrometry method that demonstrated good precision. The method showed clear differences in the numbers and contents of volatile components between the two species. 41 and 45 volatile components were identified in A. lancea and A. koreana, respectively. Atractylon (48.68%) was the primary volatile component in A. lancea, while eudesma-4(14)-en-11-ol (11.81%) was major in A. koreana. However, the most significant difference between A. lancea and A. koreana was the major component of atractylon and atractydin. Principal component analysis was utilized to reveal the correlation between volatile components and species, and the analysis was used to successfully discriminate between A. lancea and A. koreana samples. These results suggest that different species of Atractylodes rhizome may yield essential oils that differ significantly in content and composition. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Review on Ethnopharmacological Applications, Pharmacological Activities, and Bioactive Compounds of Mangifera indica (Mango)

PubMed Central

2017-01-01

Mangifera indica (family Anacardiaceae), commonly known as mango, is a pharmacologically, ethnomedically, and phytochemically diverse plant. Various parts of M. indica tree have been used in traditional medicine for the treatment of different ailments, and a number of bioactive phytochemical constituents of M. indica have been reported, namely, polyphenols, terpenes, sterols, carotenoids, vitamins, and amino acids, and so forth. Several studies have proven the pharmacological potential of different parts of mango trees such as leaves, bark, fruit peel and flesh, roots, and flowers as anticancer, anti-inflammatory, antidiabetic, antioxidant, antibacterial, antifungal, anthelmintic, gastroprotective, hepatoprotective, immunomodulatory, antiplasmodial, and antihyperlipemic. In the present review, a comprehensive study on ethnopharmacological applications, pharmacological activities, and bioactive compounds of M. indica has been described. PMID:29456572

[Studies on the pharmacological effects of saffron(Crocus sativus L.)--a review].

PubMed

Deng, Ying; Guo, Zhi-gang; Zeng, Zhao-lin; Wang, Zhao

2002-08-01

Reviewing the studies on the chemical components and medicinal value. Philological method. Saffron is a conventional effective medicine in improving blood circulation and curing the bruise. The late of evidesnces indicate that saffron possesses anticancer activity against a wide spectrum of tumors, such as leukemia, ovarian carcinoma, colon adenocarcinoma, rhabdomyosarcoma, papilloma, squamous cell carcinoma, and soft tissue sarcoma. It has low biochemical toxic effects on animals. In addition, saffron can be used to cure coronary heart disease and hepatitis, and to promote immunity. Saffron is a highly valuable medicine. And producing it in a large quantity has a wide application prosperity.

Cryoradiation sterilization—Contemporary state and outlook

NASA Astrophysics Data System (ADS)

Talrose, V. L.; Trofimov, V. I.

1995-02-01

The new approach of radiation sterilization — cryoradiosterilization with programmed freezing — was developed for pharmaceutical solutions. Both scientific and technical problems are solved, the results are discussed. Programmed freezing of vials with the drug's solutions provides the high stability of soluted components with biological activity at sterilizing irradiation without significant change of sterilization doses. Physical, chemical, biological and pharmacological properties of a lot of drug solutions for injection satisfy official requirements after cryoradiation sterilization treatment. This method seems to be especially important for the protein systems which could be infected by dangerous viruses (VIH, hepatitis B): blood plasma, diagnostic sera, protein preparations manufactured from donor's blood, etc.

Neurophysiology of arthritis pain.

PubMed

McDougall, Jason J; Linton, Patrick

2012-12-01

Arthritis pain is a complex phenomenon involving intricate neurophysiological processing at all levels of the pain pathway. The treatment options available to alleviate joint pain are fairly limited and most arthritis patients report only modest pain relief with current treatments. A better understanding of the neural mechanisms responsible for musculoskeletal pain and the identification of new targets will help in the development of future pharmacological therapies. This article reviews some of the latest research into factors which contribute to joint pain and covers areas such as cannabinoids, proteinase activated receptors, sodium channels, cytokines and transient receptor potential channels. The emerging hypothesis that osteoarthritis may have a neuropathic component is also discussed.

New Antiresorptive Therapies for Postmenopausal Osteoporosis

PubMed Central

2015-01-01

Osteoporosis is a systemic skeletal disease whose risk increases with age and it is common among postmenopausal women. Currently, almost all pharmacological agents for osteoporosis target the bone resorption component of bone remodeling activity. Current antiresorptive agents are effective, but the effectiveness of some agents is limited by real or perceived intolerance, longterm adverse events (AEs), coexisting comorbidities, and inadequate long-term adherence. New antiresorptive therapies that may expand options for the prevention and treatment of osteoporosis include denosumab, combination of conjugated estrogen/bazedoxifene and cathepsin K inhibitors. However, the long-term efficacy and AEs of these antiresorptive therapies need to be confirmed in studies with a longer follow-up period. PMID:26046031

Network pharmacology-based identification of protective mechanism of Panax Notoginseng Saponins on aspirin induced gastrointestinal injury.

PubMed

Zhu, Baochen; Zhang, Wantong; Lu, Yang; Hu, Shaonan; Gao, Rui; Sun, Zongxi; Chen, Xiaonan; Ma, Junming; Guo, Shuang; Du, Shouying; Li, Pengyue

2018-05-29

Aspirin is the first line therapy for cardiovascular and cerebrovascular diseases and is widely used. However aspirin-induced gastrointestinal injury is one of its most common side effect which limits long-term use. Panax Notoginseng Saponins(PNS) which is also used to prevent thrombus may alleviate this side effect according to previous clinical evidences. Owing to the complexity of drug combination, the protective mechanism of PNS on aspirin-induced gastrointestinal injury remains unclear. Therefore, a network pharmacology-based strategy was proposed in this study to address this problem. A network pharmacology approach comprising multiple components, candidate targets of each component, known therapeutic targets, network analysis has been used in this study. Also, we establish aspirin-induced gastrointestinal injury model by the oral administration of aspirin (0.5 g/kg body weight) to verify the predicted targets from network pharmacology. All rats was randomly allocated to control groups (n = 6),aspirin groups (n = 6)and aspirin + PNS groups (n = 6) and conducted H&E staining and ELISA for VEGFA. The comprehensive systematic approach was successfully to identify 5 compounds and 154 candidate targets in PNS and 479 candidate targets in aspirin. After network establishment and analysis, 27 potential targets hit by PNS, aspirin and 6 kind of gastrointestinal diseases were found. The experiments results indicated that aspirin group has visible inflammation and lesions while aspirin + PNS group have not. The higher expression of VEGFA in aspirin + PNS group verified the predicted potential protective targets of PNS. PNS may have protective function for aspirin-induced gastrointestinal injury through increasing VEGFA expression. Network pharmacology strategy may provide a forceful tool for exploring the mechanism of herb medicine and discovering novel bioactive ingredients. Copyright © 2018. Published by Elsevier Masson SAS.

Network pharmacology-based identification of key pharmacological pathways of Yin-Huang-Qing-Fei capsule acting on chronic bronchitis.

PubMed

Yu, Guohua; Zhang, Yanqiong; Ren, Weiqiong; Dong, Ling; Li, Junfang; Geng, Ya; Zhang, Yi; Li, Defeng; Xu, Haiyu; Yang, Hongjun

2017-01-01

For decades in China, the Yin-Huang-Qing-Fei capsule (YHQFC) has been widely used in the treatment of chronic bronchitis, with good curative effects. Owing to the complexity of traditional Chinese herbal formulas, the pharmacological mechanism of YHQFC remains unclear. To address this problem, a network pharmacology-based strategy was proposed in this study. At first, the putative target profile of YHQFC was predicted using MedChem Studio, based on structural and functional similarities of all available YHQFC components to the known drugs obtained from the DrugBank database. Then, an interaction network was constructed using links between putative YHQFC targets and known therapeutic targets of chronic bronchitis. Following the calculation of four topological features (degree, betweenness, closeness, and coreness) of each node in the network, 475 major putative targets of YHQFC and their topological importance were identified. In addition, a pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes pathway database indicated that the major putative targets of YHQFC are significantly associated with various pathways involved in anti-inflammation processes, immune responses, and pathological changes caused by asthma. More interestingly, eight major putative targets of YHQFC (interleukin [IL]-3, IL-4, IL-5, IL-10, IL-13, FCER1G, CCL11, and EPX) were demonstrated to be associated with the inflammatory process that occurs during the progression of asthma. Finally, a molecular docking simulation was performed and the results exhibited that 17 pairs of chemical components and candidate YHQFC targets involved in asthma pathway had strong binding efficiencies. In conclusion, this network pharmacology-based investigation revealed that YHQFC may attenuate the inflammatory reaction of chronic bronchitis by regulating its candidate targets, which may be implicated in the major pathological processes of the asthma pathway.

Network pharmacology-based identification of key pharmacological pathways of Yin–Huang–Qing–Fei capsule acting on chronic bronchitis

PubMed Central

Yu, Guohua; Zhang, Yanqiong; Ren, Weiqiong; Dong, Ling; Li, Junfang; Geng, Ya; Zhang, Yi; Li, Defeng; Xu, Haiyu; Yang, Hongjun

2017-01-01

For decades in China, the Yin–Huang–Qing–Fei capsule (YHQFC) has been widely used in the treatment of chronic bronchitis, with good curative effects. Owing to the complexity of traditional Chinese herbal formulas, the pharmacological mechanism of YHQFC remains unclear. To address this problem, a network pharmacology-based strategy was proposed in this study. At first, the putative target profile of YHQFC was predicted using MedChem Studio, based on structural and functional similarities of all available YHQFC components to the known drugs obtained from the DrugBank database. Then, an interaction network was constructed using links between putative YHQFC targets and known therapeutic targets of chronic bronchitis. Following the calculation of four topological features (degree, betweenness, closeness, and coreness) of each node in the network, 475 major putative targets of YHQFC and their topological importance were identified. In addition, a pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes pathway database indicated that the major putative targets of YHQFC are significantly associated with various pathways involved in anti-inflammation processes, immune responses, and pathological changes caused by asthma. More interestingly, eight major putative targets of YHQFC (interleukin [IL]-3, IL-4, IL-5, IL-10, IL-13, FCER1G, CCL11, and EPX) were demonstrated to be associated with the inflammatory process that occurs during the progression of asthma. Finally, a molecular docking simulation was performed and the results exhibited that 17 pairs of chemical components and candidate YHQFC targets involved in asthma pathway had strong binding efficiencies. In conclusion, this network pharmacology-based investigation revealed that YHQFC may attenuate the inflammatory reaction of chronic bronchitis by regulating its candidate targets, which may be implicated in the major pathological processes of the asthma pathway. PMID:28053519

Medicinal cannabis: rational guidelines for dosing.

PubMed

Carter, Gregory T; Weydt, Patrick; Kyashna-Tocha, Muraco; Abrams, Donald I

2004-05-01

The medicinal value of cannabis (marijuana) is well documented in the medical literature. Cannabinoids, the active ingredients in cannabis, have many distinct pharmacological properties. These include analgesic, anti-emetic, anti-oxidative, neuroprotective and anti-inflammatory activity, as well as modulation of glial cells and tumor growth regulation. Concurrent with all these advances in the understanding of the physiological and pharmacological mechanisms of cannabis, there is a strong need for developing rational guidelines for dosing. This paper will review the known chemistry and pharmacology of cannabis and, on that basis, discuss rational guidelines for dosing.

Myosin II Activity Softens Cells in Suspension.

PubMed

Chan, Chii J; Ekpenyong, Andrew E; Golfier, Stefan; Li, Wenhong; Chalut, Kevin J; Otto, Oliver; Elgeti, Jens; Guck, Jochen; Lautenschläger, Franziska

2015-04-21

The cellular cytoskeleton is crucial for many cellular functions such as cell motility and wound healing, as well as other processes that require shape change or force generation. Actin is one cytoskeleton component that regulates cell mechanics. Important properties driving this regulation include the amount of actin, its level of cross-linking, and its coordination with the activity of specific molecular motors like myosin. While studies investigating the contribution of myosin activity to cell mechanics have been performed on cells attached to a substrate, we investigated mechanical properties of cells in suspension. To do this, we used multiple probes for cell mechanics including a microfluidic optical stretcher, a microfluidic microcirculation mimetic, and real-time deformability cytometry. We found that nonadherent blood cells, cells arrested in mitosis, and naturally adherent cells brought into suspension, stiffen and become more solidlike upon myosin inhibition across multiple timescales (milliseconds to minutes). Our results hold across several pharmacological and genetic perturbations targeting myosin. Our findings suggest that myosin II activity contributes to increased whole-cell compliance and fluidity. This finding is contrary to what has been reported for cells attached to a substrate, which stiffen via active myosin driven prestress. Our results establish the importance of myosin II as an active component in modulating suspended cell mechanics, with a functional role distinctly different from that for substrate-adhered cells. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Improving cancer treatment with cyclotron produced radionuclides. Comprehensive progress report, February 1, 1992--July 15, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1995-07-17

This research continues the long term goals of promoting nuclear medicine applications by improving the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. This program fits into the nuclear medicine component of DOE`s mission, which is aimed at enhancing the beneficial applications of radiation, radionuclides, and stable isotopes in the diagnosis, study and treatment of human diseases. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology/Immunology; and Imaging Physics. An essential strategy is as follows: novel radionuclides and radiotracers developed in the Radiochemistry/Section under the DOE grant during the 1992--1995more » will be employed in the Pharmacology/Immunology component in the period 1996--1999. Imaging Physics resolves relevant imaging related physics issues that arise during the experimentation that results. In addition to the basic research mission, this project also provides a basis for training of research scientists in radiochemistry, immunology, bioengineering and imaging physics.« less

Clinical pharmacology in Russia-historical development and current state.

PubMed

Zagorodnikova Goryachkina, Ksenia; Burbello, Aleksandra; Sychev, Dmitry; Frolov, Maxim; Kukes, Vladimir; Petrov, Vladimir

2015-02-01

Clinical pharmacology in Russia has long history and is currently active, but rather unrecognized internationally. It is governmentally approved as a teaching/scientific specialty since 1983 and as a medical specialty since 1997. Courses of clinical pharmacology are included in the undergraduate curricula in the 5th and/or 6th year of education at all medical schools in the Russian Federation. Postgraduate education includes initial specialization in internal medicine with further residency in clinical pharmacology. Governmental legislation recommends that every healthcare institution has either a department or a single position of clinical pharmacologist. Major routine duties include information about and monitoring of medication use, consultations in difficult clinical situations, pharmacogenetic counseling, therapeutic drug monitoring, pharmacovigilance, and participation in drug and therapeutics (formulary) committees. There are official experts in clinical pharmacology in Russia responsible for coordinating relevant legislative issues. The chief expert clinical pharmacologist represents the discipline directly at the Ministry of Health. Research in clinical pharmacology in Russia is extensive and variable, but only some of it is published internationally. Russia is a participant of international societies of clinical pharmacology and therapeutics and collaboration is actively ongoing. There are still certain problems related to the development of the discipline in Russia-some healthcare institutions do not see the need for clinical pharmacology. However, the number of clinical pharmacologists in Russia is increasing as well as their role in physicians' education, national healthcare, and research.

Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States.

PubMed

Kim, Jong Wook; Abudayyeh, Omar O; Yeerna, Huwate; Yeang, Chen-Hsiang; Stewart, Michelle; Jenkins, Russell W; Kitajima, Shunsuke; Konieczkowski, David J; Medetgul-Ernar, Kate; Cavazos, Taylor; Mah, Clarence; Ting, Stephanie; Van Allen, Eliezer M; Cohen, Ofir; Mcdermott, John; Damato, Emily; Aguirre, Andrew J; Liang, Jonathan; Liberzon, Arthur; Alexe, Gabriella; Doench, John; Ghandi, Mahmoud; Vazquez, Francisca; Weir, Barbara A; Tsherniak, Aviad; Subramanian, Aravind; Meneses-Cime, Karina; Park, Jason; Clemons, Paul; Garraway, Levi A; Thomas, David; Boehm, Jesse S; Barbie, David A; Hahn, William C; Mesirov, Jill P; Tamayo, Pablo

2017-08-23

The systematic sequencing of the cancer genome has led to the identification of numerous genetic alterations in cancer. However, a deeper understanding of the functional consequences of these alterations is necessary to guide appropriate therapeutic strategies. Here, we describe Onco-GPS (OncoGenic Positioning System), a data-driven analysis framework to organize individual tumor samples with shared oncogenic alterations onto a reference map defined by their underlying cellular states. We applied the methodology to the RAS pathway and identified nine distinct components that reflect transcriptional activities downstream of RAS and defined several functional states associated with patterns of transcriptional component activation that associates with genomic hallmarks and response to genetic and pharmacological perturbations. These results show that the Onco-GPS is an effective approach to explore the complex landscape of oncogenic cellular states across cancers, and an analytic framework to summarize knowledge, establish relationships, and generate more effective disease models for research or as part of individualized precision medicine paradigms. Copyright © 2017 Elsevier Inc. All rights reserved.

A review on the inhibitory potential of Nigella sativa against pathogenic and toxigenic fungi.

PubMed

Shokri, Hojjatollah

2016-01-01

Nigella sativa (N. sativa) grows in various parts of the world, particularly in Iran. It has been traditionally used as a folk remedy to treat a number of diseases. The seeds of this plant contain moisture, proteins, carbohydrates, crude fiber, alkaloids, saponins, ash, fixed oils and essential oil. The major components of the essential oil are thymoquinone, p-cymene, trans-anethole, 2-methyl-5(1-methyl ethyl)-Bicyclo[3.1.0]hex-2-en and γ-terpinene. So far, several pharmacological effects such as anti-oxidant, anti-inflammatory, anti-cancer and anti-microbial have been reported for N. sativa or its active compounds. Thymoquinone, thymohydroquinone and thymol are the most active constituents which have different beneficial properties. The oil, extracts and some of N. sativa active components possessed moderate in vitro and in vivo inhibitory activity against pathogenic yeasts, dermatophytes, non-dermatophytic filamentous fungi and aflatoxin-producing fungi. The main morphological changes of pathogenic and toxigenic fungi treated with N. sativa oil were observed in the cell wall, plasma membrane and membranous organelles, particularly in the nuclei and mitochondria. Although this review represents first step in the search for a new anti-fungal drug, the full potential of N. sativa as a fungitoxic agent has not been exploited and necessitates further investigations.

Fibrin(ogen)olytic activity of bumblebee venom serine protease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu Yuling; Joint Laboratory between Dong-A University and Shenyang Pharmaceutical University, Shenyang Pharmaceutical University, Shenyang; Choo, Young Moo

Bee venom is a rich source of pharmacologically active components; it has been used as an immunotherapy to treat bee venom hypersensitivity, and venom therapy has been applied as an alternative medicine. Here, we present evidence that the serine protease found in bumblebee venom exhibits fibrin(ogen)olytic activity. Compared to honeybee venom, bumblebee venom contains a higher content of serine protease, which is one of its major components. Venom serine proteases from bumblebees did not cross-react with antibodies against the honeybee venom serine protease. We provide functional evidence indicating that bumblebee (Bombus terrestris) venom serine protease (Bt-VSP) acts as a fibrin(ogen)olyticmore » enzyme. Bt-VSP activates prothrombin and directly degrades fibrinogen into fibrin degradation products. However, Bt-VSP is not a plasminogen activator, and its fibrinolytic activity is less than that of plasmin. Taken together, our results define roles for Bt-VSP as a prothrombin activator, a thrombin-like protease, and a plasmin-like protease. These findings offer significant insight into the allergic reaction sequence that is initiated by bee venom serine protease and its potential usefulness as a clinical agent in the field of hemostasis and thrombosis. - Graphical abstract: Display Omitted Highlights: > Bumblebee venom serine protease (Bt-VSP) is a fibrin(ogen)olytic enzyme. > Bt-VSP activates prothrombin. > Bt-VSP directly degrades fibrinogen into fibrin degradation products. > Bt-VSP is a hemostatically active protein that is a potent clinical agent.« less

Morinda officinalis How. - A comprehensive review of traditional uses, phytochemistry and pharmacology.

PubMed

Zhang, Jian-Hua; Xin, Hai-Liang; Xu, Yue-Ming; Shen, Yi; He, Yu-Qiong; Hsien-Yeh; Lin, Bing; Song, Hong-Tao; Juan-Liu; Yang, Hai-Yue; Qin, Lu-Ping; Zhang, Qiao-Yan; Du, Juan

2018-03-01

The medicinal plant Morinda officinalisHow. (MO) and its root have long been used in traditional medicines in China and northeast Asia as tonics for nourishing the kidney, strengthening the bone and enhancing immunofunction in the treatment of impotence, osteoporosis, depression and inflammatory diseases such as rheumatoid arthritis and dermatitis. This review aims to sum up updated and comprehensive information about traditional usage, phytochemistry, pharmacology and toxicology of MO and provide insights into potential opportunities for future research and development of this plant. A bibliographic investigation was performed by analyzing the information available on MO in the internationally accepted scientific databases including Pubmed, Scopus and Web of Science, SciFinder, Google Scholar, Yahoo, Ph.D. and M.Sc. dissertations in Chinese. Information was also obtained from some local and foreign books on ethnobotany and ethnomedicines. The literature supported the ethnomedicinal uses of MO as recorded in China for various purposes. The ethnomedical uses of MO have been recorded in many regions of China. More than 100 chemical compounds have been isolated from this plant, and the major constituents have been found to be polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides. Crude extracts and pure compounds of this plant are used as effective agents in the treatment of depression, osteoporosis, fatigue, rheumatoid arthritis, and infertility due to their anti-depressant, anti-osteoporosis, pro-fertility, anti-radiation, anti-Alzheimer disease, anti-rheumatoid, anti-fatigue, anti-aging, cardiovascularprotective, anti-oxidation, immune-regulatory, and anti-inflammatory activities. Pharmacokinetic studies have demonstrated that the main components of MO including monotropein and deacetyl asperulosidic acid are distributed in various organs and tissues. The investigation on acute toxicity and genotoxicity indicated that MO is nontoxic. There have no reports on significant adverse effect at a normal dose in clinical application, but MO at dose of more than 1000mg/kg may cause irritability, insomnia and unpleasant sensations in individual cases. MO has emerged as a good source of traditional medicines. Some uses of this plant in traditional medicines have been validated by pharmacological investigations. However, the molecular mechanism, structure-activity relationship, and potential synergistic and antagonistic effects of its multi-components such as polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides need to be further elucidated, and the structural feature of polysaccharides also need to be further clarified. Sophisticated analytical technologies should be developed to comprehensively evaluate the quality of MO based on HPLC-fingerprint and content determination of the active constituents, knowing that these investigations will help further utilize this plant. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS.

PubMed

Brown, Audrey E; Dibnah, Beth; Fisher, Emily; Newton, Julia L; Walker, Mark

2018-06-29

Skeletal muscle fatigue and post-exertional malaise are key symptoms of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (ME/CFS). We have previously shown that AMP-activated protein kinase (AMPK) activation and glucose uptake are impaired in primary human skeletal muscle cell cultures derived from patients with ME/CFS in response to electrical pulse stimulation (EPS), a method which induces contraction of muscle cells in vitro The aim of the present study was to assess if AMPK could be activated pharmacologically in ME/CFS. Primary skeletal muscle cell cultures from patients with ME/CFS and healthy controls were treated with either metformin or compound 991. AMPK activation was assessed by Western blot and glucose uptake measured. Both metformin and 991 treatment significantly increased AMPK activation and glucose uptake in muscle cell cultures from both controls and ME/CFS. Cellular ATP content was unaffected by treatment although ATP content was significantly decreased in ME/CFS compared with controls. Pharmacological activation of AMPK can improve glucose uptake in muscle cell cultures from patients with ME/CFS. This suggests that the failure of EPS to activate AMPK in these muscle cultures is due to a defect proximal to AMPK. Further work is required to delineate the defect and determine whether pharmacological activation of AMPK improves muscle function in patients with ME/CFS. © 2018 The Author(s).

Intraplantar injection of bergamot essential oil into the mouse hindpaw: effects on capsaicin-induced nociceptive behaviors.

PubMed

Sakurada, Tsukasa; Kuwahata, Hikari; Katsuyama, Soh; Komatsu, Takaaki; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Sakurada, Shinobu

2009-01-01

Despite the increasing use of aromatherapy oils, there have not been many studies exploring the biological activities of bergamot (Citrus bergamia, Risso) essential oil (BEO). Recently, we have investigated the effects of BEO injected into the plantar surface of the hindpaw in the capsaicin test in mice. The intraplantar injection of capsaicin produced an intense and short-lived licking/biting response toward the injected hindpaw. The capsaicin-induced nociceptive response was reduced significantly by intraplantar injection of BEO. The essential oils of Clary Sage (Salvia sclarea), Thyme ct. linalool (linalool chemotype of Thymus vulgaris), Lavender Reydovan (Lavandula hybrida reydovan), and True Lavender (Lavandula angustifolia), had similar antinociceptive effects on the capsaicin-induced nociceptive response, while Orange Sweet (Citrus sinensis) essential oil was without effect. In contrast to a small number of pharmacological studies of BEO, there is ample evidence regarding isolated components of BEO which are also found in other essential oils. The most abundant compounds found in the volatile fraction are the monoterpene hydrocarbons, such as limonene, gamma-terpinene, beta-pinene, and oxygenated derivatives, linalool and linalyl acetate. Of these monoterpenes, the pharmacological activities of linalool have been examined. Following intraperitoneal (i.p.) administration in mice, linalool produces antinociceptive and antihyperalgesic effects in different animal models in addition to anti-inflammatory properties. Linalool also possesses anticonvulsant activity in experimental models of epilepsy. We address the importance of linalool or linalyl acetate in BEO-or the other essential oil-induced antinociception.

Receptor Activity-modifying Protein-directed G Protein Signaling Specificity for the Calcitonin Gene-related Peptide Family of Receptors.

PubMed

Weston, Cathryn; Winfield, Ian; Harris, Matthew; Hodgson, Rose; Shah, Archna; Dowell, Simon J; Mobarec, Juan Carlos; Woodlock, David A; Reynolds, Christopher A; Poyner, David R; Watkins, Harriet A; Ladds, Graham

2016-10-14

The calcitonin gene-related peptide (CGRP) family of G protein-coupled receptors (GPCRs) is formed through the association of the calcitonin receptor-like receptor (CLR) and one of three receptor activity-modifying proteins (RAMPs). Binding of one of the three peptide ligands, CGRP, adrenomedullin (AM), and intermedin/adrenomedullin 2 (AM2), is well known to result in a Gα s -mediated increase in cAMP. Here we used modified yeast strains that couple receptor activation to cell growth, via chimeric yeast/Gα subunits, and HEK-293 cells to characterize the effect of different RAMP and ligand combinations on this pathway. We not only demonstrate functional couplings to both Gα s and Gα q but also identify a Gα i component to CLR signaling in both yeast and HEK-293 cells, which is absent in HEK-293S cells. We show that the CGRP family of receptors displays both ligand- and RAMP-dependent signaling bias among the Gα s , Gα i , and Gα q/11 pathways. The results are discussed in the context of RAMP interactions probed through molecular modeling and molecular dynamics simulations of the RAMP-GPCR-G protein complexes. This study further highlights the importance of RAMPs to CLR pharmacology and to bias in general, as well as identifying the importance of choosing an appropriate model system for the study of GPCR pharmacology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Pharmacological Potential of Phylogenetically Diverse Actinobacteria Isolated from Deep-Sea Coral Ecosystems of the Submarine Avilés Canyon in the Cantabrian Sea.

PubMed

Sarmiento-Vizcaíno, Aida; González, Verónica; Braña, Alfredo F; Palacios, Juan J; Otero, Luis; Fernández, Jonathan; Molina, Axayacatl; Kulik, Andreas; Vázquez, Fernando; Acuña, José L; García, Luis A; Blanco, Gloria

2017-02-01

Marine Actinobacteria are emerging as an unexplored source for natural product discovery. Eighty-seven deep-sea coral reef invertebrates were collected during an oceanographic expedition at the submarine Avilés Canyon (Asturias, Spain) in a range of 1500 to 4700 m depth. From these, 18 cultivable bioactive Actinobacteria were isolated, mainly from corals, phylum Cnidaria, and some specimens of phyla Echinodermata, Porifera, Annelida, Arthropoda, Mollusca and Sipuncula. As determined by 16S rRNA sequencing and phylogenetic analyses, all isolates belong to the phylum Actinobacteria, mainly to the Streptomyces genus and also to Micromonospora, Pseudonocardia and Myceligenerans. Production of bioactive compounds of pharmacological interest was investigated by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) techniques and subsequent database comparison. Results reveal that deep-sea isolated Actinobacteria display a wide repertoire of secondary metabolite production with a high chemical diversity. Most identified products (both diffusible and volatiles) are known by their contrasted antibiotic or antitumor activities. Bioassays with ethyl acetate extracts from isolates displayed strong antibiotic activities against a panel of important resistant clinical pathogens, including Gram-positive and Gram-negative bacteria, as well as fungi, all of them isolated at two main hospitals (HUCA and Cabueñes) from the same geographical region. The identity of the active extracts components of these producing Actinobacteria is currently being investigated, given its potential for the discovery of pharmaceuticals and other products of biotechnological interest.

Medicinal uses, phytochemistry and pharmacology of the genus Uncaria.

PubMed

Zhang, Qian; Zhao, Jiao Jiao; Xu, Jian; Feng, Feng; Qu, Wei

2015-09-15

The genus Uncaria belongs to the family Rubiaceae, which mainly distributed in tropical regions, such as Southeast Asia, Africa and Southeast America. Their leaves and hooks have long been thought to have healing powers and are already being tested as a treatment for asthma, cancer, cirrhosis, diabetes, hypertension, stroke and rheumatism. The present review aims to provide systematically reorganized information on the ethnopharmacology, phytochemistry and pharmacology of the genus Uncaria to support for further therapeutic potential of this genus. To better understanding this genus, information on the stereo-chemistry and structure-activity relationships in indole alkaloids is also represented. The literature study of this review is based on various databases search (SCIFinder, Science Direct, CNKI, Wiley online library, Spring Link, Web of Science, PubMed, Wanfang Data, Medalink, Google scholar, ACS, Tropicos, Council of Heads of Australasian Herbaria, The New York Botanical Garden, African Plants Database at Genera Botanical Garden, The Plant List and SEINet) and library search for Biological Abstract and some local books on ethnopharmacology. 19 species of the genus Uncaria are found to be important folk medicines in China, Malaysia, Phillippines, Africa and Southeast America, etc, and have been served for the treatment of asthma, rheumatism, hyperpyrexia, hypertension and headaches, etc. More than 200 compounds have been isolated from Uncaria, including indole alkaloids, triterpenes, flavonoids, phenols, phenylpropanoids, etc. As characteristic constituents, indole alkaloids have been considered as main efficacy component for hypertension, epilepsy, depressant, Parkinson's disease and Alzheimer's disease. In addition, pharmacokinetic and metabolism investigation reveal that the indole alkaloids are likely to be absorbed, metabolized and excreted at early time points. Moreover, the specific inhibition of CYP isozymes can regulate their hydroxylation metabolites at C-10 and C-11. Preliminary investigations on pharmacological properties of the Uncaria species have enlightened their efficacious remedy for hypertension, asthma, cancer, diabetes, rheumatism and neurodegenerative diseases. To ensure the safety and effectiveness in clinical application, research on bioactive compounds, pharmacological mechanisms and toxicity of the genus Uncaria as well as the stereo-chemistry and structure-activity relationships of indole alkaloids seem very important. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Conventional analgesics and non-pharmacological multidisciplinary therapeutic treatment in endometriosis: CNGOF-HAS Endometriosis Guidelines].

PubMed

Wattier, J-M

2018-03-01

A major symptom of endometriosis is pelvic pain with a wide range of intensity, rhythm, type, and expression, without clearly established relationship between pain and the disease. Endometriosis-associated pain has physical, psychological/behavioral and social consequences with a significant impact on patient quality-of-life in relation with the biopsychosocial model of chronic pain. Pain assessment in all of its dimensions, as well as assessing the consequences of pain is therefore a crucial part of therapeutic management. Conventional analgesics are commonly used although studies demonstrating their efficacy in the treatment of endometriosis-related pelvic pain are lacking. Non-steroid anti-inflammatory drugs (NSAIDs), known to be effective in dysmenorrhea unrelated to endometriosis, have not been recently re-assessed in patients with endometriosis. Following rigorous assessment, the characterization of neuropathic components of endometriosis-related pelvic pain may lead to treatment with antiepileptic of antidepressant drugs, although gabapentin and amitriptyline have yet to be specifically assessed in the setting of endometriosis-related pain. Other pharmacologically active compounds have been tested to treat endometriosis-related pain but did not demonstrate efficacy with sufficient level of evidence. Diets, dietary supplements and herbal medicine are often proposed and/or used as adjuncts without any conclusive evidence. Although the effects on endometriosis-related pain are methodologically difficult to assess, physical adjunctive therapies such as acupuncture, transcutaneous neurostimulation, osteopathy/chiropractics, physical therapy and physical activity, the long-term therapeutic relationship they establish may potentiate beneficial effects perceived by patients. However, it remains difficult to demonstrate significant effects of cognitive and/or behavioral interventions on endometriosis-related pain. The complexity of managing endometriosis-related pain requires a holistic approach with sustained attention to the patient. Treatments, either pharmacologic or non-pharmacologic, including adjuvant therapies, associate a technical expertise to which a human approach must be added in order to bring value to these treatments. Multidisciplinary and/or inter disciplinary approaches are therefore essential to the care of patients suffering from endometriosis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Determination of bioactive components in Chinese herbal formulae and pharmacokinetics of rhein in rats by UPLC-MS/MS.

