Antimutagenic action of the triterpene betulinic acid isolated from Scoparia dulcis (Scrophulariaceae).

PubMed

de Freitas, P L; Dias, A C S; Moreira, V R; Monteiro, S G; Pereira, S R F

2015-08-19

The mutagenic and antimutagenic activities of triterpene betulinic acid {3b-3-hydroxy-lup-20(29)-en-28-oic} isolated from the roots of Scoparia dulcis (Scrophulariaceae) were analyzed using the somatic mutation and recombination test (SMART) in the wings of Drosophila melanogaster. The mutagenic potential of betulinic acid was evaluated at 3 different concentrations (1.64, 3.28, and 6.57 mM). Antimutagenic activity evaluation was performed by co-treatment trials in which the flies received betulinic acid at 3 different concentrations in addition to 10 mM pro-mutagenic urethane. The results demonstrated that betulinic acid was not capable of causing DNA damage. However, the frequency of small single spots, large spots, and twin spots was significantly reduced. In the high bioactivation cross, betulinic acid was significantly active and exerted enhanced antimutagenic activity, possibly as a desmutagen.

Evaluation of the anti-Listeria potentials of some plant-derived triterpenes.

PubMed

Penduka, Dambudzo; Mosa, Rebamang; Simelane, Mthokozisi; Basson, Albert; Okoh, Anthony; Opoku, Andy

2014-07-23

Listeriosis is a fatal disease caused by pathogenic Listeria bacteria and it is most prevalent in immune-compromised individuals. The increase in numbers of immune-compromised individuals against a background of Listeria antibiotic resistance, limits listeriosis treatment options. This therefore calls for research into substitute treatments, of which, medicinal plants derived compounds offer a viable alternative. The broth microdilution assay was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of three plant triterpenes namely 3β-hydroxylanosta-9,24-dien-21-oic acid, methyl-3β-hydroxylanosta-9,24-dien-21-oate and 3β-acetylursolic acid, against Listeria monocytogenes, Listeria ivanovii and Listeria grayi species. The chequerboard method was used to assess the interactions between the triterpenes and conventional antibiotics: ampicillin, neomycin, gentamicin and penicillin G. The lactate dehydrogenase membrane damage method was used to assess the triterpenes' membrane damaging potentials against the Listeria bacteria. The triterpenes' MIC values were found to range from 0.185 to 1.67 mg/ml while, the MBC determination assay results revealed that the test triterpenes were bacteriostatic against the Listeria bacteria. The interactions involving 3β-hydroxylanosta-9,24-dien-21-oic acid were mainly additive with ampicillin and synergistic with neomycin, gentamicin and penicillin G. The interactions involving methyl-3β-hydroxylanosta-9,24-dien-21-oate were mainly antagonistic with ampicillin, indifferent with neomycin, ranging from synergistic to indifference with gentamicin and synergistic with penicillin G. The interactions involving 3β-acetylursolic acid were mainly indifferent with ampicillin, synergistic with neomycin and gentamicin while ranging between synergistic and additive with penicillin G. The low levels of cytosolic lactate dehydrogenase released from the cells treated with 4× MIC concentration

Regional variation in shea butter lipid and triterpene composition in four African countries.

PubMed

Di Vincenzo, Daria; Maranz, Steve; Serraiocco, Arnaldo; Vito, Raffaella; Wiesman, Zeev; Bianchi, Giorgio

2005-09-21

The triacylglycerol, fatty acid, and polycyclic triterpene compositions of shea butter were determined for 150 samples from the sub-Saharan countries of Mali, Burkina Faso, Nigeria, and Uganda. The compositional profiles showed high variability in all three classes of compounds. Shea butter is made up mainly of four triglycerides (TAG) differing in carbon number (CN) by two, starting from CN 50 to CN 56. The greatest source of variation was in the CN 54 TAG. Shea butter is characterized by 16 saturated and unsaturated fatty acids in greatly varying proportion, the major ones being the even homologues in the range of C(16)-C(20). Oleic acid is dominant in Ugandan provenances, whereas stearic acid is dominant in West African shea butter. Acetyl and cinnamyl polycyclic triterpene means for countries ranged from 3.69 to 12.57%, with the highest values found in Nigerian provenances. Statistical comparisons of fat composition show that the geographic distance between shea populations is reflected in the degree of separation of their chemical profiles.

EGFR inhibition by pentacyclic triterpenes exhibit cell cycle and growth arrest in breast cancer cells.

PubMed

Sathya, Shanmugaraj; Sudhagar, Selvaraj; Sarathkumar, Baskaran; Lakshmi, Baddireddi Subhadra

2014-01-24

Pentacyclic triterpenes are a group of molecules with promising anticancer potential, although their precise molecular target remains elusive. The current work aims to investigate the antiproliferative and associated mechanisms of triterpenes in breast cancer cells in vitro. Effect of triterpenes on cell cycle distribution, ROS and key regulatory proteins were analyzed in three breast cancer cells in vitro. Growth inhibition, new DNA synthesis, colony formation assays and Western blot analysis were performed to assess the EGFR inhibitory effect of triterpenes. Molecular docking was performed to study the interaction between EGFR and triterpenes. We have demonstrated the ability of dimethyl melaleucate (DMM), a pentacyclic triterpene to exhibit cell cycle arrest at G0/G1 phase by down-regulation of cyclin D1 through PI3K/AKT inhibition. Further, to identify the upstream target of DMM, potential EGFR inhibitory activity of DMM and three structurally related pentacyclic triterpenes, ursolic acid, 18α-glycyrrhetinic acid and carbenoxolone was investigated. Interestingly, pentacyclic triterpenes limit EGF mediated breast cancer proliferation through sustained inhibition of EGFR and its downstream effectors STAT3 and cyclin D1 in breast cancer lines. We also show pentacyclic triterpenes to bind at the ATP binding pocket of tyrosine kinase domain of EGFR leading to the hypothesis that pentacyclic triterpenes could be a novel class of EGFR inhibitors. In conclusion, pentacyclic triterpenes inhibit EGFR activation through binding with tyrosine kinase domain thereby suppressing breast cancer proliferation. Pentacyclic triterpenes may serve as a potential platform for development of novel drugs against breast cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Fruit quality and olive leaf and stone addition affect Picual virgin olive oil triterpenic content.

PubMed

Allouche, Yosra; Uceda, Marino; Jiménez, Antonio; Aguilera, M Paz; Gaforio, José Juan; Beltrán, Gabriel

2009-10-14

The present research aimed to evaluate whether Picual virgin olive oil triterpenic compounds are affected by the addition of variable quantities of stones and leaves before processing or by fruit resting on the ground during 3 months. Results showed that stone addition did not influence triterpenic dialcohol content (uvaol and erythrodiol), whereas triterpenic acids (oleanolic and maslinic) increased significantly when 20 and 30% stones were added. Leaves added at 2% increased significantly oleanolic acid, maslinic acid, and erythrodiol content by 83, 41, and 36%, respectively. During fruit resting on the ground, olive oils showed no differences in uvaol content, a slight increase in erythrodiol, and a gradual increase in both oleanolic and maslinic acids, obtaining at the end of the experiment contents nearly 10- and 3-fold higher than control oils. These results confirm that olive oil triterpenic composition is modified by the factors analyzed.

Dianthosaponins G-I, triterpene saponins, an anthranilic acid amide glucoside and a flavonoid glycoside from the aerial parts of Dianthus japonicus and their cytotoxicity.

PubMed

Kanehira, Yuka; Kawakami, Susumu; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki

2016-10-01

Extensive isolation work on the 1-BuOH-soluble fraction of a MeOH extract of the aerial parts of Dianthus japonicus afforded three further triterpene glycosyl estsers, termed dianthosaponins G-I, an anthranilic acid amide glucoside and a C-glycosyl flavonoid along with one known triterpene saponin. Their structures were elucidated from spectroscopic evidence. The cytotoxicity of the isolated compounds toward A549 cells was evaluated.

Preparation of Conjugates of Cytotoxic Lupane Triterpenes with Biotin.

PubMed

Soural, Miroslav; Hodon, Jiri; Dickinson, Niall J; Sidova, Veronika; Gurska, Sona; Dzubak, Petr; Hajduch, Marian; Sarek, Jan; Urban, Milan

2015-12-16

To better understand the mechanism of action of antitumor triterpenes, we are developing methods to identify their molecular targets. A promising method is based on combination of quantitative proteomics with SILAC and uses active compounds anchored to magnetic beads via biotin-streptavidin interaction. We developed a simple and fast solid-phase synthetic technique to connect terpenes to biotin through a linker. Betulinic acid was biotinylated from three different conjugation sites for use as a standard validation tool since many molecular targets of this triterpene are already known. Then, a set of four other cytotoxic triterpenoids was biotinylated. Biotinylated terpenes were similarly cytotoxic to their nonbiotinylated parents, which suggests that the target identification should not be influenced by linker or biotin. The developed solid-phase synthetic approach is the first attempt to use solid-phase synthesis to connect active triterpenes to biotin and is applicable as a general procedure for routine conjugation of triterpenes with other molecules of choice.

Antinociceptive and Anti-inflammatory Effects of Triterpenes from Pluchea quitoc DC. Aerial Parts

PubMed Central

Nobre da Silva, Francisco Alcione; de Farias Freire, Sônia Maria; da Rocha Borges, Marilene Oliveira; Vidal Barros, Francisco Erivaldo; da de Sousa, Maria; de Sousa Ribeiro, Maria Nilce; Pinheiro Guilhon, Giselle Maria Skelding; Müller, Adolfo Henrique; Romão Borges, Antonio Carlos

2017-01-01

Background: Pluchea quitoc DC. (Asteraceae), a medicinal plant known as “quitoco,” “caculucage,” “tabacarana” and “madre-cravo,” is indicated for inflammatory conditions such as bronchitis, arthritis, and inflammation in the uterus and digestive system. Objective: This study evaluated the analgesic and anti-inflammatory activities of the triterpenes compounds obtained from P. quitoc aerial parts. Materials and Methods: The triterpenes compounds β-amyrin, taraxasterol and pseudo-taraxasterol in a mixture (T); β-amyrin, taraxasterol and pseudo-taraxasterol acetates in a mixture (Ta); β-amyrin, taraxasterol, pseudo-taraxasterol acetates in a mixture with β-amyrin, taraxasterol and pseudo-taraxasterol myristates (Tafe) were analyzed in the models of nociception and inflammation. The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing and tail-flick tests while leukocyte migration to the peritoneal cavity was used for anti-inflammatory profile. Results: The oral administration of T or Tafe (40 mg/kg and 70 mg/kg) and Ta (70 mg/kg) to mice reduced acetic acid-induced writhing. The tail-flick response of mice was not affected by T or Tafe (40 mg/kg). T or Tafe (40 mg/kg) and Ta (70 mg/kg) also inhibited peritoneal leukocyte infiltration following the injection of carrageenan. Conclusion: The results demonstrate the anti-inflammatory and peripheral antinociceptive activity of the triterpenes β-amyrin, taraxasterol, and pseudo-taraxasterol that were decreased when these were acetylated; while the acetylated triterpenes in mixture with myristyloxy triterpenes improved this activity. These compounds seem, at least in part, to be related to the plant’s reported activity. SUMMARY The mixtures of hydroxylated, acetylated, and myristate triterpenes isolated from hexanic extracts of Pluchea quitoc DC. were analyzed in the models of nociception and inflammation in mice. The results demonstrate the anti-inflammatory and

High Triterpenic Acids Production in Callus Cultures from Fruit Pulp of Two Apple Varieties.

PubMed

Verardo, Giancarlo; Gorassini, Andrea; Ricci, Donata; Fraternale, Daniele

2017-01-01

Very rarely fruit pulp has been used in in vitro culture to produce secondary metabolites useful in promoting health. The aims of this work were the study of the best conditions to obtain the callus cultures from the pulp of two varieties of apples, Golden Delicious (GD) and "Mela Rosa Marchigiana" (MRM), and the quali-quantitative analysis of secondary metabolites produced by the two in vitro callus cultures. Callus was induced on both Murashige and Skoog and Gamborg B5 media containing various combinations of supplements. To achieve the maximum recovery of secondary metabolites produced, preliminary extraction tests were carried out on GD apple culture using two different organic solvents (MeOH and EtOAc). The quali-quantitative analysis of the methanolic extract of both cultures was carried out by ESI-MS n and GC-MS techniques. The GC-MS analysis revealed the presence of triterpenic acids, in particular, oleanolic, ursolic, maslinic, pomolic, tormentic, corosolic and annurcoic acid along with a phytosterol, β-sitosterol. In addition, GD callus culture produced phloridzin, absent in the MRM culture. In this last culture, however, the total amount of secondary metabolites was markedly higher. The in vivo production of these bioactive compounds were also quantified in the GD and MRM apple pulps. Apple pulps produced higher amounts of triterpenic acids in vitro than in vivo. The present work can be considered a method to amplify the production of important secondary metabolites which exert beneficial effects on human health. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Quantitative determination of cucurbitane-type triterpenes and triterpene glycosides in dietary supplements containing bitter melon (Momordica charantia) by HPLC-MS/MS.