PubMed

Hou, Mei-Ling; Chang, Li-Wen; Lin, Chi-Hung; Lin, Lie-Chwen; Tsai, Tung-Hu

2014-04-02

Rhein (4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid, cassic acid) is a pharmacological active component found in Rheum palmatum L. the major herb of San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we have determined multiple bioactive components in SHXXT and investigated the comparative pharmacokinetics of rhein in rats. A sensitive and specific method combining liquid chromatography with electrospray ionization tandem mass spectrometry has been developed and validated to simultaneously quantify six active compounds in the pharmaceutical herbal product SHXXT to further study their pharmacokinetics in rats. Multiple reaction monitoring (MRM) was employed for quantification with switching electrospray ion source polarity between positive and negative modes in a single run. There were no significant matrix effects in the quantitative analysis and the mean recovery for rhein in rat plasma was 91.6%±3.4%. The pharmacokinetic data of rhein demonstrate that the herbal formulae or the single herbal extract provide significantly higher absorption rate than the pure compound. This phenomenon suggests that the other herbal ingredients of SHXXT and rhubarb extract significantly enhance the absorption of rhein in rats. In conclusion, the herbal formulae (SHXXT) are more efficient than the single herb (rhubarb) or the pure compound (rhein) in rhein absorption.

How do the top 12 pharmaceutical companies operate safety pharmacology?

PubMed

Ewart, Lorna; Gallacher, David J; Gintant, Gary; Guillon, Jean-Michel; Leishman, Derek; Levesque, Paul; McMahon, Nick; Mylecraine, Lou; Sanders, Martin; Suter, Willi; Wallis, Rob; Valentin, Jean-Pierre

2012-09-01

How does safety pharmacology operate in large pharmaceutical companies today? By understanding our current position, can we prepare safety pharmacology to successfully navigate the complex process of drug discovery and development? A short anonymous survey was conducted, by invitation, to safety pharmacology representatives of the top 12 pharmaceutical companies, as defined by 2009 revenue figures. A series of multiple choice questions was designed to explore group size, accountabilities, roles and responsibilities of group members, outsourcing policy and publication record. A 92% response rate was obtained. Six out of 11 companies have 10 to 30 full time equivalents in safety pharmacology, who hold similar roles and responsibilities; although the majority of members are not qualified at PhD level or equivalent. Accountabilities were similar across companies and all groups have accountability for core battery in vivo studies and problem solving activities but differences do exist for example with in vitro safety screening and pharmacodynamic/pharmokinetic modeling (PK/PD). The majority of companies outsource less than 25% of studies, with in vitro profiling being the most commonly outsourced activity. Finally, safety pharmacology groups are publishing 1 to 4 articles each year. This short survey has highlighted areas of similarity and differences in the way large pharmaceutical companies operate safety pharmacology. Copyright © 2012 Elsevier Inc. All rights reserved.

Marine pharmacology in 2003-4: marine compounds with anthelmintic antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems, and other miscellaneous mechanisms of action.

PubMed

Mayer, Alejandro M S; Rodríguez, Abimael D; Berlinck, Roberto G S; Hamann, Mark T

2007-05-01

The current marine pharmacology review that covers the peer-reviewed literature during 2003 and 2004 is a sequel to the authors' 1998-2002 reviews, and highlights the preclinical pharmacology of 166 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria. Anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 67 marine chemicals. Additionally 45 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as possessing anti-inflammatory effects. Finally, 54 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2003-2004, research on the pharmacology of marine natural products which involved investigators from Argentina, Australia, Brazil, Belgium, Canada, China, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Morocco, the Netherlands, New Zealand, Norway, Panama, the Philippines, Portugal, Russia, Slovenia, South Korea, Spain, Thailand, Turkey, United Kingdom, and the United States, contributed numerous chemical leads for the continued global search for novel therapeutic agents with broad spectrum activity.

Marine pharmacology in 2003-4: Marine Compounds with Anthelminthic, Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiplatelet, Antiprotozoal, Antituberculosis, and Antiviral Activities; affecting the Cardiovascular, Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

PubMed Central

Mayer, Alejandro M.S.; Rodriguez, Abimael D.; Berlinck, Roberto G.S.; Hamann, Mark T.

2007-01-01

The current marine pharmacology review that covers the peer-reviewed literature during 2003 and 2004 is a sequel to the authors' 1998-2002 reviews, and highlights the preclinical pharmacology of 166 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria. Anthelminthic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 67 marine chemicals. Additionally 45 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as possessing anti-inflammatory effects. Finally, 54 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2003-2004, research on the pharmacology of marine natural products which involved investigators from Argentina, Australia, Brazil, Belgium, Canada, China, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Morocco, the Netherlands, New Zealand, Norway, Panama, the Philippines, Portugal, Russia, Slovenia, South Korea, Spain, Thailand, Turkey, United Kingdom, and the United States, contributed numerous chemical leads for the continued global search for novel therapeutic agents with broad spectrum activity. PMID:17392033

Medicinal Plants from Mexico, Central America, and the Caribbean Used as Immunostimulants

PubMed Central

Juárez-Vázquez, María del Carmen; Campos-Xolalpa, Nimsi

2016-01-01

A literature review was undertaken by analyzing distinguished books, undergraduate and postgraduate theses, and peer-reviewed scientific articles and by consulting worldwide accepted scientific databases, such as SCOPUS, Web of Science, SCIELO, Medline, and Google Scholar. Medicinal plants used as immunostimulants were classified into two categories: (1) plants with pharmacological studies and (2) plants without pharmacological research. Medicinal plants with pharmacological studies of their immunostimulatory properties were subclassified into four groups as follows: (a) plant extracts evaluated for in vitro effects, (b) plant extracts with documented in vivo effects, (c) active compounds tested on in vitro studies, and (d) active compounds assayed in animal models. Pharmacological studies have been conducted on 29 of the plants, including extracts and compounds, whereas 75 plants lack pharmacological studies regarding their immunostimulatory activity. Medicinal plants were experimentally studied in vitro (19 plants) and in vivo (8 plants). A total of 12 compounds isolated from medicinal plants used as immunostimulants have been tested using in vitro (11 compounds) and in vivo (2 compounds) assays. This review clearly indicates the need to perform scientific studies with medicinal flora from Mexico, Central America, and the Caribbean, to obtain new immunostimulatory agents. PMID:27042188

Medicinal Plants from Mexico, Central America, and the Caribbean Used as Immunostimulants.

PubMed

Alonso-Castro, Angel Josabad; Juárez-Vázquez, María Del Carmen; Campos-Xolalpa, Nimsi

2016-01-01

A literature review was undertaken by analyzing distinguished books, undergraduate and postgraduate theses, and peer-reviewed scientific articles and by consulting worldwide accepted scientific databases, such as SCOPUS, Web of Science, SCIELO, Medline, and Google Scholar. Medicinal plants used as immunostimulants were classified into two categories: (1) plants with pharmacological studies and (2) plants without pharmacological research. Medicinal plants with pharmacological studies of their immunostimulatory properties were subclassified into four groups as follows: (a) plant extracts evaluated for in vitro effects, (b) plant extracts with documented in vivo effects, (c) active compounds tested on in vitro studies, and (d) active compounds assayed in animal models. Pharmacological studies have been conducted on 29 of the plants, including extracts and compounds, whereas 75 plants lack pharmacological studies regarding their immunostimulatory activity. Medicinal plants were experimentally studied in vitro (19 plants) and in vivo (8 plants). A total of 12 compounds isolated from medicinal plants used as immunostimulants have been tested using in vitro (11 compounds) and in vivo (2 compounds) assays. This review clearly indicates the need to perform scientific studies with medicinal flora from Mexico, Central America, and the Caribbean, to obtain new immunostimulatory agents.

[PROFESSOR VLADIMIR V. NIKOLAEV AND RUSSIAN PHARMACOLOGY.

PubMed

Bondarchuk, N G; Fisenko, V P

2016-01-01

Various stages of scientific research activity of Prof. Vladimir V. Nikolaev are analyzed. The importance of Prof. Nikolaev's discovery of the two-neuron parasympathetic nervous system and some new methods of pharmacological substances evaluation is shown. Prof. Nikolaev is known as the editor of the first USSR Pharmacopoeia. Peculiarities of pharmacology teaching at the First Moscow Medical institute under conditions of changing social demands are described. Successful research of Prof. Nikolaev with colleagues in studying new mechanisms of drug action and developing original pharmacological substances is summarized.

Characterization of the in vitro propagation of epileptiform electrophysiological activity in organotypic hippocampal slice cultures coupled to 3D microelectrode arrays.

PubMed

Pisciotta, Marzia; Morgavi, Giovanna; Jahnsen, Henrik

2010-10-28

Dynamic aspects of the propagation of epileptiform activity have so far received little attention. With the aim of providing new insights about the spatial features of the propagation of epileptic seizures in the nervous system, we studied in vitro the initiation and propagation of traveling epileptiform waves of electrophysiological activity in the hippocampus by means of substrate three-dimensional microelectrode arrays (MEAs) for extracellular measurements. Pharmacologically disinhibited hippocampal slices spontaneously generate epileptiform bursts mostly originating in CA3 and propagating to CA1. Our study specifically addressed the activity-dependent changes of the propagation of traveling electrophysiological waves in organotypic hippocampal slices during epileptiform discharge and in particular our question is: what happens to the epileptic signals during their propagation through the slice? Multichannel data analysis enabled us to quantify an activity-dependent increase in the propagation velocity of spontaneous bursts. Moreover, through the evaluation of the coherence of the signals, it was possible to point out that only the lower-frequency components (<95Hz) of the electrical activity are completely coherent with respect to the activity originating in the CA3, while components at higher frequencies lose the coherence, possibly suggesting that the cellular mechanism mediating propagation of electrophysiological activity becomes ineffective for those firing rates exceeding an upper bound or that some noise of neuronal origin was added to the signal during propagation. Copyright © 2010 Elsevier B.V. All rights reserved.

The Promising Pharmacological Effects and Therapeutic/Medicinal applications of Punica Granatum L. (Pomegranate) as a Functional Food in Humans and Animals.

PubMed

Saeed, Muhammad; Naveed, Muhammad; BiBi, Jannat; Kamboh, Asghar Ali; Arain, Muhammad Asif; Shah, Qurban Ali; Alagawany, Mahmoud; Abd El-Hack, Mohamed Ezzat; Abdel-Latif, Mervat A.; Yatoo, Mohd. Iqbal; Tiwari, Ruchi; Chakraborty, Sandip; Dhama, Kuldeep

2018-02-21

Punica granatum L (pomegranate), is a shrub mostly available in the Mediterranean Sea region. The fruits have gained the substantial attention among researchers due to its promising biological activities including anti-inflammatory, antibacterial, antidiarrheal, immune modulatory, antitumor, wound healing and antifungal that have been attributed to various constituents of seeds, bark, juice, pericarp and leaf of this tree across the globe. The phenolic compounds of pomegranate have been documented to possess numbers of prophylactic and therapeutic utilities against various pathological infections as well as non-infectious disorders. The current review expedites the pharmacological role of Punica granatum L. in curing elements related to infectious and non-infectious disorders. Commencing a thorough review of the published literature and patents available on Punica granatum and its therapeutic role in countering infectious disorders present review is prepared by using various published resources available on PubMed, Med line, PubMed Central, Science Direct and other scientific databases. The information retrieved has been compiled and analyzed pertaining to the theme of the study. Multi-dimensional beneficial application of pomegranate plant is recorded. The pomegranate seed oil has phytoestrogenic compounds and the fruit is rich in phenolic compounds with strong antioxidant activity. The fruit and bark of pomegranate are used against intestinal parasites, dysentery, and diarrhea in different animals and human models. Since, ancient time the juice and seeds had considered the best therapy for throat and heart disorders. Ellagic acid is one of the main components of pomegranate with potent antioxidant activity. Results from different studies reported that Punica granatum L or its byproducts can be used as natural food additives in human and animal nutrition in order to boost immunity, microbial safety and provide the housing environment without affecting body weight gain. In addition, Punica granatum L. byproducts can modulate immune function and gut microbiota of broiler chickens as well as reduce the odorous gas emissions from excreta. Naturally occurring polyphenols in pomegranate can be a potential alternative medicine for the prevention of avian Colibacillosis diseases and can also be used as an intestine astringent to relieve diarrhea and enteritis in chickens. Present review gives the insight towards major components of pomegranate as well as their pharmacological activities against pathological disorders. In spite of many beneficial properties of Punica granatum L., more research evidence on molecular basis are needed to find out the molecular mechanism of action in various animals and human models to validate the usefulness of Punica granatum L. as a potent therapeutic agent. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Advance in studies on areca nuts and their active substances].

PubMed

Jiang, Zhi; Chen, Qi-Cheng; Cao, Li-Xing; Chen, Zhi-Qiang

2013-06-01

A number of clinical practices and studies indicated that areca nuts showed such effects as anthelmintic, food retention removal, qi activation and diuresis, and elimination of wetness and jaundice. Arecoline is the most important pharmacological active ingredient for healthcare from areca plants with a wide influence on human functions. In recent years, a lot of studies have been made on areca nuts and arecoline's pharmacology, physiology and immunity. The article summarizes areca nuts and their active substances.

Phytochemistry and pharmacology of ornamental gingers, Hedychium coronarium and Alpinia purpurata: a review.

PubMed

Chan, Eric Wei Chiang; Wong, Siu Kuin

2015-11-01

In this review, the phytochemistry and pharmacology of two ornamental gingers, Hedychium coronarium (butterfly ginger) and Alpinia purpurata (red ginger), are updated, and their botany and uses are described. Flowers of H. coronarium are large, showy, white, yellow or white with a yellow centre and highly fragrant. Inflorescences of A. purpurata are erect spikes with attractive red or pink bracts. Phytochemical investigations on the rhizomes of H. coronarium generated research interest globally. This resulted in the isolation of 53 labdane-type diterpenes, with little work done on the leaves and flowers. Pharmacological properties of H. coronarium included antioxidant, antibacterial, antifungal, cytotoxic, chemopreventive, anti-allergic, larvicidal, anthelminthic, analgesic, anti-inflammatory, anti-urolithiatic, anti-angiogenic, neuro-pharmacological, fibrinogenolytic, coagulant and hepatoprotective activities. On the contrary, little is known on the phytochemistry of A. purpurata with pharmacological properties of antioxidant, antibacterial, larvicidal, cytotoxic and vasodilator activities reported in the leaves and rhizomes. There is much disparity in terms of research effort within and between these two ornamental gingers.

Optimized microwave-assisted extraction of 6-gingerol from Zingiber officinale Roscoeand evaluation of antioxidant activity in vitro.

PubMed

Liu, Wei; Zhou, Chun-Li; Zhao, Jing; Chen, Dong; Li, Quan-Hong

2014-01-01

6-Gingerol is one of the most pharmacologically active and abundant components in ginger, which has a wide array of biochemical and pharmacologic activities. In recent years, the application of microwave-assisted extraction (MAE) for obtaining bioactive compounds from plant materials has shown tremendous research interest and potential. In this study, an efficient microwave-assisted extraction (MAE) technique was developed to extract 6-gingerol from ginger. The extraction efficiency of MAE was also compared with conventional extraction techniques. Fresh gingers (Zingiber officinale Rose.) were harvested at commercial maturity (originally from Shandong, laiwu, China). In single-factor experiments for the recovery of 6-gingerol, proper ranges of ratio of liquid to solid, ethanol proportion, microwave power, extraction time were determined. Based on the values obtained in single-factor experiments, a Box-Behnken design (BBD) was applied to determine the best combination of extraction variables on the yield of 6-gingerol. The optimum extraction conditions were as follows: microwave power 528 W, ratio of liquid to solid 26 mL·g(-1), extraction time 31 s and ethanol proportion 78%. Furthermore, more 6-gingerol and total polyphenols contents were extracted by MAE than conventional methods including Maceration (MAC), Stirring Extraction (SE), Heat reflux extraction (HRE), Ultrasound-assisted extraction (UAE), as well as the antioxidant capacity. Microwave-assisted extraction showed obvious advantages in terms of high extraction efficiency and antioxidant activity of extract within shortest extraction time. Scanning electron microscopy (SEM) images of ginger powder materials after different extractions were obtained to provide visual evidence of the disruption effect. To our best knowledge, this is the first report about usage of MAE of 6-gingerol extraction from ginger, which could be referenced for the extraction of other active compounds from herbal plants.

Electromechanical delay components during skeletal muscle contraction and relaxation in patients with myotonic dystrophy type 1.

PubMed

Esposito, Fabio; Cè, Emiliano; Rampichini, Susanna; Limonta, Eloisa; Venturelli, Massimo; Monti, Elena; Bet, Luciano; Fossati, Barbara; Meola, Giovanni

2016-01-01

The electromechanical delay during muscle contraction and relaxation can be partitioned into mainly electrochemical and mainly mechanical components by an EMG, mechanomyographic, and force combined approach. Component duration and measurement reliability were investigated during contraction and relaxation in a group of patients with myotonic dystrophy type 1 (DM1, n = 13) and in healthy controls (n = 13). EMG, mechanomyogram, and force were recorded in DM1 and in age- and body-matched controls from tibialis anterior (distal muscle) and vastus lateralis (proximal muscle) muscles during maximum voluntary and electrically-evoked isometric contractions. The electrochemical and mechanical components of the electromechanical delay during muscle contraction and relaxation were calculated off-line. Maximum strength was significantly lower in DM1 than in controls under both experimental conditions. All electrochemical and mechanical components were significantly longer in DM1 in both muscles. Measurement reliability was very high in both DM1 and controls. The high reliability of the measurements and the differences between DM1 patients and controls suggest that the EMG, mechanomyographic, and force combined approach could be utilized as a valid tool to assess the level of neuromuscular dysfunction in this pathology, and to follow the efficacy of pharmacological or non-pharmacological interventions. Copyright © 2015 Elsevier B.V. All rights reserved.

Label-free integrative pharmacology on-target of drugs at the β2-adrenergic receptor

NASA Astrophysics Data System (ADS)

Ferrie, Ann M.; Sun, Haiyan; Fang, Ye

2011-07-01

We describe a label-free integrative pharmacology on-target (iPOT) method to assess the pharmacology of drugs at the β2-adrenergic receptor. This method combines dynamic mass redistribution (DMR) assays using an array of probe molecule-hijacked cells with similarity analysis. The whole cell DMR assays track cell system-based, ligand-directed, and kinetics-dependent biased activities of the drugs, and translates their on-target pharmacology into numerical descriptors which are subject to similarity analysis. We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs.

Inhibitory effects of bee venom and its components against viruses in vitro and in vivo.

PubMed

Uddin, Md Bashir; Lee, Byeong-Hoon; Nikapitiya, Chamilani; Kim, Jae-Hoon; Kim, Tae-Hwan; Lee, Hyun-Cheol; Kim, Choul Goo; Lee, Jong-Soo; Kim, Chul-Joong

2016-12-01

Bee venom (BV) from honey bee (Apis Melifera L.) contains at least 18 pharmacologically active components including melittin (MLT), phospholipase A 2 (PLA 2 ), and apamin etc. BV is safe for human treatments dose dependently and proven to possess different healing properties including antibacterial and antiparasitidal properties. Nevertheless, antiviral properties of BV have not well investigated. Hence, we identified the potential antiviral properties of BV and its component against a broad panel of viruses. Co-incubation of non-cytotoxic amounts of BV and MLT, the main component of BV, significantly inhibited the replication of enveloped viruses such as Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Respiratory Syncytial Virus (RSV), and Herpes Simplex Virus (HSV). Additionally, BV and MLT also inhibited the replication of non-enveloped viruses such as Enterovirus-71 (EV-71) and Coxsackie Virus (H3). Such antiviral properties were mainly explained by virucidal mechanism. Moreover, MLT protected mice which were challenged with lethal doses of pathogenic influenza A H1N1 viruses. Therefore, these results provides the evidence that BV and MLT could be a potential source as a promising antiviral agent, especially to develop as a broad spectrum antiviral agent.

Screening and analysis of the multiple absorbed bioactive components and metabolites in rat plasma after oral administration of Jitai tablets by high-performance liquid chromatography/diode-array detection coupled with electrospray ionization tandem mass spectrometry.

PubMed

Wang, Shu-Ping; Liu, Lei; Wang, Ling-Ling; Jiang, Peng; Zhang, Ji-Quan; Zhang, Wei-Dong; Liu, Run-Hui

2010-06-15

Based on the serum pharmacochemistry technique and high-performance liquid chromatography/diode-array detection (HPLC/DAD) coupled with electrospray tandem mass spectrometry (HPLC/ESI-MS/MS), a method for screening and analysis of the multiple absorbed bioactive components and metabolites of Jitai tablets (JTT) in orally dosed rat plasma was developed. Plasma was treated by methanol precipitation prior to liquid chromatography, and the separation was carried out on a Symmetry C(18) column, with a linear gradient (0.1% formic acid/water/acetonitrile). Mass spectra were acquired in negative and positive ion modes, respectively. As a result, 26 bioactive components originated from JTT and 5 metabolites were tentatively identified in orally dosed rat plasma by comparing their retention times and MS spectra with those of authentic standards and literature data. It is concluded that an effective and reliable analytical method was set up for screening the bioactive components of Chinese herbal medicine, which provided a meaningful basis for further pharmacology and active mechanism research of JTT. Copyright (c) 2010 John Wiley & Sons, Ltd.

[Advances in research of chemical constituents and pharmacological activities of common used spices].

PubMed

Sun, Chao-nan; Zhu, Yuan; Xu, Xi-ming; Yu, Jiang-nan

2014-11-01

Spices have enjoyed a long history and a worldwide application. Of particular interest is the pharmaceutical value of spices in addition to its basic seasoning function in cooking. Concretely, equipped with complex chemical compositions, spices are of significant importance in pharmacologic actions, like antioxidant, antibacterial, antitumor, as well as therapeutical effects in gastrointestinal disorders and cardiovascular disease. Although increasing evidences in support of its distinct role in the medical field has recently reported, little information is available for substantive, thorough and sophisticated researches on its chemical constituents and pharmacological activities, especially mechanism of these actions. Therefore, in popular wave of studies directed at a single spice, this review presents systematic studies on the chemical constituents and pharmacological activities associated with common used spices, together with current typical individual studies on functional mechanism, in order to pave the way for the exploitation and development of new medicines derived from the chemical compounds of spice (such as, piperine, curcumin, geniposide, cinnamaldehyde, cinnamic acid, linalool, estragole, perillaldehyde, syringic acid, crocin).

Phytochemistry, pharmacology, and clinical trials of Morus alba.

PubMed

Chan, Eric Wei-Chiang; Lye, Phui-Yan; Wong, Siu-Kuin

2016-01-01

The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti-diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti-obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Chemical Composition and Antimicrobial Activity of Essential Oils from the Aerial Parts of Asteriscus graveolens (Forssk.) Less. and Pulicaria incisa (Lam.) DC.: Two Asteraceae Herbs Growing Wild in the Hoggar.

PubMed

Chaib, Faiza; Allali, Hocine; Bennaceur, Malika; Flamini, Guido

2017-08-01

In recent years, antimicrobial activities of essential oils have been intensively explored, mainly in researching and developing new antimicrobial agents to overcome microbial resistance. The present study investigates the chemical composition and antimicrobial activities of essential oils obtained from two Asteraceae: Asteriscus graveolens (Forssk.) Less. and Pulicaria incisa (Lam.) DC. Chemical analysis was performed using a combination of capillary GC-FID and GC/MS analytical techniques. The major component of Asteriscus graveolens were cis-chrysanthenyl acetate (31.1%), myrtenyl acetate (15.1%), and kessane (11.5%), while for Pulicaria incisa the main components were chrysanthenone (45.3%) and 2,6-dimethylphenol (12.6%). The oils obtained from the aerial parts were tested against sixteen microbial strains by agar well diffusion technique and dilution methods and showed minimum inhibitory concentrations (MIC) in the range of 19 - 1250 μg/ml. A good antibacterial activity against a common nosocomial pathogen, Acinetobacter baumanniiATCC 19606 was observed, especially from Pulicaria incisa essential oil, with a MIC value up to 19 μg/ml. These results give significant information about the pharmacological activity of these essential oils, which suggest their benefits to human health, having the potential to be used for medical purposes. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Potential drug interactions associated with glycyrrhizin and glycyrrhetinic acid.

PubMed

Feng, Xinchi; Ding, Liqin; Qiu, Feng

2015-05-01

Glycyrrhizin (GZ), the main active component of licorice, is a widely used therapeutic in the clinic. Depending on the disease, the treatment may involve a long course of high dose GZ. Another component of licorice, glycyrrhetinic acid (GA), is the main active metabolite of GZ and is thought to be responsible for the majority of the pharmacological properties of GZ. Therefore, GZ and GA are both used for therapeutic purposes. In addition, GZ and GA are also widely used to sweeten and flavor foods. Due to this widespread, multifaceted use of these substances, potential drug interactions with GZ and GA have recently gained attention. Along these lines, this review covers the known effects of GZ and GA on drug-metabolizing enzymes and efflux transporters. We conclude that both GZ and GA may have an effect on the activity of CYPs. For example, GZ may induce CYP3A activity through activation of PXR. Also, GZ and GA may affect glucuronidation in rats and humans. Furthermore, 18β-GA is a potent inhibitor of P-gp, while GZ and GA are inhibitors of MRP1, MRP2 and BCRP. The pharmacokinetics and pharmacodynamics of many medications may be altered when used concurrently with GZ or GA, which is also covered in this review. Overall, GZ, GA or related products should be taken with caution when taken with additional medications due to the possible drug interactions.

α-Pinene, linalool, and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2.

PubMed

Li, Xiao-Jun; Yang, Yan-Jing; Li, Yu-Sang; Zhang, Wei Kevin; Tang, He-Bin

2016-02-17

Frankincense oil and water extracts (FOE, FWE) have long been used for external treatment of inflammation and pain. The present study was conducted to identify the active ingredients responsible for the anti-inflammatory and analgesic effects and to determine the underlying mechanisms. The compositions of FOE and FWE were identified and compared by GC-MS. The anti-inflammatory and analgesic activities of the two extracts and their possible active ingredients (α-pinene, linalool, and 1-octanol) were evaluated and compared in a xylene-induced ear edema model and a formalin-inflamed hind paw model. Inflammatory infiltrates and cyclooxygenase-2 (COX-2) expression in hind paw skin were investigated by histological staining. The contents of α-pinene, linalool, and 1-octanol in FOE were much higher than those in FWE. Mice treated with FOE exhibited greater and faster lessening of swelling and pain than mice treated with FWE. The combination of the three components had more potent pharmacological effects on hind paw inflammation and COX-2 overexpression than the three components used alone. These findings suggest that topical application of FOE or its active ingredients (including α-pinene, linalool, and 1-octanol) exhibit significantly anti-inflammatory and analgesic effects through inhibiting nociceptive stimulus-induced inflammatory infiltrates and COX-2 overexpression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

State of the art analgesia-Recent developments pharmacological approaches to acute pain management in dogs and cats: Part 2.

PubMed

Bradbrook, C; Clark, L

2018-06-01

There has been considerable interest in the area of acute pain management over recent years, focusing on pain assessment, pharmacological and non-pharmacological interventions. The evidence base for our clinical decision making and treatment of patients is ever increasing and becoming more robust. There is still a tendency to base some aspects of pain management on poor quality evidence and this requires further input in years to come. With new literature come new ideas and this review will detail the current knowledge base behind pharmacological management of acute pain in dogs and cats. The known mechanisms of action of each analgesic and its evidence will be considered. The second part of this review will consider the non-traditional analgesics, describing their component drugs individually, thereby focusing on their mechanisms of action and the current evidence for their use in acute pain management. Copyright © 2018 Elsevier Ltd. All rights reserved.

State of the art analgesia- recent developments in pharmacological approaches to acute pain management in dogs and cats. Part 1.

PubMed

Bradbrook, C A; Clark, L

2018-06-06

There has been considerable interest in acute pain management over recent years, focusing on pain assessment, pharmacological and non-pharmacological interventions. The evidence base for our clinical decision making and treatment of patients is increasing and becoming more robust. There is still a tendency to base some aspects of pain management on poor quality evidence and this requires further input in years to come. With new literature come new ideas and this review will detail the current knowledge base behind pharmacological management of acute pain in dogs and cats. The known mechanisms of action of each analgesic and its evidence will be considered. The first part of this review will consider the opioid and anti-inflammatory analgesics, describing their component drugs individually, thereby focusing on their mechanisms of action and the current evidence for their use in acute pain management. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Application progress of proteomic in pharmacological study of Chinese medicinal formulae].

PubMed

Liu, Yu-Qian; Zhan, Shu-Yu; Ruan, Yu-Er; Zuo, Zhi-Yan; Ji, Xiao-Ming; Wang, Shuai-Jie; Ding, Bao-Yue

2017-10-01

Chinese medicinal formulae are the important means of clinical treatment in traditional Chinese medicine. It is urgent to use modern advanced scientific and technological means to reveal the complicated mechanism of Chinese medicinal formulae because they have the function characteristics of multiple components, multiple targets and integrated regulation. The systematic and comprehensive research model of proteomic is in line with the function characteristics of Chinese medicinal formulae, and proteomic has been widely used in the study of pharmacological mechanism of Chinese medicinal formulae. The recent applications of proteomic in pharmacological study of Chinese medicinal formulae in anti-cardiovascular and cerebrovascular diseases, anti-liver disease, antidiabetic, anticancer, anti-rheumatoid arthritis and other diseases were reviewed in this paper, and then the future development direction of proteomic in pharmacological study of Chinese medicinal formulae was put forward. This review is to provide the ideas and method for proteomic research on function mechanism of Chinese medicinal formulae. Copyright© by the Chinese Pharmaceutical Association.

Pressor mechanism evaluation for phytochemical compounds using in silico compound-protein interaction prediction.

PubMed

He, Min; Cao, Dong-Sheng; Liang, Yi-Zeng; Li, Ya-Ping; Liu, Ping-Le; Xu, Qing-Song; Huang, Ren-Bin

2013-10-01

In this study, a method was applied to evaluate pressor mechanisms through compound-protein interactions. Our method assumed that the compounds with different pressor mechanisms should bind to different target proteins, and thereby these mechanisms could be differentiated using compound-protein interactions. Twenty-six phytochemical components and 46 tested target proteins related to blood pressure (BP) elevation were collected. Then, in silico compound-protein interactions prediction probabilities were calculated using a random forest model, which have been implemented in a web server, and the credibility was judged using related literature and other methods. Further, a heat map was constructed, it clearly showed different prediction probabilities accompanied with hierarchical clustering analysis results. Followed by a compound-protein interaction network was depicted according to the results, we can see the connectivity layout of phytochemical components with different target proteins within the BP elevation network, which guided the hypothesis generation of poly-pharmacology. Lastly, principal components analysis (PCA) was carried out upon the prediction probabilities, and pressor targets could be divided into three large classes: neurotransmitter receptors, hormones receptors and monoamine oxidases. In addition, steroid glycosides seem to be close to the region of hormone receptors, and a weak difference existed between them. This work explored the possibility for pharmacological or toxicological mechanism classification using compound-protein interactions. Such approaches could also be used to deduce pharmacological or toxicological mechanisms for uncharacterized compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

21 CFR 201.66 - Format and content requirements for over-the-counter (OTC) drug product labeling.

Code of Federal Regulations, 2010 CFR

2010-04-01

... general pharmacological category(ies) or the principal intended action(s) of the drug or, where the drug... actions of each active ingredient. When an OTC drug monograph contains a statement of identity, the pharmacological action described in the statement of identity shall also be stated as the purpose of the active...

[Perspectives on pharmacological and clinical benefits from sirtuin 1 activators in oxidative damage].

PubMed

Kutinová, Canová Nikolina; Gaier, Norbert; Farghali, Hassan

2012-01-01

Sirtuins, named after their homology to the Saccharomyces cerevisiae Silent Information Regulator Two, constitute a family of highly conserved nicotinamide adenine dinucleotide-dependent enzymes that deacetylate histones and residues of acetylated lysine. The main aim of this article is to put forward the pharmacological importance of major sirtuin 1 activators of natural or synthetic origin tested in last years in cases of oxidative tissue damage. The related bioactivity of these activators as "leading" compounds in the search for new drugs and remedies is also described. With the recent development of our knowledge on the cross talks between sirtuin 1 and its modulators (e.g. resveratrol), pharmacological and clinical research on this topic is getting a new horizon.

What Is Ganoderma lucidum in the Molecular Era?

PubMed

Papp, Viktor; Dima, Bálint; Wasser, Solomon P

2017-01-01

The scientific name Ganoderma lucidum has long been used in the global medicinal mushroom market, and many publications have proven its pharmacological properties and chemical components. Although several Ganoderma species have been described worldwide as having morphology considerably similar to that of G. lucidum s. str., this binomial is still the most frequently used in pharmacological studies. However, the use of particularly divergent nomenclature has caused major difficulties in the evaluation of the results of pharmacological studies. This article is intended to provide a nomenclatural and taxonomic overview of the medically important G. lucidum group, that is, G. lucidum aggregate and G. lingzhi. Moreover, we evaluate the possibilities of how nomenclatural changes can help to avoid misunderstandings in thousands of publications and highlight scientifically correct interpretations for future studies.

Carum copticum L.: A Herbal Medicine with Various Pharmacological Effects

PubMed Central

Boskabady, Mohammad Hossein; Alitaneh, Saeed; Alavinezhad, Azam

2014-01-01

Carum copticum L. commonly known as “Ajwain” is cultivated in many regions of the world including Iran and India, states of Gujarat and Rajasthan. Traditionally, C. copticum has been used in the past for various therapeutic effects including bloating, fatigue, diarrhea, abdominal tumors, abdominal pain, respiratory distress, and loss of appetite. It has other health benefits such as antifungal, antioxidant, antibacterial, antiparasitic, and hypolipidemic effects. This plant contains different important components such as carbohydrates, glucosides, saponins and phenolic compounds (carvacrol), volatile oils (thymol), terpiene, paracymene and beta-pinene, protein, fat, fiber, and minerals including calcium, phosphorus, iron, and nicotinic acid (niacin). In the previous studies, several pharmacological effects were shown for C. copticum. Therefore, in this paper, the pharmacological effects of the plant were reviewed. PMID:25089273

Constellation Pharmacology: A new paradigm for drug discovery

PubMed Central

Schmidt, Eric W.; Olivera, Baldomero M.

2015-01-01

Constellation Pharmacology is a cell-based high-content phenotypic-screening platform that utilizes subtype-selective pharmacological agents to elucidate the cell-specific combinations (“constellations”) of key signaling proteins that define specific cell types. Heterogeneous populations of native cells, in which the different individual cell types have been identified and characterized, are the foundation for this screening platform. Constellation Pharmacology is useful for screening small molecules or for deconvoluting complex mixtures of biologically-active natural products. This platform has been used to purify natural products and discover their molecular mechanisms. In the on-going development of Constellation Pharmacology, there is a positive-feedback loop between the pharmacological characterization of cell types and screening for new drug candidates. As Constellation Pharmacology is used to discover compounds with novel targeting-selectivity profiles, those new compounds then further help to elucidate the constellations of specific cell types, thereby increasing the content of this high-content platform. PMID:25562646

Anti-MRSA Activity of Fruiting Body Extracts of Spectacular Rustgill Mushroom, Gymnopilus junonius (Agaricomycetes).

PubMed

Barneche, Stephanie; Alborés, Silvana; Borthagaray, Graciela; Cerdeiras, María Pía; Vázquez, Alvaro

2017-01-01

Despite the great advances in chemotherapeutics, infectious diseases are still one of the leading causes of death worldwide. Among some of the clinically relevant pathogens, methicillin-resistant Staphylococcus aureus (MRSA) ranks as one of the most difficult bacteria to treat. It is a common cause of skin, soft-tissue, and endovascular infections, as well as pneumonia, septic arthritis, endocarditis, osteomyelitis, and sepsis. The research on Basidiomycota is extensive; many species show a broad spectrum of pharmacological activities, including antimicrobial activity. The vast majority of the literature to date generally focuses on screening the antibacterial properties of mushroom extracts. A gap still exists in the identification of the individual compounds responsible for these properties, and few low molecular weight compounds have been described. Gymnopilus junonius, the big laughter mushroom, grows wild in Uruguay, especially on Eucalyptus spp. plantations; it is known as the "eucalyptus fungus." In this work, we report the bioguided isolation, structural elucidation, and antistaphylococcal activity of the main antimicrobial components of fresh basidiocarps of G. junonius.

Novel Role of Endogenous Catalase in Macrophage Polarization in Adipose Tissue.

PubMed

Park, Ye Seul; Uddin, Md Jamal; Piao, Lingjuan; Hwang, Inah; Lee, Jung Hwa; Ha, Hunjoo

2016-01-01

Macrophages are important components of adipose tissue inflammation, which results in metabolic diseases such as insulin resistance. Notably, obesity induces a proinflammatory phenotypic switch in adipose tissue macrophages, and oxidative stress facilitates this switch. Thus, we examined the role of endogenous catalase, a key regulator of oxidative stress, in the activity of adipose tissue macrophages in obese mice. Catalase knockout (CKO) exacerbated insulin resistance, amplified oxidative stress, and accelerated macrophage infiltration into epididymal white adipose tissue in mice on normal or high-fat diet. Interestingly, catalase deficiency also enhanced classical macrophage activation (M1) and inflammation but suppressed alternative activation (M2) regardless of diet. Similarly, pharmacological inhibition of catalase activity using 3-aminotriazole induced the same phenotypic switch and inflammatory response in RAW264.7 macrophages. Finally, the same phenotypic switch and inflammatory responses were observed in primary bone marrow-derived macrophages from CKO mice. Taken together, the data indicate that endogenous catalase regulates the polarization of adipose tissue macrophages and thereby inhibits inflammation and insulin resistance.

Insulin-like Growth Factor 1 (IGF-1) Stabilizes Nascent Blood Vessels*

PubMed Central

Jacobo, Sarah Melissa P.; Kazlauskas, Andrius

2015-01-01

Here we report that VEGF-A and IGF-1 differ in their ability to stabilize newly formed blood vessels and endothelial cell tubes. Although VEGF-A failed to support an enduring vascular response, IGF-1 stabilized neovessels generated from primary endothelial cells derived from various vascular beds and mouse retinal explants. In these experimental systems, destabilization/regression was driven by lysophosphatidic acid (LPA). Because previous studies have established that Erk antagonizes LPA-mediated regression, we considered whether Erk was an essential component of IGF-dependent stabilization. Indeed, IGF-1 lost its ability to stabilize neovessels when the Erk pathway was inhibited pharmacologically. Furthermore, stabilization was associated with prolonged Erk activity. In the presence of IGF-1, Erk activity persisted longer than in the presence of VEGF or LPA alone. These studies reveal that VEGF and IGF-1 can have distinct inputs in the angiogenic process. In contrast to VEGF, IGF-1 stabilizes neovessels, which is dependent on Erk activity and associated with prolonged activation. PMID:25564613

Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity.

PubMed

Hollands, Andrew; Corriden, Ross; Gysler, Gabriela; Dahesh, Samira; Olson, Joshua; Raza Ali, Syed; Kunkel, Maya T; Lin, Ann E; Forli, Stefano; Newton, Alexandra C; Kumar, Geetha B; Nair, Bipin G; Perry, J Jefferson P; Nizet, Victor

2016-07-01

Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Saikosaponin d protects against acetaminophen-induced hepatotoxicity by inhibiting NF-κB and STAT3 signaling.

PubMed

Liu, Aiming; Tanaka, Naoki; Sun, Lu; Guo, Bin; Kim, Jung-Hwan; Krausz, Kristopher W; Fang, Zhongze; Jiang, Changtao; Yang, Julin; Gonzalez, Frank J

2014-11-05

Overdose of acetaminophen (APAP) can cause acute liver injury that is sometimes fatal, requiring efficient pharmacological intervention. The traditional Chinese herb Bupleurum falcatum has been widely used for the treatment of several liver diseases in eastern Asian countries, and saikosaponin d (SSd) is one of its major pharmacologically-active components. However, the efficacy of Bupleurum falcatum or SSd on APAP toxicity remains unclear. C57/BL6 mice were administered SSd intraperitoneally once daily for 5days, followed by APAP challenge. Biochemical and pathological analysis revealed that mice treated with SSd were protected against APAP-induced hepatotoxicity. SSd markedly suppressed phosphorylation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) and reversed the APAP-induced increases in the target genes of NF-κB, such as pro-inflammatory cytokine Il6 and Ccl2, and those of STAT3, such as Socs3, Fga, Fgb and Fgg. SSd also enhanced the expression of the anti-inflammatory cytokine Il10 mRNA. Collectively, these results demonstrate that SSd protects mice from APAP-induced hepatotoxicity mainly through down-regulating NF-κB- and STAT3-mediated inflammatory signaling. This study unveils one of the possible mechanisms of hepatoprotection caused by Bupleurum falcatum and/or SSd. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Signaling properties and pharmacological analysis of two sulfakinin receptors from the red flour beetle, Tribolium castaneum.

PubMed

Zels, Sven; Verlinden, Heleen; Dillen, Senne; Vleugels, Rut; Nachman, Ronald J; Vanden Broeck, Jozef

2014-01-01

Sulfakinin is an insect neuropeptide that constitutes an important component of the complex network of hormonal and neural factors that regulate feeding and digestion. The key modulating functions of sulfakinin are mediated by binding and signaling via G-protein coupled receptors. Although a substantial amount of functional data have already been reported on sulfakinins in different insect species, only little information is known regarding the properties of their respective receptors. In this study, we report on the molecular cloning, functional expression and characterization of two sulfakinin receptors in the red flour beetle, Tribolium castaneum. Both receptor open reading frames show extensive sequence similarity with annotated sulfakinin receptors from other insects. Comparison of the sulfakinin receptor sequences with homologous vertebrate cholecystokinin receptors reveals crucial conserved regions for ligand binding and receptor activation. Quantitative reverse transcriptase PCR shows that transcripts of both receptors are primarily expressed in the central nervous system of the beetle. Pharmacological characterization using 29 different peptide ligands clarified the essential requirements for efficient activation of these sulfakinin receptors. Analysis of the signaling pathway in multiple cell lines disclosed that the sulfakinin receptors of T. castaneum can stimulate both the Ca²⁺ and cyclic AMP second messenger pathways. This in depth characterization of two insect sulfakinin receptors may provide useful leads for the further development of receptor ligands with a potential applicability in pest control and crop protection.

Screening antiallergic components from Carthamus tinctorius using rat basophilic leukemia 2H3 cell membrane chromatography combined with high-performance liquid chromatography and tandem mass spectrometry.

PubMed

Han, Shengli; Huang, Jing; Cui, Ronghua; Zhang, Tao

2015-02-01

Carthamus tinctorius, used in traditional Chinese medicine, has many pharmacological effects, such as anticoagulant effects, antioxidant effects, antiaging effects, regulation of gene expression, and antitumor effects. However, there is no report on the antiallergic effects of the components in C. tinctorius. In the present study, we investigated the antiallergic components of C. tinctorius and its mechanism of action. A rat basophilic leukemia 2H3/cell membrane chromatography coupled online with high-performance liquid chromatography and tandem mass spectrometry method was developed to screen antiallergic components from C. tinctorius. The screening results showed that Hydroxysafflor yellow A, from C. tinctorius, was the targeted component that retained on the rat basophilic leukemia 2H3/cell membrane chromatography column. We measured the amount of β-hexosaminidase and histamine released in mast cells and the key markers of degranulation. The release assays showed that Hydroxysafflor yellow A could attenuate the immunoglobulin E induced release of allergic cytokines without affecting cell viability from 1.0 to 50.0 μM. In conclusion, the established rat basophilic leukemia 2H3 cell membrane chromatography coupled with online high-performance liquid chromatography and tandem mass spectrometry method successfully screened and identified Hydroxysafflor yellow A from C. tinctorius as a potential antiallergic component. Pharmacological analysis elucidated that Hydroxysafflor yellow A is an effective natural component for inhibiting immunoglobulin E-antigen-mediated degranulation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hericium erinaceus (Yamabushitake): a unique resource for developing functional foods and medicines.

PubMed

Wang, Mingxing; Gao, Yang; Xu, Duoduo; Konishi, Tetsuya; Gao, Qipin

2014-12-01

Hericium erinaceus (HE) is a fungus inhabiting the mountainous areas of the northeast territories in Asia. HE has been used in traditional folk medicine and medicinal cuisine in China, Korea and Japan. Evidence has been adduced for a variety of physiological effects, including anti-aging, anti-cancer, anti-gastritis, and anti-metabolic disease properties. Hence, HE is an attractive target resource for developing not only medicines, but also functional foods. Basic studies on the physiological functions of HE and on the chemical identification of its active ingredients have progressed in recent decades. In this article, we provide an overview of the biochemical and pharmacological studies on HE, especially of its antitumor and neuroprotective functions, together with a survey of recent developments in the chemical analysis of its polysaccharides, which comprise its major active components.

Lipid Raft: A Floating Island Of Death or Survival

PubMed Central

George, Kimberly S.; Wu, Shiyong

2012-01-01

Lipid rafts are microdomains of the plasma membrane enriched in cholesterol and sphingolipids, and play an important role in the initiation of many pharmacological agent-induced signaling pathways and toxicological effects. The structure of lipid rafts is dynamic, resulting in an ever-changing content of both lipids and proteins. Cholesterol, as a major component of lipid rafts, is critical for the formation and configuration of lipid rafts microdomains, which provide signaling platforms capable of activating both pro-apoptotic and anti-apoptotic signaling pathways. A change of cholesterol level can result in lipid rafts disruption and activate or deactivate raft-associated proteins, such as death receptor proteins, protein kinases, and calcium channels. Several anti-cancer drugs are able to suppress growth and induce apoptosis of tumor cells through alteration of lipid raft contents via disrupting lipid raft integrity. PMID:22289360

Screening and analysis of potential anti-tumor components from the stipe of Ganoderma sinense using high-performance liquid chromatography/time-of-flight mass spectrometry with multivariate statistical tool.

PubMed

Chan, Kar-Man; Yue, Grace Gar-Lee; Li, Ping; Wong, Eric Chun-Wai; Lee, Julia Kin-Ming; Kennelly, Edward J; Lau, Clara Bik-San

2017-03-03

According to Chinese Pharmacopoeia 2015 edition, Ganoderma (Lingzhi) is a species complex that comprise of Ganoderma lucidum and Ganoderma sinense. The bioactivity and chemical composition of G. lucidium had been studied extensively, and it was shown to possess antitumor activities in pharmacological studies. In contrast, G. sinense has not been studied in great detail. Our previous studies found that the stipe of G. sinense exhibited more potent antitumor activity than the pileus. To identify the antitumor compounds in the stipe of G. sinense, we studied its chemical components by merging the bioactivity results with liquid chromatography-mass spectrometry-based chemometrics. The stipe of G. sinense was extracted with water, followed by ethanol precipitation and liquid-liquid partition. The resulting residue was fractionated using column chromatography. The antitumor activity of these fractions were analysed using MTT assay in murine breast tumor 4T1 cells, and their chemical components were studied using the LC-QTOF-MS with multivariate statistical tools. The chemometric and MS/MS analysis correlated bioactivity with five known cytotoxic compounds, 4-hyroxyphenylacetate, 9-oxo-(10E,12E)-octadecadienoic acid, 3-phenyl-2-propenoic acid, 13-oxo-(9E,11E)-octadecadienoic acid and lingzhine C, from the stipe of G. sinense. To the best of our knowledge, 4-hyroxyphenylacetate, 3-phenyl-2-propenoic acid and lingzhine C are firstly reported to be found in G. sinense. These five compounds will be investigated for their antitumor activities in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Principles of Safety Pharmacology

PubMed Central

Pugsley, M K; Authier, S; Curtis, M J

2008-01-01

Safety Pharmacology is a rapidly developing discipline that uses the basic principles of pharmacology in a regulatory-driven process to generate data to inform risk/benefit assessment. The aim of Safety Pharmacology is to characterize the pharmacodynamic/pharmacokinetic (PK/PD) relationship of a drug's adverse effects using continuously evolving methodology. Unlike toxicology, Safety Pharmacology includes within its remit a regulatory requirement to predict the risk of rare lethal events. This gives Safety Pharmacology its unique character. The key issues for Safety Pharmacology are detection of an adverse effect liability, projection of the data into safety margin calculation and finally clinical safety monitoring. This article sets out to explain the drivers for Safety Pharmacology so that the wider pharmacology community is better placed to understand the discipline. It concludes with a summary of principles that may help inform future resolution of unmet needs (especially establishing model validation for accurate risk assessment). Subsequent articles in this issue of the journal address specific aspects of Safety Pharmacology to explore the issues of model choice, the burden of proof and to highlight areas of intensive activity (such as testing for drug-induced rare event liability, and the challenge of testing the safety of so-called biologics (antibodies, gene therapy and so on.). PMID:18604233

EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin

PubMed Central

Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R.; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Tehran, Domenico Azarnia; Montecucco, Cesare; Barth, Holger

2016-01-01

The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins. PMID:27043629

EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin.

PubMed

Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Azarnia Tehran, Domenico; Montecucco, Cesare; Barth, Holger

2016-04-01

The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins.

Non-pharmacological self-management for people living with migraine or tension-type headache: a systematic review including analysis of intervention components.

PubMed

Probyn, Katrin; Bowers, Hannah; Mistry, Dipesh; Caldwell, Fiona; Underwood, Martin; Patel, Shilpa; Sandhu, Harbinder Kaur; Matharu, Manjit; Pincus, Tamar

2017-08-11

To assess the effect of non-pharmacological self-management interventions against usual care, and to explore different components and delivery methods within those interventions PARTICIPANTS: People living with migraine and/or tension-type headache INTERVENTIONS: Non-pharmacological educational or psychological self-management interventions; excluding biofeedback and physical therapy.We assessed the overall effectiveness against usual care on headache frequency, pain intensity, mood, headache-related disability, quality of life and medication consumption in meta-analysis.We also provide preliminary evidence on the effectiveness of intervention components and delivery methods. We found a small overall effect for the superiority of self-management interventions over usual care, with a standardised mean difference (SMD) of -0.36 (-0.45 to -0.26) for pain intensity; -0.32 (-0.42 to -0.22) for headache-related disability, 0.32 (0.20 to 0.45) for quality of life and a moderate effect on mood (SMD=0.53 (-0.66 to -0.40)). We did not find an effect on headache frequency (SMD=-0.07 (-0.22 to 0.08)).Assessment of components and characteristics suggests a larger effect on pain intensity in interventions that included explicit educational components (-0.51 (-0.68 to -0.34) vs -0.28 (-0.40 to -0.16)); mindfulness components (-0.50 (-0.82 to -0.18) vs 0.34 (-0.44 to -0.24)) and in interventions delivered in groups vs one-to-one delivery (0.56 (-0.72 to -0.40) vs -0.39 (-0.52 to -0.27)) and larger effects on mood in interventions including a cognitive-behavioural therapy (CBT) component with an SMD of -0.72 (-0.93 to -0.51) compared with those without CBT -0.41 (-0.58 to -0.24). Overall we found that self-management interventions for migraine and tension-type headache are more effective than usual care in reducing pain intensity, mood and headache-related disability, but have no effect on headache frequency. Preliminary findings also suggest that including CBT, mindfulness and educational components in interventions, and delivery in groups may increase effectiveness. PROSPERO 2016:CRD42016041291. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Practical aspects of estimating energy components in rodents

PubMed Central

van Klinken, Jan B.; van den Berg, Sjoerd A. A.; van Dijk, Ko Willems

2013-01-01

Recently there has been an increasing interest in exploiting computational and statistical techniques for the purpose of component analysis of indirect calorimetry data. Using these methods it becomes possible to dissect daily energy expenditure into its components and to assess the dynamic response of the resting metabolic rate (RMR) to nutritional and pharmacological manipulations. To perform robust component analysis, however, is not straightforward and typically requires the tuning of parameters and the preprocessing of data. Moreover the degree of accuracy that can be attained by these methods depends on the configuration of the system, which must be properly taken into account when setting up experimental studies. Here, we review the methods of Kalman filtering, linear, and penalized spline regression, and minimal energy expenditure estimation in the context of component analysis and discuss their results on high resolution datasets from mice and rats. In addition, we investigate the effect of the sample time, the accuracy of the activity sensor, and the washout time of the chamber on the estimation accuracy. We found that on the high resolution data there was a strong correlation between the results of Kalman filtering and penalized spline (P-spline) regression, except for the activity respiratory quotient (RQ). For low resolution data the basal metabolic rate (BMR) and resting RQ could still be estimated accurately with P-spline regression, having a strong correlation with the high resolution estimate (R2 > 0.997; sample time of 9 min). In contrast, the thermic effect of food (TEF) and activity related energy expenditure (AEE) were more sensitive to a reduction in the sample rate (R2 > 0.97). In conclusion, for component analysis on data generated by single channel systems with continuous data acquisition both Kalman filtering and P-spline regression can be used, while for low resolution data from multichannel systems P-spline regression gives more robust results. PMID:23641217

Advances in the development of AMPK-activating compounds.

PubMed

Sriwijitkamol, Apiradee; Musi, Nicolas

2008-10-01

AMP-activated protein kinase (AMPK) is an energy sensing enzyme that controls glucose and lipid metabolism. This review summarizes the present data on AMPK as a pharmacologic target for the treatment of metabolic disorders. The mechanisms governing AMPK activity and how this enzyme controls different metabolic pathways are reviewed briefly, and details about the effect that AMPK activators have on glucose metabolism are provided. Evidence obtained using the AMPK-activating compound 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) suggests that AMPK promotes glucose transport into skeletal muscles and that this enzyme inhibits hepatic glucose production. AICAR also induces fatty acid oxidation in muscle and inhibits cholesterol synthesis in the liver. The metabolic effects of AICAR on glucose and lipid metabolism indicate that AMPK may be a good pharmacologic target for the treatment of type 2 diabetes and hypercholesterolemia. Novel AMPK-specific compounds are allowing researchers to examine whether this enzyme is a useful pharmacologic target for the treatment of human disease and whether chronic activation of AMPK will be safe.

Multi-Response Extraction Optimization Based on Anti-Oxidative Activity and Quality Evaluation by Main Indicator Ingredients Coupled with Chemometric Analysis on Thymus quinquecostatus Celak.

PubMed

Chang, Yan-Li; Shen, Meng; Ren, Xue-Yang; He, Ting; Wang, Le; Fan, Shu-Sheng; Wang, Xiu-Huan; Li, Xiao; Wang, Xiao-Ping; Chen, Xiao-Yi; Sui, Hong; She, Gai-Mei

2018-04-19

Thymus quinquecostatus Celak is a species of thyme in China and it used as condiment and herbal medicine for a long time. To set up the quality evaluation of T. quinquecostatus , the response surface methodology (RSM) based on its 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was introduced to optimize the extraction condition, and the main indicator components were found through an UPLC-LTQ-Orbitrap MS n method. The ethanol concentration, solid-liquid ratio, and extraction time on optimum conditions were 42.32%, 1:17.51, and 1.8 h, respectively. 35 components having 12 phenolic acids and 23 flavonoids were unambiguously or tentatively identified both positive and negative modes to employ for the comprehensive analysis in the optimum anti-oxidative part. A simple, reliable, and sensitive HPLC method was performed for the multi-component quantitative analysis of T. quinquecostatus using six characteristic and principal phenolic acids and flavonoids as reference compounds. Furthermore, the chemometrics methods (principal components analysis (PCA) and hierarchical clustering analysis (HCA)) appraised the growing areas and harvest time of this herb closely relative to the quality-controlled. This study provided full-scale qualitative and quantitative information for the quality evaluation of T. quinquecostatus , which would be a valuable reference for further study and development of this herb and related laid the foundation of further study on its pharmacological efficacy.

Cannabidiol in medicine: a review of its therapeutic potential in CNS disorders.

PubMed

Scuderi, Caterina; Filippis, Daniele De; Iuvone, Teresa; Blasio, Angelo; Steardo, Antonio; Esposito, Giuseppe

2009-05-01

Cannabidiol (CBD) is the main non-psychotropic component of the glandular hairs of Cannabis sativa. It displays a plethora of actions including anticonvulsive, sedative, hypnotic, antipsychotic, antiinflammatory and neuroprotective properties. However, it is well established that CBD produces its biological effects without exerting significant intrinsic activity upon cannabinoid receptors. For this reason, CBD lacks the unwanted psychotropic effects characteristic of marijuana derivatives, so representing one of the bioactive constituents of Cannabis sativa with the highest potential for therapeutic use.The present review reports the pharmacological profile of CBD and summarizes results from preclinical and clinical studies utilizing CBD, alone or in combination with other phytocannabinoids, for the treatment of a number of CNS disorders.

In silico pharmacology for drug discovery: applications to targets and beyond

PubMed Central

Ekins, S; Mestres, J; Testa, B

2007-01-01

Computational (in silico) methods have been developed and widely applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure-activity relationships, similarity searching, pharmacophores, homology models and other molecular modeling, machine learning, data mining, network analysis tools and data analysis tools that use a computer. Such methods have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The first part of this review discussed the methods that have been used for virtual ligand and target-based screening and profiling to predict biological activity. The aim of this second part of the review is to illustrate some of the varied applications of in silico methods for pharmacology in terms of the targets addressed. We will also discuss some of the advantages and disadvantages of in silico methods with respect to in vitro and in vivo methods for pharmacology research. Our conclusion is that the in silico pharmacology paradigm is ongoing and presents a rich array of opportunities that will assist in expediating the discovery of new targets, and ultimately lead to compounds with predicted biological activity for these novel targets. PMID:17549046

Modulation of Regulatory T Cell Activity by TNF Receptor Type II-Targeting Pharmacological Agents

PubMed Central

Zou, Huimin; Li, Ruixin; Hu, Hao; Hu, Yuanjia; Chen, Xin

2018-01-01

There is now compelling evidence that tumor necrosis factor (TNF)–TNF receptor type II (TNFR2) interaction plays a decisive role in the activation, expansion, and phenotypical stability of suppressive CD4+Foxp3+ regulatory T cells (Tregs). In an effort to translate this basic research finding into a therapeutic benefit, a number of agonistic or antagonistic TNFR2-targeting biological agents with the capacity to activate or inhibit Treg activity have been developed and studied. Recent studies also show that thalidomide analogs, cyclophosphamide, and other small molecules are able to act on TNFR2, resulting in the elimination of TNFR2-expressing Tregs. In contrast, pharmacological agents, such as vitamin D3 and adalimumab, were reported to induce the expansion of Tregs by promoting the interaction of transmembrane TNF (tmTNF) with TNFR2. These studies clearly show that TNFR2-targeting pharmacological agents represent an effective approach to modulating the function of Tregs and thus may be useful in the treatment of major human diseases such as autoimmune disorders, graft-versus-host disease (GVHD), and cancer. In this review, we will summarize and discuss the latest progress in the study of TNFR2-targeting pharmacological agents and their therapeutic potential based on upregulation or downregulation of Treg activity. PMID:29632537

The Genus Spilanthes Ethnopharmacology, Phytochemistry, and Pharmacological Properties: A Review

PubMed Central

Paulraj, Jayaraj; Govindarajan, Raghavan; Palpu, Pushpangadan

2013-01-01

Spilanthes spp. are popular, over-the-counter remedies; they are sold over the internet under various names and are widely used in traditional medicine in various cultures. This review will summarize the important reports on the ethnopharmacology, botany, phytochemistry, and pharmacological properties as described in the literature from recent years (1920 to 2013). Spilanthes spp. are used for more than 60 types of disorders. They are reported to contain a number of biologically active phytochemicals, although a large number of ethnopharmacological uses have been documented; only a few of these species have been investigated for their chemical and biological activities. The studies are carried out mainly on Spilanthes extracts and a few metabolites substantiate the uses of these plants in traditional medicine. Well-conducted pharmacological studies are still needed for several traditional indications, and the mechanisms of action by which the plant extracts and the active compounds exert their pharmacological effects remain to be studied. They are predominantly used as extracts in personal care products, traditional medicines, and the pharmaceutical and culinary areas. Suggestions are made regarding some of the possible mechanisms of action as to how the known compounds may exert their biological activity. PMID:24454346

Effects of non-pharmacological pain treatments on brain states

PubMed Central

Jensen, Mark P.; Sherlin, Leslie H.; Askew, Robert L.; Fregni, Felipe; Witkop, Gregory; Gianas, Ann; Howe, Jon D.; Hakimian, Shahin

2013-01-01

Objective To (1) evaluate the effects of a single session of four non-pharmacological pain interventions, relative to a sham tDCS procedure, on pain and electroencephalogram- (EEG-) assessed brain oscillations, and (2) determine the extent to which procedure-related changes in pain intensity are associated with changes in brain oscillations. Methods 30 individuals with spinal cord injury and chronic pain were given an EEG and administered measures of pain before and after five procedures (hypnosis, meditation, transcranial direct current stimulation [tDCS], and neurofeedback) and a control sham tDCS procedure. Results Each procedure was associated with a different pattern of changes in brain activity, and all active procedures were significantly different from the control procedure in at least three bandwidths. Very weak and mostly non-significant associations were found between changes in EEG-assessed brain activity and pain. Conclusions Different non-pharmacological pain treatments have distinctive effects on brain oscillation patterns. However, changes in EEG-assessed brain oscillations are not significantly associated with changes in pain, and therefore such changes do not appear useful for explaining the benefits of these treatments. Significance The results provide new findings regarding the unique effects of four non-pharmacological treatments on pain and brain activity. PMID:23706958

Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity, Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions.

PubMed

Tolba, Mai F; Omar, Hany A; Azab, Samar S; Khalifa, Amani E; Abdel-Naim, Ashraf B; Abdel-Rahman, Sherif Z

2016-10-02

Propolis, a honey bee product, has been used in folk medicine for centuries for the treatment of abscesses, canker sores and for wound healing. Caffeic acid phenethyl ester (CAPE) is one of the most extensively investigated active components of propolis which possess many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anti-cancer effects. CAPE is a polyphenolic compound characterized by potent antioxidant and cytoprotective activities and protective effects against ischemia-reperfusion (I/R)-induced injury in multiple tissues such as brain, retina, heart, skeletal muscles, testis, ovaries, intestine, colon, and liver. Furthermore, several studies indicated the protective effects of CAPE against chemotherapy-induced adverse drug reactions (ADRs) including several antibiotics (streptomycin, vancomycin, isoniazid, ethambutol) and chemotherapeutic agents (mitomycin, doxorubicin, cisplatin, methotrexate). Due to the broad spectrum of pharmacological activities of CAPE, this review makes a special focus on the recently published data about CAPE antioxidant activity as well as its protective effects against I/R-induced injury and many adverse drug reactions.

Lowered Insulin Signalling Ameliorates Age-Related Sleep Fragmentation in Drosophila

PubMed Central

Hendrich, Oliver; Hinze, Yvonne; Birras, Ulrike; Partridge, Linda

2014-01-01

Sleep fragmentation, particularly reduced and interrupted night sleep, impairs the quality of life of older people. Strikingly similar declines in sleep quality are seen during ageing in laboratory animals, including the fruit fly Drosophila. We investigated whether reduced activity of the nutrient- and stress-sensing insulin/insulin-like growth factor (IIS)/TOR signalling network, which ameliorates ageing in diverse organisms, could rescue the sleep fragmentation of ageing Drosophila. Lowered IIS/TOR network activity improved sleep quality, with increased night sleep and day activity and reduced sleep fragmentation. Reduced TOR activity, even when started for the first time late in life, improved sleep quality. The effects of reduced IIS/TOR network activity on day and night phenotypes were mediated through distinct mechanisms: Day activity was induced by adipokinetic hormone, dFOXO, and enhanced octopaminergic signalling. In contrast, night sleep duration and consolidation were dependent on reduced S6K and dopaminergic signalling. Our findings highlight the importance of different IIS/TOR components as potential therapeutic targets for pharmacological treatment of age-related sleep fragmentation in humans. PMID:24690889

[High blood pressure and physical exercise].

PubMed

Sosner, P; Gremeaux, V; Bosquet, L; Herpin, D

2014-06-01

High blood pressure is a frequent pathology with many cardiovascular complications. As highlighted in guidelines, the therapeutic management of hypertension relies on non-pharmacological measures, which are diet and regular physical activity, but both patients and physicians are reluctant to physical activity prescription. To acquire the conviction that physical activity is beneficial, necessary and possible, we can take into account some fundamental and clinical studies, as well as the feedback of our clinical practice. Physical inactivity is a major risk factor for cardiovascular morbidity and mortality, and hypertension contributes to increase this risk. Conversely, regular practice of physical activity decreases very significantly the risk by up to 60%. The acute blood pressure changes during exercise and post-exercise hypotension differs according to the dynamic component (endurance or aerobic and/or strength exercises), but the repetition of the sessions leads to the chronic hypotensive benefit of physical activity. Moreover, physical activity prescription must take into account the assessment of global cardiovascular risk, the control of the hypertension, and the opportunities and desires of the patient in order to promote good adherence and beneficial lifestyle change. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Alterations in pharmacological and behavioural responses in recombinant mouse line with an increased predisposition to catalepsy: role of the 5-HT1A receptor.

PubMed

Kulikova, E A; Bazovkina, D V; Akulov, A E; Tsybko, A S; Fursenko, D V; Kulikov, A V; Naumenko, V S; Ponimaskin, E; Kondaurova, E M

2016-07-01

One important syndrome of psychiatric disorders in humans is catalepsy. Here, we created mice with different predispositions to catalepsy and analysed their pharmacological and behavioural properties. Two mouse lines, B6-M76C and B6-M76B, were created by transfer of the main locus of catalepsy containing the 5-HT1A receptor gene to the C57BL/6 genetic background. Behaviour, brain morphology, expression of key components of the serotoninergic system, and pharmacological responses to acute and chronic stimulation of the 5-HT1A receptor were compared. B6-M76B mice were not cataleptic, whereas 14% of B6-M76C mice demonstrated catalepsy and decreased depressive-like behaviour. Acute administration of the 5-HT1A receptor agonist 8-OH-DPAT resulted in dose-dependent hypothermia and in decreased locomotion in both lines. Chronic 8-OH-DPAT administration abolished the 5-HT1A receptor-mediated hypothermic response in B6-M76C mice and increased locomotor activity in B6-M76B mice. In addition, 5-HT metabolism was significantly reduced in the hippocampus of B6-M76C mice, and this effect was accompanied by an increased expression of the 5-HT1A receptor. Our findings indicate that transfer of the main locus of hereditary catalepsy containing the 5-HT1A receptor from CBA mice to the C57BL/6 genetic background led to increased postsynaptic and decreased presynaptic functional responses of the 5-HT1A receptor. This characteristic establishes the B6-M76C line as an attractive model for the pharmacological screening of 5-HT1A receptor-related drugs specifically acting on either pre- or postsynaptic receptors. This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc. © 2016 The British Pharmacological Society.