PubMed

Ma, Jun; Krynitsky, Alexander J; Grundel, Erich; Rader, Jeanne I

2012-01-01

Momordica charantia L. (Cucurbitaceae), commonly known as bitter melon, is widely cultivated in many tropical and subtropical areas of the world. It is a common food staple; its fruits, leaves, seeds, stems, and roots also have a long history of use in traditional medicine. In the United States, dietary supplements labeled as containing bitter melon can be purchased over-the-counter and from Internet suppliers. Currently, no quantitative analytical method is available for monitoring the content of cucurbitane-type triterpenes and triterpene glycosides, the major constituents of bitter melon, in such supplements. We investigated the use of HPLC-electrospray ionization (ESI)-MS/MS for the quantitative determination of such compounds in dietary supplements containing bitter melon. Values for each compound obtained from external calibration were compared with those obtained from the method of standard additions to address matrix effects associated with ESI. In addition, the cucurbitane-type triterpene and triterpene glycoside contents of two dietary supplements determined by the HPLC-ESI-MS/MS method with standard additions were compared with those measured by an HPLC method with evaporative light scattering detection, which was recently developed for quantification of such compounds in dried fruits of M. charantia. The contents of five cucurbitane-type triterpenes and triterpene glycosides in 10 dietary supplements were measured using the HPLC-ESI-MS/MS method with standard additions. The total contents of the five compounds ranged from 17 to 3464 microg/serving.

Self-assembly modes of glycyrrhetinic acid esters in view of the crystal packing of related triterpene molecules.

PubMed

Langer, Dominik; Wicher, Barbara; Szczołko, Wojciech; Gdaniec, Maria; Tykarska, Ewa

2016-08-01

The crystal structures of three ester derivatives of glycyrrhetinic acid (GE) are reported. X-ray crystallography revealed that despite differences in the size of the ester substituents (ethyl, isopropyl and 2-morpholinoethyl) the scheme of molecular self-assembly is similar in all three cases but differs significantly from that observed in other known GE esters. According to our analysis, the two basic patterns of self-assembly of GE esters observed in their unsolvated crystals correspond to two distinct orientations of the ester groups relative to the triterpene backbone. Moreover, comparison of the self-assembly modes of GE esters in their unsolvated forms with the supramolecular organization of GE and carbenoxolone in their solvated crystals revealed that ester substituents replace solvent molecules hydrogen bonded to the COOH group at the triterpene skeleton, resulting in similar packing arrangements of these compounds.

Anti-trypanosomal activity of pentacyclic triterpenes isolated from Austroplenckia populnea (Celastraceae).

PubMed

Duarte, Lucienir Pains; Vieira Filho, Sidney Augusto; Silva, Grácia Divina de Fátima; de Sousa, José Rego; Pinto, Artur da Silveira

2002-01-01

Four pentacyclic triterpenes isolated from Austroplenckia populnea and four compounds of known anti T. cruzi or anti-malarial activity were tested. Of those triterpenes tested 20alpha-hydroxy-tingenone showed high activity, epikatonic acid was less active, while populnilic and populninic acids were inactive against the trypanosome of the subgenus Schizotrypanum tested. Benzonidazole, nifurtimox, ketoconazole and primaquine presented a remarkable dose-dependent inhibitory effect reaching practically to a total growth inhibition of the parasite at the end of incubation time. The trypanosome tested appear to be a suitable model for preliminary screen for anti T. (S.) cruzi compounds.

Lanostane triterpenes from the mushroom Ganoderma resinaceum and their inhibitory activities against α-glucosidase.

PubMed

Chen, Xian-Qiang; Zhao, Jing; Chen, Ling-Xiao; Wang, Shen-Fei; Wang, Ying; Li, Shao-Ping

2018-05-01

Eighteen previously undescribed lanostane triterpenes and thirty known analogues were obtained from the fruiting bodies of Ganoderma resinaceum. Resinacein C was isolated from a natural source for the first time. The structures of all the above compounds were elucidated by extensive spectroscopic analysis and comparisons of their spectroscopic data with those reported in the literature. Furthermore, in an in vitro assay, Resinacein C, ganoderic acid Y, lucialdehyde C, 7-oxo-ganoderic acid Z 3 , 7-oxo-ganoderic acid Z, and lucidadiol showed strong inhibitory effects against α-glucosidase compared with the positive control drug acarbose. The structure-activity relationships of ganoderma triterpenes on α-glucosidase inhibition showed that the C-24/C-25 double bond is necessary for α-glucosidase inhibitory activity. Moreover, the carboxylic acid group at C-26 and the hydroxy group at C-15 play important roles in enhancing inhibitory effects of these triterpenes. Copyright © 2018. Published by Elsevier Ltd.

Lupane-Type Triterpenes of Phoradendron vernicosum.

PubMed

Valencia-Chan, Lía S; García-Cámara, Isabel; Torres-Tapia, Luis W; Moo-Puc, Rosa E; Peraza-Sánchez, Sergio R

2017-11-22

Three new lupane-type triterpenes, 3α,24-dihydroxylup-20(29)-en-28-oic acid (1), 3α,23-dihydroxy-30-oxolup-20(29)-en-28-oic acid (2), and 3α,23-O-isopropylidenyl-3α,23-dihydroxylup-20(29)-en-28-oic acid (3), together with eight known compounds (4-11) were isolated from a methanol extract of Phoradendron vernicosum aerial parts. The chemical structures of 1-3 were determined on the basis of spectroscopic data interpretation. The isolated compounds were tested against seven human cancer cell lines and two normal cell lines.

Evaluation of the antibacterial activity of the methylene chloride extract of Miconia ligustroides, isolated triterpene acids, and ursolic acid derivatives.

PubMed

Cunha, Wilson R; de Matos, Geilton X; Souza, Maria Goreti M; Tozatti, Marcos G; Andrade e Silva, Márcio L; Martins, Carlos H G; da Silva, Rosangela; Da Silva Filho, Ademar A

2010-02-01

The methylene chloride extract of Miconia ligustroides (DC.) Naudin (Melastomataceae), the isolated compounds ursolic and oleanolic acids and a mixture of these acids, and ursolic acid derivatives were evaluated against the following microorganisms: Bacillus cereus (ATCC 14579), Vibrio cholerae (ATCC 9458), Salmonella choleraesuis (ATCC 10708), Klebsiella pneumoniae (ATCC 10031), and Streptococcus pneumoniae (ATCC 6305). The microdilution method was used for determination of the minimum inhibitory concentration (MIC) during evaluation of the antibacterial activity. The methylene chloride extract showed no activity against the selected microorganisms. Ursolic acid was active against B. cereus, showing a MIC value of 20 microg/mL. Oleanolic acid was effective against B. cereus and S. pneumoniae with a MIC of 80 microg/mL in both cases. The mixture of triterpenes, ursolic and oleanolic acids, did not enhance the antimicrobial activity. However, the acetyl and methyl ester derivatives, prepared from ursolic acid, increased the inhibitory activity for S. pneumoniae.

Bioactive properties of the main triterpenes found in olives, virgin olive oil, and leaves of Olea europaea.

PubMed

Sánchez-Quesada, Cristina; López-Biedma, Alicia; Warleta, Fernando; Campos, María; Beltrán, Gabriel; Gaforio, José J

2013-12-18

Oleanolic acid, maslinic acid, uvaol, and erythrodiol are the main triterpenes present in olives, olive tree leaves, and virgin olive oil. Their concentration in virgin olive oil depends on the quality of the olive oil and the variety of the olive tree. These triterpenes are described to present different properties, such as antitumoral activity, cardioprotective activity, anti-inflammatory activity, and antioxidant protection. Olive oil triterpenes are a natural source of antioxidants that could be useful compounds for the prevention of multiple diseases related to cell oxidative damage. However, special attention has to be paid to the concentrations used, because higher concentration may lead to cytotoxic or biphasic effects. This work explores all of the bioactive properties so far described for the main triterpenes present in virgin olive oil.

Effects of hydroxy pentacyclic triterpene acids from Forsythia viridissima on asthmatic responses to ovalbumin challenge in conscious guinea pigs.

PubMed

Lee, Ji Yun; Moon, Hee; Kim, Chang Jong

2010-01-01

For the identification of anti-inflammatory ingredients from Forsythiae fructus (FF), we isolated three hydroxyl pentacyclic triterpene acids (HTAs), namely, oleanolic acid, ursolic acid, and betulinic acid, from an ethylacetate fraction of FF, and evaluated the effect of these triterpene acids on asthmatic guinea pigs by measuring specific airway resistance (sRaw) during both immediate-phase response (IAR) and late-phase response (LAR) following ovalbumin challenge using a double-chambered plethysmograph. Evaluation of leukocytes and chemical mediators in bronchoalveolar lavage fluid (BALF), in addition to a histopathological survey, was also performed. Ursolic, oleanolic and betulinic acids dosed at 12.5 mg/kg significantly (p<0.05) decreased sRaw by 46.80%, 46.54% and 44.27% during in IAR, respectively. And ursolic acid (25 mg/kg), and oleanolic and betulinic acids (50 mg/kg) significantly (p<0.05) decreased sRaw by 38.19%, 38.15% and 35.55% in LAR, respectively. Histamine and phospholipase A(2) activity in BALF were significantly decreased by HTAs at 12.5 mg/kg, whereas eosinophil peroxide (EPO) activity in BALF and recruitment of eosinophils were significantly decreased by HTAs at 25 mg/kg, as well as improvement of pathological changes. However, betulinic acid at 12.5 mg/kg, and ursolic and oleanolic acids at 25 mg/kg significantly inhibited leukocytes in BALF, especially eosinophils and neutrophils. Three HTAs were found to have dose-dependent anti-asthmatic effects and ursolic acid is the most active, but their activities were less than those of sodium cromoglycate, salbutamol, and dexamethasone. These results indicate HTAs had anti-asthmatic activity by decreasing of sRaw, and eosinophil recruitment and release of inflammatory mediators into the lungs.

Pentacyclic triterpenes as α-glucosidase and α-amylase inhibitors: Structure-activity relationships and the synergism with acarbose.

PubMed

Zhang, Bo-Wei; Xing, Yan; Wen, Chen; Yu, Xiao-Xia; Sun, Wen-Long; Xiu, Zhi-Long; Dong, Yue-Sheng

2017-11-15

In this paper, the inhibition of α-amylase and α-glucosidase by nine pentacyclic triterpenes was determined. For α-amylase inhibitory activity, the IC 50 values of ursolic acid, corosolic acid, and oleanolic acid were 22.6±2.4μM, 31.2±3.4μM, and 94.1±6.7μM, respectively. For α-glucosidase inhibition, the IC 50 values of ursolic acid, corosolic acid, betulinic acid, and oleanolic acid were 12.1±1.0μM, 17.2±0.9μM, 14.9±1.9μM, and 35.6±2.6μM, respectively. The combination of corosolic acid and oleanolic acid with acarbose showed synergistic inhibition against α-amylase. The combination of the tested triterpenes with acarbose mainly exhibited additive inhibition against α-glucosidase. Kinetic studies revealed that corosolic acid and oleanolic acid showed non-competitive inhibition and acarbose showed mixed-type inhibition against α-amylase. The results provide valuable implications for the triterpenes (ursolic acid, corosolic acid, and oleanolic acid) alone or in combination with acarbose as a therapeutic agent for the treatment of diabetes mellitus. Copyright © 2017 Elsevier Ltd. All rights reserved.

Triterpenes with healing activity: A systematic review.

PubMed

Agra, Lais C; Ferro, Jamylle N S; Barbosa, Fabiano T; Barreto, Emiliano

2015-10-01

The purpose of this review was to systematically evaluate the literature on the efficacy of triterpenes for wound healing. We searched for original studies in the Medline, SCIDIRECT and LILACS databases published from 1910 to 2013. For each study, the title, abstract and full article were evaluated by two reviewers. We identified 2181 studies; however, after application of the inclusion and exclusion criteria, only 12 studies were subjected to further review. In surgical wounds, the triterpenes induced a reduction in time to closure, and this effect was reported in virtually all wound types. Triterpenes also modulate the production of ROS in the wound microenvironment, accelerating the process of tissue repair. Triterpenes may also induce cell migration, cell proliferation and collagen deposition. Although the pharmacological effects of triterpenes are well characterized, little is known about their effects in cells involved in healing, such as keratinocytes and fibroblasts. In addition, the lack of studies on the risks associated with the therapeutic use of triterpenes is worrisome. Our study reveals that triterpenes seem to favor wound healing; however, toxicological studies with these compounds are required. Taken together, these findings show that the triterpenes are a class of molecules with significant promise that leads for the development of new drugs to treat skin injury.

Conformation of flexibly linked triterpene dimers by using RDC-enhanced NMR spectroscopy

NASA Astrophysics Data System (ADS)

Lakshmi, Jerripothula K.; Pattnaik, Banita; Kavitha, Rachineni; Mallavadhani, Uppuluri V.; Jagadeesh, Bharatam

2018-06-01

Dimers of flexibly linked pentacyclic triterpene ursolic acid (UA) and its related frameworks such as asiatic acid (AA) and oleanolic acid (OA) have recently attracted significant attention due to their enhanced anti-cancer and anti-HCV activity compared to their respective monomers. Determination of conformation/inter-monomer orientation of these molecules is very important to understand their structure-activity relationship and to develop new scaffolds, which, however, is difficult through conventional NOE based solution-state NMR spectroscopy, due to lack of long-range NOEs. In the present work, we report a precise determination of conformation of two 1,2,3-triazole-linked triterpene dimer molecules, UA-AA and UA-OA, by employing one-bond Csbnd H residual dipolar couplings (RDCs) as additional long-range orientational restraints, measured in anisotropic PDMS/CDCl3 solvent medium.

Antihistaminic and antieicosanoid effects of oleanolic and ursolic acid fraction from Helichrysum picardii.

PubMed

Santos Rosa, C; García Gimenez, M D; Saenz Rodriguez, M T; De la Puerta Vazquez, R

2007-06-01

Helichrysum picardii Boiss. & Reuter is a Mediterranean vegetal species from the Asteraceae family. From the methanolic extract of the aerial flowering parts of this plant, a fraction of two pentacyclic triterpenes has been isolated. Gas chromatography revealed that the triterpene isomers ursolic and oleanolic acids comprised 69% and 29% respectively of the composition of this fraction. The triterpene isomeric fraction was tested in two phagocyte cell systems. It inhibited compound 48/80-induced histamine release from rat peritoneal mast cells in an approximately percentage of 45% at 100 microM and myeloperoxidase secretion from A23187-ionophore-stimulated rat peritoneal leukocytes in a significant manner at doses of 50 and 100 miroM. Furthermore, the triterpene isomers very significantly and dose-dependently inhibited generation of the cyclo-oxygenase metabolite prostaglandin E2 (41% inhibition at 50 miroM) and the 5-lipoxygenase metabolite leukotriene B4 (79% inhibition at 50 microM) from activated rat leukocytes. This anti-eicosanoid activity of the triterpene fraction was more potent than that produced by the pure triterpene oleanolic acid used for comparision, indicating a stronger action of the ursolic acid, the major compound of the isolated triterpene fraction. From these data, it can be suggested that the triterpene isomers oleanolic and ursolic acids present in the medicinal plant Helichrysum picardii contribute to the anti-inflammatory profile of this vegetal species.

Engineering Triterpene and Methylated Triterpene Production in Plants Provides Biochemical and Physiological Insights into Terpene Metabolism1[OPEN

PubMed Central

Jiang, Zuodong; Kempinski, Chase; Bush, Caroline J.; Nybo, S. Eric; Chappell, Joe

2016-01-01

Linear, branch-chained triterpenes, including squalene (C30), botryococcene (C30), and their methylated derivatives (C31–C37), generated by the green alga Botryococcus braunii race B have received significant attention because of their utility as chemical and biofuel feedstocks. However, the slow growth habit of B. braunii makes it impractical as a production system. In this study, we evaluated the potential of generating high levels of botryococcene in tobacco (Nicotiana tabacum) plants by diverting carbon flux from the cytosolic mevalonate pathway or the plastidic methylerythritol phosphate pathway by the targeted overexpression of an avian farnesyl diphosphate synthase along with two versions of botryococcene synthases. Up to 544 µg g−1 fresh weight of botryococcene was achieved when this metabolism was directed to the chloroplasts, which is approximately 90 times greater than that accumulating in plants engineered for cytosolic production. To test if methylated triterpenes could be produced in tobacco, we also engineered triterpene methyltransferases (TMTs) from B. braunii into wild-type plants and transgenic lines selected for high-level triterpene accumulation. Up to 91% of the total triterpene contents could be converted to methylated forms (C31 and C32) by cotargeting the TMTs and triterpene biosynthesis to the chloroplasts, whereas only 4% to 14% of total triterpenes were methylated when this metabolism was directed to the cytoplasm. When the TMTs were overexpressed in the cytoplasm of wild-type plants, up to 72% of the total squalene was methylated, and total triterpene (C30+C31+C32) content was elevated 7-fold. Altogether, these results point to innate mechanisms controlling metabolite fluxes, including a homeostatic role for squalene. PMID:26603654

Pentacyclic triterpene in Olea europaea L: A simultaneous determination by high-performance liquid chromatography coupled to mass spectrometry.

PubMed

Giménez, Estela; Juan, M Emília; Calvo-Melià, Sara; Barbosa, José; Sanz-Nebot, Victoria; Planas, Joana M

2015-09-04

Pentacyclic triterpenes are gaining interest due to their beneficial health effects, as anti-inflammatory, anti-diabetic and anti-tumoral, among others. In this study, an analytical LC-MS method was developed for the simultaneous determination of maslinic, oleanolic and ursolic acids along with erythrodiol and uvaol, which are the main triterpenic compounds present in the fruits and leaves of Olea europaea L. A Zorbax Eclipse PAH column at 30°C with mobile phase of water (17%) and methanol (83%) at 0.8mL/min conformed the optimal chromatographic conditions that allowed the separation of the compounds of interest, two pairs of which are isomers differing only in the position of one methyl group (oleanolic-ursolic and erythrodiol-uvaol). The ionization was performed in an APCI source at 450°C programmed in negative mode for the triterpenic acids, and in positive for the alcohols. An ion trap (LC-IT-MS) and a triple quadrupole (LC-QqQ-MS) were assessed for maximal sensitivity that was achieved with LC-QqQ-MS. The LODs of triterpenic acids were lower than 1nM, whereas for erythrodiol and uvaol were 4.5 and 7.5nM, respectively. The method was linear for the five analytes in the range of concentrations from 0.005 to 15μM with correlation coefficients exceeding 0.99. The precision and accuracy were ≤9.90% and ≤9.57%, respectively. The applicability of the validated method was assessed in the analysis of the pentacyclic triterpenes in Marfil table olives, after the optimization of the extraction procedure. The developed method constitutes the first step for future studies of triterpenic compounds present in foods that would allow establishing their effects on human health. Copyright © 2015 Elsevier B.V. All rights reserved.

Lupane, friedelane, oleanane, and ursane triterpenes from the stem of Siphonodon celastrineus Griff.

PubMed

Kaweetripob, Wirongrong; Mahidol, Chulabhorn; Prawat, Hunsa; Ruchirawat, Somsak

2013-12-01

Twenty-one triterpenes consisting of a lupane derivative, two friedelanes, an oleanane derivative, and 17 ursane-type triterpenoids, together with three known triterpenes, three sterols, a fatty acid, a sesquiterpene alkaloid, and a glycerol derivative, were isolated from the stem of Siphonodon celastrineus. Their structures were characterized by various spectroscopic techniques, as well as comparison with literature data. Twenty-seven metabolites of these were evaluated for cytotoxic activity against six human cancer cell lines. The biosynthetic formation of a 1,4-dioxane bridge is also discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Distinguishing commercially grown Ganoderma lucidum from Ganoderma lingzhi from Europe and East Asia on the basis of morphology, molecular phylogeny, and triterpenic acid profiles.

PubMed

Hennicke, Florian; Cheikh-Ali, Zakaria; Liebisch, Tim; Maciá-Vicente, Jose G; Bode, Helge B; Piepenbring, Meike

2016-07-01

In China and other countries of East Asia, so-called Ling-zhi or Reishi mushrooms are used in traditional medicine since several centuries. Although the common practice to apply the originally European name 'Ganoderma lucidum' to these fungi has been questioned by several taxonomists, this is still generally done in recent publications and with commercially cultivated strains. In the present study, two commercially sold strains of 'G. lucidum', M9720 and M9724 from the company Mycelia bvba (Belgium), are compared for their fruiting body (basidiocarp) morphology combined with molecular phylogenetic analyses, and for their secondary metabolite profile employing an ultra-performance liquid chromatography-electrospray ionization mass spectrometry (UPLC-ESIMS) in combination with a high resolution electrospray ionization mass spectrometry (HR-ESI-MS). According to basidiocarp morphology, the strain M9720 was identified as G. lucidum s.str. whereas M9724 was determined as Ganoderma lingzhi. In molecular phylogenetic analyses, the M9720 ITS and beta-tubulin sequences grouped with sequences of G. lucidum s.str. from Europe whereas those from M9724 clustered with sequences of G. lingzhi from East Asia. We show that an ethanol extract of ground basidiocarps from G. lucidum (M9720) contains much less triterpenic acids than found in the extract of G. lingzhi (M9724). The high amount of triterpenic acids accounts for the bitter taste of the basidiocarps of G. lingzhi (M9724) and of its ethanol extract. Apparently, triterpenic acids of G. lucidum s.str. are analyzed here for the first time. These results demonstrate the importance of taxonomy for commercial use of fungi. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

New triterpenes from Barringtonia asiatica.

PubMed

Ragasa, Consolacion Yasaña; Espineli, Dinah Lorenzana; Shen, Chien-Chang

2011-01-01

The leaves of Barringtonia asiatica afforded two new triterpenes, germanicol caffeoyl ester (1) and camelliagenone (2). Their structures were elucidated by extensive 1D- and 2D-NMR spectroscopy. It also afforded germanicol trans-coumaroyl ester (3), germanicol cis-coumaroyl ester (4), germanicol (5), camelliagenin A (6), spinasterol, sitosterol, squalene, lutein and trilinolein. Compounds 3, spinasterol and trilinolein were isolated from the fruits, while the seeds yielded spinasterol, squalene, linoleic acid and trilinolein. Compounds 1-5 exhibited antifungal activity against Candida albicans, 1-3 and 5 showed antibacterial activity against Staphylococcus aureus, while 5 is active against Pseudomonas aeruginosa.

Triterpene constituents from the seedling of Aronia melanocarpa.

PubMed

Yu, M; Li, X; Zhao, C-C; Xu, J; Zhang, P

2007-01-01

Two new triterpene saponins, 16-O-acetyl-21-O-angeloyltheasapogenol A 3-O-[beta-D-galactopyranosyl(1 --> 2)][beta-D-xylopyranosyl(1 --> 2)-alpha-L-arabinopyranosyl (1 --> 3)]-beta-D-glucopyranosiduronic acid (1) and 16,28-O-diacetyl-21-O-tigloyltheasapogenol A 3-O-[beta-D-galactopyranosyl(1 --> 2)][beta-D-xylopyranosyl(1 --> 2)-alpha-L-arabinopyranosyl (1 --> 3)]-beta-D-glucopyranosiduronic acid (2), together with four known triterpenenes, have been isolated from the dried seedling of Aronia melanocarpa, and their structures established by spectroscopic and chemical evidence.

Allspice and Clove As Source of Triterpene Acids Activating the G Protein-Coupled Bile Acid Receptor TGR5

PubMed Central

Ladurner, Angela; Zehl, Martin; Grienke, Ulrike; Hofstadler, Christoph; Faur, Nadina; Pereira, Fátima C.; Berry, David; Dirsch, Verena M.; Rollinger, Judith M.

2017-01-01

Worldwide, metabolic diseases such as obesity and type 2 diabetes have reached epidemic proportions. A major regulator of metabolic processes that gained interest in recent years is the bile acid receptor TGR5 (Takeda G protein-coupled receptor 5). This G protein-coupled membrane receptor can be found predominantly in the intestine, where it is mainly responsible for the secretion of the incretins glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). The aim of this study was (i) to identify plant extracts with TGR5-activating potential, (ii) to narrow down their activity to the responsible constituents, and (iii) to assess whether the intestinal microbiota produces transformed metabolites with a different activity profile. Chenodeoxycholic acid (CDCA) served as positive control for both, the applied cell-based luciferase reporter gene assay for TGR5 activity and the biotransformation assay using mouse fecal slurry. The suitability of the workflow was demonstrated by the biotransformation of CDCA to lithocholic acid resulting in a distinct increase in TGR5 activity. Based on a traditional Tibetan formula, 19 plant extracts were selected and investigated for TGR5 activation. Extracts from the commonly used spices Syzygium aromaticum (SaroE, clove), Pimenta dioica (PdioE, allspice), and Kaempferia galanga (KgalE, aromatic ginger) significantly increased TGR5 activity. After biotransformation, only KgalE showed significant differences in its metabolite profile, which, however, did not alter its TGR5 activity compared to non-transformed KgalE. UHPLC-HRMS (high-resolution mass spectrometry) analysis revealed triterpene acids (TTAs) as the main constituents of the extracts SaroE and PdioE. Identification and quantification of TTAs in these two extracts as well as comparison of their TGR5 activity with reconstituted TTA mixtures allowed the attribution of the TGR5 activity to TTAs. EC50s were determined for the main TTAs, i.e., oleanolic acid (2.2 ± 1.6 μM), ursolic

An unusual plant triterpene synthase with predominant α-amyrin-producing activity identified by characterizing oxidosqualene cyclases from Malus × domestica.

PubMed

Brendolise, Cyril; Yauk, Yar-Khing; Eberhard, Ellen D; Wang, Mindy; Chagne, David; Andre, Christelle; Greenwood, David R; Beuning, Lesley L

2011-07-01

The pentacyclic triterpenes, in particular ursolic acid and oleanolic acid and their derivatives, exist abundantly in the plant kingdom, where they are well known for their anti-inflammatory, antitumour and antimicrobial properties. α-Amyrin and β-amyrin are the precursors of ursolic and oleanolic acids, respectively, formed by concerted cyclization of squalene epoxide by a complex synthase reaction. We identified three full-length expressed sequence tag sequences in cDNA libraries constructed from apple (Malus × domestica 'Royal Gala') that were likely to encode triterpene synthases. Two of these expressed sequence tag sequences were essentially identical (> 99% amino acid similarity; MdOSC1 and MdOSC3). MdOSC1 and MdOSC2 were expressed by transient expression in Nicotiana benthamiana leaves and by expression in the yeast Pichia methanolica. The resulting products were analysed by GC and GC-MS. MdOSC1 was shown to be a mixed amyrin synthase (a 5 : 1 ratio of α-amyrin to β-amyrin). MdOSC1 is the only triterpene synthase so far identified in which the level of α-amyrin produced is > 80% of the total product and is, therefore, primarily an α-amyrin synthase. No product was evident for MdOSC2 when expressed either transiently or in yeast, suggesting that this putative triterpene synthase is either encoded by a pseudogene or does not express well in these systems. Transcript expression analysis in Royal Gala indicated that the genes are mostly expressed in apple peel, and that the MdOSC2 expression level was much lower than that of MdOSC1 and MdOSC3 in all the tissues tested. Amyrin content analysis was undertaken by LC-MS, and demonstrated that levels and ratios differ between tissues, but that the true consequence of synthase activity is reflected in the ursolic/oleanolic acid content and in further triterpenoids derived from them. Phylogenetic analysis placed the three triterpene synthase sequences with other triterpene synthases that encoded either �

Determination of triterpene glycosides in sea cucumber (Stichopus japonicus) and its related products by high-performance liquid chromatography.