[Herbalism, botany and components analysis study on original plants of frankincense].

PubMed

Sun, Lei; Xu, Jimin; Jin, Hongyu; Tian, Jingai; Lin, Ruichao

2011-01-01

In order to clarify original plants of traditional Chinese medicine (TCM) frankincense, a GC method for determination essential oils and a HPLC method for determination boswellic acids were carried out together with analysis of herbalism, botany, components and pharmacology papers of frankincense. It was concluded that original plants of TCM frankincense include at least Boswellia sacra, B. papyrifera and B. serrata.

Phytochemical and pharmacological investigation of Spiraea chamaedryfolia: a contribution to the chemotaxonomy of Spiraea genus.

PubMed

Kiss, Tivadar; Cank, Kristóf Bence; Orbán-Gyapai, Orsolya; Liktor-Busa, Erika; Zomborszki, Zoltán Péter; Rutkovska, Santa; Pučka, Irēna; Németh, Anikó; Csupor, Dezső

2017-12-21

Diterpene alkaloids are secondary plant metabolites and chemotaxonomical markers with a strong biological activity. These compounds are characteristic for the Ranunculaceae family, while their occurrence in other taxa is rare. Several species of the Spiraea genus (Rosaceae) are examples of this rarity. Screening Spiraea species for alkaloid content is a chemotaxonomical approach to clarify the classification and phylogeny of the genus. Novel pharmacological findings make further investigations of Spiraea diterpene alkaloids promising. Seven Spiraea species were screened for diterpene alkaloids. Phytochemical and pharmacological investigations were performed on Spiraea chamaedryfolia, the species found to contain diterpene alkaloids. Its alkaloid-rich fractions were found to exert a remarkable xanthine-oxidase inhibitory activity and a moderate antibacterial activity. The alkaloid distribution within the root was clarified by microscopic techniques.

A new agent developed by biotransformation of polyphyllin VII inhibits chemoresistance in breast cancer.

PubMed

He, Dong-Xu; Li, Guo-Hong; Gu, Xiao-Ting; Zhang, Liang; Mao, Ai-Qin; Wei, Juan; Liu, De-Quan; Shi, Gui-Yang; Ma, Xin

2016-05-31

Biotransformation by the endophytes of certain plants changes various compounds, and this 'green' chemistry becomes increasingly important for finding new products with pharmacological activity. In this study, polyphyllin VII (PPL7) was biotransformed by endophytes from the medicinal plant Paris polyphylla Smith, var. yunnanensis. This produced a new compound, ZH-2, with pharmacological activity in vitro and in vivo. ZH-2 was more potent than PPL7 in selectively killing more chemoresistant than chemosensitive breast cancer cells. ZH-2 also re-sensitized chemoresistant breast cancer cells, as evidenced by the improved anti-cancer activity of commonly-used chemotherapeutic agent in vitro, in vivo, and in clinical samples. This anti-chemoresistance effect of ZH-2 was associated with inhibiting the epithelial-mesenchymal transition (EMT) pathway. Taken together, our findings are the first one to link biotransformation with a biomedicine. The results provide insights into developing new pharmacologically-active agents via biotransformation by endophytes.

Ethnopharmacological uses, phytochemistry, biological activities, and therapeutic applications of Clinacanthus nutans (Burm. f.) Lindau: A comprehensive review.

PubMed

Kamarudin, Muhamad Noor Alfarizal; Sarker, Md Moklesur Rahman; Kadir, Habsah Abdul; Ming, Long Chiau

2017-07-12

Clinacanthus nutans (Burm. f.) Lindau, a widely used medicinal plant, is extensively grown in tropical Asia and Southeast Asian countries. C. nutans, with its broad spectrum of pharmacological activities, has been traditionally used to treat cancer, inflammatory disorders, diabetes, insect bites, and skin problems, consumed as a vegetable, mixed with fresh juices, in concoctions, and as a whole plant. The present review analyzes the advances in the ethnopharmacology, phytochemistry, pharmacology, and toxicology of C. nutans. In addition, the needs and perspectives for future investigation of this plant are addressed. This review aims to provide a comprehensive report on the ethnomedicinal use, phytochemistry, pharmacological activities, molecular mechanisms, and nutritional values of C. nutans. The present review will open new avenues for further in-depth pharmacological studies of C. nutans for it to be developed as a potential nutraceutical and to improve the available products in the market. All the available information on C. nutans was collected using the key words "Clinacanthus nutans" and/or "ethnomedicine" and/or "phytochemicals" and/or "anticancer" and/or "anti-inflammatory" and/or "antiviral" through an electronic search of the following databases: PubMed, Web of Science, EMBASE, Cochrane Library, Clinical Trials.org, SciFinder Scholar, Scopus, and Google Scholar. In addition, unpublished materials, Ph.D. and M.Sc. dissertations, conference papers, and ethnobotanical textbooks were used. The Plant List (www.theplantlist.org) and International Plant Name Index databases were used to validate the scientific name of the plant. The literature supported the ethnomedicinal uses of C. nutans as recorded in Thailand, Indonesia, and Malaysia for various purposes. Bioactivities experimentally proven for C. nutans include cytotoxic, anticancer, antiviral, anti-inflammatory, immunomodulatory, antidiabetic, antioxidant, antihyperlipidemic, antimicrobial, and chemotherapeutic (in aquaculture) activities. Most of these activities have so far only been investigated in chemical, cell-based, and animal assays. Various groups of phytochemicals including five sulfur-containing glycosides, eight chlorophyll derivatives, nine cerebrosides, and a monoacylmonogalactosyl glycerol are present in C. nutans. The presence of two glycerolipids, four sulfur-containing compounds, six known flavones, a flavanol, four flavonols, two phytosterols, one polypeptide, and various phenolics and fatty acids largely influences its diverse bioactivities. Numerous reports justify the ethnomedicinal use of C. nutans as an antiviral agent in treating herpes simplex virus and varicella-zoster virus infections and as part of a traditional anticancer anti-inflammatory concoction agent for various inflammatory diseases. C. nutans tea was reported to have a good percentage of carbohydrate, crude protein, minerals, essential amino acids, nonessential amino acids, and essential fatty acids. Acute, subacute, and subchronic toxicity studies demonstrated that oral administration of ethanol and methanol extracts of C. nutans to male Swiss albino mice and male Sprague-Dawley (SD) rats, respectively, did not lead to any toxicity or adverse effects on the animal behavior and organs when used in amounts as high as 2g/kg. The collected literatures demonstrated that, as an important traditional medicine, C. nutans is a promising ethnomedicinal plant with various extracts and bioactive compounds exhibiting multifarious bioactivities. However, it is important for future studies to conduct further in vitro and in vivo bioactivity evaluations systematically, following the standard pharmacology guidelines. It is crucial to elucidate in-depth molecular mechanisms, structure-activity relationships, and potential synergistic and antagonistic effects of multi-component extracts and bioactive constituents derived from C. nutans. Further studies should also focus on comprehensive toxicity that includes long-term effects and adverse effects on target organs of C. nutans and bioactive compounds in correlation with the specific pharmacological effects. Copyright © 2017. Published by Elsevier B.V.

Fraxinus: A Plant with Versatile Pharmacological and Biological Activities.

PubMed

Sarfraz, Iqra; Rasul, Azhar; Jabeen, Farhat; Younis, Tahira; Zahoor, Muhammad Kashif; Arshad, Muhammad; Ali, Muhammad

2017-01-01

Fraxinus , a member of the Oleaceae family, commonly known as ash tree is found in northeast Asia, north America, east and western France, China, northern areas of Pakistan, India, and Afghanistan. Chemical constituents of Fraxinus plant include various secoiridoids, phenylethanoids, flavonoids, coumarins, and lignans; therefore, it is considered as a plant with versatile biological and pharmacological activities. Its tremendous range of pharmacotherapeutic properties has been well documented including anticancer, anti-inflammatory, antioxidant, antimicrobial, and neuroprotective. In addition, its bioactive phytochemicals and secondary metabolites can be effectively used in cosmetic industry and as a competent antiaging agent. Fraxinus presents pharmacological effectiveness by targeting the novel targets in several pathological conditions, which provide a spacious therapeutic time window. Our aim is to update the scientific research community with recent endeavors with specifically highlighting the mechanism of action in different diseases. This potentially efficacious pharmacological drug candidate should be used for new drug discovery in future. This review suggests that this plant has extremely important medicinal utilization but further supporting studies and scientific experimentations are mandatory to determine its specific intracellular targets and site of action to completely figure out its pharmacological applications.

Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides.

PubMed

Iwamoto, Naoki; Butler, David C D; Svrzikapa, Nenad; Mohapatra, Susovan; Zlatev, Ivan; Sah, Dinah W Y; Meena; Standley, Stephany M; Lu, Genliang; Apponi, Luciano H; Frank-Kamenetsky, Maria; Zhang, Jason Jingxin; Vargeese, Chandra; Verdine, Gregory L

2017-09-01

Whereas stereochemical purity in drugs has become the standard for small molecules, stereoisomeric mixtures containing as many as a half million components persist in antisense oligonucleotide (ASO) therapeutics because it has been feasible neither to separate the individual stereoisomers, nor to synthesize stereochemically pure ASOs. Here we report the development of a scalable synthetic process that yields therapeutic ASOs having high stereochemical and chemical purity. Using this method, we synthesized rationally designed stereopure components of mipomersen, a drug comprising 524,288 stereoisomers. We demonstrate that phosphorothioate (PS) stereochemistry substantially affects the pharmacologic properties of ASOs. We report that Sp-configured PS linkages are stabilized relative to Rp, providing stereochemical protection from pharmacologic inactivation of the drug. Further, we elucidated a triplet stereochemical code in the stereopure ASOs, 3'-SpSpRp, that promotes target RNA cleavage by RNase H1 in vitro and provides a more durable response in mice than stereorandom ASOs.

Pharmacological inhibition of cathepsin K: A promising novel approach for postmenopausal osteoporosis therapy.

PubMed

Mukherjee, Kakoli; Chattopadhyay, Naibedya

2016-10-01

Osteoporosis is a metabolic bone disease that is characterized by heightened state of bone resorption accompanied by diminished bone formation, leading to a reduction of bone mineral density (BMD) and deterioration of bone quality, thus increasing the risk of developing fractures. Molecular insight into bone biology identified cathepsin K (CatK) as a novel therapeutic target. CatK is a lysosomal cysteine protease secreted by activated osteoclasts during bone resorption, whose primary substrate is type I collagen, the major component of organic bone matrix. Available anti-resorptive drugs affect osteoclast survival and influence both resorption and formation of bone. CatK inhibitors are distinct from the existing anti-resorptives as they only target the resorption process itself without impairing osteoclast differentiation and do not interfere with bone formation. An inhibitor of CatK, odanacatib, robustly increased both trabecular and cortical BMD in postmenopausal osteoporosis patients. The phase III fracture prevention trial with odanacatib ended early due to good efficacy and a favorable benefit/risk profile, thus, enhancing the opportunity for CatK as a pharmacological target for osteoporosis. So far, all the inhibitors that reached to the stage of clinical trial targeted active site of CatK to abrogate the entire proteolytic activity of the enzyme in addition to the desired blockage of excessive elastin and collagen degradation, and could thus pose safety concerns with long term use. Identification of selective exosite inhibitors that inhibit CatK's elastase and/or collagenase activity but do not affect the hydrolysis of other physiologically relevant substrates of CatK would be an improved strategy to inhibit this enzyme. Copyright © 2016 Elsevier Inc. All rights reserved.

Ethnobotany as a Pharmacological Research Tool and Recent Developments in CNS-active Natural Products from Ethnobotanical Sources

PubMed Central

McClatchey, Will C.; Mahady, Gail B.; Bennett, Bradley C.; Shiels, Laura; Savo, Valentina

2009-01-01

The science of ethnobotany is reviewed in light of its multidisciplinary contributions to natural product research for the development of pharmaceuticals and pharmacological tools. Some of the issues reviewed involve ethical and cultural perspectives of healthcare and medicinal plants. While these are not usually part of the discussion of pharmacology, cultural concerns potentially provide both challenges and insight for field and laboratory researchers. Plant evolutionary issues are also considered as they relate to development of plant chemistry and accessing this through ethnobotanical methods. The discussion includes presentation of a range of CNS-active medicinal plants that have been recently examined in the field, laboratory and/or clinic. Each of these plants is used to illustrate one or more aspects about the valuable roles of ethnobotany in pharmacological research. We conclude with consideration of mutually beneficial future collaborations between field ethnobotanists and pharmacologists. PMID:19422851

Emerging drugs which target the renin-angiotensin-aldosterone system.

PubMed

Steckelings, Ulrike Muscha; Paulis, Ludovit; Unger, Thomas; Bader, Michael

2011-12-01

The renin-angiotensin-aldosterone system (RAAS) is already the most important target for drugs in the cardiovascular system. However, still new developments are underway to interfere with the system on different levels. The novel strategies to interfere with RAAS aim to reduce the synthesis of the two major RAAS effector hormones, angiotensin (Ang) II and aldosterone, or interfere with their receptors, AT1 and mineralocorticoid receptor, respectively. Moreover, novel targets have been identified in RAAS, such as the (pro)renin receptor, and molecules, which counteract the classical actions of Ang II and are therefore beneficial in cardiovascular diseases. These include the AT2 receptor and the ACE2/Ang-(1-7)/Mas axis. The search for drugs activating these tissue-protective arms of RAAS is therefore the most innovative field in RAAS pharmacology. Most of the novel pharmacological strategies to inhibit the classical RAAS need to prove their superiority above the existing treatment in clinical trials and then have to compete against these now quite cheap drugs in a competitive market. The newly discovered targets have functions beyond the cardiovascular system opening up novel therapeutic areas for drugs interfering with RAAS components.

Review of the chemistry and pharmacology of 7-Methyljugulone.

PubMed

Mbaveng, Armelle T; Kuete, Victor

2014-03-01

Naphthoquinone is a class of phenolic compounds derived from naphthalene. 7-Methyljuglone (7-MJ) is a naphthoquinone also known as ramentaceone or 6-Methyl-8-hydroxy-1,4-naphthoquinone or 5-Hydroxy-7-methyl-1,4-naphthoquinone or 7-Methyl-5-hydroxy-1,4-naphthoquinone or 5-Hydroxy-7-methyl-,1,4-naphtoquinone or 7-Methyl-5-hydroxynaphthalene-1,4-dione. This compound is a biologically active naphtoquinone, with a molecular weight of 188 g/mol mostly isolated in the genus Diospyros and Euclea. This review was aimed at providing available chemically and pharmacological data on 7-MJ. The chemical and pharmacological data were retrieved from the well-known scientific websites such as Pubmed, Google Scholar, Reaxys, Scirus, Scopus, Sciencedirect, Web-of-knowledge and Scifinder. 7-MJ was reported to have a variety of pharmacological activities such as antibacterial, antifungal, anticancer, antitubercular, anti-inflammatory and antiviral activities. The hemi-synthesis of the compound have been described. The present review pooled out together the knowledge on 7-MJ, and can serve as the start point for future research and valorization accomplishments.

The Alkylating-HDAC Inhibition Fusion Principle: Taking Chemotherapy to the Next Level with the First in Class Molecule EDO-S101.

PubMed

Mehrling, Thomas; Chen, Yi

2016-01-01

Chemotherapy may still be an essential component to treat cancer in combination with new targeted therapies. But chemotherapy needs to get smarter in order to make those combination regimens more effective and also more tolerable, particularly for an aging population. We describe the first time the synthesis and pharmacological testing of a fusion molecule comprising of the alkylator bendamustine and the HDAC-inhibitor vorinostat. The drug was designed to allow for the exploitation of both mechanisms of action simultaneously with the goal to provide a molecule with superior efficacy over the single agents. The pharmacological testing confirms the full functional capacity of both moieties and encouraging pharmacological data raises the hope that the drug may turn out to be a great addition to the armentarium of anticancer agents.

Spinal GABA-B receptor modulates neutrophil recruitment to the knee joint in zymosan-induced arthritis.

PubMed

Bassi, Gabriel S; do C Malvar, David; Cunha, Thiago M; Cunha, Fernando Q; Kanashiro, Alexandre

2016-08-01

Recent studies have demonstrated that the central nervous system controls inflammatory responses by activating complex efferent neuroimmune pathways. The present study was designed to evaluate the role that central gamma-aminobutyric acid type B (GABA-B) receptor plays in neutrophil migration in a murine model of zymosan-induced arthritis by using different pharmacological tools. We observed that intrathecal administration of baclofen, a selective GABA-B agonist, exacerbated the inflammatory response in the knee after zymosan administration characterized by an increase in the neutrophil recruitment and knee joint edema, whereas saclofen, a GABA-B antagonist, exerted the opposite effect. Intrathecal pretreatment of the animals with SB203580 (an inhibitor of p38 mitogen-activated protein kinase) blocked the pro-inflammatory effect of baclofen. On the other hand, systemic administration of guanethidine, a sympatholytic drug that inhibits catecholamine release, and nadolol, a beta-adrenergic receptor antagonist, reversed the effect of saclofen. Moreover, saclofen suppressed the release of the pro-inflammatory cytokines into the knee joint (ELISA) and pain-related behaviors (open field test). Since the anti-inflammatory effect of saclofen depends on the sympathetic nervous system integrity, we observed that isoproterenol, a beta-adrenergic receptor agonist, mimics the central GABA-B blockade decreasing knee joint neutrophil recruitment. Together, these results demonstrate that the pharmacological manipulation of spinal GABAergic transmission aids control of neutrophil migration to the inflamed joint by modulating the activation of the knee joint-innervating sympathetic terminal fibers through a mechanism dependent on peripheral beta-adrenergic receptors and central components, such as p38 MAPK.

Hematopoietic Colony Formation from Human Growth Factor-Dependent TF1 Cells and Human Cord Blood Myeloid Progenitor Cells Depends on SHP2 Phosphatase Function

PubMed Central

Etienne-Julan, Maryse; Gotoh, Akihiko; Braun, Stephen E.; Lu, Li; Cooper, Scott; Feng, Gen-Sheng; Li, Xing Jun

2013-01-01

The protein tyrosine phosphatase, SHP2, is widely expressed; however, previous studies demonstrated that hematopoietic cell development more stringently requires Shp2 expression compared to other tissues. Furthermore, somatic gain-of-function SHP2 mutants are commonly found in human myeloid leukemias. Given that pharmacologic inhibitors to SHP2 phosphatase activity are currently in development as putative antileukemic agents, we conducted a series of experiments examining the necessity of SHP2 phosphatase activity for human hematopoiesis. Anti-sense oligonucleotides to human SHP2 coding sequences reduced human cord blood- and human cell line, TF1-derived colony formation. Expression of truncated SHP2 bearing its Src homology 2 (SH2) domains, but lacking the phosphatase domain similarly reduced human cord blood- and TF1-derived colony formation. Mechanistically, expression of truncated SHP2 reduced the interaction between endogenous, full-length SHP2 with the adapter protein, Grb2. To verify the role of SHP2 phosphatase function in human hematopoietic cell development, human cord blood CD34+ cells were transduced with a leukemia-associated phosphatase gain-of-function SHP2 mutant or with a phosphatase dead SHP2 mutant, which indicated that increased phosphatase function enhanced, while decreased SHP2 phosphatase function reduced, human cord blood-derived colonies. Collectively, these findings indicate that SHP2 phosphatase function regulates human hematopoietic cell development and imply that the phosphatase component of SHP2 may serve as a pharmacologic target in human leukemias bearing increased SHP2 phosphatase activity. PMID:23082805

Hematopoietic colony formation from human growth factor-dependent TF1 cells and human cord blood myeloid progenitor cells depends on SHP2 phosphatase function.

PubMed

Broxmeyer, Hal E; Etienne-Julan, Maryse; Gotoh, Akihiko; Braun, Stephen E; Lu, Li; Cooper, Scott; Feng, Gen-Sheng; Li, Xing Jun; Chan, Rebecca J

2013-03-15

The protein tyrosine phosphatase, SHP2, is widely expressed; however, previous studies demonstrated that hematopoietic cell development more stringently requires Shp2 expression compared to other tissues. Furthermore, somatic gain-of-function SHP2 mutants are commonly found in human myeloid leukemias. Given that pharmacologic inhibitors to SHP2 phosphatase activity are currently in development as putative antileukemic agents, we conducted a series of experiments examining the necessity of SHP2 phosphatase activity for human hematopoiesis. Anti-sense oligonucleotides to human SHP2 coding sequences reduced human cord blood- and human cell line, TF1-derived colony formation. Expression of truncated SHP2 bearing its Src homology 2 (SH2) domains, but lacking the phosphatase domain similarly reduced human cord blood- and TF1-derived colony formation. Mechanistically, expression of truncated SHP2 reduced the interaction between endogenous, full-length SHP2 with the adapter protein, Grb2. To verify the role of SHP2 phosphatase function in human hematopoietic cell development, human cord blood CD34+ cells were transduced with a leukemia-associated phosphatase gain-of-function SHP2 mutant or with a phosphatase dead SHP2 mutant, which indicated that increased phosphatase function enhanced, while decreased SHP2 phosphatase function reduced, human cord blood-derived colonies. Collectively, these findings indicate that SHP2 phosphatase function regulates human hematopoietic cell development and imply that the phosphatase component of SHP2 may serve as a pharmacologic target in human leukemias bearing increased SHP2 phosphatase activity.

Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

PubMed Central

Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

2012-01-01

Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an IKr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. PMID:22745159

TLR3 dsRNA agonist inhibits growth and invasion of HepG2.2.15 HCC cells.

PubMed

Chen, Li; Xu, Yu-Yin; Zhou, Jia-Ming; Wu, Yuan-Yuan; E, Qun; Zhu, Yuan-Yuan

2012-07-01

Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in immune signaling and plays a crucial role in survival by being able to recognize various viral components including double-stranded RNA (dsRNA). TLR3 expression and function in cancer cells are not well understood. In this study, we investigated whether TLR3 agonist dsRNA (BM-06) can inhibit proliferation and invasion, and promote apoptosis in HepG2.2.15 cells. HepG2.2.15 cells secreting hepatitis B virus (HBV) were treated with BM-06 and poly(I:C). Western blot analysis and PCR were employed to determine pharmacodynamic changes in biomarkers relevant to TLR3 signaling. Cell proliferation, invasion and apoptosis were analyzed by CCK-8 assay, transwell assay and flow cytometry. The expression of HBsAg, and HBcAg was observed by immunohistochemistry. Compared with untreated cells, pharmacological NF-κB activity of the TLR3 pathway by BM-06 (1.734-fold) or poly(I:C) (1.377-fold) was induced. By western blot analysis, we found that dsRNA induced TLR3-activated HepG2.2.15 cells which expressed NF-κB levels predominantly in the cytoplasmic fraction but fewer signals in the nucleus. BM-06 inhibited the proliferation, invasion and secretion of HBV, and induced apoptosis in HepG2.2.15 cells. In addition, the antitumor effects of BM-06 were superior to poly(I:C). Pharmacological activation of the TLR3 pathway by BM-06 can inhibit HepG2.2.15 cell growth.

From field to health: a simple way to increase the nutraceutical content of grape as shown by NO-dependent vascular relaxation.

PubMed

Fumagalli, Francesca; Rossoni, Mara; Iriti, Marcello; di Gennaro, Antonio; Faoro, Franco; Borroni, Emanuele; Borgo, Michele; Scienza, Attilio; Sala, Angelo; Folco, Giancarlo

2006-07-26

Polyphenolic grapevine components involved in plant resistance against pathogens possess various pharmacological properties that include nitric oxide (NO)-dependent vasodilation and anti-inflammatory and free radical scavenging activities, which may explain the protective effect of moderate red wine consumption against cardiovascular disease. The aim of this work was (a) to verify the possibility that preharvest treatments of grapevine with a plant activator, benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH), could lead to an enriched nutraceutical potential of wine and (b) to characterize the profile of metabolites responsible for pharmacological activity. Plant spraying at the end of veraison, with a water suspension of BTH (0.3 mM), led to increased whole anthocyanin content as confirmed by HPLC comparative analysis. Extracts from berry skins of BTH-treated grapevines caused NO-dependent vasorelaxation, with a concentration-response curve that was significantly shifted to the left of the control non-BTH-treated curve. Moreover, 1:1000 dilutions of berry extracts from BTH-treated plants significantly increased basal production of guanosine 3',5'-cyclic monophosphate (cGMP) in human vascular endothelial cells when compared to the corresponding extracts of untreated plants. These results show that BTH treatment increases anthocyanin content of grape extracts, as well as their ability to induce NO-mediated vasoprotection. No increase of anthocyanin content was observed in the wine extracts from BTH-treated vines. It is concluded that BTH treatment could be exploited to increase the nutraceutical potential of grapes.

Inhibition of Mycobacterial Infection by the Tumor Suppressor PTEN*

PubMed Central

Huang, Guochang; Redelman-Sidi, Gil; Rosen, Neal; Glickman, Michael S.; Jiang, Xuejun

2012-01-01

The tumor suppressor PTEN is a lipid phosphatase that is frequently mutated in various human cancers. PTEN suppresses tumor cell proliferation, survival, and growth mainly by inhibiting the PI3K-Akt signaling pathway through dephosphorylation of phosphatidylinositol 3,4,5-triphosphate. In addition to it role in tumor suppression, the PTEN-PI3K pathway controls many cellular functions, some of which may be important for cellular resistance to infection. Currently, the intersection between tumorigenic signaling pathways and cellular susceptibility to infection is not well defined. In this study we report that PTEN signaling regulates infection of both noncancerous and cancerous cells by multiple intracellular mycobacterial pathogens and that pharmacological modulation of PTEN signaling can affect mycobacterial infection. We found that PTEN deficiency renders multiple types of cells hyper-susceptible to infection by Mycoplasma and Mycobacterium bovis Bacillus Calmette-Guérin (BCG). The lipid phosphatase activity of PTEN is required for attenuating infection. Furthermore, we found mycobacterial infection activates host cell Akt phosphorylation, and pharmacological inhibition of Akt or PI3K activity reduced levels of intracellular infection. Intriguingly, inhibition of mTOR, one of the downstream components of the Akt signaling and a promising cancer therapeutic target, also lowered intracellular Bacillus Calmette-Guérin levels in mammary epithelial cancer MCF-7 cells. These findings demonstrate a critical role of PTEN-regulated pathways in pathogen infection. The relationship of PTEN-PI3K-Akt mTOR status and susceptibility to mycobacterial infection suggests that the interaction of mycobacterial pathogens with cancer cells may be influenced by genetic alterations in the tumor cells. PMID:22613768

[Advances in the pharmacological study of Morus alba L].

PubMed

Yang, Shuang; Wang, Bao-Lian; Li, Yan

2014-06-01

Morus alba L. (mulberry) is a well-known deciduous tree, belonging to the genus of Morus of Moraceae famlily. Its leaves, twigs, roots (bark) and fruits are widely used in the traditional Chinese medicine. The active constituents of mulberry contained flavonoids, alkaloids, steroids, coumarins, with the significant hypoglycemic, hypolipidemic, antihypertension, anti-oxidation, anti-inflammatory, anti-bacterial, anti-tumor and immunomodulatory activities. This review summarized the research progress of the major pharmacological activity, pharmacokinetics and drug-drug interaction based on CYPs and transporters of mulberry and its active constituents.

Consecutive pharmacological activation of PKA and PKC mimics the potent cardioprotection of temperature preconditioning

PubMed Central

Khaliulin, Igor; Parker, Joanna E.; Halestrap, Andrew P.

2010-01-01

Aims Temperature preconditioning (TP) provides very powerful protection against ischaemia/reperfusion. Understanding the signalling pathways involved may enable the development of effective pharmacological cardioprotection. We investigated the interrelationship between activation of protein kinase A (PKA) and protein kinase C (PKC) in the signalling mechanisms of TP and developed a potent pharmacological intervention based on this mechanism. Methods and results Isolated rat hearts were subjected to TP, 30 min global ischaemia, and 60 min reperfusion. Other control and TP hearts were perfused with either sotalol (β-adrenergic blocker) or H-89 (PKA inhibitor). Some hearts were pre-treated with either isoproterenol (β-adrenergic agonist) or adenosine (PKC activator) that were given alone, simultaneously, or sequentially. Pre-treatment with isoproterenol, adenosine, and the consecutive isoproterenol/adenosine treatment was also combined with the PKC inhibitor chelerythrine. Cardioprotection was evaluated by haemodynamic function recovery, lactate dehydrogenase release, measurement of mitochondrial permeability transition pore opening, and protein carbonylation during reperfusion. Cyclic AMP and PKA activity were increased in TP hearts. H-89 and sotalol blocked the cardioprotective effect of TP and TP-induced PKC activation. Isoproterenol, adenosine, and the consecutive treatment increased PKC activity during pre-ischaemia. Isoproterenol significantly reduced myocardial glycogen content. Isoproterenol and adenosine, alone or simultaneously, protected hearts but the consecutive treatment gave the highest protection. Cardioprotective effects of adenosine were completely blocked by chelerythrine but those of the consecutive treatment only attenuated. Conclusion The signal transduction pathway of TP involves PKA activation that precedes PKC activation. Pharmacologically induced consecutive PKA/PKC activation mimics TP and induces extremely potent cardioprotection. PMID:20558443

Development of Clinical Pharmacology in the Russian Federation.

PubMed

Petrov, V I; Kagramanyan, I N; Khokhlov, A L; Frolov, M U; Lileeva, E G

2016-05-01

The article aims to provide the history, organization, and approaches to clinical pharmacology in the Russian Federation. This article is based on major international and Russian documents, along with groundbreaking historical facts and scientific articles related to the development of modern clinical pharmacology the Russian Federation. Improving the quality of drug therapy is the main goal of clinical pharmacology in the Russian Federation. Decisions of the World Health Organization, scientific achievements, and the work of well-known scientists among the world community and in the Russian Federation have strongly influenced the development of clinical pharmacology the Russian Federation. Clinical pharmacology in the Russian Federation addresses a wide range of problems; it actively engages in modern scientific research, education; and clinical practice. Clinical pharmacologists participate in studies of new drugs and often have a specific area of expertise. The future development of clinical pharmacology in the Russian Federation will be related to improvements in training, refinement of the framework that regulates clinical pharmacologists, and the creation of clinical pharmacology laboratories with modern equipment. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

The Pharmacological Basis of Cannabis Therapy for Epilepsy.

PubMed

Reddy, Doodipala Samba; Golub, Victoria M

2016-04-01

Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy, both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics that would not interfere with normal function in patients with refractory epilepsy and conditions associated with refractory seizures. The two chief cannabinoids are Δ-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana. Claims of clinical efficacy in epilepsy of CBD-predominant cannabis or medical marijuana come mostly from limited studies, surveys, or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid receptors CB1 and CB2; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy of their use in the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other potential treatment options. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Secondary metabolites of Eichhornia crassipes (Waterhyacinth): a review (1949 to 2011).

PubMed

Lalitha, Pottail; Sripathi, Shubashini K; Jayanthi, Ponnusamy

2012-09-01

Eichhornia crassipes (Mart.) Solms (Waterhyacinth), an aquatic perennial herb present throughout the world, has a myriad of metabolites. Phenalenone compounds and sterols have been isolated from this plant. Extracts, as well as pure compounds isolated from this plant, have been demonstrated to possess pharmacological activities. An account of the phytochemistry, pharmacological activities and several applications ofwaterhyacinth are included in this review.

Localization of ginsenosides in Panax ginseng with different age by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry imaging.

PubMed

Bai, Hangrui; Wang, Shujuan; Liu, Jianjun; Gao, Dan; Jiang, Yuyang; Liu, Hongxia; Cai, Zongwei

2016-07-15

The root of Panax ginseng C.A. Mey. (P. ginseng) is one of the most popular traditional Chinese medicines, with ginsenosides as its main bioactive components. Because different ginsenosides have varied pharmacological effects, extraction and separation of ginsenosides are usually required for the investigation of pharmacological effects of different ginsenosides. However, the contents of ginsenosides vary with the ages and tissues of P. ginseng root. In this research, an efficient method to explore the distribution of ginsenosides and differentiate P. ginseng roots with different ages was developed based on matrix assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI). After a simple sample preparation, there were 18 peaks corresponding to 31 ginsenosides with distinct localization in the mass range of m/z 700-1400 identified by MALDI-TOF-MSI and MALDI-TOF-MS/MS. All the three types of ginsenosides were successfully detected and visualized in images, which could be correlated with anatomical features. The P. ginseng at the ages of 2, 4 and 6 could be differentiated finely through the principal component analysis of data collected from the cork based on the ion images but not data from the whole tissue. The experimental result implies that the established method for the direct analysis of metabolites in plant tissues has high potential for the rapid identification of metabolites and analysis of their localizations in medicinal herbs. Furthermore, this technique also provides valuable information for the component-specific extraction and pharmacological research of herbs. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of TRP Channels in Dinoflagellate Mechanotransduction.

PubMed

Lindström, J B; Pierce, N T; Latz, M I

2017-10-01

Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences. In a phylogenetic tree including all mammalian TRP subfamilies and TRP channel sequences from unicellular and multicellular organisms, the L. polyedra sequences grouped with the TRPM, TPPML, and TRPP clades. In pharmacological experiments, we used the intrinsic bioluminescence of L. polyedra as a reporter of mechanoresponsivity. Capsaicin and RN1734, agonists of mammalian TRPV, and arachidonic acid, an agonist of mammalian TRPV, TRPA, TRPM, and Drosophila TRP, all stimulated bioluminescence in L. polyedra. Mechanical stimulation of bioluminescence, but not capsaicin-stimulated bioluminescence, was inhibited by gadolinium (Gd 3+ ), a general inhibitor of mechanosensitive ion channels, and the phospholipase C (PLC) inhibitor U73122. These pharmacological results are consistent with the involvement of TRP-like channels in mechanosensing by L. polyedra. The TRP channels do not appear to be mechanoreceptors but rather are components of the mechanotransduction signaling pathway and may be activated via a PLC-dependent mechanism. The presence and function of TRP channels in a dinoflagellate emphasize the evolutionary conservation of both the channel structures and their functions.

Process Pharmacology: A Pharmacological Data Science Approach to Drug Development and Therapy.

PubMed

Lötsch, Jörn; Ultsch, Alfred

2016-04-01

A novel functional-genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in "big data" providing comprehensive information about the drugs' targets and their functional genomics is proposed. In "process pharmacology", drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high-dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a short list of candidate drugs, including one that was recently proposed as novel rescue medication for lymphocytic leukemia. The pharmacological data science approach provides successful selections of drug candidates within development and repurposing tasks. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics.

PubMed

Coccarelli, Alberto; Edwards, David Hughes; Aggarwal, Ankush; Nithiarasu, Perumal; Parthimos, Dimitris

2018-02-01

Arterial wall dynamics arise from the synergy of passive mechano-elastic properties of the vascular tissue and the active contractile behaviour of smooth muscle cells (SMCs) that form the media layer of vessels. We have developed a computational framework that incorporates both these components to account for vascular responses to mechanical and pharmacological stimuli. To validate the proposed framework and demonstrate its potential for testing hypotheses on the pathogenesis of vascular disease, we have employed a number of pharmacological probes that modulate the arterial wall contractile machinery by selectively inhibiting a range of intracellular signalling pathways. Experimental probes used on ring segments from the rabbit central ear artery are: phenylephrine, a selective α 1-adrenergic receptor agonist that induces vasoconstriction; cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase; and ryanodine, a diterpenoid that modulates Ca 2+ release from the sarcoplasmic reticulum. These interventions were able to delineate the role of membrane versus intracellular signalling, previously identified as main factors in smooth muscle contraction and the generation of vessel tone. Each SMC was modelled by a system of nonlinear differential equations that account for intracellular ionic signalling, and in particular Ca 2+ dynamics. Cytosolic Ca 2+ concentrations formed the catalytic input to a cross-bridge kinetics model. Contractile output from these cellular components forms the input to the finite-element model of the arterial rings under isometric conditions that reproduces the experimental conditions. The model does not account for the role of the endothelium, as the nitric oxide production was suppressed by the action of L-NAME, and also due to the absence of shear stress on the arterial ring, as the experimental set-up did not involve flow. Simulations generated by the integrated model closely matched experimental observations qualitatively, as well as quantitatively within a range of physiological parametric values. The model also illustrated how increased intercellular coupling led to smooth muscle coordination and the genesis of vascular tone. © 2018 The Authors.

Glycosylation and Activities of Natural Products.

PubMed

Huang, Gangliang; Lv, Meijiao; Hu, Jinchuan; Huang, Kunlin; Xu, Hong

2016-01-01

Natural products are widely found in nature, their number and variety are numerous, the structures are complex and diverse. These natural products have many physiological and pharmacological activities. Glycosylation can increase the diversity of structure and function of natural product, it has become the focus of drug research and development. The impacts of glycosylation of natural products to water solubility, pharmacological activities, bioavailability, or others were described in this review, which provides a reference for the development and application of glycosylated natural products.

21 CFR 514.1 - Applications.

Code of Federal Regulations, 2011 CFR

2011-04-01

... post office address of, and must be countersigned by, an authorized attorney, agent, or official... pharmacologically related drugs. (c) Description of dosage form and quantitative composition. (ii) Scientific... quantitative statement of composition. Reasonable alternatives for any listed component may be specified. (ii...

21 CFR 514.1 - Applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... post office address of, and must be countersigned by, an authorized attorney, agent, or official... pharmacologically related drugs. (c) Description of dosage form and quantitative composition. (ii) Scientific... quantitative statement of composition. Reasonable alternatives for any listed component may be specified. (ii...

21 CFR 514.1 - Applications.

Code of Federal Regulations, 2012 CFR

2012-04-01

... post office address of, and must be countersigned by, an authorized attorney, agent, or official... pharmacologically related drugs. (c) Description of dosage form and quantitative composition. (ii) Scientific... quantitative statement of composition. Reasonable alternatives for any listed component may be specified. (ii...

21 CFR 514.1 - Applications.

Code of Federal Regulations, 2014 CFR

2014-04-01

... post office address of, and must be countersigned by, an authorized attorney, agent, or official... pharmacologically related drugs. (c) Description of dosage form and quantitative composition. (ii) Scientific... quantitative statement of composition. Reasonable alternatives for any listed component may be specified. (ii...

21 CFR 514.1 - Applications.

Code of Federal Regulations, 2013 CFR

2013-04-01

... post office address of, and must be countersigned by, an authorized attorney, agent, or official... pharmacologically related drugs. (c) Description of dosage form and quantitative composition. (ii) Scientific... quantitative statement of composition. Reasonable alternatives for any listed component may be specified. (ii...

Phytochemical Composition and Biological Activities of Dyssodia tagetiflora Lag.

PubMed

García-Bores, Ana María; Arciniegas-Arciniegas, Amira; Reyna-Campos, Alma; Céspedes-Acuña, Carlos; Avila-Suárez, Betsaida; Alarcón-Enos, Julio; Flores-Maya, Saul; Espinosa-González, Adriana Montserrat; de Vivar-Romo, Alfonso Romo; Pérez-Plasencia, Carlos; Avila-Acevedo, José Guillermo

2018-02-01

While plants of the genus Dyssodia are used by man to a certain extent, few phytochemical and pharmacological studies have been performed with species of this genus. D. tagetiflora is an endemic plant of Mexico and has been used as fodder. The aim of this research was to isolate and identify the main bioactive components and evaluate the insecticidal, antioxidant, genotoxic and cytoprotective activities of D. tagetiflora. The isolated substances included an essential oil composed of six monoterpenes, and extracts containing two flavonols, three flavonol-glycosides and four thiophenes. The compounds were characterized using spectroscopic and spectrometric methods, including GC/MS, MS and NMR. The essential oil showed insecticidal activity against Drosophila melanogaster larvae. The methanolic extract of D. tagetiflora (DTME) had strong antioxidant activity against DPPH and ABTS radicals; DTME showed no evidence of genotoxic or cytotoxic effects. In contrast, DTME showed a cytoprotective effect attenuating the formation of H 2 O 2 -induced micronuclei in Vicia faba roots. This report is the first to describe the phytochemical and biological activity of D. tagetiflora. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway

PubMed Central

Ahmed, Mohammed I.; Alam, Majid; Emelianov, Vladimir U.; Poterlowicz, Krzysztof; Patel, Ankit; Sharov, Andrey A.; Mardaryev, Andrei N.

2014-01-01

Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators β-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify β-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging. PMID:25422376

Identification of quality markers of Yuanhu Zhitong tablets based on integrative pharmacology and data mining.

PubMed

Li, Ke; Li, Junfang; Su, Jin; Xiao, Xuefeng; Peng, Xiujuan; Liu, Feng; Li, Defeng; Zhang, Yi; Chong, Tao; Xu, Haiyu; Liu, Changxiao; Yang, Hongjun

2018-03-07

The quality evaluation of traditional Chinese medicine (TCM) formulations is needed to guarantee the safety and efficacy. In our laboratory, we established interaction rules between chemical quality control and biological activity evaluations to study Yuanhu Zhitong tablets (YZTs). Moreover, a quality marker (Q-marker) has recently been proposed as a new concept in the quality control of TCM. However, no appropriate methods are available for the identification of Q-markers from the complex TCM systems. We aimed to use an integrative pharmacological (IP) approach to further identify Q-markers from YZTs through the integration of multidisciplinary knowledge. In addition, data mining was used to determine the correlation between multiple constituents of this TCM and its bioactivity to improve quality control. The IP approach was used to identify the active constituents of YZTs and elucidate the molecular mechanisms by integrating chemical and biosynthetic analyses, drug metabolism, and network pharmacology. Data mining methods including grey relational analysis (GRA) and least squares support vector machine (LS-SVM) regression techniques, were used to establish the correlations among the constituents and efficacy, and dose efficacy in multiple dimensions. Seven constituents (tetrahydropalmatine, α-allocryptopine, protopine, corydaline, imperatorin, isoimperatorin, and byakangelicin) were identified as Q-markers of YZT using IP based on their high abundance, specific presence in the individual herbal constituents and the product, appropriate drug-like properties, and critical contribution to the bioactivity of the mixture of YZT constituents. Moreover, three Q-markers (protopine, α-allocryptopine, and corydaline) were highly correlated with the multiple bioactivities of the YZTs, as found using data mining. Finally, three constituents (tetrahydropalmatine, corydaline, and imperatorin) were chosen as minimum combinations that both distinguished the authentic components from false products and indicated the intensity of bioactivity to improve the quality control of YZTs. Tetrahydropalmatine, imperatorin, and corydaline could be used as minimum combinations to effectively control the quality of YZTs. Copyright © 2018. Published by Elsevier GmbH.

Preserved pharmacological activity of hepatocytes-treated extracts of valerian and St. John's wort.

PubMed

Simmen, Urs; Saladin, Caroline; Kaufmann, Priska; Poddar, Manisha; Wallimann, Christine; Schaffner, Willi

2005-07-01

The two herbal extracts valerian (Valeriana officinalis L.) and St. John's wort (Hypericum perforatum L.) were studied for their metabolic changes upon incubation with freshly prepared rat hepatocytes and subsequently analysed phytochemically as well as pharmacologically in vitro. Quantitative HPLC analysis of valerian extracts revealed considerable metabolic activities with regard to sesquiterpenes and iridoids. The amount of acetoxyvalerenic acid decreased 9-fold, while that of hydroxyvalerenic acid correspondingly increased 9-fold due to O-deacetylation. The valepotriates didrovaltrate, isovaltrate and valtrate decreased 2-, 18- and 16-fold, respectively. However, the binding affinities of the incubated extracts to the benzodiazepine and picrotoxin binding site of the GABA (A) receptor were quite similar to those of the non-incubated extracts. Neither valerenic acids nor valepotriates exhibited any significant effect on the two binding sites when tested as single compounds. Therefore, either other constituents represent the active ones or multiple compounds are necessary for the observed inhibitory and allosteric effects at the GABA (A) receptor. Extracts of St. John's wort were less potently metabolised than valerian. The amount of pseudohypericin and the main flavonoids (hyperoside, rutin, isoquercitrin, quercitrin, quercetin and I3,II8-biapigenin) slightly decreased during the 4-h incubation period. Both the antagonist effect at the corticotropin-releasing factor (CRF) type 1 receptor and the binding inhibition at the 5-HT transporter were attenuated during the metabolic treatment. The reduced antagonist effect correlates with the decreasing amount of pseudohypericin known to be a CRF (1) receptor antagonist. In conclusion, the incubation of plant extracts with freshly prepared rat hepatocytes represents a useful approach to study the pharmacological action of metabolised plant extracts. The consistent pharmacological activity of both valerian and St. John's wort is concordant with the known clinical efficacy of pharmacological activities.

Greater Celandine's Ups and Downs−21 Centuries of Medicinal Uses of Chelidonium majus From the Viewpoint of Today's Pharmacology

PubMed Central

Zielińska, Sylwia; Jezierska-Domaradzka, Anna; Wójciak-Kosior, Magdalena; Sowa, Ireneusz; Junka, Adam; Matkowski, Adam M.

2018-01-01

As antique as Dioscorides era are the first records on using Chelidonium as a remedy to several sicknesses. Inspired by the “signatura rerum” principle and an apparent ancient folk tradition, various indications were given, such as anti-jaundice and cholagogue, pain-relieving, and quite often mentioned—ophthalmological problems. Central and Eastern European folk medicine has always been using this herb extensively. In this region, the plant is known under many unique vernacular names, especially in Slavonic languages, associated or not with old Greek relation to “chelidon”—the swallow. Typically for Papaveroidae subfamily, yellow-colored latex is produced in abundance and leaks intensely upon injury. Major pharmacologically relevant components, most of which were first isolated over a century ago, are isoquinoline alkaloids—berberine, chelerythrine, chelidonine, coptisine, sanguinarine. Modern pharmacology took interest in this herb but it has not ended up in gaining an officially approved and evidence-based herbal medicine status. On the contrary, the number of relevant studies and publications tended to drop. Recently, some controversial reports and sometimes insufficiently proven studies appeared, suggesting anticancer properties. Anticancer potential was in line with anecdotical knowledge spread in East European countries, however, in the absence of directly-acting cytostatic compounds, some other mechanisms might be involved. Other properties that could boost the interest in this herb are antimicrobial and antiviral activities. Being a common synanthropic weed or ruderal plant, C. majus spreads in all temperate Eurasia and acclimates well to North America. Little is known about the natural variation of bioactive metabolites, including several aforementioned isoquinoline alkaloids. In this review, we put together older and recent literature data on phytochemistry, pharmacology, and clinical studies on C. majus aiming at a critical evaluation of state-of-the-art from the viewpoint of historical and folk indications. The controversies around this herb, the safety and drug quality issues and a prospective role in phytotherapy are discussed as well. PMID:29713277

[Progress in research for pharmacological effects of Pu-erh tea].

PubMed

Gu, Xiao-Pan; Pan, Bo; Wu, Zhen; Zhao, Yun-Fang; Tu, Peng-Fei; Zheng, Jiao

2017-06-01

Pu-erh tea has gradually aroused general concern with social development and people's enhanced awareness of health. Pu-erh tea is rich in multiple active constitute such as flavonoids, catechins, phenolic acids, flavanols polymer, purine alkaloids, and hydrolysable tannin as a microbial-fermented tea.It is reported that Pu-erh tea have a variety of pharmacologically activities, such as anti-hyperlipidemic, anti-diabetic, anti-oxidative, anti-tumor, anti-bacterial, anti-inflammatory, and anti-viral effects. In this paper, the main pharmacological effects of Pu-erh tea are reviewed. We wish this work will provide some references and clues for further research of Pu-erh tea. Copyright© by the Chinese Pharmaceutical Association.

Snake Venom L-Amino Acid Oxidases: Trends in Pharmacology and Biochemistry

PubMed Central

Izidoro, Luiz Fernando M.; Sobrinho, Juliana C.; Mendes, Mirian M.; Costa, Tássia R.; Grabner, Amy N.; Rodrigues, Veridiana M.; da Silva, Saulo L.; Zanchi, Fernando B.; Zuliani, Juliana P.; Fernandes, Carla F. C.; Calderon, Leonardo A.; Stábeli, Rodrigo G.; Soares, Andreimar M.

2014-01-01

L-amino acid oxidases are enzymes found in several organisms, including venoms of snakes, where they contribute to the toxicity of ophidian envenomation. Their toxicity is primarily due to enzymatic activity, but other mechanisms have been proposed recently which require further investigation. L-amino acid oxidases exert biological and pharmacological effects, including actions on platelet aggregation and the induction of apoptosis, hemorrhage, and cytotoxicity. These proteins present a high biotechnological potential for the development of antimicrobial, antitumor, and antiprotozoan agents. This review provides an overview of the biochemical properties and pharmacological effects of snake venom L-amino acid oxidases, their structure/activity relationship, and supposed mechanisms of action described so far. PMID:24738050

Pharmacological Properties of Biocompounds from Spores of the Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes): A Review.

PubMed

Soccol, Carlos Ricardo; Bissoqui, Lucas Yamasaki; Rodrigues, Cristine; Rubel, Rosalia; Sella, Sandra R B R; Leifa, Fan; de Souza Vandenberghe, Luciana Porto; Soccol, Vanete Thomaz

2016-01-01

Ganoderma lucidum is a well-known representative of mushrooms that have been used in traditional Chinese medicine for centuries. New discoveries related to this medicinal mushroom and its biological properties are frequently reported. However, only recently have scientists started to pay special attention to G. lucidum spores. This is in part because of the recent development of methods for breaking the spore wall and extracting biocompounds from the spore. Although some research groups are working with G. lucidum spores, data in the literature are still limited, and the methods used have not been systematized. This review therefore describes the main advances in techniques for breaking the spore wall and extracting biocompounds from the spore. In addition, the major active components identified and their biological properties, such as neurological activity and antiaging and cell-protective effects, are investigated because these are of importance for potential drug development.

Ribosomal protein S6 kinase 1 signaling regulates mammalian lifespan

PubMed Central

Selman, Colin; Tullet, Jennifer M.A.; Wieser, Daniela; Irvine, Elaine; Lingard, Steven J.; Choudhury, Agharul I.; Claret, Marc; Al-Qassab, Hind; Carmignac, Danielle; Ramadani, Faruk; Woods, Angela; Robinson, Iain C.A.; Schuster, Eugene; Batterham, Rachel L.; Kozma, Sara C.; Thomas, George; Carling, David; Okkenhaug, Klaus; Thornton, Janet M.; Partridge, Linda; Gems, David; Withers, Dominic J.

2016-01-01

Caloric restriction (CR) protects against aging and disease but the mechanisms by which this affects mammalian lifespan are unclear. We show in mice that deletion of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway component ribosomal S6 protein kinase 1 (S6K1) led to increased lifespan and resistance to age-related pathologies such as bone, immune and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian lifespan, and suggest therapeutic manipulation of S6K1 and AMPK might mimic CR and provide broad protection against diseases of aging. PMID:19797661

Separation of three anthraquinone glycosides including two isomers by preparative high-performance liquid chromatography and high-speed countercurrent chromatography from Rheum tanguticum Maxim. ex Balf.

PubMed

Chen, Tao; Li, Hongmei; Zou, Denglang; Liu, Yongling; Chen, Chen; Zhou, Guoying; Li, Yulin

2016-08-01

Anthraquinone glycosides, such as chrysophanol 1-O-β-d-glucoside, chrysophanol 8-O-β-d-glucoside, and physion 8-O-β-d-glucoside, are the accepted important active components of Rheum tanguticum Maxim. ex Balf. due to their pharmacological properties: antifungal, antimicrobial, cytotoxic, and antioxidant activities. However, an effective method for the separation of the above-mentioned anthraquinone glycosides from this herb is not currently available. Especially, greater difficulty existed in the separation of the two isomers chrysophanol 1-O-β-d-glucoside and chrysophanol 8-O-β-d-glucoside. This study demonstrated an efficient strategy based on preparative high-performance liquid chromatography and high-speed countercurrent chromatography for the separation of the above-mentioned anthraquinone glycosides from Rheum tanguticum Maxim.ex Balf. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Remote control of therapeutic T cells through a small molecule-gated chimeric receptor

PubMed Central

Wu, Chia-Yung; Roybal, Kole T.; Puchner, Elias M.; Onuffer, James; Lim, Wendell A.

2016-01-01

There is growing promise in using engineered cells as therapeutic agents. For example, synthetic Chimeric Antigen Receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, excessive activity and poor control over such engineered T cells can cause severe toxicities. We present the design of “ON-switch” CARs that enable small molecule-control over T cell therapeutic functions, while still retaining antigen specificity. In these split receptors, antigen binding and intracellular signaling components only assemble in the presence of a heterodimerizing small molecule. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. This work illustrates the potential of combining cellular engineering with orthogonal chemical tools to yield safer therapeutic cells that tightly integrate both cell autonomous recognition and user control. PMID:26405231

Remote control of therapeutic T cells through a small molecule-gated chimeric receptor.

PubMed

Wu, Chia-Yung; Roybal, Kole T; Puchner, Elias M; Onuffer, James; Lim, Wendell A

2015-10-16

There is growing interest in using engineered cells as therapeutic agents. For example, synthetic chimeric antigen receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, these engineered T cells can exhibit excessive activity that is difficult to control and can cause severe toxicity. We designed "ON-switch" CARs that enable small-molecule control over T cell therapeutic functions while still retaining antigen specificity. In these split receptors, antigen-binding and intracellular signaling components assemble only in the presence of a heterodimerizing small molecule. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. This work illustrates the potential of combining cellular engineering with orthogonal chemical tools to yield safer therapeutic cells that tightly integrate cell-autonomous recognition and user control. Copyright © 2015, American Association for the Advancement of Science.

Synthesis and pharmacological investigation of 2-(4-dimethylaminophenyl)-3,5-disubstituted thiazolidin-4-ones as anticonvulsants.

PubMed

Senthilraja, Manavalan; Alagarsamy, Veerachamy

2012-10-01

A new series of 2-(4-dimethylaminophenyl)-3-substituted thiazolidin-4-one-5-yl-acetyl acetamides/benzamides were synthesized by the nucleophilic substitution of 3-substituted-2-(4-dimethylaminophenyl)-thiazolidin-4-one-5-yl-acetylchloride with acetamide and benzamide. The starting material 3-substituted-2-(4-dimethylaminophenyl)-thiazolidin-4-one-5-yl-acetylchloride was synthesized from 3-substituted-2-(4-dimethylaminophenyl)-thiazolidin-4-one-5-yl-acetic acid, which in turn was prepared by one-pot reaction of amino component, p-dimethylamino benzaldehyde and mercapto succinic acid. The title compounds were investigated for their anticonvulsant activities; among the test compounds, compound 2-(4-dimethylaminophenyl)-3-phenylamino-thiazolidine-4-one-5-yl-acetylbenzamide (14) emerged as the most active compound of the series and as moderately more potent than the reference standard diazepam. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Some Pharmacological Actions of Cotton Dust and Other Vegetable Dusts

PubMed Central

Nicholls, P. J.

1962-01-01

Aqueous extracts of cotton and other vegetable dusts cause contraction of the isolated ileum and tracheal muscle of the guinea-pig, and of isolated human bronchial muscle. The levels of this contractor activity place the dusts of cotton, flax, and jute in the order of the probable incidence of byssinosis occurring in the mills spinning these fibres. Extracts of cotton dust possess a histamine-liberating activity and contain a permeability-increasing component. These actions are of plant origin and are found in the pericarp and bracts of the cotton boll. Histamine and 5-hydroxytryptamine have also been found in some cotton dust samples. The formation of histamine by bacterial action in cotton dust does not take place under conditions found in cotton mills. The smooth muscle contractor substance is organic in nature, relatively heat-stable, and dialysable. The relevance of these results to the symptoms of byssinosis is discussed. PMID:14479451

Effects of chocolate on cognitive function and mood: a systematic review.

PubMed

Scholey, Andrew; Owen, Lauren

2013-10-01

A systematic review was conducted to evaluate whether chocolate or its constituents were capable of influencing cognitive function and/or mood. Studies investigating potentially psychoactive fractions of chocolate were also included. Eight studies (in six articles) met the inclusion criteria for assessment of chocolate or its components on mood, of which five showed either an improvement in mood state or an attenuation of negative mood. Regarding cognitive function, eight studies (in six articles) met the criteria for inclusion, of which three revealed clear evidence of cognitive enhancement (following cocoa flavanols and methylxanthine). Two studies failed to demonstrate behavioral benefits but did identify significant alterations in brain activation patterns. It is unclear whether the effects of chocolate on mood are due to the orosensory characteristics of chocolate or to the pharmacological actions of chocolate constituents. Two studies have reported acute cognitive effects of supplementation with cocoa polyphenols. Further exploration of the effect of chocolate on cognitive facilitation is recommended, along with substantiation of functional brain changes associated with the components of cocoa.

A Review: Molecular Aberrations within Hippo Signaling in Bone and Soft-Tissue Sarcomas

PubMed Central

Deel, Michael D.; Li, Jenny J.; Crose, Lisa E. S.; Linardic, Corinne M.

2015-01-01

The Hippo signaling pathway is an evolutionarily conserved developmental network vital for the regulation of organ size, tissue homeostasis, repair and regeneration, and cell fate. The Hippo pathway has also been shown to have tumor suppressor properties. Hippo transduction involves a series of kinases and scaffolding proteins that are intricately connected to proteins in developmental cascades and in the tissue microenvironment. This network governs the downstream Hippo transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs, as well as other transcription factors responsible for cellular proliferation, self-renewal, differentiation, and survival. Surprisingly, there are few oncogenic mutations within the core components of the Hippo pathway. Instead, dysregulated Hippo signaling is a versatile accomplice to commonly mutated cancer pathways. For example, YAP and TAZ can be activated by oncogenic signaling from other pathways, or serve as co-activators for classical oncogenes. Emerging evidence suggests that Hippo signaling couples cell density and cytoskeletal structural changes to morphogenic signals and conveys a mesenchymal phenotype. While much of Hippo biology has been described in epithelial cell systems, it is clear that dysregulated Hippo signaling also contributes to malignancies of mesenchymal origin. This review will summarize the known molecular alterations within the Hippo pathway in sarcomas and highlight how several pharmacologic compounds have shown activity in modulating Hippo components, providing proof-of-principle that Hippo signaling may be harnessed for therapeutic application in sarcomas. PMID:26389076

A Review: Molecular Aberrations within Hippo Signaling in Bone and Soft-Tissue Sarcomas.

PubMed

Deel, Michael D; Li, Jenny J; Crose, Lisa E S; Linardic, Corinne M

2015-01-01

The Hippo signaling pathway is an evolutionarily conserved developmental network vital for the regulation of organ size, tissue homeostasis, repair and regeneration, and cell fate. The Hippo pathway has also been shown to have tumor suppressor properties. Hippo transduction involves a series of kinases and scaffolding proteins that are intricately connected to proteins in developmental cascades and in the tissue microenvironment. This network governs the downstream Hippo transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs, as well as other transcription factors responsible for cellular proliferation, self-renewal, differentiation, and survival. Surprisingly, there are few oncogenic mutations within the core components of the Hippo pathway. Instead, dysregulated Hippo signaling is a versatile accomplice to commonly mutated cancer pathways. For example, YAP and TAZ can be activated by oncogenic signaling from other pathways, or serve as co-activators for classical oncogenes. Emerging evidence suggests that Hippo signaling couples cell density and cytoskeletal structural changes to morphogenic signals and conveys a mesenchymal phenotype. While much of Hippo biology has been described in epithelial cell systems, it is clear that dysregulated Hippo signaling also contributes to malignancies of mesenchymal origin. This review will summarize the known molecular alterations within the Hippo pathway in sarcomas and highlight how several pharmacologic compounds have shown activity in modulating Hippo components, providing proof-of-principle that Hippo signaling may be harnessed for therapeutic application in sarcomas.

[CHANGE OF CHARACTER OF INTERSYSTEMIC INTERACTIONS IN NEWBORN RAT PUPS UNDER CONDITIONS OF A DECREASE OF MOTOR ACTIVITY].

PubMed

Sizonov, V A; Dmitrieva, L E; Kuznetsov, S V

2015-01-01

Interaction of slow-wave.rhythmic components of cardiac, respiratory.and motor activity was investigated in newborn rat pups on the first day after birth under normal conditions and after pharmacological depression of spontaneous periodic motor activity (SPMA) produced by injecting myocuran (myanesin) at low (100 mg/pg, i/p) and maximal (235 mg/pg, i/p) dosages. The data obtained allow to infer that in rat pups after birth the intersystemic interactions are realized mainly via slow-wave oscillations of about-one- and many-minute ranges whereas the rhythms of decasecond range do not play a significant role in integrative processes. Injection of miocuran at a dose causing no muscle relaxation and no inhibition of motor activity produces changes of the cardiac and respiratory rhythms as well as a transitory decrease of the magnitude of coordinate relations mediated by the rhythms of about-one- and many-minute ranges. The consequences of muscle relaxant injection were found to be more significant for intersystemic interactions with participation of the respiratory system. An increase of the dosage and, correspondingly, the total inhibition of SPMA is accompanied by reduction of the slow-wave components from the pattern of cardiac and respiratory rhythms. The cardiorespiratory interactions, more expressed in intact rat pups, are reduced in the about-one- and many-minute ranges of modulation whereas in the decasecond range of modulation they are slightly increased. Key words: early ontogenesis, intersystemic interactions, cardiac rhythm, respiration, motor activity, myocuran (myanesin).

Anti-influenza virus effect of aqueous extracts from dandelion

PubMed Central

2011-01-01

Background Human influenza is a seasonal disease associated with significant morbidity and mortality. Anti-flu Traditional Chinese Medicine (TCM) has played a significant role in fighting the virus pandemic. In TCM, dandelion is a commonly used ingredient in many therapeutic remedies, either alone or in conjunction with other natural substances. Evidence suggests that dandelion is associated with a variety of pharmacological activities. In this study, we evaluated anti-influenza virus activity of an aqueous extract from dandelion, which was tested for in vitro antiviral activity against influenza virus type A, human A/PR/8/34 and WSN (H1N1). Results Results obstained using antiviral assays, minigenome assay and real-time reverse transcription-PCR analysis showed that 0.625-5 mg/ml of dandelion extracts inhibited infections in Madin-Darby canine kidney (MDCK) cells or Human lung adenocarcinoma cell line (A549) of PR8 or WSN viruses, as well as inhibited polymerase activity and reduced virus nucleoprotein (NP) RNA level. The plant extract did not exhibit any apparent negative effects on cell viability, metabolism or proliferation at the effective dose. This result is consistent with the added advantage of lacking any reported complications of the plant's utility in traditional medicine over several centuries. Conclusion The antiviral activity of dandelion extracts indicates that a component or components of these extracts possess anti-influenza virus properties. Mechanisms of reduction of viral growth in MDCK or A549 cells by dandelion involve inhibition on virus replication. PMID:22168277

Pharmacology, signaling and physiological relevance of the G protein-coupled receptor 55.

PubMed

Balenga, Nariman A B; Henstridge, Christopher M; Kargl, Julia; Waldhoer, Maria

2011-01-01

According to The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), ∼70 million European adults have consumed cannabis on at least one occasion. Cannabis consumption leads to a variety of psychoactive effects due to the presence of the constituent Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Δ(9)-THC interacts with the endocannabinoid system (ECS), which consists of the seven transmembrane spanning (7TM)/G protein-coupled receptors (GPCRs) CB(1) and CB(2), their respective ligands (endocannabinoids), and enzymes involved in their biosynthesis and degradation. This system plays a critical role in many physiological processes such as learning and memory, appetite control, pain sensation, motor coordination, lipogenesis, modulation of immune response, and the regulation of bone mass. Therefore, a huge effort has been spent trying to fully elucidate the composition and function of the ECS. The G protein-coupled receptor 55 (GPR55) was recently proposed as a novel component of this system; however, its classification as a cannabinoid receptor has been significantly hampered by its complex pharmacology, signaling, and cellular function. GPR55 is phylogenetically distinct from the traditional cannabinoid receptors, but in some experimental paradigms, it is activated by endocannabinoids, phytocannabinoids, and synthetic cannabinoid ligands. However, the most potent compound appears to be a lysophospholipid known as lysophosphatidylinositol (LPI). Here, we provide a comprehensive evaluation of the current pharmacology and signaling of GPR55 and review the proposed role of this receptor in a number of physiological and pathophysiological processes. Copyright © 2011 Elsevier Inc. All rights reserved.

Pharmacodynamics of selective androgen receptor modulators.

PubMed

Yin, Donghua; Gao, Wenqing; Kearbey, Jeffrey D; Xu, Huiping; Chung, Kiwon; He, Yali; Marhefka, Craig A; Veverka, Karen A; Miller, Duane D; Dalton, James T

2003-03-01

The present study aimed to identify selective androgen receptor modulators (SARMs) with in vivo pharmacological activity. We examined the in vitro and in vivo pharmacological activity of four chiral, nonsteroidal SARMs synthesized in our laboratories. In the in vitro assays, these compounds demonstrated moderate to high androgen receptor (AR) binding affinity, with K(i) values ranging from 4 to 37 nM, and three of the compounds efficaciously stimulated AR-mediated reporter gene expression. The compounds were then administered subcutaneously to castrated rats to appraise their in vivo pharmacological activity. Androgenic activity was evaluated by the ability of these compounds to maintain the weights of prostate and seminal vesicle, whereas levator ani muscle weight was used as a measure of anabolic activity. The maximal response (E(max)) and dose for half-maximal effect (ED(50)) were determined for each compound and compared with that observed for testosterone propionate (TP). Compounds S-1 and S-4 demonstrated in vivo androgenic and anabolic activity, whereas compounds S-2 and S-3 did not. The activities of S-1 and S-4 were tissue-selective in that both compounds stimulated the anabolic organs more than the androgenic organs. These two compounds were less potent and efficacious than TP in androgenic activity, but their anabolic activity was similar to or greater than that of TP. Neither S-1 nor S-4 caused significant luteinizing hormone or follicle stimulating hormone suppression at doses near the ED(50) value. Thus, compounds S-1 and S-4 were identified as SARMs with potent and tissue-selective in vivo pharmacological activity, and represent the first members of a new class of SARMs with selective anabolic effects.

PAR(2) and temporomandibular joint inflammation in the rat.