PubMed

Dong, Ping; Xue, Chang-Hu; Yu, Lin-Fang; Xu, Jie; Chen, Shi-Guo

2008-07-09

A creative and sensitive method has been developed for the determination of triterpene glycosides concentrations in sea cucumber ( Stichopus japonicus) and related products by using d-quinovose (6-deoxyglucose) as the measurement standard by reverse-phase high-performance liquid chromatography (HPLC) and variable-wavelength detection. d-quinovose, which is a unique monosaccharide in holostane triterpene glycosides, was liberated by acid hydrolysis and precolumn derivatized by 1-phenyl-3-methyl-5-pyrazolone (PMP). PMP-quinovose was analyzed by HPLC with 22% acetonitrile in 0.05 M KH2PO4 aquatic solution (pH 5.2) as mobile phase. The calibration curves of d-quinovose were linear within the range of 6.56-164 mg/L (r(2) > 0.995). The contents of triterpene glycosides in various S. japonicus products were determined after appropriate pretreatment methods. The concentration of triterpene glycosides was calculated by the formula C = C(qui) x alpha (alpha = 8.5). The result showed that this method was a simple, rapid, and stable method for the determination of triterpene glycosides in S. japonicus products.

Caffeoyl triterpenes from pear (Pyrus pyrifolia Nakai) fruit peels and their antioxidative activities against oxidation of rat blood plasma.

PubMed

Cho, Jeong-Yong; Kim, Chan Mi; Lee, Hyoung Jae; Lee, Sang-Hyun; Cho, Jeong-An; Kim, Wol-Soo; Park, Keun-Hyung; Moon, Jae-Hak

2013-05-15

Six triterpenes, including three caffeoyl triterpenes, were purified and isolated from pear fruit ( Pyrus pyrifolia Nakai cv. Chuwhangbae) peel extracts using various column chromatography techniques with a guided 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging assay. The isolated compounds were identified as betulinic aldehyde (1), lupeol (2), betulinic acid (3), 3-O-cis-caffeoylbetulinic acid (4), 3-O-trans-caffeoylbetulinic acid (5), and 3-O-trans-caffeoyloleanolic acid (6) on the basis of nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. Four compounds (1, 4-6) were identified from Asian pear fruit for the first time. In addition, compounds 4-6, containing a caffeic acid moiety, showed higher DPPH radical-scavenging and suppression effects against copper ion-induced oxidation of rat blood plasma than other compounds without a caffeic acid moiety.

Protective effect and mechanism of action of lupane triterpenes from Cornus walteri in cisplatin-induced nephrotoxicity.

PubMed

Lee, Seulah; Jung, Kiwon; Lee, Dahae; Lee, Seoung Rak; Lee, Kang Ro; Kang, Ki Sung; Kim, Ki Hyun

2015-12-01

The present study reports a renoprotective effect and the mechanism of action of lupane triterpenes isolated from Cornus walteri in cisplatin-induced renal toxicity. A phytochemical investigation of the MeOH extract of the stems and stem bark of C. walteri resulted in the isolation and identification of twelve lupane triterpenes. Among these, betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 125 μM. Upregulated phosphorylation of JNK, ERK, and p38 following cisplatin treatment were markedly decreased after co-treatment with betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol. In addition, the protein expression level of cleaved caspase-3 and the percentage of apoptotic cells were also significantly reduced after co-treatment with betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol. These results show that blocking the MAPK signaling cascade plays a critical role in mediating the renoprotective effect of betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol isolated from C. walteri extract. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential partitioning of triterpenes and triterpene esters in apple peel

USDA-ARS?s Scientific Manuscript database

Apple peel functions as a protective barrier against biotic and abiotic stresses, and preserving the integrity and appearance of peel critical for market acceptance. Peel epidermal cells and epicuticular wax are a rich source of secondary metabolites, including triterpenes. Several studies have ou...

Unusual immuno-modulatory triterpene-caffeates in the skins of russeted varieties of apples and pears.

PubMed

Andre, Christelle M; Larsen, Lesley; Burgess, Elaine J; Jensen, Dwayne J; Cooney, Janine M; Evers, Danièle; Zhang, Jingli; Perry, Nigel B; Laing, William A

2013-03-20

Three triterpene-caffeates have been isolated from skins of a russeted apple cultivar "Merton Russet" and identified by LC-MS and NMR as betulinic acid-3-cis-caffeate, betulinic acid-3-trans-caffeate, and oleanolic acid-3-trans-caffeate. Betulinic acid-3-trans-caffeate and oleanolic acid-3-trans-caffeate were also found in russeted pear skins. These compounds have not been previously reported in apples or pears, or in any other foods. Their presence was related to suberized tissue as they were only found in russet portions of the partially russeted apple cultivar "Cox's Orange Pippin" and were not detected in the waxy apple cultivar "Royal Gala". High concentrations of betulinic acid-3-trans-caffeate were found in the bark of both "Merton Russet" and "Royal Gala" trees. The three triterpene-caffeates showed anti-inflammatory activity in vitro, inhibiting NF-κB activation with IC50's of 6-9 μM. Betulinic acid-3-trans-caffeate, the predominant compound in the apples, was immuno-modulatory at around 10 μM in the in vitro and ex vivo bioassays, boosting production of the pro-inflammatory cytokine TNFα in cells stimulated with bacterial lipopolysaccharides.

Triterpene saponin hemi-biosynthesis of a leaf beetle's (Platyphora kollari) defensive secretion

NASA Astrophysics Data System (ADS)

Ghostin, Jean; Habib-Jiwan, Jean-Louis; Rozenberg, Raoul; Daloze, Désiré; Pasteels, Jacques M.; Braekman, Jean-Claude

2007-07-01

The adults of the leaf beetle Platyphora kollari (Chrysomelidae) are able to metabolise the oleanane triterpene β-amyrin (1) into the glycoside 3-O-β-d-glucopyranosyl-(1→4)-β-d-glucuronopyranosyl-hederagenin (2) that is stored in their defensive glands. The aim of this study was to test the hypothesis that oleanolic acid (3) is an intermediate in the conversion of 1 into 2 and to check whether the sequestration of pentacyclic triterpenes is selective in favour of β-amyrin (1). To this end, adults of P. kollari were fed with Ipomoea batatas leaf disks painted with a solution of [2,2,3-2H3]oleanolic acid or [2,2,3-2H3]α-amyrin and the secretion of their defensive glands analysed by HPLC ESIMS. The data presented in this work indicated that the first step of the transformation of β-amyrin (1) into the sequestered glycoside 2 is its oxidation into oleanolic acid (3) and that this conversion is selective but not specific in favour of β-amyrin (1).

Oleanane triterpenes with protein tyrosine phosphatase 1B inhibitory activity from aerial parts of Lantana camara collected in Indonesia and Japan.

PubMed

Abdjul, Delfly B; Yamazaki, Hiroyuki; Maarisit, Wilmar; Rotinsulu, Henki; Wewengkang, Defny S; Sumilat, Deiske A; Kapojos, Magie M; Losung, Fitje; Ukai, Kazuyo; Namikoshi, Michio

2017-12-01

During the search for new protein tyrosine phosphatase (PTP) 1B inhibitors, EtOH extracts from the aerial parts of Lantana camara L. (lantana) collected at Manado (Indonesia) and two subtropical islands in Japan (Ishigaki and Iriomote Islands, Okinawa) exhibited potent inhibitory activities against PTP1B in an enzyme assay. Four previously undescribed oleanane triterpenes were isolated together with known triterpenes and flavones from the Indonesian lantana. The EtOH extracts of lantana collected in Ishigaki and Iriomote Islands exhibited different phytochemical profiles from each other and the Indonesian lantana. Triterpenes with a 24-OH group were isolated from the Indonesian lantana only. Five known triterpene compounds were detected in the Ishigaki lantana, and two oleanane triterpenes with an ether linkage between 3β and 25 were the main components together with five known triterpenes as minor components in the Iriomote lantana. The structures of previously undescribed compounds were assigned on the basis of their spectroscopic data. Among the compounds obtained in this study, oleanolic acid exhibited the most potent activity against PTP1B, and is used as a positive control in studies on PTP1B. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protein modelling of triterpene synthase genes from mangrove plants using Phyre2 and Swiss-model

NASA Astrophysics Data System (ADS)

Basyuni, M.; Wati, R.; Sulistiyono, N.; Hayati, R.; Sumardi; Oku, H.; Baba, S.; Sagami, H.

2018-03-01

Molecular cloning of five oxidosqualene cyclases (OSC) genes from Bruguiera gymnorrhiza, Kandelia candel, and Rhizophora stylosa had previously been cloned, characterized, and encoded mono and -multi triterpene synthases. The present study analyzed protein modelling of triterpene synthase genes from mangrove using Phyre2 and Swiss-model. The diversity was noted within protein modelling of triterpene synthases using Phyre2 from sequence identity (38-43%) and residue (696-703). RsM2 was distinguishable from others for template structure; it used lanosterol synthase as a template (PDB ID: w6j.1.A). By contrast, other genes used human lanosterol synthase (1w6k.1.A). The predicted bind sites were correlated with the product of triterpene synthase, the product of BgbAS was β-amyrin, while RsM1 contained a significant amount of β-amyrin. Similarly BgLUS and KcMS, both main products was lupeol, on the other hand, RsM2 with the outcome of taraxerol. Homology modelling revealed that 696 residues of BgbAS, BgLUS, RsM1, and RsM2 (91-92% of the amino acid sequence) had been modelled with 100% confidence by the single highest scoring template using Phyre2. This coverage was higher than Swiss-model (85-90%). The present study suggested that molecular cloning of triterpene genes provides useful tools for studying the protein modelling related regulation of isoprenoids biosynthesis in mangrove forests.

Antiepileptic activity of total triterpenes isolated from Poria cocos is mediated by suppression of aspartic and glutamic acids in the brain.

PubMed

Gao, Yanqiong; Yan, Hua; Jin, Ruirui; Lei, Peng

2016-11-01

Triterpenes from Poria cocos Wolf (Polyporaceae) have been used to treat various diseases in traditional Chinese medicine. However, the antiepileptic effects and mechanism are not fully understood. The objective of this study is to investigate the antiepileptic properties of total triterpenes (TTP) from the whole P. cocos. The ethanol extract TTP was identified by HPLC fingerprint analysis. Male ICR mice were gavaged (i.g.) with TTP (5, 20, 80 or 160 mg/kg) or reference drugs twice a day for 7 d. Antiepileptic activities of TTP were evaluated by maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizures in mice for 30 and 60 min, respectively. Locomotor activity and Rota-rod tests were performed for 60 min and 5 min, respectively. The levels of glutamic acid (Glu), aspartic acid (Asp), γ-aminobutyric acid (GABA) and glycine (Gly) in convulsive mice were estimated. The chronic epileptic model of Wistar rats was built to measure expressions of glutamate decarboxylase 65 (GAD65) and GABA A in rat brain after TTP treatment. The LC 50 of TTP (i.g.) was above 6 g/kg. TTP (5-160 mg/kg) protected mice against MES- and PTZ-induced convulsions at 65.0% and 62.5%, respectively, but have no effect on rota-rod treadmill; TTP (20-160 mg/kg) significantly reduced the locomotor activities, shortened the onset of pentobarbital sodium-induced sleep; TTP decreased Glu and Asp levels in convulsive mice, but increased the GAD65 and GABA A expressions in chronic epileptic rats at doses usage. TTP extracted from P. cocos possessed potential antiepileptic properties and is a candidate for further antiepileptic drug development.

A new ursane triterpene from Monochaetum vulcanicum that inhibits DNA polymerase beta lyase.

PubMed

Chaturvedula, V S Prakash; Gao, Zhijie; Jones, Shannon H; Feng, Xizhi; Hecht, Sidney M; Kingston, David G I

2004-05-01

Bioassay-directed fractionation of a butanone extract of Monochaetum vulcanicum resulted in the isolation of a new triterpene (1) and four known compounds, ursolic acid (2), 2alpha-hydroxyursolic acid (3), 3-(p-coumaroyl)ursolic acid (4), and beta-sitosteryl-beta-d-galactoside (5). The structure of the new compound 1 was established as 3beta-acetoxy-2alpha-hydroxyurs-12-en-28-oic acid on the basis of extensive 1D and 2D NMR spectroscopic interpretation and chemical derivatization. Compounds 1-3 and 5 exhibited polymerase beta lyase activity.

[Preparation of Ganoderma lucidum polysaccharides and triterpenes microemulsion and its anticancer effect in mice with transplant Heps tumors].

PubMed

Chen, Yan; Lu, Hui; Song, Shihua; Jia, Xiaobin

2010-10-01

To research the microemulsion preparation of Ganoderma lucidum polysaccharides and triterpenes and investigate its properities. Evaluate the effects of polysaccharides and triterpenes microemulsions against transplant tumor growth. The microemulsion formula was optimized by constructing the pseudo-ternary phase diagrams of blank microemulsion. The polysaccharides and triterpenes microemulsions were prepared on the blank microemulsions. The appearance, particle distribution and Zeta potential were investigated by transmission electron microscope and grain size analyzer. The Heps mice were randomly administered with polysaccharides and triterpenes microemulsions (114.5, 57.25 mg x kg(-1) x d(-1)) for 7 days. The effectiveness was assessed based on tumor inhibitory ratio of mice with Heps tumors. The toxicity was evaluated by measurements of the mice weight, immune organ weight. The optimal microemulsion formula was composed of tween 20, dimethyl carbinol, water and 9-octadecenoic acid with the ratio of 14.3: 14.3: 33. 3:2. Polysaccharides and triterpenes microemulsions in transmission electron microscope were consisted of small spherical drop. The average particle size was 32.43 nm and the Zeta potential was -3.41 mV. The polysaccharides and triterpenes microemulsions showed an inhibition rate of 37.66% (57.25 mg x kg(-1) x d(-1)) and 52.34% (114.5 mg x kg(-1) x d(-1)) respectively against Heps tumor growth. The acquired microemulsion with small particle size is stable. It significantly inhibits the tumor growth in Heps mice.

Identification of triterpenes from milkweed (Asclepias syriaca).

PubMed

Háznagy-Radnai, Erzsébet; Wéber, Edit; Czigle, Szilvia; Máthé, Imre

2012-09-01

The chloroform extract of Asclepias syriaca stem were investigated. Three triterpenes were isolated by TLC, VLC, and preparative chromatography, and their structures established by one and two-dimensional NMR spectroscopy. Lupenyl acetate has been isolated for the first time from A. syriaca; this is thefirst representative of a triterpene bearing a lupane skeleton in this species. In addition, alpha-amyrin acetate and alpha-amyrin butyrate were isolated.

Triterpenes from the exudate of Gardenia urvillei.

PubMed

Mai, Hoang Linh; Grellier, Philippe; Prost, Elise; Lemoine, Pascale; Poullain, Cyril; Dumontet, Vincent; Deguin, Brigitte; Vo, Thi Bach Hue; Michel, Sylvie; Grougnet, Raphaël

2016-02-01

A cycloartane gardurvilleic acid, three 3,4-seco-cycloartanes securvienol, secodienurvilleic acid, securvitriol, a 3,4;9,10-seco-cycloartane gardheptlactone, two dammaranes urvilone, urvilol, along with eight known cycloartanes and 3,4-seco-cycloartanes and four known dammaranes have been isolated from the bud exudate of Gardenia urvillei, an endemic tree to the New Caledonian dry forest. Two other dammarane derivatives have been obtained by semisynthesis. The structures of the original compounds were determined by spectroscopic methods and chemical correlations. In association with previously published data, the description of oxidized side-chains in position 17 are now available for two couples of diastereoisomers. Evaluation of anti-parasite activity and cytotoxicity has shown noticeable results for some of the isolated triterpenes. Copyright © 2015 Elsevier Ltd. All rights reserved.

One single standard substance for the simultaneous determination of 17 triterpenes in Ganoderma lingzhi and its related species using high-performance liquid chromatography.

PubMed

Liu, Wei; Zhang, Jingsong; Han, Wei; Liu, Yanfang; Feng, Jie; Tang, Chuanhong; Feng, Na; Tang, Qingjiu

2017-11-15

Due to the difficulty and high cost for the preparation of triterpenes, one single standard for the simultaneous determination of multi-components (SSDMC) with high performance liquid chromatography (HPLC) is an advanced solution for multi-component analysis. Experiments were carried out to investigate the feasibility of SSDMC for the analysis of Ganoderma triterpenes, with external standard method (ESM) compared, and the samples of Ganoderma were classified by the content of Ganoderma triterpenes. The analysis was performed by using a Fortis Speed Core-C18 column (150mm×4.6mm I.D., 2.6μm) at gradient elution of 0.01% glacial acetic acid-water (V/V) and acetonitrile with diode array detection (252nm), at a flow rate of 1mL/min. The results showed that all calibration curves had good linearity (r 2 >0.9999) within test ranges. The LOD and LOQ were lower than 2.52ng and 6.43ng, respectively. The RSD for intra-day and inter-day of the seventeen analytes were less than 3.12% at three levels, and the recoveries were 91.4-103.0%. The contents of other 16 triterpenes were determined with ganoderic acid A by SSDMC, which showed that there were few differences compared with the results obtained by ESM. Moreover, the classification of 25 different species and strains of Ganoderma by using the content of triterpenes intuitively reflected the distinction among Ganoderma. In summary, the developed method could be readily utilized as a method of quality evaluation for Ganoderma triterpenes. Copyright © 2017. Published by Elsevier B.V.

Steroids and triterpenes from the fruit bodies of Ganoderma lucidum and their anti-complement activity.

PubMed

Seo, Hyo Won; Hung, Tran Manh; Na, MinKyun; Jung, Hyun Ju; Kim, Jin Cheol; Choi, Jae Sue; Kim, Jung Hee; Lee, Hyeong-Kyu; Lee, IkSoo; Bae, KiHwan; Hattori, Masao; Min, Byung Sun

2009-11-01

To determine the anti-complement activity of natural triterpenes, chromatographic separation of the EtOAc-soluble fraction from the fruiting body of Ganoderma lucidum led to the isolation of three steroids and five triterpenoids. They were identified as ergosterol peroxide (1), ergosterol (2), genoderic acid Sz (3), stella sterol (4), ganoderic aic C1 (5), ganoderic acid A (6), methyl ganoderate A (7), and lucidenic acid A (8) based on spectroscopic evidence and physicochemical properties. These compounds were examined for their anti-complement activity against the classical pathway of the complement system. Compounds 2 and 3 showed potent anti-complement activity with IC50 values of 52.0 and 44.6 microM, respectively. Compound 1 exhibited significant inhibitory activity with an IC50 value of 126.8 microM, whereas compounds 4-8 were inactive. Our findings suggested that in addition to the ketone group at C-3, the delta7(8), delta9(11)-lanostadiene type triterpene also plays an important role in inhibiting the hemolytic activity of human serum against erythrocytes.

Isolation of angiotensin converting enzyme (ACE) inhibiting triterpenes from Schinus molle.

PubMed

Olafsson, K; Jaroszewski, J W; Smitt, U W; Nyman, U

1997-08-01

Bioactivity-guided fractionation of extracts of Schinus molle leaves, using an in vitro assay, led to the isolation of ACE-inhibitory steroidal triterpenes of the euphane type, identified by means of NMR spectroscopic methods. One of the triterpenes was isolated as an equilibrium mixture of epimeric aldehydes. The triterpenes showed moderate ACE-inhibitory activity (IC(50) about 250 microM).

Simultaneous determination and characterization of tannins and triterpene saponins from the fruits of various species of Terminalia and Phyllantus emblica using a UHPLC-UV-MS method: application to triphala.

PubMed

Avula, Bharathi; Wang, Yan-Hong; Wang, Mei; Shen, Yun-Heng; Khan, Ikhlas A

2013-01-01

Terminalia species are a rich source of tannins. Many preparations of these species are used in traditional medicine and have many different ethnobotanical applications. A simple UHPLC method was developed for the simultaneous analysis of such hydrolysable tannins and triterpene saponins from the fruit rinds of different species of Terminalia (T. chebula, T. arjuna, T. bellirica) and Phyllantus emblica. A separation by LC was achieved using a reversed-phase column and a water/acetonitrile mobile phase, both containing formic acid, using a gradient system and a temperature of 40°C. Eight hydrolysable tannins (gallic acid, gallic acid methyl ester, corilagin, chebulagic acid, 1,2,3,6-tetra-O-galloyl-β-D-glucose, ellagic acid, chebulinic acid, and 1,2,3,4,6-penta-O-galloyl-β-D-glucose) and six triterpene saponins (arjunglucoside-I, arjunglucoside-III, chebuloside II, bellericoside, arjunetin, and arjunglucoside-II) could be separated within 20 minutes. The wavelength used for detection with the diode array detector was 254 and 275 nm for tannins and 205 nm for triterpene saponins. The method was validated for linearity, repeatability, limits of detection, and limits of quantification. The developed method is economical, fast, and especially suitable for quality control analysis of tannins and triterpene saponins in various plant samples and commercial products of Terminalia. Georg Thieme Verlag KG Stuttgart · New York.

Quantitative determination of triterpenes from Amphiptherygium adstringens by liquid chromatography and thin-layer chromatography and morphological analysis of cuachalalate preparations.

PubMed

Navarrete, Andres; Avula, Bharathi; Joshi, Vaishali C; Ji, Xiuhong; Hersh, Paul; Khan, Ikhlas A

2006-01-01

Amphiptherygium adstringens (Anacardiaceae/Julianaceae), local name "cuachalalate," is used in folk medicine for the treatment of cholelithiasis, fevers, fresh wounds, hypercholesterolemia, gastritis, gastric ulcers, and cancer of the gastrointestinal tract. The development of column high-performance liquid chromatography-photodiode array detector (LC-PDA) and high-performance thin-layer chromatography (HPTLC)-densitometry methods for the determination of masticadienonic acid and 3-hydroxymasticadienonic acid in cuachalalate preparations is described in this paper. Good separation of the compounds could be achieved by both methods. Either might be preparable depending on the requirements. The LC separation was performed on a Phenomenex Synergi MAX-RP 80A reversed-phase column operated at 40 degrees C with detection at 215 nm. The plant materials were extracted with methanol by sonication. The triterpenes present in the plant material and commercial extracts were separated with an acetonitrile-water reagent alcohol isocratic system. The limit of detection was 0.1-0.2 microg/mL. The relative standard deviation values for the determination of triterpenes in plant extracts were less than 1.00%. This is the first report of an analytical method developed for the quantitative analysis of triterpenes from Amphiptherygium adstringens by LC-PDA and HPTLC. The stem bark showed higher amounts of triterpenes, and low amounts in root and stem root. The microscopic description of the crude drug of cuachalalate was also provided.

Liquid chromatography tandem mass spectrometric determination of triterpenes in human fluids: Evaluation of markers of dietary intake of olive oil and metabolic disposition of oleanolic acid and maslinic acid in humans.

PubMed

Pozo, Oscar J; Pujadas, Mitona; Gleeson, Sarah Biel; Mesa-García, Maria Dolores; Pastor, Antoni; Kotronoulas, Aristotelis; Fitó, Montserrat; Covas, Maria-Isabel; Navarro, José Ramón Fernández; Espejo, Juan Antonio; Sanchez-Rodriguez, Estefania; Marchal, Rosa; Calleja, Miguel Angel; de la Torre, Rafael

2017-10-16

Olive oil is rich in several minor components like maslinic (MA) and oleanolic (OA) acids which have cardioprotective, antitumor, and anti-inflammatory properties. In order to assess the health benefits in humans provided by the olive oil triterpenes (MA and OA), suitable analytical methods able to quantify the low concentrations expected in human fluids are required. In this study, the LC-MS/MS quantification of both OA and MA in plasma and urine has been evaluated. The plasmatic method is based on the direct determination of the analytes. The urinary detection requires more sensitivity which was reached by derivatization with 2-picolylamine. Additionally, the urinary species present after MA and OA ingestion were evaluated by the direct detection of several phase II metabolites previously synthesized. Our results showed that OA is metabolized as both sulfate and glucuronide conjugates whereas MA is mainly excreted as glucuronide. Based on this information, the method for the urinary detection of MA and OA involved an enzymatic hydrolysis. Both plasmatic and urinary methods were validated with suitable precision and accuracy at all tested levels. Required sensitivity was achieved in both matrices. Up to our knowledge, this is the first method able to quantify the low concentration levels of triterpenes present in urine. Samples from two healthy volunteers who received virgin olive oils with different triterpenes content were analyzed. Some preliminary clues on the metabolic disposition of OA and MA after olive oil intake are provided. Copyright © 2017 Elsevier B.V. All rights reserved.

Differentiation- and apoptosis-inducing activities by pentacyclic triterpenes on a mouse melanoma cell line.

PubMed

Hata, Keishi; Hori, Kazuyuki; Takahashi, Saori

2002-05-01

In a study to investigate the relationship between the chemical structure and the differentiation-inducing activity of pentacyclic triterpenes, several lupane, oleanane, and ursane triterpenes were prepared and their effects on B16 2F2 melanoma cell differentiation and growth were examined. Eleven lupane triterpenes used in this study acted on the melanoma cells as a melanogen, but no induction of melanogenesis of B16 2F2 cells by oleanane and ursane was detected. The differences at C-17 of the lupane series and acetylation of the OH group at C-3 did not markedly influence their activities. However, the ED(50) value for up-regulation of melanin biosynthesis was markedly decreased by the oxidation of the OH group at C-3 of lupeol (1). Betulinic acid (11), its methyl ester (12), lup-28-al-20(29)-ene-3beta-ol (9), and lup-28-al-20(29)-en-3-one (10) inhibited B16 2F2 cell proliferation by induction of apoptosis. These findings suggested that the carbonyl group at C-17 might be essential for the apoptotic effects of these compounds on B16 2F2 cells.

Bioactive Pentacyclic Triterpene Ester Derivatives from Alnus viridis ssp. viridis Bark.