PubMed

Denadai-Souza, A; Cenac, N; Casatti, C A; Câmara, P R de Souza; Yshii, L M; Costa, S K P; Vergnolle, N; Muscará, M N

2010-10-01

The proteinase-activated receptor 2 (PAR(2)) is a putative therapeutic target for arthritis. We hypothesized that the early pro-inflammatory effects secondary to its activation in the temporomandibular joint (TMJ) are mediated by neurogenic mechanisms. Immunofluorescence analysis revealed a high degree of neurons expressing PAR(2) in retrogradely labeled trigeminal ganglion neurons. Furthermore, PAR(2) immunoreactivity was observed in the lining layer of the TMJ, co-localizing with the neuronal marker PGP9.5 and substance-P-containing peripheral sensory nerve fibers. The intra-articular injection of PAR(2) agonists into the TMJ triggered a dose-dependent increase in plasma extravasation, neutrophil influx, and induction of mechanical allodynia. The pharmacological blockade of natural killer 1 (NK(1)) receptors abolished PAR(2)-induced plasma extravasation and inhibited neutrophil influx and mechanical allodynia. We conclude that PAR(2) activation is pro-inflammatory in the TMJ, through a neurogenic mechanism involving NK(1) receptors. This suggests that PAR(2) is an important component of innate neuro-immune response in the rat TMJ.

[Royal jelly: component efficiency, analysis, and standardisation].

PubMed

Oršolić, Nada

2013-09-01

Royal jelly is a viscous substance secreted by the hypopharyngeal and mandibular glands of worker honeybees (Apis mellifera) that contains a considerable amount of proteins, free amino acids, lipids, vitamins, sugars, and bioactive substances such as 10-hydroxy-trans-2-decenoic acid, antibacterial protein, and 350-kDa protein. These properties make it an attractive ingredient in various types of healthy foods. This article brings a brief review of the molecular mechanisms involved in the development of certain disorders that can be remedied by royal jelly, based on a selection of in vivo and in vitro studies. It also describes current understanding of the mechanisms and beneficial effects by which royal jelly helps to combat aging-related complications. Royal jelly has been reported to exhibit beneficial physiological and pharmacological effects in mammals, including vasodilative and hypotensive activities, antihypercholesterolemic activity, and antitumor activity. As its composition varies significantly (for both fresh and dehydrated samples), the article brings a few recommendations for defining new quality standards.

Pharmacological Beta-Adrenergic Receptor Activation Attenuates Neutrophil Recruitment by a Mechanism Dependent on Nicotinic Receptor and the Spleen.

PubMed

Silva, Rangel L; Castanheira, Fernanda V; Figueiredo, Jozi G; Bassi, Gabriel S; Ferreira, Sérgio H; Cunha, Fernando Q; Cunha, Thiago M; Kanashiro, Alexandre

2016-08-01

The aim of this study was to identify the effect of beta-adrenergic receptor activation on neutrophil migration in experimental peritonitis elucidating the neuroimmune components involved such as nicotinic receptors and the spleen. Mice pre-treated with mecamylamine (nicotinic antagonist) and propranolol (beta-adrenergic antagonist) or splenectomized animals were treated with isoproterenol (beta-adrenergic agonist) prior to intraperitoneal injection of carrageenan. After 4 h, the infiltrating neutrophils and the local cytokine/chemokine levels were evaluated in the peritoneal lavage. The effect of isoproterenol on neutrophil chemotaxis was investigated in a Boyden chamber. Isoproterenol inhibited neutrophil trafficking, reducing the cytokine/chemokine release and neutrophil chemotaxis. Surprisingly, the isoproterenol effect on neutrophil migration was totally reverted by splenectomy and mecamylamine pre-treatment. In contrast, the inhibitory effect of nicotine on neutrophil migration was abrogated only by splenectomy but not by propranolol pre-treatment. Collectively, our data show that beta-adrenergic receptor activation regulates the acute neutrophil recruitment via splenic nicotinic receptor.

Naturally Occurring Cinnamic Acid Sugar Ester Derivatives.

PubMed

Tian, Yuxin; Liu, Weirui; Lu, Yi; Wang, Yan; Chen, Xiaoyi; Bai, Shaojuan; Zhao, Yicheng; He, Ting; Lao, Fengxue; Shang, Yinghui; Guo, Yu; She, Gaimei

2016-10-24

Cinnamic acid sugar ester derivatives (CASEDs) are a class of natural product with one or several phenylacrylic moieties linked with the non-anomeric carbon of a glycosyl skeleton part through ester bonds. Their notable anti-depressant and brains protective activities have made them a topic of great interest over the past several decades. In particular the compound 3',6-disinapoylsucrose, the index component of Yuanzhi (a well-known Traditional Chinese Medicine or TCM), presents antidepressant effects at a molecular level, and has become a hotspot of research on new lead drug compounds. Several other similar cinnamic acid sugar ester derivatives are reported in traditional medicine as compounds to calm the nerves and display anti-depression and neuroprotective activity. Interestingly, more than one third of CASEDs are distributed in the family Polygalaceae . This overview discusses the isolation of cinnamic acid sugar ester derivatives from plants, together with a systematic discussion of their distribution, chemical structures and properties and pharmacological activities, with the hope of providing references for natural product researchers and draw attention to these interesting compounds.

Berberine, a natural product, combined with cisplatin enhanced apoptosis through a mitochondria/caspase-mediated pathway in HeLa cells.

PubMed

Youn, Myung-Ja; So, Hong-Seob; Cho, Hea-Joong; Kim, Hyung-Jin; Kim, Yunha; Lee, Jeong-Han; Sohn, Jung Sook; Kim, Yong Kyu; Chung, Sang-Young; Park, Raekil

2008-05-01

Berberine, a main component of Coptidis Rhizoma, has been extensively studied and is known to exhibit multiple pharmacologic activities. In this study, we investigated whether the combination of berberine and cisplatin exhibited significant cytotoxicity in HeLa cells. Apoptosis was evaluated based on DNA fragmentation and cytofluorometrically with the annexin-V/propidium iodide labeling method. Combined treatment with berberine and cisplatin acted in concert to induce loss of mitochondrial membrane potential (Delta Psi m), release of cytochrome-c from mitochondria, and decreased expression of antiapoptotic Bcl-2, Bcl-x/L, resulting in activation of caspases and apoptosis. Further study showed that cell death induced by the combined treatment was associated with increased reactive oxygen species generation and lipid peroxidation. Moreover, we discovered that the combined treatment-induced apoptosis was mediated by the activation of the caspase cascade. These results indicated that the potential of cytotoxicity mediated through the mitochondria-caspase pathway is primarily involved in the combined treatment-induced apoptosis.

Effect of Chlorogenic Acid (5-Caffeoylquinic Acid) Isolated from Baccharis oxyodonta on the Structure and Pharmacological Activities of Secretory Phospholipase A2 from Crotalus durissus terrificus

PubMed Central

Toyama, Daniela O.; Ferreira, Marcelo J. P.; Romoff, Paulete; Fávero, Oriana A.; Gaeta, Henrique H.; Toyama, Marcos H.

2014-01-01

The aim of this paper was to investigate the effect of chlorogenic acid (5-caffeoylquinic acid, 5CQA), isolated from Baccharis oxyodonta, on the structure and pharmacological effect of secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus. All in vitro and in vivo experiments were conducted using a purified sPLA2 compared under the same experimental conditions with sPLA2 : 5CQA. 5CQA induced several discrete modifications in the secondary structure and the hydrophobic characteristics of native sPLA2 that induced slight changes in the α-helical content, increase in the random coil structure, and decrease of fluorescence of native sPLA2. Moreover, 5CQA significantly decreased the enzymatic activity and the oedema and myonecrosis induced by native sPLA2. As the catalytic activity of sPLA2 plays an important role in several of its biological and pharmacological properties, antibacterial activity was used to confirm the decrease in its enzymatic activity by 5CQA, which induced massive bacterial cell destruction. We found that 5CQA specifically abolished the enzymatic activity of sPLA2 and induced discrete protein unfolding that mainly involved the pharmacological site of sPLA2. These results showed the potential application of 5CQA in the snake poisoning treatment and modulation of the pathological effect of inflammation induced by secretory PLA2. PMID:25258715

[Analysis on "component-target-pathway" of Paeonia lactiflora in treating cardiac diseases based on data mining].

PubMed

Liu, Yang; Zhang, Fang-Bo; Tang, Shi-Huan; Wang, Ping; Li, Sen; Su, Jin; Zhou, Rong-Rong; Zhang, Jia-Qi; Sun, Hui-Feng

2018-04-01

Based on the literature review and modern application of Paeonia lactiflora in heart diseases, this article would predict the target of drug and disease by intergrative pharmacology platform of traditional Chinese medicine (TCMIP, http://www.tcmip.cn), and then explore the molecular mechanism of P. lactiflora in treatment of heart disease, providing theoretical basis and method for further studies on P. lactiflora. According to the ancient books, P. lactiflora with functions of "removing the vascular obstruction, removing the lumps, relieving pain, diuretic, nutrient qi" and other effects, have been used for many times to treat heart disease. Some prescriptions are also favored by the modern physicians nowadays. With the development of science, the chemical components that play a role in heart disease and the interrelation between these components and the body become the research hotspot. In order to further reveal the pharmacological substance base and molecular mechanism of P. lactiflora for the treatment of such diseases, TCM-IP was used to obtain multiple molecular targets and signaling pathways in treatment of heart disease. ATP1A1, a common target of drug and disease, was related to energy, and HDAC2 mainly regulated cardiomyocyte hypertrophy gene and cardiomyocyte expression. Other main drug targets such as GCK, CHUK and PRKAA2 indirectly regulated heart disease through many pathways; multiple disease-associated signaling pathways interfered with various heart diseases including coronary heart disease, myocardial ischemia and myocardial hypertrophy through influencing energy metabolism, enzyme activity and gene expression. In conclusion, P. lactiflora plays a role in protecting heart function by regulating the gene expression of cardiomyocytes directly. Meanwhile, it can indirectly intervene in other pathways of heart function, and thus participate in the treatment of heart disease. In this paper, the molecular mechanism of P. lactiflora for treatment of heart disease was in computer prediction analysis level, and the specific mechanism of action still needs further experimental verification. Copyright© by the Chinese Pharmaceutical Association.

CogChamps - a model of implementing evidence-based care in hospitals: study protocol.

PubMed

Travers, Catherine; Graham, Frederick; Henderson, Amanda; Beattie, Elizabeth

2017-03-14

Delirium and dementia (cognitive impairment; CI), are common in older hospital patients, and both are associated with serious adverse outcomes. Despite delirium often being preventable, it is frequently not recognized in hospital settings, which may be because hospital nurses have not received adequate education or training in recognizing or caring for those with CI. However, the most effective way of increasing nurses' awareness about delirium and dementia, and initiating regular patient screening and monitoring to guide best practices for these patients in hospital settings is not known. Hence this current project, conducted in 2015-2017, aims to redress this situation by implementing a multi-component non-pharmacological evidence-based intervention for patients with CI, through educating and mentoring hospital nurses to change their practice. The development of the practice change component is informed by recent findings from implementation science that focuses on facilitation as the active ingredient in knowledge uptake and utilization. This component focuses on educating and empowering experienced nurses to become Cognition Champions (CogChamps) across six wards in a large Australian tertiary referral hospital. The CogChamps will, in turn, educate other nursing team members to more effectively care for patients with CI. The hospital leadership team are supportive of the project and are directly involved in selecting the CogChamps. CogChamps will be provided with comprehensive education in evidence-based delirium assessment, prevention and management, and practice change management skills. They will receive continuing support from research and education staff about raising awareness, upskilling other staff in delirium assessment and in the adoption of best practices for preventing and managing delirium. Both qualitative and quantitative data are being collected at multiple time-points to evaluate process, impact and outcome, and to provide clarity regarding the most effective aspects of the intervention. This paper describes the study protocol for the implementation of multi-component evidence-based non-pharmacological practices designed to improve the care of older hospital patients with CI. Findings will inform subsequent initiatives directed towards enhancing the capacity of the nursing workforce to implement best practices for providing high quality care for this growing patient population throughout their acute care hospital stay.

New pharmacological approaches to the cholinergic system: an overview on muscarinic receptor ligands and cholinesterase inhibitors.

PubMed

Greig, Nigel H; Reale, Marcella; Tata, Ada M

2013-08-01

The cholinergic system is expressed in neuronal and in non-neuronal tissues. Acetylcholine (ACh), synthesized in and out of the nervous system can locally contribute to modulation of various cell functions (e.g. survival, proliferation). Considering that the cholinergic system and its functions are impaired in a number of disorders, the identification of new pharmacological approaches to regulate cholinergic system components appears of great relevance. The present review focuses on recent pharmacological drugs able to modulate the activity of cholinergic receptors and thereby, cholinergic function, with an emphasis on the muscarinic receptor subtype, and additionally covers the cholinesterases, the main enzymes involved in ACh hydrolysis. The presence and function of muscarinic receptor subtypes both in neuronal and non-neuronal cells has been demonstrated using extensive pharmacological data emerging from studies on transgenic mice. The possible involvement of ACh in different pathologies has been proposed in recent years and is becoming an important area of study. Although the lack of selective muscarinic receptor ligands has for a long time limited the definition of therapeutic treatment based on muscarinic receptors as targets, some muscarinic ligands such as cevimeline (patents US4855290; US5571918) or xanomeline (patent, US5980933) have been developed and used in pre-clinical or in clinical studies for the treatment of nervous system diseases (Alzheimer' and Sjogren's diseases). The present review focuses on the potential implications of muscarinic receptors in different pathologies, including tumors. Moreover, the future use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that some muscarinic antagonists currently used in the treatment of genitourinary disease (e.g. darifenacin, patent, US5096890; US6106864) have also been demonstrated to arrest tumor progression in nude mice. The involvement of muscarinic receptors in nociception also is over-viewed. In fact, muscarinic agonists such as vedaclidine, CMI-936 and CMI-1145 have been demonstrated to have analgesic effects in animal models comparable or more pronounced to those produced by morphine or opiates. Likewise, the crucial role of cholinesterases (acetylcholinesterase and butirylcholinesterase) in neural transmission is discussed, as large number of drugs inhibiting cholinesterase activity have become of increasing relevance particularly for the treatment of neurodegenerative disorders. Herein we summarize the current knowledge of the cholinesterase inhibitors with particular attention to recent patents for Alzheimer's disease drugs.

New advances in pharmacological approaches to the cholinergic system: an overview on muscarinic receptor ligands and cholinesterase inhibitors

PubMed Central

Greig, Nigel H.; Reale, Marcella; Tata, Ada Maria

2016-01-01

The cholinergic system is expressed in neuronal and in non-neuronal tissues. Acetylcholine (ACh), synthesized in and out of the nervous system can locally contribute to modulation of various cell functions (e.g. survival, proliferation). Considering that the cholinergic system and its functions are impaired in a number of disorders, the identification of new pharmacological approaches to regulate cholinergic system components appears of great relevance. The present review focuses on recent pharmacological drugs able to modulate the activity of cholinergic receptors and thereby, cholinergic function, with an emphasis on the muscarinic receptor subtype, and additionally covers the cholinesterases, the main enzymes involved in ACh hydrolysis. The presence and function of muscarinic receptor subtypes both in neuronal and non-neuronal cells has been demonstrated using extensive pharmacological data emerging from studies on transgenic mice. The possible involvement of ACh in different pathologies has been proposed in recent years and is becoming an important area of study. Although the lack of selective muscarinic receptor ligands has for a long time limited the definition of therapeutic treatment based on muscarinic receptors as targets, some muscarinic ligands such as cevimeline (patents US4855290; US5571918) or xanomeline (patent, US5980933) have been developed and used in pre-clinical or in clinical studies for the treatment of nervous system diseases (Alzheimer’ and Sjogren’s diseases). The present review focuses on the potential implications of muscarinic receptors in different pathologies, including tumors. Moreover, the future use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that some muscarinic antagonists currently used in the treatment of genitourinary disease (e.g. darifenacin, patent, US5096890; US6106864) have also been demonstrated to arrest tumor progression in nude mice. The involvement of muscarinic receptors in nociception also is over-viewed. In fact, muscarinic agonists such as vedaclidine, CMI-936 and CMI-1145 have been demonstrated to have analgesic effects in animal models comparable or more pronounced to those produced by morphine or opiates. Likewise, the crucial role of cholinesterases (acetylcholinesterase and butirylcholinesterase) in neural transmission is discussed, as large number of drugs inhibiting cholinesterase activity have become of increasing relevance particularly for the treatment of neurodegenerative disorders. Herein we summarize the current knowledge of the cholinesterase inhibitors with particular attention to recent patents for Alzheimer’s disease drugs. PMID:23597304

The Sedative Effect of Non-Alcoholic Beer in Healthy Female Nurses

PubMed Central

Franco, Lourdes; Sánchez, Cristina; Bravo, Rafael; Rodríguez, Ana B.; Barriga, Carmen; Romero, Eulalia; Cubero, Javier

2012-01-01

Introduction The hop (Humulus lupulus L.), a component of beer, is a sedative plant whose pharmacological activity is principally due to its bitter resins, in particular to the α-acid degradation product 2-methyl-3-buten-2-ol. The mechanism of action of hop resin consists of raising the levels of the neurotransmitter γ-aminobutyric acid (GABA), an inhibitory neurotransmitter acting in the central nervous system (CNS). Objectives To analyze the sedative effect of hops as a component of non-alcoholic beer on the sleep/wake rhythm in a work-stressed population. Methods The experiment was conducted with healthy female nurses (n = 17) working rotating and/or night shifts. Overnight sleep and chronobiological parameters were assessed by actigraphy (Actiwatch®) after moderate ingestion of non-alcoholic beer containing hops (333 ml with 0,0% alcohol) with supper for 14 days (treatment). Data were obtained in comparison with her own control group without consumption of beer during supper. Results Actigraphy results demonstrated improvement of night sleep quality as regards the most important parameters: Sleep Latency diminished (p≤0.05) in the Treatment group (12.01±1.19 min) when compared to the Control group (20.50±4.21 min), as also did Total Activity (p≤0.05; Treatment group = 5284.78±836.99 activity pulses vs Control = 7258.78±898.89 activity pulses). In addition, anxiety as indexed by the State-Trait Anxiety Inventory (STAI) decreased in the Treatment group (State Anxiety 18.09±3.8 vs Control 20.69±2.14). Conclusion The moderate consumption of non-alcoholic beer will favour night-time rest, due in particular to its hop components, in addition to its other confirmed benefits for the organism. PMID:22815680

Pharmacological correction of long QT-linked mutations in KCNH2 (hERG) increases the trafficking of Kv11.1 channels stored in the transitional endoplasmic reticulum.

PubMed

Smith, Jennifer L; Reloj, Allison R; Nataraj, Parvathi S; Bartos, Daniel C; Schroder, Elizabeth A; Moss, Arthur J; Ohno, Seiko; Horie, Minoru; Anderson, Corey L; January, Craig T; Delisle, Brian P

2013-11-01

KCNH2 encodes Kv11.1 and underlies the rapidly activating delayed rectifier K(+) current (IKr) in the heart. Loss-of-function KCNH2 mutations cause the type 2 long QT syndrome (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channels. Drugs that bind to Kv11.1 and block IKr (e.g., E-4031) can act as pharmacological chaperones to increase the trafficking and functional expression for most LQT2 channels (pharmacological correction). We previously showed that LQT2 channels are selectively stored in a microtubule-dependent compartment within the endoplasmic reticulum (ER). We tested the hypothesis that pharmacological correction promotes the trafficking of LQT2 channels stored in this compartment. Confocal analyses of cells expressing the trafficking-deficient LQT2 channel G601S showed that the microtubule-dependent ER compartment is the transitional ER. Experiments with E-4031 and the protein synthesis inhibitor cycloheximide suggested that pharmacological correction promotes the trafficking of G601S stored in this compartment. Treating cells in E-4031 or ranolazine (a drug that blocks IKr and has a short half-life) for 30 min was sufficient to cause pharmacological correction. Moreover, the increased functional expression of G601S persisted 4-5 h after drug washout. Coexpression studies with a dominant-negative form of Rab11B, a small GTPase that regulates Kv11.1 trafficking, prevented the pharmacological correction of G601S trafficking from the transitional ER. These data suggest that pharmacological correction quickly increases the trafficking of LQT2 channels stored in the transitional ER via a Rab11B-dependent pathway, and we conclude that the pharmacological chaperone activity of drugs like ranolazine might have therapeutic potential.

Pharmacological correction of long QT-linked mutations in KCNH2 (hERG) increases the trafficking of Kv11.1 channels stored in the transitional endoplasmic reticulum

PubMed Central

Smith, Jennifer L.; Reloj, Allison R.; Nataraj, Parvathi S.; Bartos, Daniel C.; Schroder, Elizabeth A.; Moss, Arthur J.; Ohno, Seiko; Horie, Minoru; Anderson, Corey L.; January, Craig T.

2013-01-01

KCNH2 encodes Kv11.1 and underlies the rapidly activating delayed rectifier K+ current (IKr) in the heart. Loss-of-function KCNH2 mutations cause the type 2 long QT syndrome (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channels. Drugs that bind to Kv11.1 and block IKr (e.g., E-4031) can act as pharmacological chaperones to increase the trafficking and functional expression for most LQT2 channels (pharmacological correction). We previously showed that LQT2 channels are selectively stored in a microtubule-dependent compartment within the endoplasmic reticulum (ER). We tested the hypothesis that pharmacological correction promotes the trafficking of LQT2 channels stored in this compartment. Confocal analyses of cells expressing the trafficking-deficient LQT2 channel G601S showed that the microtubule-dependent ER compartment is the transitional ER. Experiments with E-4031 and the protein synthesis inhibitor cycloheximide suggested that pharmacological correction promotes the trafficking of G601S stored in this compartment. Treating cells in E-4031 or ranolazine (a drug that blocks IKr and has a short half-life) for 30 min was sufficient to cause pharmacological correction. Moreover, the increased functional expression of G601S persisted 4–5 h after drug washout. Coexpression studies with a dominant-negative form of Rab11B, a small GTPase that regulates Kv11.1 trafficking, prevented the pharmacological correction of G601S trafficking from the transitional ER. These data suggest that pharmacological correction quickly increases the trafficking of LQT2 channels stored in the transitional ER via a Rab11B-dependent pathway, and we conclude that the pharmacological chaperone activity of drugs like ranolazine might have therapeutic potential. PMID:23864605

Traditional uses, phytochemistry, and pharmacology of the genus Acer (maple): A review.

PubMed

Bi, Wu; Gao, Ying; Shen, Jie; He, Chunnian; Liu, Haibo; Peng, Yong; Zhang, Chunhong; Xiao, Peigen

2016-08-02

The genus Acer (Aceraceae), commonly known as maple, comprises approximately 129 species that primarily grow in the northern hemisphere, especially in the temperate regions of East Asia, eastern North America, and Europe. These plants have been traditionally used to treat a wide range of diseases in East Asia and North America. Moreover, clinical studies have shown that medicinal plants belonging to Acer are highly effective in the treatment of rheumatism, bruises, hepatic disorders, eye disease, and pain, and in detoxification. This review provides a systematic and constructive overview of the traditional uses, chemical constituents, and pharmacological activities of plants of the genus Acer. This review is based on a literature study of scientific journals and books from libraries and electronic sources such as SciFinder, ScienceDirect, Springer, PubMed, CNKI, Google Scholar, Baidu Scholar, and Web of Science. The literature in this review related to chemical constituents and pharmacological activities dates from 1922 to the end of October 2015. Furthermore, ethnopharmacological information on this genus was obtained from libraries and herbaria in China and USA. In traditional medicine, 40 species, 11 subspecies, and one varieta of the genus Acer are known to exhibit a broad spectrum of biological activities. To date, 331 compounds have been identified from 34 species of the genus Acer, including flavonoids, tannins, phenylpropanoids, diarylheptanoids, terpenoids, benzoic acid derivatives, and several other types of compounds, such as phenylethanoid glycosides and alkaloids. Preliminary pharmacological studies have shown that the extracts and compounds isolated from this genus exhibit a broad spectrum of biological activities such as antioxidant, antitumor, anti-inflammatory, antidiabetic, hepatoprotective, and antiobesity activities, as well as promoting osteoblast differentiation. To date, reports on the toxicity of Acer species to humans are very limited, and the major safety concern of these plants is in the veterinary field. Based on our systematic review, Acer species can be used to treat rheumatism, hepatic disorders, eye disease, pain, etc. effectively. Some indications from ethnomedicine have been validated by pharmacological activities, such as the anti-inflammatory and hepatoprotective activities of the species. The available literature showed that most of the activities of these species can be attributed to flavonoids and tannins. To ensure the safety and efficacy in clinical practice in the future, studies identifying active molecules and clarifying their pharmacological mechanisms as well as toxicity are needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Epigallocatechin-3-gallate(EGCG) : mechanisms and the combined applications.

PubMed

Song, Xuekun; Du, Juan; Zhao, Wenyuan; Guo, Zheng

2017-12-17

EGCG is the most important pharmacological component in tea. Researches have confirmed its effects, including anti-tumor, anti-inflammation, anti-aging, anti-obesity, anti-diabetic, cardiovascular disease prevention and protection, immunoregulation and neuroprotection. Paradoxically, the clinical application of EGCG is very rare. One of the most important reasons is its poor stability and low bioavailability. Excepting for altering the dosage form or synthesizing the analogues to overcome the loss during absorption, an increasing number of studies indicate that EGCG can exert certain auxiliary effect and enhance chemosensitivity in combined medication. The pharmacological action, the pharmacology network including mutation of signaling receptor and modulation of intracellular signaling pathway, and the combination treatment strategy of EGCG are clarified and sorted out, both the possible targets and combinatorial applications based on the characteristics of EGCG are systematically summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels.

PubMed

Corcoran, Jenna; Winter, Matthew J; Lange, Anke; Cumming, Rob; Owen, Stewart F; Tyler, Charles R

2015-04-01

In mammals, the peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating various genes involved in lipid metabolism, bile acid synthesis and cholesterol homeostasis, and is activated by a diverse group of compounds collectively termed peroxisome proliferators (PPs). Specific PPs have been detected in the aquatic environment; however little is known on their pharmacological activity in fish. We investigated the bioavailability and persistence of the human PPARα ligand clofibric acid (CFA) in carp, together with various relevant endpoints, at a concentration similar to therapeutic levels in humans (20mg/L) and for an environmentally relevant concentration (4μg/L). Exposure to pharmacologically-relevant concentrations of CFA resulted in increased transcript levels of a number of known PPARα target genes together with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid metabolism pathways in carp which are known to be similarly activated in mammals. Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels of several biotransformation genes were also increased, paralleling previous reports in mammals and indicating a potential role in hepatic detoxification for PPARα in carp. Importantly, transcription of some of these genes (and Acox1 activity) were affected at exposure concentrations comparable with those reported in effluent discharges. Collectively, these data suggest that CFA is pharmacologically active in carp and has the potential to invoke PPARα-related responses in fish exposed in the environment, particularly considering that CFA may represent just one of a number of PPAR-active compounds present to which wild fish may be exposed. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels

PubMed Central

Corcoran, Jenna; Winter, Matthew J.; Lange, Anke; Cumming, Rob; Owen, Stewart F.; Tyler, Charles R.

2015-01-01

In mammals, the peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating various genes involved in lipid metabolism, bile acid synthesis and cholesterol homeostasis, and is activated by a diverse group of compounds collectively termed peroxisome proliferators (PPs). Specific PPs have been detected in the aquatic environment; however little is known on their pharmacological activity in fish. We investigated the bioavailability and persistence of the human PPARα ligand clofibric acid (CFA) in carp, together with various relevant endpoints, at a concentration similar to therapeutic levels in humans (20 mg/L) and for an environmentally relevant concentration (4 μg/L). Exposure to pharmacologically-relevant concentrations of CFA resulted in increased transcript levels of a number of known PPARα target genes together with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid metabolism pathways in carp which are known to be similarly activated in mammals. Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels of several biotransformation genes were also increased, paralleling previous reports in mammals and indicating a potential role in hepatic detoxification for PPARα in carp. Importantly, transcription of some of these genes (and Acox1 activity) were affected at exposure concentrations comparable with those reported in effluent discharges. Collectively, these data suggest that CFA is pharmacologically active in carp and has the potential to invoke PPARα-related responses in fish exposed in the environment, particularly considering that CFA may represent just one of a number of PPAR-active compounds present to which wild fish may be exposed. PMID:25749508

Marine Pharmacology in 2000: Marine Compounds with Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiplatelet, Antituberculosis, and Antiviral Activities; Affecting the Cardiovascular, Immune, and Nervous Systems and Other Miscellaneous Mechanisms of Action

PubMed Central

Mayer, Alejandro M. S.; Hamann, Mark T.

2016-01-01

During 2000 research on the pharmacology of marine chemicals involved investigators from Australia, Brazil, Canada, Egypt, France, Germany, India, Indonesia, Israel, Italy, Japan, the Netherlands, New Zealand, Phillipines, Singapore, Slovenia, South Korea, Spain, Sweden, Switzerland, United Kingdom, and the United States. This current review, a sequel to the authors’ 1998 and 1999 reviews, classifies 68 peer-reviewed articles on the basis of the reported preclinical pharmacologic properties of marine chemicals derived from a diverse group of marine animals, algae, fungi, and bacteria. Antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antituberculosis, or antiviral activity was reported for 35 marine chemicals. An additional 20 marine compounds were shown to have significant effects on the cardiovascular and nervous system, and to possess anti-inflammatory or immunosuppressant properties. Finally, 23 marine compounds were reported to act on a variety of molecular targets and thus could potentially contribute to several pharmacologic classes. Thus, as in 1998 and 1999, during 2000 pharmacologic research with marine chemicals continued to contribute potentially novel chemical leads to the ongoing global search for therapeutic agents in the treatment of multiple disease categories. PMID:14583811

Fraxinus: A Plant with Versatile Pharmacological and Biological Activities

PubMed Central

Sarfraz, Iqra; Jabeen, Farhat; Younis, Tahira; Arshad, Muhammad; Ali, Muhammad

2017-01-01

Fraxinus, a member of the Oleaceae family, commonly known as ash tree is found in northeast Asia, north America, east and western France, China, northern areas of Pakistan, India, and Afghanistan. Chemical constituents of Fraxinus plant include various secoiridoids, phenylethanoids, flavonoids, coumarins, and lignans; therefore, it is considered as a plant with versatile biological and pharmacological activities. Its tremendous range of pharmacotherapeutic properties has been well documented including anticancer, anti-inflammatory, antioxidant, antimicrobial, and neuroprotective. In addition, its bioactive phytochemicals and secondary metabolites can be effectively used in cosmetic industry and as a competent antiaging agent. Fraxinus presents pharmacological effectiveness by targeting the novel targets in several pathological conditions, which provide a spacious therapeutic time window. Our aim is to update the scientific research community with recent endeavors with specifically highlighting the mechanism of action in different diseases. This potentially efficacious pharmacological drug candidate should be used for new drug discovery in future. This review suggests that this plant has extremely important medicinal utilization but further supporting studies and scientific experimentations are mandatory to determine its specific intracellular targets and site of action to completely figure out its pharmacological applications. PMID:29279716

Marine pharmacology in 2001–2002: Marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other miscellaneous mechanisms of action

PubMed Central

Mayer, Alejandro M.S.; Hamann, Mark T.

2016-01-01

During 2001–2002, research on the pharmacology of marine chemicals continued to be global in nature involving investigators from Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Pakistan, the Philippines, Russia, Singapore, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Thailand, United Kingdom, and the United States. This current article, a sequel to the authors’ 1998, 1999 and 2000 marine pharmacology reviews, classifies 106 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria, on the basis of peer-reviewed preclinical pharmacology. Anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 56 marine chemicals. An additional 19 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as to possess anti-inflammatory and antidiabetic effects. Finally, 31 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2001–2002 pharmacological research with marine chemicals continued to contribute potentially novel chemical leads for the ongoing global search for therapeutic agents for the treatment of multiple disease categories. PMID:15919242

Bitter gourd (Momordica charantia) as a rich source of bioactive components to combat cancer naturally: Are we on the right track to fully unlock its potential as inhibitor of deregulated signaling pathways.