PubMed

Novakovic, Miroslav; Nikodinovic-Runic, Jasmina; Veselinovic, Jovana; Ilic-Tomic, Tatjana; Vidakovic, Vera; Tesevic, Vele; Milosavljevic, Slobodan

2017-05-26

Seven derivatives of pentacyclic triterpene acids (1-7) were isolated from the bark of Alnus viridis ssp. viridis using a combination of column chromatography and semipreparative HPLC. Compounds 1-3, 6, and 7 were determined to be new after spectroscopic data interpretation and were assigned as 27-hydroxyalphitolic acid derivatives (1-3), a 27-hydroxybetulinic acid derivative (6), and a 3-epi-maslinic acid derivative (7), respectively. Pentacyclic triterpenoids with a C-27 hydroxymethyl group have been found in species of the genus Alnus for the first time. These compounds were subjected to cytotoxicity testing against a number of cancer cell lines. Also, selected pentacyclic triterpenoids were selected as potential inhibitors of topoisomerases I and IIα for an in silico investigation.

Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters

PubMed Central

Lin, Yuguang; Vermeer, Mario A.; Trautwein, Elke A.

2011-01-01

Hawthorn (Crataegus pinnatifida) is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT) activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA) and ursolic acid (UA)) contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE) were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w) cholesterol (control) or the same diet supplemented with (i) 0.37% hawthorn dichloromethane extract, (ii) 0.24% PSE, (iii) hawthorn dichloromethane extract (0.37%) plus PSE (0.24%) or (iv) OA/UA mixture (0.01%) for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL) cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA) enhanced the cholesterol lowering effect of plant sterols. PMID:19228775

Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters.

PubMed

Lin, Yuguang; Vermeer, Mario A; Trautwein, Elke A

2011-01-01

Hawthorn (Crataegus pinnatifida) is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT) activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA) and ursolic acid (UA)) contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE) were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w) cholesterol (control) or the same diet supplemented with (i) 0.37% hawthorn dichloromethane extract, (ii) 0.24% PSE, (iii) hawthorn dichloromethane extract (0.37%) plus PSE (0.24%) or (iv) OA/UA mixture (0.01%) for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL) cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA) enhanced the cholesterol lowering effect of plant sterols.

Triterpenes and saponins from Rudgea viburnioides.

PubMed

Young, M C; Araújo, A R; da Silva, C A; Lopes, M N; Trevisan, L M; Bolzani, V S

1998-07-01

A novel triterpene, viburgenin (1), has been isolated from an extract of the ripe fruit rinds of Rudgea viburnioides, together with the known saponins, arjunglucoside I and trachelosperosides B-1 and E-1, and the triterpenes trachelosperogenin B (2) and arjungenin. Compound 2 was previously obtained as a product from enzymatic hydrolysis, and it is reported for the first time as a natural product. The structure of compound 1 was determined as 2alpha,3beta, 19alpha,23,24-pentahydroxyurs-12-ene by extensive use of 1D and 2D NMR spectroscopic methods. Compound 1 exhibited moderate antifungal activity against Cladosporium cladosporioides.

Triterpene derivatives from Abies spectabilis leaves of Nepalese origin.

PubMed

Dall'Acqua, Stefano; Minesso, Paola; Comai, Stefano; Shrestha, Bharat Babu; Gewali, Mohan Bikram; Jha, Pramod Kumar; Innocenti, Gabbriella

2011-06-01

Our ongoing studies of Nepalese medicinal plants has led to the isolation and characterization of five new triterpenes, two known triterpenes and two phenolic derivatives from Abies spectabilis (D.Don) Mirb leaves grown in the high mountain. The structures of the isolated compounds were characterized by means of 1D and 2D NMR spectroscopic and MS techniques.

On the Significance of Bacterial triterpenic Biomarkers in Sediments

NASA Astrophysics Data System (ADS)

Rohmer, M.

2004-12-01

Triterpenic biomarkers are ubiquitous in the organic matter of sediments. Bacterial contribution is essential for several series. Despite the numerous investigations performed over the last decades, little is known about the distribution of triterpenoids in Eubacteria. An updated survey of triterpene distribution in Eubacteria points out a much broader diversity of the structures than expected ten years ago. Hopanoids characterized by their C35 skeleton resulting from a carbon/carbon linkage between the triterpene hopane skeleton and a D-ribose derivative are the most frequent ones. Their distribution cannot be readily interpreted and may result from lateral gene transfer. Many groups, such as strict anaerobes, are underrepresented in the screenings, mainly because of the complex techniques required for their growth. Most of the bacterial hopanoids belong to the (17α H,21β H) series, corresponding to the stereochemistry of hopanoid biomarkers from non-mature sediments. (17β H,21α H)- and especially (17α ,21β H)-hopanoids are derived from the former series via diagenesis and maturation of the organic matter. Both series were, however, recently found in widespread soil bacteria (Frankia spp., Geodermatophilus spp.) questioning at least partially their significance as maturation indicators. Quasi-hopanoids with the gammacerane skeleton were first found in ciliate protozoa. They are also present in high concentrations in the phylogenetically related bacteria Rhodopseudomonas palustris and all Bradyrhizobium spp. In all closely investigated hopanoid producing bacteria, a complex mixture of triterpene hydrocarbons accompanied in small amounts hop-22(29)-ene. They include pentacyclic triterpenes (rearranged hopenes, fernenes) as well as tetracyclic triterpenes (dammaradienes, euphadienes) and result from a lack of strict control of the cyclization process by the squalene/hopene cyclase. Triterpenoids related to sterol biosynthesis (lanosterol, cycloartenol) have

Analgesic activity of a triterpene isolated from Scoparia dulcis L. (Vassourinha).

PubMed

Freire, S M; Torres, L M; Roque, N F; Souccar, C; Lapa, A J

1991-01-01

Analgesic and anti-inflammatory activities of water (WE) and ethanolic (EE) extracts of Scoparia dulcis L. were investigated in rats and mice, and compared to the effects induced by Glutinol, a triterpene isolated by purification of EE. Oral administration (p.o.) of either WE or EE (up to 2 g/kg) did not alter the normal spontaneous activity of mice and rats. The sleeping time induced by sodium pentobarbital (50 mg/kg, i.p.) was prolonged by 2 fold in mice pretreated with 0.5 g/kg EE, p.o. Neither extract altered the tail flick response of mice in immersion test, but previous administration of EE (0.5 g/kg, p.o.) reduced writhings induced by 0.8% acetic acid (0.1 ml/10 g, i.p.) in mice by 47%. EE (0.5 and 1 g/kg, p.o.) inhibited the paw edema induced by carrageenan in rats by respectively 46% and 58% after 2 h, being ineffective on the paw edema induced by dextran. No significant analgesic or anti-edema effects were detected in animals pretreated with WE (1 g/kg, p.o.). Administration of Glutinol (30 mg/kg, p.o.) reduced writhing induced by acetic acid in mice by 40% and the carrageenan induced paw edema in rats by 73%. The results indicate that the analgesic activity of S. dulcis L. may be explained by an anti-inflammatory activity probably related to the triterpene Glutinol.

Methyl Jasmonate-Elicited Transcriptional Responses and Pentacyclic Triterpene Biosynthesis in Sweet Basil1[C][W

PubMed Central

Misra, Rajesh Chandra; Maiti, Protiti; Chanotiya, Chandan Singh; Shanker, Karuna; Ghosh, Sumit

2014-01-01

Sweet basil (Ocimum basilicum) is well known for its diverse pharmacological properties and has been widely used in traditional medicine for the treatment of various ailments. Although a variety of secondary metabolites with potent biological activities are identified, our understanding of the biosynthetic pathways that produce them has remained largely incomplete. We studied transcriptional changes in sweet basil after methyl jasmonate (MeJA) treatment, which is considered an elicitor of secondary metabolites, and identified 388 candidate MeJA-responsive unique transcripts. Transcript analysis suggests that in addition to controlling its own biosynthesis and stress responses, MeJA up-regulates transcripts of the various secondary metabolic pathways, including terpenoids and phenylpropanoids/flavonoids. Furthermore, combined transcript and metabolite analysis revealed MeJA-induced biosynthesis of the medicinally important ursane-type and oleanane-type pentacyclic triterpenes. Two MeJA-responsive oxidosqualene cyclases (ObAS1 and ObAS2) that encode for 761- and 765-amino acid proteins, respectively, were identified and characterized. Functional expressions of ObAS1 and ObAS2 in Saccharomyces cerevisiae led to the production of β-amyrin and α-amyrin, the direct precursors of oleanane-type and ursane-type pentacyclic triterpenes, respectively. ObAS1 was identified as a β-amyrin synthase, whereas ObAS2 was a mixed amyrin synthase that produced both α-amyrin and β-amyrin but had a product preference for α-amyrin. Moreover, transcript and metabolite analysis shed light on the spatiotemporal regulation of pentacyclic triterpene biosynthesis in sweet basil. Taken together, these results will be helpful in elucidating the secondary metabolic pathways of sweet basil and developing metabolic engineering strategies for enhanced production of pentacyclic triterpenes. PMID:24367017

Mastering analytical challenges for the characterization of pentacyclic triterpene mono- and diesters of Calendula officinalis flowers by non-aqueous C30 HPLC and hyphenation with APCI-QTOF-MS.

PubMed

Nicolaus, Christoph; Sievers-Engler, Adrian; Murillo, Renato; D'Ambrosio, Michele; Lämmerhofer, Michael; Merfort, Irmgard

2016-01-25

Pentacyclic triterpene mono- and diesters have been isolated from Calendula officinalis flowers. GC-MS, APCI-Exactive Orbitrap HR-MS and NMR allowed to identify the triterpene skeleton in various samples (different triterpene mixtures from Calendula n-hexane extract). NMR provided evidence that triterpene diesters are present in the samples as well. However, the corresponding quasi-molecular ions could not be detected by APCI-Exactive Orbitrap HR-MS. Instability of triterpene diesters and loss of a fatty acid residue, respectively, in the ion-source made their MS detection challenging. Thus, a set of new APCI-QTOF-MS methods (using the TripleTOF 5600+ mass spectrometer) were developed which made it eventually possible to solve this problem and confirm the diester structures by MS via quasi-molecular ion [M+H](+) detection. Direct infusion APCI-QTOF MS experiments in MS/MS high sensitivity scan mode with low collision energy and multi-channel averaging acquisition (MCA) allowed the detection of quasi-molecular ions of triterpene diesters for the first time and unequivocally confirmed the presence of faradiol 3,16-dimyristate and -dipalmitate, as well as the corresponding mixed diesters faradiol 3-myristate,16-palmitate and faradiol 3-palmitate,16-myristate. Preferential loss of the fatty acid in 16-position made it possible to distinguish the mixed diesters by MS/MS spectra. Their chromatographic separations turned out to be challenging due to their bulkiness and extended molecular dimensions. However, separation could be achieved by an uncommon non-aqueous RPLC mode with an in-house synthesized C30 phase. Finally, two (U)HPLC-APCI-QTOF-MS methods with C18- and C30-based non-aqueous RPLC provided suitable, sensitive assays to monitor the presence of monoesters and diesters of various triterpenes (faradiol, maniladiol, arnidiol, arnitriol A and lupane-3β,16β,20-triol esters) in the n-hexane extract of C. officinalis with high mass resolution and good mass accuracy

Identification of triterpene hydroxycinnamates with in vitro antitumor activity from whole cranberry fruit (Vaccinium macrocarpon).

PubMed

Murphy, Brian T; MacKinnon, Shawna L; Yan, Xiaojun; Hammond, Gerald B; Vaisberg, Abraham J; Neto, Catherine C

2003-06-04

Bioactivity-guided fractionation of cranberry fruit was used to determine the identity of triterpenoid esters from Vaccinium macrocarpon, which inhibit tumor cell growth and may play a role in cancer prevention. In our previous study, a fraction from whole fruit exhibited tumor cell growth inhibition in vitro. The major components of this fraction were isolated by chromatographic separation of ethyl acetate extracts, purified by semipreparative HPLC, and identified by NMR as cis- (1) and trans- (2) isomers of 3-O-p-hydroxycinnamoyl ursolic acid. These triterpenoid esters have not been previously reported in Vaccinium fruit. Bioassay of the purified triterpene cinnamates in tumor cell lines in vitro showed slightly greater activity of compound 1 in most cell lines, with GI(50) values of approximately 20 microM in MCF-7 breast, ME180 cervical and PC3 prostate tumor cell lines. Quercetin was slightly less active than 1, while cyanidin-3-galactoside exhibited much lower cytotoxicity, with GI(50) greater than 250 microM in all cell lines. Phenylboronic acid (3) was also isolated from the fruit but showed insignificant antitumor activity.

Friedelin Synthase from Maytenus ilicifolia: Leucine 482 Plays an Essential Role in the Production of the Most Rearranged Pentacyclic Triterpene

PubMed Central

Souza-Moreira, Tatiana M.; Alves, Thaís B.; Pinheiro, Karina A.; Felippe, Lidiane G.; De Lima, Gustavo M. A.; Watanabe, Tatiana F.; Barbosa, Cristina C.; Santos, Vânia A. F. F. M.; Lopes, Norberto P.; Valentini, Sandro R.; Guido, Rafael V. C.; Furlan, Maysa; Zanelli, Cleslei F.

2016-01-01

Among the biologically active triterpenes, friedelin has the most-rearranged structure produced by the oxidosqualene cyclases and is the only one containing a cetonic group. In this study, we cloned and functionally characterized friedelin synthase and one cycloartenol synthase from Maytenus ilicifolia (Celastraceae). The complete coding sequences of these 2 genes were cloned from leaf mRNA, and their functions were characterized by heterologous expression in yeast. The cycloartenol synthase sequence is very similar to other known OSCs of this type (approximately 80% identity), although the M. ilicifolia friedelin synthase amino acid sequence is more related to β-amyrin synthases (65–74% identity), which is similar to the friedelin synthase cloned from Kalanchoe daigremontiana. Multiple sequence alignments demonstrated the presence of a leucine residue two positions upstream of the friedelin synthase Asp-Cys-Thr-Ala-Glu (DCTAE) active site motif, while the vast majority of OSCs identified so far have a valine or isoleucine residue at the same position. The substitution of the leucine residue with valine, threonine or isoleucine in M. ilicifolia friedelin synthase interfered with substrate recognition and lead to the production of different pentacyclic triterpenes. Hence, our data indicate a key role for the leucine residue in the structure and function of this oxidosqualene cyclase. PMID:27874020

Friedelin Synthase from Maytenus ilicifolia: Leucine 482 Plays an Essential Role in the Production of the Most Rearranged Pentacyclic Triterpene

NASA Astrophysics Data System (ADS)

Souza-Moreira, Tatiana M.; Alves, Thaís B.; Pinheiro, Karina A.; Felippe, Lidiane G.; de Lima, Gustavo M. A.; Watanabe, Tatiana F.; Barbosa, Cristina C.; Santos, Vânia A. F. F. M.; Lopes, Norberto P.; Valentini, Sandro R.; Guido, Rafael V. C.; Furlan, Maysa; Zanelli, Cleslei F.

2016-11-01

Among the biologically active triterpenes, friedelin has the most-rearranged structure produced by the oxidosqualene cyclases and is the only one containing a cetonic group. In this study, we cloned and functionally characterized friedelin synthase and one cycloartenol synthase from Maytenus ilicifolia (Celastraceae). The complete coding sequences of these 2 genes were cloned from leaf mRNA, and their functions were characterized by heterologous expression in yeast. The cycloartenol synthase sequence is very similar to other known OSCs of this type (approximately 80% identity), although the M. ilicifolia friedelin synthase amino acid sequence is more related to β-amyrin synthases (65-74% identity), which is similar to the friedelin synthase cloned from Kalanchoe daigremontiana. Multiple sequence alignments demonstrated the presence of a leucine residue two positions upstream of the friedelin synthase Asp-Cys-Thr-Ala-Glu (DCTAE) active site motif, while the vast majority of OSCs identified so far have a valine or isoleucine residue at the same position. The substitution of the leucine residue with valine, threonine or isoleucine in M. ilicifolia friedelin synthase interfered with substrate recognition and lead to the production of different pentacyclic triterpenes. Hence, our data indicate a key role for the leucine residue in the structure and function of this oxidosqualene cyclase.

Identification in Rat Plasma and Urine by Linear Trap Quadrupole-Orbitrap Mass Spectrometry of the Metabolites of Maslinic Acid, a Triterpene from Olives.

PubMed

Sánchez-González, Marta; Lozano-Mena, Glòria; Parra, Andrés; Juan, M Emília; Planas, Joana M

2015-02-04

Maslinic acid is a natural pentacyclic triterpenoid widely distributed in edible and medicinal plants with health-promoting activities. The identification and quantification of its metabolites is a requirement for a better understanding of the biological effects of this triterpene. Therefore, maslinic acid was orally administered to Sprague-Dawley rats at a dose of 50 mg/kg of body weight. Blood and urine were withdrawn at 45 min. Samples were extracted with ethyl acetate prior to liquid chromatography-atmospheric pressure chemical ionization-linear trap quadrupole-Orbitrap (LC-APCI-LTQ-Orbitrap) analysis. Screening of plasma yielded four monohydroxylated derivatives (M1-M4), one monohydroxylated and dehydrogenated metabolite (M5), and two dihydroxylated and dehydrogenated compounds (M6 and M7). In urine, M1, M4, M5, and M6 were detected. Quantification by LC-APCI-mass spectrometry (MS) revealed maslinic acid as the prevalent compound in both plasma (81.8%) and urine (73.9%), which indicates that metabolism is low and mainly attributable to phase I reactions.

Ganoderma lucidum total triterpenes attenuate DLA induced ascites and EAC induced solid tumours in Swiss albino mice.

PubMed

Smina, T P; Mathew, J; Janardhanan, K K

2016-04-30

G. lucidum total triterpenes were assessed for its apoptosis-inducing and anti-tumour activities. The ability of the total triterpenes to induce apoptosis was evaluated in Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines. Total triterpenes were found to be highly cytotoxic to DLA and EAC cell lines with IC50 values 5 ± 0.32 and 7.9 ± 0.2 µg/ml respectively. Total triterpenes induced apoptosis in both cell lines which is evident from the DNA fragmentation assay. Anti-tumour activity was accessed using DLA induced solid and EAC induced ascites tumour models in Swiss albino mice. Administration of 10, 50 and 100 mg/kg b. wt. total triterpenes showed 11.86, 27.27 and 40.57% increase in life span of animals in ascites tumour model. Treatment with 10, 50 and 100 mg/kg b. wt. total triterpenes exhibited 76.86, 85.01 and 91.03% inhibition in tumour volume and 67.96, 72.38 and 77.90% inhibition in tumour weight respectively in the solid tumour model. The study reveals the significant dose-dependent anti-tumour activity of total triterpenes in both models. Total triterpenes were more active against the solid tumour than the ascites tumour. The anti-oxidant potential and ability to induce cell-specific apoptosis could be contributing to its anti-tumour activities.

Kinetics of the sorption of triterpene saponin by hypercrosslinked polystyrene

NASA Astrophysics Data System (ADS)

Mironenko, N. V.; Brezhneva, T. A.; Selemenev, V. F.

2013-03-01

The kinetics of sorption of triterpene saponin by the polymer sorbent NM-200 is considered. The influence of the surface activity of glycoside on the rate of formation and structure of the adsorption layer on the sorbent's surface is established. The rate-determining step of sorption is found to be diffusion into the sorbent grain. The value of the activation energy demonstrates the determining role of dispersion forces in the interaction between triterpene saponin and the polymer sorbent MN-200.

Nonsterol Triterpenoids as Major Constituents of Olea europaea

PubMed Central

Stiti, Naïm; Hartmann, Marie-Andrée

2012-01-01

Plant triterpenoids represent a large and structurally diverse class of natural products. A growing interest has been focused on triterpenoids over the past decade due to their beneficial effects on human health. We show here that these bioactive compounds are major constituents of several aerial parts (floral bud, leaf bud, stem, and leaf) of olive tree, a crop exploited so far almost exclusively for its fruit and oil. O. europaea callus cultures were analyzed as well. Twenty sterols and twenty-nine nonsteroidal tetra- and pentacyclic triterpenoids belonging to seven types of carbon skeletons (oleanane, ursane, lupane, taraxerane, taraxastane, euphane, and lanostane) were identified and quantified by GC and GC-MS as free and esterified compounds. The oleanane-type compounds, oleanolic acid and maslinic acid, were largely predominant in all the organs tested, whereas they are practically absent in olive oil. In floral buds, they represented as much as 2.7% of dry matter. In callus cultures, lanostane-type compounds were the most abundant triterpenoids. In all the tissues analyzed, free and esterified triterpene alcohols exhibited different distribution patterns of their carbon skeletons. Taken together, these data provide new insights into largely unknown triterpene secondary metabolism of Olea europaea. PMID:22523691

24-Methylenelanost-9(11)-en-3beta-ol, new triterpene alcohol from shea butter.

PubMed

Itoh, T; Tamura, T; Matsumoto, T

1975-08-01

A new triterpene alcohol was isolated fron shea butter and its structure was shown to be 24-methylenelanost-9(11)-en-3beta-ol. Gas chromatographic correlations between this triterpene alcohol and other related compounds are discussed.

Antimycobacterial triterpenes from the Canadian medicinal plant Sarracenia purpurea.

PubMed

Morrison, Steven A; Li, Haoxin; Webster, Duncan; Johnson, John A; Gray, Christopher A

2016-07-21

The purple pitcher plant, Sarracenia purpurea, is a medicinal plant used by the Canadian First Nations to treat a wide variety of illnesses. The Mi'kmaq and Wolastoqiyik (Maliseet) peoples of Eastern Canada have traditionally used infusions of S. purpurea for the treatment of tuberculosis-like symptoms. Previous investigations have shown methanolic extracts of S. purpurea to possess antimycobacterial activity. To isolate and identify antimycobacterial constituents from S. purpurea. Methanolic extracts of S. purpurea were subjected to bioassay guided fractionation using the microplate resazurin assay (MRA) to assess inhibitory activity against Mycobacterium tuberculosis strain H37Ra. The antimycobacterial constituents were identified by NMR, MS and polarimetry. The triterpenes betulinaldehyde, β-sitosterol, betulinic acid, and ursolic acid were isolated from S. purpurea. Betulinaldehyde, betulinic acid, and ursolic acid exhibited MICs of 450, 950, and 450μM and IC50s of 98, 169, and 93μM against M. tuberculosis H37Ra respectively whilst β-sitosterol was inactive (MIC and IC50 of >1000μM). Betulinaldehyde, betulinic acid, and ursolic acid were identified as the principal constituents responsible for the antimycobacterial activity of S. purpurea. This work is consistent with the ethnopharmacological use of S. purpurea by Canadian First Nations as a treatment against infectious diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Saponin Biosynthesis in Saponaria vaccaria. cDNAs Encoding β-Amyrin Synthase and a Triterpene Carboxylic Acid Glucosyltransferase1[OA

PubMed Central

Meesapyodsuk, Dauenpen; Balsevich, John; Reed, Darwin W.; Covello, Patrick S.

2007-01-01

Saponaria vaccaria (Caryophyllaceae), a soapwort, known in western Canada as cowcockle, contains bioactive oleanane-type saponins similar to those found in soapbark tree (Quillaja saponaria; Rosaceae). To improve our understanding of the biosynthesis of these saponins, a combined polymerase chain reaction and expressed sequence tag approach was taken to identify the genes involved. A cDNA encoding a β-amyrin synthase (SvBS) was isolated by reverse transcription-polymerase chain reaction and characterized by expression in yeast (Saccharomyces cerevisiae). The SvBS gene is predominantly expressed in leaves. A S. vaccaria developing seed expressed sequence tag collection was developed and used for the isolation of a full-length cDNA bearing sequence similarity to ester-forming glycosyltransferases. The gene product of the cDNA, classified as UGT74M1, was expressed in Escherichia coli, purified, and identified as a triterpene carboxylic acid glucosyltransferase. UGT74M1 is expressed in roots and leaves and appears to be involved in monodesmoside biosynthesis in S. vaccaria. PMID:17172290

The photosynthetic bacteria Rhodobacter capsulatus and Synechocystis sp. PCC 6803 as new hosts for cyclic plant triterpene biosynthesis

PubMed Central

Hage-Hülsmann, Jennifer; Dietsch, Maximilian; Kranz-Finger, Sarah; Hüren, Vanessa; Metzger, Sabine; Urlacher, Vlada B.; Gigolashvili, Tamara; Kopriva, Stanislav; Axmann, Ilka M.; Jaeger, Karl-Erich

2017-01-01

Cyclic triterpenes constitute one of the most diverse groups of plant natural products. Besides the intriguing biochemistry of their biosynthetic pathways, plant triterpenes exhibit versatile bioactivities, including antimicrobial effects against plant and human pathogens. While prokaryotes have been extensively used for the heterologous production of other classes of terpenes, the synthesis of cyclic triterpenes, which inherently includes the two-step catalytic formation of the universal linear precursor 2,3-oxidosqualene, is still a major challenge. We thus explored the suitability of the metabolically versatile photosynthetic α-proteobacterium Rhodobacter capsulatus SB1003 and cyanobacterium Synechocystis sp. PCC 6803 as alternative hosts for biosynthesis of cyclic plant triterpenes. Therefore, 2,3-oxidosqualene production was implemented and subsequently combined with different cyclization reactions catalyzed by the representative oxidosqualene cyclases CAS1 (cycloartenol synthase), LUP1 (lupeol synthase), THAS1 (thalianol synthase) and MRN1 (marneral synthase) derived from model plant Arabidopsis thaliana. While successful accumulation of 2,3-oxidosqualene could be detected by LC-MS analysis in both hosts, cyclase expression resulted in differential production profiles. CAS1 catalyzed conversion to only cycloartenol, but expression of LUP1 yielded lupeol and a triterpenoid matching an oxidation product of lupeol, in both hosts. In contrast, THAS1 expression did not lead to cyclic product formation in either host, whereas MRN1-dependent production of marnerol and hydroxymarnerol was observed in Synechocystis but not in R. capsulatus. Our findings thus indicate that 2,3-oxidosqualene cyclization in heterologous phototrophic bacteria is basically feasible but efficient conversion depends on both the respective cyclase enzyme and individual host properties. Therefore, photosynthetic α-proteo- and cyanobacteria are promising alternative candidates for providing

Triterpenic acids-enriched fraction from Cyclocarya paliurus attenuates non-alcoholic fatty liver disease via improving oxidative stress and mitochondrial dysfunction.