PubMed

Farooqi, Ammad Ahmad; Khalid, Sumbul; Tahir, Fatima; Sabitaliyevich, Uteuliev Yerzhan; Yaylim, Ilhan; Attar, Rukset; Xu, Baojun

2018-05-10

Research over decades has progressively explored pharmacological actions of bitter gourd (Momordica charantia). Biologically and pharmacologically active molecules isolated from M. charantia have shown significant anti-cancer activity in cancer cell lines and xenografted mice. In this review spotlight was set on the bioactive compounds isolated from M. charantia that effectively inhibited cancer development and progression via regulation of protein network in cancer cells. We summarize most recent high-quality research work in cancer cell lines and xenografted mice related to tumor suppressive role-play of M. charantia and its bioactive compounds. Although M. charantia mediated health promoting, anti-diabetic, hepatoprotective, anti-inflammatory effects have been extensively investigated, there is insufficient information related to regulation of signaling networks by bioactive molecules obtained from M. charantia in different cancers. M. charantia has been shown to modulate AKT/mTOR/p70S6K signaling, p38MAPK-MAPKAPK-2/HSP-27 pathway, cell cycle regulatory proteins and apoptosis-associated proteins in different cancers. However, still there are visible knowledge gaps related to the drug targets in different cancers because we have not yet developed comprehensive understanding of the M. charantia mediated regulation of signal transduction pathways. To explore these questions, experimental platforms are needed that can prove to be helpful in getting a step closer to personalized medicine. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pharmacological and Toxicological Effects of Synthetic Cannabinoids and Their Metabolites

PubMed Central

Tai, Sherrica

2017-01-01

Commercial preparations containing synthetic cannabinoids (SCBs) are rapidly emerging as drugs of abuse. Although often assumed to be “safe” and “legal” alternatives to cannabis, reports indicate that SCBs induce toxicity not often associated with the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). This chapter will summarize the evidence that use of SCBs poses greater health risks relative to marijuana and suggest that distinct pharmacological properties and metabolism of SCBs relative to Δ9-THC may contribute to this increased toxicity. Studies reviewed will indicate that in contrast to partial agonist properties of Δ9-THC typically observed in vitro, SCBs act as full CB1 and CB2 receptor agonists both in cellular assays and animal studies. Furthermore, unlike Δ9-THC metabolism, several SCB metabolites retain high affinity for and exhibit a range of intrinsic activities at CB1 and CB2 receptors. Finally, the potential for SCBs to cause adverse drug–drug interactions with other drugs of abuse, as well as with common therapeutic agents, will be discussed. Collectively, the evidence provided in this chapter indicates that SCBs should not be considered safe and legal alternatives to marijuana. Instead, the enhanced toxicity of SCBs relative to marijuana, perhaps resulting from the combined actions of a complex mixture of different SCBs present and their active metabolites that retain high affinity for CB1 and CB2 receptors, highlights the inherent danger that may accompany use of these substances. PMID:28012093

Cannabinoids and cancer: pros and cons of an antitumour strategy

PubMed Central

Bifulco, Maurizio; Laezza, Chiara; Pisanti, Simona; Gazzerro, Patrizia

2006-01-01

In the last two decades, research has dramatically increased the knowledge of cannabinoids biology and pharmacology. In mammals, compounds with properties similar to active components of Cannabis sativa, the so called ‘endocannabinoids', have been shown to modulate key cell-signalling pathways involved in cancer cell growth, invasion and metastasis. To date, cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, but increased evidences showed direct antiproliferative actions of cannabinoid agonists on several tumour cells in vitro and in animal models. In this article, we will review the principal molecular pathways modulated by cannabinoids on cancer and summarize pros and cons evidence on the possible future use of endocannabinoid-based drugs in cancer therapy. PMID:16501583

Functional screening of pharmacological chaperones via restoration of enzyme activity upon denaturation.

PubMed

Shanmuganathan, Meera; Britz-McKibbin, Philip

2012-10-02

Pharmacological chaperones (PCs) are small molecules that stabilize and promote protein folding. Enzyme inhibition is widely used for PC selection; however, it does not accurately reflect chaperone activity. We introduce a functional assay for characterization of PCs based on their capacity to restore enzyme activity that is abolished upon chemical denaturation. Dose-dependent activity curves were performed as a function of urea to assess the chaperone potency of various ligands to β-glucocerebrosidase as a model system. Restoration of enzyme activity upon denaturation allows direct screening of PCs for treatment of genetic disorders associated with protein deficiency, such as Gaucher disease.

Growth hormone isoforms release in response to physiological and pharmacological stimuli.

PubMed

Pagani, S; Cappa, M; Meazza, C; Ubertini, G; Travaglino, P; Bozzola, E; Bozzola, M

2008-06-01

Ten healthy subjects used to performing regular physical activity and eight subjects affected by idiopathic isolated GH deficiency (GHD) were enrolled; 22- and 20-kDa GH secretion and its biological activity were evaluated in response to pharmacological stimuli such as arginine, L-dopa or glucagon in GHD children, while the hormonal response to exercise was studied according to Bruce protocol in healthy subjects. We found a significant increase in 22- and 20-kDa GH level in healthy subjects after monitored physical exercise (MPE; basal 0.28+/-0.12 vs 7.37+/-2.08 ng/ml and basal 0.076+/-0.04 vs 0.18+/-0.05 ng/ml, respectively). Furthermore, the 22-kDa/20-kDa ratio significantly increased in children who had undergone MPE and the GH bioactivity basal mean value also increased significantly after exercise (basal 2.86+/-0.76 vs 7.64+/-1.9 ng/ml). The mean value of 22-kDa GH in GHD patients increased significantly following GH pharmacological stimulation (2.78+/-0.63 ng/ml) when compared with mean basal (0.20+/-0.11 ng/ml) value. In the GHD group the basal concentration of 20-kDa GH significantly increased following GH pharmacological stimulation (0.34+/-0.11 vs 0.72+/-0.2 ng/ml); the 22-kDa/20-kDa ratio significantly increased too. Likewise, GH bioactivity in children with GHD increased significantly after pharmacological stimulation test (basal 2.53+/-0.56 vs 7.33+/-1.26 ng/ml). Both GH isoform concentrations and their biological activity are significantly increased in healthy subjects after submaximal exercise protocol and in GHD children after pharmacological stimuli.

Physiological characteristics, dry matter, and active component accumulation patterns of Changium smyrnioides in response to a light intensity gradient.

PubMed

Wang, Chang-Lin; Guo, Qiao-Sheng; Zhu, Zai-Biao; Cheng, Bo-Xing

2017-12-01

Changium smyrnioides Wolff (Apiaceae) is an endangered medicinal plant with numerous pharmacological uses. To investigate the effect of light intensity levels on the growth and accumulation of secondary metabolites of C. smyrnioides, cultivated seedlings were subjected to different relative light intensities via sun-shading. Changium smyrnioides seedlings were subjected to five irradiance treatments (100, 60.54, 44.84, 31.39, and 10.56% sunlight) in glasshouse for 9 months. Enzymatic and non-enzymatic antioxidants with spectrophotometric method, photosynthetic parameters with Li-6400XT, dry matter accumulation and active component contents in the root with spectrophotometric and HPLC method were analyzed. With an increase in relative light intensity levels, activities of enzymatic and non-enzymatic antioxidants, and malondialdehyde (MDA) contents were increased overall, while net photosynthetic rate (P n ) and dry matter accumulation patter first increased and then declined. The highest net photosynthetic rate (30.68 μmol/m 2 ·s) and dry root weight (5.07 g) were achieved under 60.54% sunlight. Lower relative light intensity levels stimulated the accumulation levels of bioactive compounds in the roots so that the highest contents of mannitol (1.35%) and choline (405.58 μg/g) were recorded under 31.39% sunlight, and the highest polysaccharide content (10.80%) were achieved under 44.84% sunlight. With a decrease in the relative light intensity levels, the water-soluble component content increased first and then decreased. The results revealed that 31.39-60.54% sunlight serve as appropriate relative light intensity conditions for cultivated C. smyrnioides.

Cannabinoid-Induced Changes in the Activity of Electron Transport Chain Complexes of Brain Mitochondria.

PubMed

Singh, Namrata; Hroudová, Jana; Fišar, Zdeněk

2015-08-01

The aim of this study was to investigate changes in the activity of individual mitochondrial respiratory chain complexes (I, II/III, IV) and citrate synthase induced by pharmacologically different cannabinoids. In vitro effects of selected cannabinoids on mitochondrial enzymes were measured in crude mitochondrial fraction isolated from pig brain. Both cannabinoid receptor agonists, Δ(9)-tetrahydrocannabinol, anandamide, and R-(+)-WIN55,212-2, and antagonist/inverse agonists of cannabinoid receptors, AM251, and cannabidiol were examined in pig brain mitochondria. Different effects of these cannabinoids on mitochondrial respiratory chain complexes and citrate synthase were found. Citrate synthase activity was decreased only by Δ(9)-tetrahydrocannabinol and AM251. Significant increase in the complex I activity was induced by anandamide. At micromolar concentration, all the tested cannabinoids inhibited the activity of electron transport chain complexes II/III and IV. Stimulatory effect of anandamide on activity of complex I may participate on distinct physiological effects of endocannabinoids compared to phytocannabinoids or synthetic cannabinoids. Common inhibitory effect of cannabinoids on activity of complex II/III and IV confirmed a non-receptor-mediated mechanism of cannabinoid action on individual components of system of oxidative phosphorylation.

An overview of the safety pharmacology society strategic plan.

PubMed

Pugsley, M K; Authier, S; Koerner, J E; Redfern, W S; Markgraf, C G; Brabham, T; Correll, K; Soloviev, M V; Botchway, A; Engwall, M; Traebert, M; Valentin, J-P; Mow, T J; Greiter-Wilke, A; Leishman, D J; Vargas, H M

2018-01-09

Safety Pharmacology studies are conducted to characterize the confidence by which biologically active new chemical entities (NCE) may be anticipated as safe. Non-clinical safety pharmacology studies aim to detect and characterize potentially undesirable pharmacodynamic activities using an array of in silico, in vitro and in vivo animal models. While a broad spectrum of methodological innovation and advancement of the science occurs within the Safety Pharmacology Society, the society also focuses on partnerships with health authorities and technology providers and facilitates interaction with organizations of common interest such as pharmacology, physiology, neuroscience, cardiology and toxicology. Education remains a primary emphasis for the society through content derived from regional and annual meetings, webinars and publication of its works it seeks to inform the general scientific and regulatory community. In considering the future of safety pharmacology the society has developed a strategy to successfully navigate forward and not be mired in stagnation of the discipline. Strategy can be defined in numerous ways but generally involves establishing and setting goals, determining what actions are needed to achieve those goals, and mobilizing resources within the society to accomplish the actions. The discipline remains in rapid evolution and its coverage is certain to expand to provide better guidance for more systems in the next few years. This overview from the Safety Pharmacology Society will outline the strategic plan from 2016 to 2018 and beyond and provide insight into the future of the discipline which builds upon a previous strategic plan established in 2009. Copyright © 2018 Elsevier Inc. All rights reserved.

Fibromyalgia syndrome: prevalence, pharmacological and non-pharmacological interventions in outpatient health care. An analysis of statutory health insurance data.

PubMed

Sauer, Kristin; Kemper, Claudia; Glaeske, Gerd

2011-01-01

Fibromyalgia syndrome (FMS) is a chronic pain condition impacting on quality of life, causing physical and psychological impairment resulting in limited participation in professional and social life. The objective of this study was to assess the prevalence, recommended pharmacological and non-pharmacological interventions of FMS, patients' characteristics and to compare findings to current research. About 1.6 Mio patients of a German statutory health insurance company (GEK) in 2007 were analyzed for: (a) the prevalence of FMS (ICD-10: M79.7); (b) and comorbid depression (ICD-10: F32/33); (c) the recommended pharmacological and non-pharmacological intervention rates; (d) and characteristics of patients associated with being prescribed recommended interventions. The (a) standardized prevalence of FMS in 2007 was 0.05% in men and 0.4% in women. (b) 51.9% of the patients with prevalent FMS had a comorbid depression in 2007 (88.2% female). (c) 66% of FMS patients received the recommended pharmacological treatment, 59% physical therapy, 6.1% cognitive-behavioural therapy and 3.4% a combination of these (multi-component therapy, MCT). (d) One year increase in age was associated with a 3% decrease in the predicted odds of receiving MCT (95%, CI 0.95-0.99). The current data indicate an FMS-prevalence that differs from epidemiological surveys and screenings, probably due to methodological differences. Especially females with comorbid depression are affected. The likelihood of receiving MCT is not associated with gender, but with younger age. Yet, the findings seem to indicate insufficient and inadequate treatment, but FMS warrants more research. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Pharmacological characterization of recombinant human and rat P2X receptor subtypes.

PubMed

Bianchi, B R; Lynch, K J; Touma, E; Niforatos, W; Burgard, E C; Alexander, K M; Park, H S; Yu, H; Metzger, R; Kowaluk, E; Jarvis, M F; van Biesen, T

1999-07-02

ATP functions as a fast neurotransmitter through the specific activation of a family of ligand-gated ion channels termed P2X receptors. In this report, six distinct recombinant P2X receptor subtypes were pharmacologically characterized in a heterologous expression system devoid of endogenous P2 receptor activity. cDNAs encoding four human P2X receptor subtypes (hP2X1, hP2X3, hP2X4, and hP2X7), and two rat P2X receptor subtypes (rP2X2 and rP2X3), were stably expressed in 1321N1 human astrocytoma cells. Furthermore, the rP2X2 and rP2X3 receptor subtypes were co-expressed in these same cells to form heteromultimeric receptors. Pharmacological profiles were determined for each receptor subtype, based on the activity of putative P2 ligands to stimulate Ca2+ influx. The observed potency and kinetics of each response was receptor subtype-specific and correlated with their respective electrophysiological properties. Each receptor subtype exhibited a distinct pharmacological profile, based on its respective sensitivity to nucleotide analogs, diadenosine polyphosphates and putative P2 receptor antagonists. Alphabeta-methylene ATP (alphabeta-meATP), a putative P2X receptor-selective agonist, was found to exhibit potent agonist activity only at the hP2X1, hP2X3 and rP2X3 receptor subtypes. Benzoylbenzoic ATP (BzATP, 2' and 3' mixed isomers), which has been reported to act as a P2X7 receptor-selective agonist, was least active at the rat and human P2X7 receptors, but was a potent (nM) agonist at hP2X1, rP2X3 and hP2X3 receptors. These data comprise a systematic examination of the functional pharmacology of P2X receptor activation.

A new agent developed by biotransformation of polyphyllin VII inhibits chemoresistance in breast cancer

PubMed Central

Zhang, Liang; Mao, Ai-Qin; Wei, Juan; Liu, De-Quan; Shi, Gui-Yang; Ma, Xin

2016-01-01

Biotransformation by the endophytes of certain plants changes various compounds, and this ‘green’ chemistry becomes increasingly important for finding new products with pharmacological activity. In this study, polyphyllin VII (PPL7) was biotransformed by endophytes from the medicinal plant Paris polyphylla Smith, var. yunnanensis. This produced a new compound, ZH-2, with pharmacological activity in vitro and in vivo. ZH-2 was more potent than PPL7 in selectively killing more chemoresistant than chemosensitive breast cancer cells. ZH-2 also re-sensitized chemoresistant breast cancer cells, as evidenced by the improved anti-cancer activity of commonly-used chemotherapeutic agent in vitro, in vivo, and in clinical samples. This anti-chemoresistance effect of ZH-2 was associated with inhibiting the epithelial-mesenchymal transition (EMT) pathway. Taken together, our findings are the first one to link biotransformation with a biomedicine. The results provide insights into developing new pharmacologically-active agents via biotransformation by endophytes. PMID:26701723

Anti-nociceptive, anti-hyperalgesic and anti-arthritic activity of amides and extract obtained from Piper amalago in rodents.

PubMed

da Silva Arrigo, Jucicléia; Balen, Eloise; Júnior, Ubirajara Lanza; da Silva Mota, Jonas; Iwamoto, Renan Donomae; Barison, Andersson; Sugizaki, Mario Mateus; Leite Kassuya, Cândida Aparecida

2016-02-17

Piper amalago (Piperaceae) has been used in folk medicine as an analgesic. This study aimed to evaluate the pharmacological effects of extract and pure amides obtained from P. amalago on pain to provide a pharmacological basis for their use in traditional medicine. This study evaluated the anti-nociceptive, anti-hyperalgesic, anti-arthritic and anti-depressive activities of the ethanolic extract of P. amalago (EEPA) and the amides N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine (1) and N-[7-(3',4'-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl] pyrrolidine (2) obtained from P. amalago in animal models. Mice treated daily with EEPA (100mg/kg, p.o.) were assayed for 20 days for knee edema (micrometer measurement), mechanical hyperalgesia (analgesiometer analysis), heat sensitivity and immobility (forced swim test) in the Complete Freund's Adjuvant (CFA) model. Cold (acetone test) and mechanical hyperalgesia (electronic von Frey analysis) responses were evaluated for 15 days in rats treated with oral EEPA (100mg/kg) in the spared nerve injury (SNI) model. Meanwhile, mice were evaluated for carrageenan-induced edema and mechanical hyperalgesia and for nociception using the formalin model after a single administration of EEPA (100mg/kg) or amides 1 and 2 (1mg/kg). Amides (1) and (2) were detected and isolated from the EEPA. The EEPA inhibited mechanical hyperalgesia, knee edema, and heat hyperalgesia, but not depressive-like behavior, induced by the intraplantar injection of CFA. When evaluated in the SNI model, the EEPA inhibited mechanical and cold hyperalgesia. The EEPA, 1 and 2 prevented the mechanical hyperalgesia induced by carrageenan and the anti-nociceptive effects in both phases of formalin nociception. The EEPA did not induce alterations in the open field test. The EEPA was effective for inhibition of pain and arthritic parameters but was not effective against depressive-like behavior; additionally, it did not alter locomotor activity. The amides obtained seemed to be the active component(s) present in the EEPA because they proved to be anti-nociceptive and anti-hyperalgesic in models of acute pain. Considering that few drugs are currently available for the treatment of chronic pain, especially neuropathic pain, the present results may have clinical relevance and open new possibilities for the development of new anti-hyperalgesic and anti-arthritic agents from P. amalago. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Contribution of TRPC3 to store-operated calcium entry and inflammatory transductions in primary nociceptors

PubMed Central

2014-01-01

Background Prolonged intracellular calcium elevation contributes to sensitization of nociceptors and chronic pain in inflammatory conditions. The underlying molecular mechanisms remain unknown but store-operated calcium entry (SOCE) components participate in calcium homeostasis, potentially playing a significant role in chronic pain pathologies. Most G protein-coupled receptors activated by inflammatory mediators trigger calcium-dependent signaling pathways and stimulate SOCE in primary afferents. The aim of the present study was to investigate the role of TRPC3, a calcium-permeable non-selective cation channel coupled to phospholipase C and highly expressed in DRG, as a link between activation of pro-inflammatory metabotropic receptors and SOCE in nociceptive pathways. Results Using in situ hybridization, we determined that TRPC3 and TRPC1 constitute the major TRPC subunits expressed in adult rat DRG. TRPC3 was found localized exclusively in small and medium diameter sensory neurons. Heterologous overexpression of TRPC3 channel subunits in cultured primary DRG neurons evoked a significant increase of Gd3+-sensitive SOCE following thapsigargin-induced calcium store depletion. Conversely, using the same calcium add-back protocol, knockdown of endogenous TRPC3 with shRNA-mediated interference or pharmacological inhibition with the selective TRPC3 antagonist Pyr10 induced a substantial decrease of SOCE, indicating a significant role of TRPC3 in SOCE in DRG nociceptors. Activation of P2Y2 purinoceptors or PAR2 protease receptors triggered a strong increase in intracellular calcium in conditions of TRPC3 overexpression. Additionally, knockdown of native TRPC3 or its selective pharmacological blockade suppressed UTP- or PAR2 agonist-evoked calcium responses as well as sensitization of DRG neurons. These data show a robust link between activation of pro-inflammatory receptors and calcium homeostasis through TRPC3-containing channels operating both in receptor- and store-operated mode. Conclusions Our findings highlight a major contribution of TRPC3 to neuronal calcium homeostasis in somatosensory pathways based on the unique ability of these cation channels to engage in both SOCE and receptor-operated calcium influx. This is the first evidence for TRPC3 as a SOCE component in DRG neurons. The flexible role of TRPC3 in calcium signaling as well as its functional coupling to pro-inflammatory metabotropic receptors involved in peripheral sensitization makes it a potential target for therapeutic strategies in chronic pain conditions. PMID:24965271

Formulation, evaluation and bioactive potential of Xylaria primorskensis terpenoid nanoparticles from its major compound xylaranic acid.

PubMed

Adnan, Mohd; Patel, Mitesh; Reddy, Mandadi Narsimha; Alshammari, Eyad

2018-01-29

In recent years, fungi have been shown to produce a plethora of new bioactive secondary metabolites of interest, as new lead structures for medicinal and other pharmacological applications. The present investigation was carried out to study the pharmacological properties of a potent and major bioactive compound: xylaranic acid, which was obtained from Xylaria primorskensis (X. primorskensis) terpenoids in terms of antibacterial activity, antioxidant potential against DPPH & H 2 O 2 radicals and anticancer activity against human lung cancer cells. Due to terpenoid nature, low water solubility and wretched bioavailability, its pharmacological use is limited. To overcome these drawbacks, a novel xylaranic acid silver nanoparticle system (AgNPs) is developed. In addition to improving its solubility and bioavailability, other advantageous pharmacological properties has been evaluated. Furthermore, enhanced anticancer activity of xylaranic acid and its AgNPs due to induced apoptosis were also confirmed by determining the expression levels of apoptosis regulatory genes p53, bcl-2 and caspase-3 via qRT PCR method. This is the first study developing the novel xylaranic acid silver nanoparticle system and enlightening its therapeutic significance with its improved physico-chemical properties and augmented bioactive potential.

Non-pharmacological self-management for people living with migraine or tension-type headache: a systematic review including analysis of intervention components

PubMed Central

Bowers, Hannah; Mistry, Dipesh; Caldwell, Fiona; Underwood, Martin; Patel, Shilpa; Sandhu, Harbinder Kaur; Matharu, Manjit; Pincus, Tamar

2017-01-01

Objectives To assess the effect of non-pharmacological self-management interventions against usual care, and to explore different components and delivery methods within those interventions Participants People living with migraine and/or tension-type headache Interventions Non-pharmacological educational or psychological self-management interventions; excluding biofeedback and physical therapy. We assessed the overall effectiveness against usual care on headache frequency, pain intensity, mood, headache-related disability, quality of life and medication consumption in meta-analysis. We also provide preliminary evidence on the effectiveness of intervention components and delivery methods. Results We found a small overall effect for the superiority of self-management interventions over usual care, with a standardised mean difference (SMD) of −0.36 (−0.45 to −0.26) for pain intensity; −0.32 (−0.42 to −0.22) for headache-related disability, 0.32 (0.20 to 0.45) for quality of life and a moderate effect on mood (SMD=0.53 (−0.66 to −0.40)). We did not find an effect on headache frequency (SMD=−0.07 (−0.22 to 0.08)). Assessment of components and characteristics suggests a larger effect on pain intensity in interventions that included explicit educational components (−0.51 (−0.68 to −0.34) vs −0.28 (−0.40 to −0.16)); mindfulness components (−0.50 (−0.82 to −0.18) vs 0.34 (−0.44 to −0.24)) and in interventions delivered in groups vs one-to-one delivery (0.56 (−0.72 to −0.40) vs −0.39 (−0.52 to −0.27)) and larger effects on mood in interventions including a cognitive–behavioural therapy (CBT) component with an SMD of −0.72 (−0.93 to −0.51) compared with those without CBT −0.41 (−0.58 to −0.24). Conclusion Overall we found that self-management interventions for migraine and tension-type headache are more effective than usual care in reducing pain intensity, mood and headache-related disability, but have no effect on headache frequency. Preliminary findings also suggest that including CBT, mindfulness and educational components in interventions, and delivery in groups may increase effectiveness. Trial registration number PROSPERO 2016:CRD42016041291 PMID:28801425

[Advance in studies on antioxidant activity of propolis and its molecular mechanism].

PubMed

Zhang, Jiang-Lin; Wang, Kai; Hu, Fu-Liang

2013-08-01

Propolis is an adhesive substance mixed with plant resins collected by honeybees (Apis mellifera) and secretions from their mandibular gland and wax gland, with wide pharmacological activity and healthcare functions. Its antioxidant activity has long been regarded as one of the most important biological activities of propolis. This article summarizes studies on the antioxidant activity of propolis extracts from different geographic origins and with different extraction methods, as well as several important monomer active ingredients in propolis, and concludes the potential molecular mechanism of antioxidant activity of propolis and its monomer ingredients, with the aim of providing ideas for further studies on pharmacological activity of propolis, as well as reference for in-depth development of propolis products.

Systems biology approaches to understand the effects of nutrition and promote health.

PubMed

Badimon, Lina; Vilahur, Gemma; Padro, Teresa

2017-01-01

Within the last years the implementation of systems biology in nutritional research has emerged as a powerful tool to understand the mechanisms by which dietary components promote health and prevent disease as well as to identify the biologically active molecules involved in such effects. Systems biology, by combining several '-omics' disciplines (mainly genomics/transcriptomics, proteomics and metabolomics), creates large data sets that upon computational integration provide in silico predictive networks that allow a more extensive analysis of the individual response to a nutritional intervention and provide a more global comprehensive understanding of how diet may influence health and disease. Numerous studies have demonstrated that diet and particularly bioactive food components play a pivotal role in helping to counteract environmental-related oxidative damage. Oxidative stress is considered to be strongly implicated in ageing and the pathophysiology of numerous diseases including neurodegenerative disease, cancers, metabolic disorders and cardiovascular diseases. In the following review we will provide insights into the role of systems biology in nutritional research and focus on transcriptomic, proteomic and metabolomics studies that have demonstrated the ability of functional foods and their bioactive components to fight against oxidative damage and contribute to health benefits. © 2016 The British Pharmacological Society.

Recurrent Vascular Headache: Home-Based Behavioral Treatment versus Abortive Pharmacological Treatment.

ERIC Educational Resources Information Center

Holroyd, Kenneth A.; And Others

1988-01-01

Compared the effectiveness of a home-based behavioral intervention (relaxation and thermal biofeedback training) with an abortive pharmacological intervention (with compliance training) for treating recurrent migraine and migraine/tension headaches. Both interventions yielded reductions in headache activity, psychosomatic symptoms, and daily life…

The Chemistry and Pharmacology of Citrus Limonoids.

PubMed

Gualdani, Roberta; Cavalluzzi, Maria Maddalena; Lentini, Giovanni; Habtemariam, Solomon

2016-11-13

Citrus limonoids (CLs) are a group of highly oxygenated terpenoid secondary metabolites found mostly in the seeds, fruits and peel tissues of citrus fruits such as lemons, limes, oranges, pumellos, grapefruits, bergamots, and mandarins. Represented by limonin, the aglycones and glycosides of CLs have shown to display numerous pharmacological activities including anticancer, antimicrobial, antioxidant, antidiabetic and insecticidal among others. In this review, the chemistry and pharmacology of CLs are systematically scrutinised through the use of medicinal chemistry tools and structure-activity relationship approach. Synthetic derivatives and other structurally-related limonoids from other sources are include in the analysis. With the focus on literature in the past decade, the chemical classification of CLs, their physico-chemical properties as drugs, their biosynthesis and enzymatic modifications, possible ways of enhancing their biological activities through structural modifications, their ligand efficiency metrics and systematic graphical radar plot analysis to assess their developability as drugs are among those discussed in detail.

Mechanisms of acetylcholine- and bradykinin-induced preconditioning.

PubMed

Critz, Stuart D; Cohen, Michael V; Downey, James M

2005-01-01

Acetylcholine (ACh) and bradykinin (BK) are potent pharmacological agents which mimic ischemic preconditioning (IPC) enabling hearts to resist infarction during a subsequent period of ischemia. The cardioprotective pathways activated by BK but not ACh may also protect when activated at reperfusion. ACh and BK stimulate Gi/o-linked receptors and ultimately mediate protection by opening mitochondrial ATP-sensitive potassium channels with the generation of reactive oxygen species that act as second messengers to activate protein kinase C (PKC). There appear to be key differences, however, in the pathways prior to potassium channel opening for these two receptors. This review aims to summarize what is currently known about pharmacological preconditioning by ACh and BK with an emphasis on differences that are seen in the signal transduction cascades. Understanding the cellular basis of protection by ACh and BK is a critical step towards developing pharmacological agents that will prevent infarction during ischemia resulting from coronary occlusion or heart attack.

The phytochemistry, traditional uses and pharmacology of Piper Betel. linn (Betel Leaf): A pan-asiatic medicinal plant.

PubMed

Fazal, Farhan; Mane, Prajwal P; Rai, Manoj P; Thilakchand, Karadka R; Bhat, Harshith P; Kamble, Prathibha S; Palatty, Princy L; Baliga, Manjeshwar Shrinath

2014-08-26

Since antiquity, Piper betel. Linn, commonly known as betel vine, has been used as a religious, recreational and medicinal plant in Southeast Asia. The leaves, which are the most commonly used plant part, are pungent with aromatic flavor and are widely consumed as a mouth freshener. It is carminative, stimulant, astringent and is effective against parasitic worms. Experimental studies have shown that it possess diverse biological and pharmacological effects, which includes antibacterial, antifungal, larvicidal, antiprotozal, anticaries, gastroprotective effects, free radical scavenging, antioxidant, anti-inflammatory hepatoprotective, immunomodulatory, antiulcer and chemopreventive activities. The active principles hydroxychavicol, allylpyrocatechol and eugenol with their plethora of pharmacological properties may also have the potential to develop as bioactive lead molecule. In this review, an attempt is made to summarize the religious, traditional uses, phytochemical composition and experimentally validated pharmacological properties of Piper betel. Emphasis is also placed on aspects warranting detail studies for it to be of pharmaceutical/clinical use to humans.

A Complete Profile on Blind-your-eye Mangrove Excoecaria Agallocha L. (Euphorbiaceae): Ethnobotany, Phytochemistry, and Pharmacological Aspects.

PubMed

Mondal, Sumanta; Ghosh, Debjit; Ramakrishna, K

2016-01-01

Traditional system of medicine consists of large number of plants with various medicinal and pharmacological importances. This article provides a comprehensive review of the complete profile of an important mangrove plant Excoecaria agallocha L. ( Euphorbiaceae ) and elaborately describing the ethnobotany, phytochemistry, and pharmacological properties. It is used traditionally in the treatment of various diseases such as epilepsy, ulcers, leprosy, rheumatism, and paralysis. The latex obtained from the bark is poisonous in nature and may cause temporary blindness, thus it is also known as the blind-your-eye mangrove plant. Many phytoconstituents were isolated from the plant, which were mainly diterpenoids, triterpenoids, flavonoids, sterols, and few other compounds. The plant also showed many pharmacological activities such as antioxidant, antimicrobial, anti-inflammatory, analgesic, antiulcer, anticancer, antireverse transcriptase, antihistamine-release, antifilarial, DNA damage protective, antidiabetic, and antitumor protecting activities. Hence, this review could help guide researchers anticipating to undertake further investigations in these directions.

Divergent Label-free Cell Phenotypic Pharmacology of Ligands at the Overexpressed β2-Adrenergic Receptors

NASA Astrophysics Data System (ADS)

Ferrie, Ann M.; Sun, Haiyan; Zaytseva, Natalya; Fang, Ye

2014-01-01

We present subclone sensitive cell phenotypic pharmacology of ligands at the β2-adrenergic receptor (β2-AR) stably expressed in HEK-293 cells. The parental cell line was transfected with green fluorescent protein (GFP)-tagged β2-AR. Four stable subclones were established and used to profile a library of sixty-nine AR ligands. Dynamic mass redistribution (DMR) profiling resulted in a pharmacological activity map suggesting that HEK293 endogenously expresses functional Gi-coupled α2-AR and Gs-coupled β2-AR, and the label-free cell phenotypic activity of AR ligands are subclone dependent. Pathway deconvolution revealed that the DMR of epinephrine is originated mostly from the remodeling of actin microfilaments and adhesion complexes, to less extent from the microtubule networks and receptor trafficking, and certain agonists displayed different efficacy towards the cAMP-Epac pathway. We demonstrate that receptor signaling and ligand pharmacology is sensitive to the receptor expression level, and the organization of the receptor and its signaling circuitry.

Chemical and pharmacological comparison of modern and traditional dosage forms of Joshanda.

PubMed

Parveen, Sajida; Irfan Bukhari, Nadeem; Shehzadi, Naureen; Qamar, Shaista; Ali, Ejaz; Naheed, Surriya; Latif, Abida; Yuchi, Alamgeer; Hussain, Khalid

2017-12-11

Recently, a traditional remedy (Joshanda) has been replaced largely by modern ready-to-use dosage forms, which have not been compared to the original remedy. Therefore, the present study aimed to compare a number of modern dosage forms with traditional remedy. Seven brands, 3 batches each, were compared with a Lab-made formulation with reference to analytical (proximate analyses, spectroscopic and chromatographic metabolomes) and pharmacological profiles (anti-inflammatory and antibacterial activities). Chemical and pharmacological differences were found between Lab-made Joshanda and modern dosage forms. Such variations were also found within the brands and batches of modern formulations (p < 0.05). The Lab-made Joshanda showed significantly higher pharmacological activities as compared to modern brands (p ). The results of the present study indicate that modern dosage forms are unstandardised and less effective than the traditional remedy. Characteristic profiles obtained from Lab-made Joshanda may be used as reference to produce comparable dosage forms.

The pharmacological activity of medical herbs after microbiological decontamination by irradiation

NASA Astrophysics Data System (ADS)

Owczarczyk, H. B.; Migdał, W.; K ȩdzia, B.

2000-03-01

In the Institute of Nuclear Chemistry and Technology research on microbiological decontamination of medicinal herbs by irradiation has been carried out since 1996. It was shown that using ionizing radiation (a dose of 10 kGy) can obtain satisfactory results of microbiological decontamination of these products. The content of essential biologically active substances such as essential oils, flavonoids, glycosides, anthocyans, antra-compounds, poliphenoloacids, triterpene saponins, oleanosides and plants mucus did not change significantly after irradiation. Pharmacological activity of medicinal herbs has been found satisfactory after microbiological decontamination by irradiation.

Lippia: traditional uses, chemistry and pharmacology: a review.

PubMed

Pascual, M E; Slowing, K; Carretero, E; Sánchez Mata, D; Villar, A

2001-08-01

The chemical composition, pharmacological activity and traditional uses of 52 species attributed to the genus Lippia (Verbenaceae) as used in the South and Central America, and Tropical Africa, were revised and compared. A survey of the available literature shows that these species are used mostly for the treatment of gastrointestinal and respiratory disorders and as seasoning. Additionally, some of these Lippia species showed antimalarial, spasmolitic, sedative, hypotensive and, anti-inflammatory activities. Generally, the essential oil or the phenolic compounds (flavonoids) from these plant extracts are assumed to be the active principles.

Parsley: a review of ethnopharmacology, phytochemistry and biological activities.

PubMed

Farzaei, Mohammad Hosein; Abbasabadi, Zahra; Ardekani, Mohammad Reza Shams; Rahimi, Roja; Farzaei, Fatemeh

2013-12-01

To summarize comprehensive information concerning ethnomedicinal uses, phytochemistry, and pharmacological activities of parsley. Databases including PubMed, Scopus, Google Scholar, and Web of Science were searched for studies focusing on the ethnomedicinal use, phytochemical compounds and biological and pharmacological activities of parsley. Data were collected from 1966 to 2013. The search terms were: "Parsley" or "Petroselinum crispum" or "Petroselinum hortence". Parsley has been used as carminative, gastro tonic, diuretic, antiseptic of urinary tract, anti-urolithiasis, anti-dote and anti-inflammatory and for the treatment of amenorrhea, dysmenorrhea, gastrointestinal disorder, hypertension, cardiac disease, urinary disease, otitis, sniffle, diabetes and also various dermal disease in traditional and folklore medicines. Phenolic compounds and flavonoids particularly apigenin, apiin and 6"-Acetylapiin; essential oil mainly myristicin and apiol; and also coumarins are the active compounds identified in Petroselinum crispum. Wide range of pharmacological activity including antioxidant, hepatoprotective, brain protective, anti-diabetic, analgesic, spasmolytic, immunosuppressant, anti-platelet, gastroprotective, cytoprotective, laxative, estrogenic, diuretic, hypotensive, antibacterial and antifungal activities have been exhibited for this plant in modern medicine. It is expectant that this study resulted in improvement the tendencies toward Petroselinum crispum as a useful and important medicinal plant with wide range of proven medicinal activity.

Clinical Effects of Cigarette Smoking: Epidemiologic Impact and Review of Pharmacotherapy Options

PubMed Central

Onor, IfeanyiChukwu O.; Stirling, Daniel L.; Williams, Shandrika R.; Bediako, Daniel; Borghol, Amne; Harris, Martha B.; Darensburg, Tiernisha B.; Clay, Sharde D.; Okpechi, Samuel C.; Sarpong, Daniel F.

2017-01-01

Cigarette smoking—a crucial modifiable risk factor for organ system diseases and cancer—remains prevalent in the United States and globally. In this literature review, we aim to summarize the epidemiology of cigarette smoking and tobacco use in the United States, pharmacology of nicotine—the active constituent of tobacco, and health consequence of cigarette smoking. This article also reviews behavioral and pharmacologic interventions for cigarette smokers and provides cost estimates for approved pharmacologic interventions in the United States. A literature search was conducted on Google Scholar, EBSCOhost, ClinicalKey, and PubMed databases using the following headings in combination or separately: cigarette smoking, tobacco smoking, epidemiology in the United States, health consequences of cigarette smoking, pharmacologic therapy for cigarette smoking, and non-pharmacologic therapy for cigarette smoking. This review found that efficacious non-pharmacologic interventions and pharmacologic therapy are available for cessation of cigarette smoking. Given the availability of efficacious interventions for cigarette smoking cessation, concerted efforts should be made by healthcare providers and public health professionals to promote smoking cessation as a valuable approach for reducing non-smokers’ exposure to environmental tobacco smoke. PMID:28956852

Ethanol extracts of saw palmetto contain the indirectly acting sympathomimetic: tyramine.

PubMed

Chua, Thiam; Simpson, Jamie S; Ventura, Sabatino

2011-01-01

To identify the bioactive components of saw palmetto ethanol extracts that affect contractility in the rat prostate gland. A commercially available saw palmetto ethanol extract was lyophilized then subjected to fractionation using silica gel column chromatography. Composition of fractions was assessed by proton nuclear magnetic resonance ((1)H NMR) spectroscopy and mass spectrometry (MS). Contractile activity of these fractions was evaluated pharmacologically using isolated preparations of rat prostate gland and compared to the activity of crude ethanol extract. Saw palmetto ethanol extract caused contractions of the rat prostate gland which were consistent with indirectly acting sympathomimetic activity. Fractions resulting from chromatography produced contractions of isolated rat prostates that were similar in magnitude to the contractions produced by the crude extracts. Analysis of NMR and mass spectra revealed that this bioactivity was due to tyramine in the active fraction. Tyramine is present in saw palmetto ethanol extracts and causes indirect α(1)-adrenoceptor mediated contractions via the release of noradrenaline from sympathetic neurons. This has clinical implications, as tyramine interacts with MAO inhibitors to cause hypertensive crisis. © 2010 Wiley-Liss, Inc.

Evidence of two populations of GABA(A) receptors in cerebellar granule cells in culture: different desensitization kinetics, pharmacology, serine/threonine kinase sensitivity, and localization.

PubMed

Robello, M; Amico, C; Cupello, A

1999-12-20

GABA(A) receptors of rat cerebellar granule cells in culture have been studied by the whole cell patch clamp technique. The biphasic desensitization kinetic observed could be due either to different desensitization mechanisms of a single receptor population or to different receptor populations. The overall data indicate that the latter hypothesis is most probably the correct one. In fact, the fast desensitizing component was selectively potentiated by a benzodiazepine agonist and preferentially down-regulated by activation of the protein serine/threonine kinases A and G, as a consequence of the latter characteristic that receptor population was preferentially down-regulated by previous activation of N-methyl-d-aspartate glutamate receptors, via production of nitric oxide and PKG activation, most probably in dendrites. The other population is benzodiazepine insensitive and not influenced by activation of PKA or PKG. This slowly desensitizing population may correspond to the extrasynaptic delta subunit containing GABA(A) receptors described by other authors. Instead, the rapidly desensitizing population appears to represent dendritic synaptic GABA(A) receptors. Copyright 1999 Academic Press.

Quetiapine and its metabolite norquetiapine: translation from in vitro pharmacology to in vivo efficacy in rodent models

PubMed Central

Widzowski, D; Maciag, C; Zacco, A; Hudzik, T; Liu, J; Nyberg, S; Wood, M W

2015-01-01

Background and Purpose Quetiapine has a range of clinical activity distinct from other atypical antipsychotic drugs, demonstrating efficacy as monotherapy in bipolar depression, major depressive disorder and generalized anxiety disorder. The neuropharmacological mechanisms underlying this clinical profile are not completely understood; however, the major active metabolite, norquetiapine, has been shown to have a distinct in vitro pharmacological profile consistent with a broad therapeutic range and may contribute to the clinical profile of quetiapine. Experimental Approach We evaluated quetiapine and norquetiapine, using in vitro binding and functional assays of targets known to be associated with antidepressant and anxiolytic drug actions and compared these activities with a representative range of established antipsychotics and antidepressants. To determine how the in vitro pharmacological properties translate into in vivo activity, we used preclinical animal models with translational relevance to established antidepressant‐like and anxiolytic‐like drug action. Key Results Norquetiapine had equivalent activity to established antidepressants at the noradrenaline transporter (NET), while quetiapine was inactive. Norquetiapine was active in the mouse forced swimming and rat learned helplessness tests. In in vivo receptor occupancy studies, norquetiapine had significant occupancy at NET at behaviourally relevant doses. Both quetiapine and norquetiapine were agonists at 5‐HT1A receptors, and the anxiolytic‐like activity of norquetiapine in rat punished responding was blocked by the 5‐HT1A antagonist, WAY100635. Conclusions and Implications Quetiapine and norquetiapine have multiple in vitro pharmacological actions, and results from preclinical studies suggest that activity at NET and 5‐HT1A receptors contributes to the antidepressant and anxiolytic effects in patients treated with quetiapine. PMID:26436896

P21-activated kinase in inflammatory and cardiovascular disease.

PubMed

Taglieri, Domenico M; Ushio-Fukai, Masuko; Monasky, Michelle M

2014-09-01

P-21 activated kinases, or PAKs, are serine-threonine kinases that serve a role in diverse biological functions and organ system diseases. Although PAK signaling has been the focus of many investigations, still our understanding of the role of PAK in inflammation is incomplete. This review consolidates what is known about PAK1 across several cell types, highlighting the role of PAK1 and PAK2 in inflammation in relation to NADPH oxidase activation. This review explores the physiological functions of PAK during inflammation, the role of PAK in several organ diseases with an emphasis on cardiovascular disease, and the PAK signaling pathway, including activators and targets of PAK. Also, we discuss PAK1 as a pharmacological anti-inflammatory target, explore the potentials and the limitations of the current pharmacological tools to regulate PAK1 activity during inflammation, and provide indications for future research. We conclude that a vast amount of evidence supports the idea that PAK is a central molecule in inflammatory signaling, thus making PAK1 itself a promising prospective pharmacological target. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a protocol for a systematic review incorporating network meta-analyses.

PubMed

Burry, L D; Hutton, B; Guenette, M; Williamson, D; Mehta, S; Egerod, I; Kanji, S; Adhikari, N K; Moher, D; Martin, C M; Rose, L

2016-09-08

Delirium is characterized by acute changes in mental status including inattention, disorganized thinking, and altered level of consciousness, and is highly prevalent in critically ill adults. Delirium has adverse consequences for both patients and the healthcare system; however, at this time, no effective treatment exists. The identification of effective prevention strategies is therefore a clinical and research imperative. An important limitation of previous reviews of delirium prevention is that interventions were considered in isolation and only direct evidence was used. Our systematic review will synthesize all existing data using network meta-analysis, a powerful statistical approach that enables synthesis of both direct and indirect evidence. We will search Ovid MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science from 1980 to March 2016. We will search the PROSPERO registry for protocols and the Cochrane Library for published systematic reviews. We will examine reference lists of pertinent reviews and search grey literature and the International Clinical Trials Registry Platform for unpublished studies and ongoing trials. We will include randomized and quasi-randomized trials of critically ill adults evaluating any pharmacological, non-pharmacological, or multi-component intervention for delirium prevention, administered in or prior to (i.e., peri-operatively) transfer to the ICU. Two authors will independently screen search results and extract data from eligible studies. Risk of bias assessments will be completed on all included studies. To inform our network meta-analysis, we will first conduct conventional pair-wise meta-analyses for primary and secondary outcomes using random-effects models. We will generate our network meta-analysis using a Bayesian framework, assuming a common heterogeneity parameter across all comparisons, and accounting for correlations in multi-arm studies. We will perform analyses using WinBUGS software. This systematic review will address the existing knowledge gap regarding best practices for delirium prevention in critically ill adults by synthesizing evidence from trials of pharmacological, non-pharmacological, and multi-component interventions administered in or prior to transfer to the ICU. Use of network meta-analysis will clarify which delirium prevention strategies are most effective in improving clinical outcomes while causing least harm. The network meta-analysis is a novel approach and will provide knowledge users and decision makers with comparisons of multiple interventions of delirium prevention strategies. PROSPERO CRD42016036313.

Effectiveness of topiramate for tobacco dependence in patients with depression; a randomised, controlled trial

PubMed Central

Campayo, Javier García; Sobradiel, Natalia; Alda, Marta; Mas, Adoración; Andrés, Eva; Magallón, Rosa; Crucelaegui, Arantxa; Sanz, Beatriz

2008-01-01

Background Tobacco dependence management is a multi-component intervention that includes pharmacological treatments such as Nicotine Substitution Therapy (NST) or bupropion, and psychological therapy. There are some preliminary reports on topiramate efficacy for tobacco dependence. The aim of this study is to determine whether topiramate is as effective as the standard NST treatment for tobacco cessation at 1-year follow-up in patients with depression. Method/design Design: A randomised, controlled trial involving two groups, one of which is the control group consisting of patients on the standard pharmacological treatment for tobacco cessation (NST) and the other is the intervention group consisting of patients on topiramate as pharmacological treatment. Setting: 29 primary care health centres in the city of Zaragoza, Spain. Sample: 180 patients, aged 18–65 years, diagnosed with major depression, smoke more than 20 cigarettes/day, who have voluntarily asked for tobacco cessation therapy. Intervention: A multi-component programme for tobacco cessation is offered to all of the patients in the study. This programme is made up of pharmacological therapy + group cognitive-behavioural therapy. Pharmacological therapy consists of NST for the control group and topiramate (200 mg/day) for the intervention group. Psychological therapy is made up of 16 sessions of manualised group therapy. Measurements: Cessation will be assessed by patient self-declared abstinence, expired air carbon monoxide levels, and cotinine levels in saliva. Questionnaires on tobacco dependence, anxiety, depression, impulsiveness and self-efficacy will be administered. The interviewers will not know which group the patient belongs to (blind). The assessments will be carried out at baseline, D (cessation day) -1, D+1, weeks 1, 2, 3, 4, 6, 8, 10 and 13, and months 4, 5, 6, 8, 10 and 12. Main variables: Tobacco cessation rates and tobacco dependence. Analysis: The analysis will be per intent to treat. We will use the general linear models of the SPSS version 15 statistical package, to analyse the effect of the treatment on the result variable (tobacco cessation rate). Discussion It is necessary to develop new and more effective pharmacological treatments for tobacco cessation. This randomised clinical trial will determine whether topiramate is effective for tobacco cessation in patients with depression. Trial registration Current Controlled Trials ISRCTN93532081 PMID:18462502

Testing the Role of p21-Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease

DTIC Science & Technology

2016-06-01

control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. The major goal of this research project was to genetically and pharmacologically ...with three different pharmacologic PAK inhibitors to determine if targeted PAK inhibition in a preclinical model of schwannoma genesis rescues tumor...this research project was to genetically and pharmacologically test the requirement of Group A PAK signaling in Nf2 deficient schwannoma genesis. We

Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

PubMed

Russo, Ethan B

2011-08-01

Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL(-1) . They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant. http://dx.doi.org/10.1111/bph.2011.163.issue-7. © 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Assessment of Safety, Tolerability, Pharmacokinetics, and Pharmacological Effect of Orally Administered CORT125134: An Adaptive, Double-Blind, Randomized, Placebo-Controlled Phase 1 Clinical Study.

PubMed

Hunt, Hazel; Donaldson, Kirsteen; Strem, Mark; Zann, Vanessa; Leung, Pui; Sweet, Suzanne; Connor, Alyson; Combs, Dan; Belanoff, Joseph

2018-05-01

CORT125134 is an orally active, high-affinity, selective antagonist of the glucocorticoid receptor that is being developed for indications that may benefit from the modulation of cortisol activity. This first-in-human study was conducted to evaluate the dose-related safety, tolerability, pharmacokinetics and pharmacological effects of CORT125134 and its active metabolite CORT125201. Eighty-one healthy male or female subjects received a single dose of 5 to 500 mg CORT125134 or matching placebo across 9 cohorts; 1 cohort received 150 mg CORT125134 after a high-fat breakfast; and 46 subjects received 50 to 500 mg CORT125134 or matching placebo once daily for up to 14 days across 4 cohorts. CORT125134 was well tolerated at doses up to 250 mg per day for 14 days. CORT125134 was absorbed rapidly and eliminated with a mean half-life ranging from 11 to 19 hours. Steady state was achieved by day 7. Exposure increased in a greater than proportional manner, particularly at lower doses. Exposure to CORT125201 at steady state was less than 5% that of parent CORT125134. Evidence for the desired pharmacological effect (glucocorticoid receptor antagonism) was demonstrated by the ability of CORT125134 to prevent several effects of the glucocorticoid receptor agonist prednisone. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Recent Updates on the Phytochemistry, Pharmacological, and Toxicological Activities of Zingiber zerumbet (L.) Roscoe ex Sm.

PubMed

Haque, Md Areeful; Jantan, Ibrahim

2017-01-01

Zingiber zerumbet (L.) Roscoe ex Sm. (family, Zingiberaceae) is a potent medicinal herb widely known as shampoo ginger and its rhizome is used in numerous ethnomedicinal applications including antipyretic, anti-inflammatory, antibacterial, anti-diarrheal, antidiabetics, carminative, and diuretic. The aim of this review was to bring together all the scientific updates on the phytochemistry and pharmacological activities of this herb, including their toxicological studies, and critically analyzed the outcomes to provide directions for future research on the herb as potential source of bioactive metabolites for pharmaceutical and nutraceutical applications. A structured electronic search on worldwide accepted scientific databases (Web of Science, PubMed, Google Scholar, Science Direct, SciFinder, Wiley Online Library) was carried out to compile the relevant information. Some information was obtained from books and database on medicinal plants used in various countries. About 60 metabolites, mainly polyphenols, and terpenoids have been isolated and identified. However, most of the reported pharmacological studies were based on crude extracts, and only a few of those isolated metabolites, particularly zerumbone have been investigated for biological and pharmacological activities. Many of the mechanistic studies to understand the pharmacological effects of the plant are limited by many considerations with regard to design, experimentation and interpretation. The bioactive metabolites should be further investigated on their safety and more elaborate preclinical studies before clinical trials can be undertaken. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pharmacological and therapeutic potential of Cordyceps with special reference to Cordycepin.

PubMed

Tuli, Hardeep S; Sandhu, Sardul S; Sharma, A K

2014-02-01

An entomopathogenic fungus, Cordyceps sp. has been known to have numerous pharmacological and therapeutic implications, especially, in terms of human health making it a suitable candidate for ethno-pharmacological use. Main constituent of the extract derived from this fungus comprises a novel bio-metabolite called as Cordycepin (3'deoxyadenosine) which has a very potent anti-cancer, anti-oxidant and anti-inflammatory activities. The current review discusses about the broad spectrum potential of Cordycepin including biological and pharmacological actions in immunological, hepatic, renal, cardiovascular systems as well as an anti-cancer agent. The article also reviews the current efforts to delineate the mechanism of action of Cordycepin in various bio-molecular processes. The study will certainly draw the attention of scientific community to improve the bioactivity and production of Cordycepin for its commercial use in pharmacological and medical fields.

Pharmacological Properties of Melanin and its Function in Health.

PubMed

ElObeid, Adila Salih; Kamal-Eldin, Afaf; Abdelhalim, Mohamed Anwar K; Haseeb, Adil M

2017-06-01

The biological pigment melanin is present in most of the biological systems. It manifests a host of biological and pharmacological properties. Its role as a molecule with special properties and functions affecting general health, including photoprotective and immunological action, are well recognized. Its antioxidant, anti-inflammatory, immunomodulatory, radioprotective, hepatic, gastrointestinal and hypoglycaemic benefits have only recently been recognized and studied. It is also associated with certain disorders of the nervous system. In this MiniReview, we consider the steadily increasing literature on the bioavailability and functional activity of melanin. Published literature shows that melanin may play a number of possible pharmacological effects such as protective, stimulatory, diagnostic and curative roles in human health. In this MiniReview, possible health roles and pharmacological effects are considered. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

A SURVEY OF SOME DICOTYLEDONOUS PLANTS; BIOASSAY AND CHEMICAL ANALYSIS.

DTIC Science & Technology

pharmacological action and were analyzed chemically for the presence or absence of alkaloids, saponins, tannins , and flavonoids. Twenty-five species of plants...representing 17 families and 25 genera, were used. Pharmacological activity, mostly depressant, was recorded for 14 of the 25 plants. Tannins were

Averrhoa bilimbi Linn.: A review of its ethnomedicinal uses, phytochemistry, and pharmacology

PubMed Central

Alhassan, Alhassan Muhammad; Ahmed, Qamar Uddin

2016-01-01

Averrhoa bilimbi Linn. is principally cultivated for medicinal purposes in many tropical and subtropical countries of the world. Literature survey about this plant shows that A. bilimbi is mainly used as a folk medicine in the treatment of diabetes mellitus, hypertension, and as an antimicrobial agent. The prime objective of this review is to accumulate and organize literature based on traditional claims and correlate those with current findings on the use of A. bilimbi in the management of different ailments. Through interpreting already published scientific manuscripts (1995 through 2015) retrieved from the different scientific search engines, namely Medline, PubMed, EMBASE, and Science Direct databases, published articles and reports covering traditional and scientific literature related to A. bilimbi's potential role against various ailments have been thoroughly evaluated, interpreted, and discussed. Several pharmacological studies have demonstrated the ability of this plant to act as antidiabetic, antihypertensive, thrombolytic, antimicrobial, antioxidant, hepatoprotective, and hypolipidemic agent. A. bilimbi holds great value in the complementary and alternative medicine as evidenced by the substantial amount of research on it. Therefore, we aimed to compile an up-to-date and comprehensive review of A. bilimbi that covers its traditional and folk medicine uses, phytochemistry, and pharmacology. Hence, this paper presents an up-to-date and comprehensive review of the ethnomedicinal uses, different chemical constituents, and pharmacological activities of A. bilimbi. So far, the biologically active agents have not been isolated from this plant and this can be a good scientific study for the future antidiabetic, antihypertensive, and antimicrobial implications. Hence, this review targets at emphasizing the diverse traditional claims and pharmacological activities of A. bilimbi with respect to carrying out more scientific studies to isolate active principles through advanced technology. PMID:28216948

Averrhoa bilimbi Linn.: A review of its ethnomedicinal uses, phytochemistry, and pharmacology.

PubMed

Alhassan, Alhassan Muhammad; Ahmed, Qamar Uddin

2016-01-01

Averrhoa bilimbi Linn. is principally cultivated for medicinal purposes in many tropical and subtropical countries of the world. Literature survey about this plant shows that A. bilimbi is mainly used as a folk medicine in the treatment of diabetes mellitus, hypertension, and as an antimicrobial agent. The prime objective of this review is to accumulate and organize literature based on traditional claims and correlate those with current findings on the use of A. bilimbi in the management of different ailments. Through interpreting already published scientific manuscripts (1995 through 2015) retrieved from the different scientific search engines, namely Medline, PubMed, EMBASE, and Science Direct databases, published articles and reports covering traditional and scientific literature related to A. bilimbi 's potential role against various ailments have been thoroughly evaluated, interpreted, and discussed. Several pharmacological studies have demonstrated the ability of this plant to act as antidiabetic, antihypertensive, thrombolytic, antimicrobial, antioxidant, hepatoprotective, and hypolipidemic agent. A. bilimbi holds great value in the complementary and alternative medicine as evidenced by the substantial amount of research on it. Therefore, we aimed to compile an up-to-date and comprehensive review of A. bilimbi that covers its traditional and folk medicine uses, phytochemistry, and pharmacology. Hence, this paper presents an up-to-date and comprehensive review of the ethnomedicinal uses, different chemical constituents, and pharmacological activities of A. bilimbi . So far, the biologically active agents have not been isolated from this plant and this can be a good scientific study for the future antidiabetic, antihypertensive, and antimicrobial implications. Hence, this review targets at emphasizing the diverse traditional claims and pharmacological activities of A. bilimbi with respect to carrying out more scientific studies to isolate active principles through advanced technology.

ROS-dependent activation of JNK converts p53 into an efficient inhibitor of oncogenes leading to robust apoptosis

PubMed Central

Shi, Y; Nikulenkov, F; Zawacka-Pankau, J; Li, H; Gabdoulline, R; Xu, J; Eriksson, S; Hedström, E; Issaeva, N; Kel, A; Arnér, E S J; Selivanova, G

2014-01-01

Rescue of the p53 tumor suppressor is an attractive cancer therapy approach. However, pharmacologically activated p53 can induce diverse responses ranging from cell death to growth arrest and DNA repair, which limits the efficient application of p53-reactivating drugs in clinic. Elucidation of the molecular mechanisms defining the biological outcome upon p53 activation remains a grand challenge in the p53 field. Here, we report that concurrent pharmacological activation of p53 and inhibition of thioredoxin reductase followed by generation of reactive oxygen species (ROS), result in the synthetic lethality in cancer cells. ROS promote the activation of c-Jun N-terminal kinase (JNK) and DNA damage response, which establishes a positive feedback loop with p53. This converts the p53-induced growth arrest/senescence to apoptosis. We identified several survival oncogenes inhibited by p53 in JNK-dependent manner, including Mcl1, PI3K, eIF4E, as well as p53 inhibitors Wip1 and MdmX. Further, we show that Wip1 is one of the crucial executors downstream of JNK whose ablation confers the enhanced and sustained p53 transcriptional response contributing to cell death. Our study provides novel insights for manipulating p53 response in a controlled way. Further, our results may enable new pharmacological strategy to exploit abnormally high ROS level, often linked with higher aggressiveness in cancer, to selectively kill cancer cells upon pharmacological reactivation of p53. PMID:24413150

[Effect of β-cyclodextrin inclusion complex on transport of major components of Xiangfu Siwu decoction essential oil in Caco-2 cell monolayer model].

PubMed

Xi, Jun-zuan; Qian, Da-wei; Duan, Jin-ao; Liu, Pei; Zhu, Yue; Zhu, Zhen-hua; Zhang, Li

2015-08-01

Although the essential oil of Xiangfu Siwu decoction (XFSWD) has strong pharmacological activity, its special physical and chemical properties restrict the clinical application and curative effect. In this paper, Xiangfu Siwu decoction essential oil (XFS-WO) was prepared by forming inclusion complex with β-cyclodextrin (β-CD). The present study is to investigate the effect of β-CD inclusion complex on the transport of major components of XFSWO using Caco-2 cell monolayer model, thus to research the effect of this formation on the absorption of drugs with low solubility and high permeability, which belong to class 2 in biopharmaceutics classification system. A sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of senkyunolide A, 3-n-butylphthalide, Z-ligustilide, dehydrocostus lactone and α-cyperone, which are active compounds in XFSWO. The transport parameters were analyzed and compared in free oil and its β-CD inclusion complex. The result revealed that the formation of XFSWO/β-CD inclusion complex has significantly increased the transportation and absorption of major active ingredients than free oil. Accordingly, it can be speculated that cyclodextrin inclusion complex can improve bioavailability of poorly water-soluble drugs. Above all these mentioned researches, it provided foundation and basis for physiological disposition and pharmaceutical study of XFSWD.

Evidence-Based Pharmacologic Treatment of Pediatric Bipolar Disorder.

PubMed

Findling, Robert L

2016-01-01

Pharmacotherapy is an important component of treatment for children and adolescents with bipolar disorder. The body of evidence supporting safe and effective treatments in this population is growing. Available data provide information on the risks and benefits of pharmacologic agents used for acute manic, mixed, and depressive episodes as well as for maintenance treatment. Lithium, anticonvulsants, and antipsychotics comprise the armamentarium for treating pediatric bipolar disorder. When selecting treatment, clinicians must consider the efficacy and side effect profile of potential pharmacotherapies, as well as the patient's history, including the presence of comorbidities, in order to develop a treatment plan that will ensure optimal outcomes. © Copyright 2016 Physicians Postgraduate Press, Inc.

Chamomile Flower, Myrrh, and Coffee Charcoal, Components of a Traditional Herbal Medicinal Product, Diminish Proinflammatory Activation in Human Macrophages.

PubMed

Vissiennon, Cica; Hammoud, Dima; Rodewald, Steffen; Fester, Karin; Goos, Karl-Heinz; Nieber, Karen; Arnhold, Jürgen

2017-07-01

A traditional herbal medicinal product, containing myrrh, chamomile flower, and coffee charcoal, has been used in Germany for the relief of gastrointestinal complaints for decades. Clinical studies suggest its use in the maintenance therapy of inflammatory bowel disease. However, the pharmacological mechanisms underlying the clinical effects are not yet fully understood.The present study aims to elucidate immunopharmacological activities of myrrh, chamomile flower, and coffee charcoal by studying the influence of each plant extract on gene expression and protein release of activated human macrophages.The plant extracts effect on gene and protein expression of activated human monocyte-derived macrophages was investigated by microarray gene expression analysis and assessment of the release of pro- and anti-inflammatory mediators (TNF α , chemokine CXCL13, and interleukin-10) using an ELISA test system.The extracts of myrrh, chamomile flower, and coffee charcoal influenced gene expression of activated human macrophages within the cytokine/chemokine signaling pathway. Particularly, chemokine gene expression was suppressed. Subsequently, the production of CXCL13 and, to a minor extent, cytokine TNF α was inhibited by all herbal extracts. Chamomile flower and coffee charcoal extracts enhanced interleukin-10 release from activated macrophages. The observed effects on protein release were comparable to the effect of budesonide, which decreased TNF α and CXCL13 and enhanced interleukin-10 release.The components of the herbal medicinal product influence the activity of activated human macrophages on both gene and protein level. The induced alterations within chemokine/cytokine signaling could contribute to a positive effect on the immunological homeostasis, which is disturbed in patients with chronic intestinal inflammation. Georg Thieme Verlag KG Stuttgart · New York.

The Human Central Pattern Generator for Locomotion.

PubMed

Minassian, Karen; Hofstoetter, Ursula S; Dzeladini, Florin; Guertin, Pierre A; Ijspeert, Auke

2017-03-01

The ability of dedicated spinal circuits, referred to as central pattern generators (CPGs), to produce the basic rhythm and neural activation patterns underlying locomotion can be demonstrated under specific experimental conditions in reduced animal preparations. The existence of CPGs in humans is a matter of debate. Equally elusive is the contribution of CPGs to normal bipedal locomotion. To address these points, we focus on human studies that utilized spinal cord stimulation or pharmacological neuromodulation to generate rhythmic activity in individuals with spinal cord injury, and on neuromechanical modeling of human locomotion. In the absence of volitional motor control and step-specific sensory feedback, the human lumbar spinal cord can produce rhythmic muscle activation patterns that closely resemble CPG-induced neural activity of the isolated animal spinal cord. In this sense, CPGs in humans can be defined by the activity they produce. During normal locomotion, CPGs could contribute to the activation patterns during specific phases of the step cycle and simplify supraspinal control of step cycle frequency as a feedforward component to achieve a targeted speed. Determining how the human CPGs operate will be essential to advance the theory of neural control of locomotion and develop new locomotor neurorehabilitation paradigms.

Cancer-selective death of human breast cancer cells by leelamine is mediated by bax and bak activation.

PubMed

Sehrawat, Anuradha; Kim, Su-Hyeong; Hahm, Eun-Ryeong; Arlotti, Julie A; Eiseman, Julie; Shiva, Sruti S; Rigatti, Lora H; Singh, Shivendra V

2017-02-01

The present study is the first to report inhibition of breast cancer cell growth in vitro and in vivo and suppression of self-renewal of breast cancer stem cells (bCSC) by a pine bark component (leelamine). Except for a few recent publications in melanoma, anticancer pharmacology of this interesting phytochemical is largely elusive. Leelamine (LLM) dose-dependently inhibited viability of MDA-MB-231 (triple-negative), MCF-7 (estrogen receptor-positive), and SUM159 (triple-negative) human breast cancer cells in association with apoptotic cell death induction. To the contrary, a normal mammary epithelial cell line derived from fibrocystic breast disease and spontaneously immortalized (MCF-10A) was fully resistant to LLM-mediated cell growth inhibition and apoptosis induction. LLM also inhibited self-renewal of breast cancer stem cells. Apoptosis induction by LLM in breast cancer cells was accompanied by a modest increase in reactive oxygen species production, which was not due to inhibition of mitochondrial electron transport chain complexes. Nevertheless, ectopic expression of manganese superoxide dismutase conferred partial protection against LLM-induced cell death but only at a lower yet pharmacologically relevant concentration. Exposure of breast cancer cells to LLM resulted in (a) induction and/or activation of multidomain proapoptotic proteins Bax and Bak, (b) caspase-9 activation, and (c) cytosolic release of cytochrome c. Bax and Bak deficiency in immortalized fibroblasts conferred significant protection against cell death by LLM. Intraperitoneal administration of LLM (7.5 mg/kg; 5 times/wk) suppressed the growth of orthotopic SUM159 xenografts in mice without any toxicity. In conclusion, the present study provides critical preclinical data to warrant further investigation of LLM. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Electroretinogram analysis of the visual response in zebrafish larvae.

PubMed

Chrispell, Jared D; Rebrik, Tatiana I; Weiss, Ellen R

2015-03-16

The electroretinogram (ERG) is a noninvasive electrophysiological method for determining retinal function. Through the placement of an electrode on the surface of the cornea, electrical activity generated in response to light can be measured and used to assess the activity of retinal cells in vivo. This manuscript describes the use of the ERG to measure visual function in zebrafish. Zebrafish have long been utilized as a model for vertebrate development due to the ease of gene suppression by morpholino oligonucleotides and pharmacological manipulation. At 5-10 dpf, only cones are functional in the larval retina. Therefore, the zebrafish, unlike other animals, is a powerful model system for the study of cone visual function in vivo. This protocol uses standard anesthesia, micromanipulation and stereomicroscopy protocols that are common in laboratories that perform zebrafish research. The outlined methods make use of standard electrophysiology equipment and a low light camera to guide the placement of the recording microelectrode onto the larval cornea. Finally, we demonstrate how a commercially available ERG stimulator/recorder originally designed for use with mice can easily be adapted for use with zebrafish. ERG of larval zebrafish provides an excellent method of assaying cone visual function in animals that have been modified by morpholino oligonucleotide injection as well as newer genome engineering techniques such as Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9, all of which have greatly increased the efficiency and efficacy of gene targeting in zebrafish. In addition, we take advantage of the ability of pharmacological agents to penetrate zebrafish larvae to evaluate the molecular components that contribute to the photoresponse. This protocol outlines a setup that can be modified and used by researchers with various experimental goals.