PubMed

Zhao, Meng-Ge; Sheng, Xue-Ping; Huang, Ya-Ping; Wang, Yi-Ting; Jiang, Cui-Hua; Zhang, Jian; Yin, Zhi-Qi

2018-08-01

The effects of triterpenic acids-enriched fraction from Cyclocarya paliurus (CPT) on nonalcoholic fatty liver disease (NAFLD) were investigated using in vivo and in vitro models. In high fat diet-induced Wister rats, CPT significantly increased superoxide dismutase (SOD) activity and glutathione/oxidized glutathione (GSH/GSSG) ratio, reduced malondialdehyde (MDA) and protein carbonyl (PCO) levels. Moreover, CPT restored mitochondrial membrane potential dysfunction, decreased cytochrome P450 enzyme 2E1 (CYP2E1) activity, improved nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-mediated antioxidant enzyme heme oxygenase1 (HO-1) expression. In free fatty acids-induced HepG2 cells, CPT dramatically decreased ROS content, increased mitochondrial NADH dehydrogenase (Complex I) and mitochondrial cytochrome C oxidase (Complex IV) levels. Furthermore, CPT could upregulate HO-1, quinine oxidoreductase 1 (NQO1) expression, and increase Nrf2 translocation from cytoplasm-to-nucleus. The results indicated CPT could protect mitochondria function and improve oxidative stress by activating Nrf2. Therefore, it can be inferred that CPT may be a potential agent against NAFLD. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Ganoderma lucidum total triterpenes prevent γ-radiation induced oxidative stress in Swiss albino mice in vivo.

PubMed

Smina, T P; Joseph, Jini; Janardhanan, K K

2016-11-01

The in vivo radio-protective effect of total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst was evaluated using Swiss albino mice, by pre-treatment with total triterpenes for 14 days, followed by a whole body exposure to γ-radiation. The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) were analysed in liver and brain homogenates. The extent of lipid and protein peroxidation was also estimated in liver and brain homogenates after irradiation. Protection of radiation-induced DNA strand breaks in peripheral blood lymphocytes and bone marrow cells was assessed using the comet assay. Total triterpenes were highly effective in reducing the levels of lipid peroxidation and protein oxidation to near normal values in both liver and brain tissues. Total triterpenes, when administered in vivo, were also found to be successful in restoring the antioxidant enzyme activities and GSH level in liver and brain of irradiated mice. Administration of total triterpenes, prior to radiation exposure, significantly decreased the DNA strand breaks. The results of the present study thus revealed the potential therapeutic use of Ganoderma total triterpenes as an adjuvant in radiation therapy.

Dianthosaponins A-F, triterpene saponins, flavonoid glycoside, aromatic amide glucoside and γ-pyrone glucoside from Dianthus japonicus.

PubMed

Nakano, Takahiro; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki

2011-01-01

From aerial parts of Dianthus japonicus, six new and seven known oleanane-type triterpene saponins were isolated. The structures of the new saponins, named dianthosaponins A-F, were elucidated by means of high resolution mass spectrometry, and extensive inspection of one- and two-dimensional NMR spectroscopic data. A new C-glycosyl flavone, a glycosidic derivative of anthranilic acid amide and a maltol glucoside were also isolated.

Triterpenes and meroterpenes from Ganoderma lucidum with inhibitory activity against HMGs reductase, aldose reductase and α-glucosidase.

PubMed

Chen, Baosong; Tian, Jin; Zhang, Jinjin; Wang, Kai; Liu, Li; Yang, Bo; Bao, Li; Liu, Hongwei

2017-07-01

Seven new compounds including four lanostane triterpenoids, lucidenic acids Q-S (1-3) and methyl ganoderate P (4), and three triterpene-farnesyl hydroquinone conjugates, ganolucinins A-C (5-7), one new natural product ganomycin J (8), and 73 known compounds (9-81) were isolated from fruiting bodies of Ganoderma lucidum. The structures of the compounds 1-8 were determined by spectroscopic methods. Bioactivities of compounds isolated were assayed against HMG-CoA reductase, aldose reductase, α-glucosidase, and PTP1B. Ganolucidic acid η (39), ganoderenic acid K (44), ganomycin J (8), and ganomycin B (61) showed strong inhibitory activity against HMG-CoA reductase with IC 50 of 29.8, 16.5, 30.3 and 14.3μM, respectively. Lucidumol A (67) had relatively good effect against aldose reductase with IC 50 of 19.1μM. Farnesyl hydroquinones ganomycin J (8), ganomycin B (61), ganomycin I (62), and triterpene-farnesyl hydroquinone conjugates ganoleuconin M (76) and ganoleuconin O (79) possessed good inhibitory activity against α-glucosidase with IC 50 in the range of 7.8 to 21.5μM. This work provides chemical and biological evidence for the usage of extracts of G. lucidum as herbal medicine and food supplements for the control of hyperglycemic and hyperlipidemic symptoms. Copyright © 2017. Published by Elsevier B.V.

Lupane-type triterpenes and their anti-cancer activities against most common malignant tumors: A review

PubMed Central

Cháirez-Ramírez, MH; Moreno-Jiménez, MR; González-Laredo, RF; Gallegos-Infante, JA; Rocha-Guzmán, Nuria Elizabeth

2016-01-01

In recent times, a great deal of interest has been motivated on plant derived compounds known as nutraceuticals. These compounds exert important beneficial activities that improve people's health status when are consumed regularly, and now they appear as a viable option to explore their possible therapeutic effects against diseases like cancer. Particularly, lupane-type triterpenes have shown great ability to modulate multiple cancer-related signaling pathways and processes, including NF-κB, Wnt/β-catenin, PI3K/Akt, apoptosis, and many other routes related to proliferation or cell death, which are uncontrolled in malignant tumors. These investigations have promoted in vitro and in vivo studies, searching their mechanisms of action; although more research is still needed to prove its potential in human clinical trials. This review focuses on the ability of betulin, betulinic acid and lupeol to show benefits against the most common types of malignant tumors, which are considered a major global threat for public health. PMID:28337107

Anti-inflammatory and chemopreventive effects of triterpene cinnamates and acetates from shea fat.

PubMed

Akihisa, Toshihiro; Kojima, Nobuo; Kikuchi, Takashi; Yasukawa, Ken; Tokuda, Harukuni; T Masters, Eliot; Manosroi, Aranya; Manosroi, Jiradej

2010-01-01

Four triterpene acetates, alpha-amyrin acetate (1a), beta-amyrin acetate (2a), lupeol acetate (3a), and butyrospermol acetate (4a), and four triterpene cinnamates, alpha-amyrin cinnamate (1c), beta-amyrin cinnamate (2c), lupeol cinnamate (3c), and butyrospermol cinnamate (4c), were isolated from the kernel fat (n-hexane extract) of the shea tree (Vitellaria paradoxa; Sapotaceae). Upon evaluation of these eight triterpene esters for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, all of the compounds tested exhibited marked anti-inflammatory activity, with ID50 values in the range of 0.15-0.75 micromol/ear, and among which compound 3c showed the highest activity with ID(50) of 0.15 micromol/ear. Compound 3c (10 mg/kg) further exhibited anti-inflammatory activity on rat hind paw edema induced by carrageenan, with the percentage of inflammation at 1, 3, and 5 h of 35.4, 41.5, and 45.5%, respectively. The eight triterpene esters were then evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) in Raji cells as a primary screening test for inhibitors of tumor promoters. All the compounds showed moderate inhibitory effects. Furthermore, compound 3c exhibited inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz [a] anthracene (DMBA) as an initiator and TPA as a promoter. The biological activities of triterpene acetate and cinnamate esters, together with the exceptionally high levels of these triterpenes in shea fat, indicate that shea nuts and shea fat (shea butter) constitute a significant source of anti-inflammatory and anti-tumor promoting compounds.

A new triterpene from callus of Pterocarpus santalinus.

PubMed

Krishnaveni, K S; Srinivasa Rao, J V

2000-02-01

A new pentacyclic triterpene was isolated from the callus induced from the stem cuttings of Pterocarpus santalinus. Based on spectral methods, the structure of the new compound was elucidated as 3-ketooleanane (1).

Protection of radiation induced DNA and membrane damages by total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst.

PubMed

Smina, T P; Maurya, D K; Devasagayam, T P A; Janardhanan, K K

2015-05-25

The total triterpenes isolated from the fruiting bodies of Ganoderma lucidum was examined for its potential to prevent γ-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on γ-radiation-induced DNA strand breaks in pBR 322 plasmid DNA in vitro and human peripheral blood lymphocytes ex vivo were evaluated. The protective effect of total triterpenes against γ-radiation-induced micronuclei formations in mice bone marrow cells in vivo were also evaluated. The results indicated the significant effectiveness of Ganoderma triterpenes in protecting the DNA and membrane damages consequent to the hazardous effects of radiation. The findings suggest the potential use of Ganoderma triterpenes in radio therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Contents Changes of Triterpenic Acids, Nucleosides, Nucleobases, and Saccharides in Jujube (Ziziphus jujuba) Fruit During the Drying and Steaming Process.

PubMed

Guo, Sheng; Duan, Jin-Ao; Zhang, Ying; Qian, Dawei; Tang, Yuping; Zhu, Zhenhua; Wang, Hanqing

2015-12-12

Chinese jujube (Ziziphus jujuba), a medicinal and edible plant, is widely consumed in Asian countries owing to the remarkable health activities of its fruits. To facilitate selection of the suitable processing method for jujube fruits, in this study their contents of triterpenic acids, nucleosides, nucleobases and saccharides after drying and steaming treatment were determined using ultra-high performance liquid chromatography and high performance liquid chromatography coupled with evaporative light scattering detector methods. The results showed that except for sucrose, the content levels of most analytes were increasing in the jujube fruits during drying treatment at 45 °C. The levels of cyclic nucleotides such as adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, were significantly decreased after the fruits were steamed. Therefore, owing to the bioactivities of these components for human health, the dried fruits would be the better choice as medicinal material or functional food, and dried jujube fruit should not be further steamed.

Target molecules in 3T3-L1 adipocytes differentiation are regulated by maslinic acid, a natural triterpene from Olea europaea.

PubMed

Pérez-Jiménez, Amalia; Rufino-Palomares, Eva E; Fernández-Gallego, Nieves; Ortuño-Costela, M Carmen; Reyes-Zurita, Fernando J; Peragón, Juan; García-Salguero, Leticia; Mokhtari, Khalida; Medina, Pedro P; Lupiáñez, José A

2016-11-15

Metabolic syndrome is a set of pathologies among which stand out the obesity, which is related to the lipid droplet accumulation and changes to cellular morphology regulated by several molecules and transcription factors. Maslinic acid (MA) is a natural product with demonstrated pharmacological functions including anti-inflammation, anti-tumor and anti-oxidation, among others. Here we report the effects of MA on the adipogenesis process in 3T3-L1 cells. Cell viability, glucose uptake, cytoplasmic triglyceride droplets, triglycerides quantification, gene transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and adipocyte fatty acid-binding protein (aP2) and intracellular Ca 2+ levels were determined in pre-adipocytes and adipocytes of 3T3-L1 cells. MA increased glucose uptake. MA also decreased lipid droplets and triglyceride levels, which is in concordance with the down-regulation of PPARγ and aP2. Finally, MA increased the intracellular Ca 2+ concentration, which could also be involved in the demonstrated antiadipogenic effect of this triterpene. MA has been demonstrated as potential antiadipogenic compound in 3T3-L1 cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

Analysis of the transcriptome of Panax notoginseng root uncovers putative triterpene saponin-biosynthetic genes and genetic markers

PubMed Central

2011-01-01

Background Panax notoginseng (Burk) F.H. Chen is important medicinal plant of the Araliacease family. Triterpene saponins are the bioactive constituents in P. notoginseng. However, available genomic information regarding this plant is limited. Moreover, details of triterpene saponin biosynthesis in the Panax species are largely unknown. Results Using the 454 pyrosequencing technology, a one-quarter GS FLX titanium run resulted in 188,185 reads with an average length of 410 bases for P. notoginseng root. These reads were processed and assembled by 454 GS De Novo Assembler software into 30,852 unique sequences. A total of 70.2% of unique sequences were annotated by Basic Local Alignment Search Tool (BLAST) similarity searches against public sequence databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG) assignment discovered 41 unique sequences representing 11 genes involved in triterpene saponin backbone biosynthesis in the 454-EST dataset. In particular, the transcript encoding dammarenediol synthase (DS), which is the first committed enzyme in the biosynthetic pathway of major triterpene saponins, is highly expressed in the root of four-year-old P. notoginseng. It is worth emphasizing that the candidate cytochrome P450 (Pn02132 and Pn00158) and UDP-glycosyltransferase (Pn00082) gene most likely to be involved in hydroxylation or glycosylation of aglycones for triterpene saponin biosynthesis were discovered from 174 cytochrome P450s and 242 glycosyltransferases by phylogenetic analysis, respectively. Putative transcription factors were detected in 906 unique sequences, including Myb, homeobox, WRKY, basic helix-loop-helix (bHLH), and other family proteins. Additionally, a total of 2,772 simple sequence repeat (SSR) were identified from 2,361 unique sequences, of which, di-nucleotide motifs were the most abundant motif. Conclusion This study is the first to present a large-scale EST dataset for P. notoginseng root acquired by next-generation sequencing (NGS

Acetylated Triterpene Glycosides and Their Biological Activity from Holothuroidea Reported in the Past Six Decades

PubMed Central

Bahrami, Yadollah; Franco, Christopher M. M.

2016-01-01

Sea cucumbers have been valued for many centuries as a tonic and functional food, dietary delicacies and important ingredients of traditional medicine in many Asian countries. An assortment of bioactive compounds has been described in sea cucumbers. The most important and abundant secondary metabolites from sea cucumbers are triterpene glycosides (saponins). Due to the wide range of their potential biological activities, these natural compounds have gained attention and this has led to their emergence as high value compounds with extended application in nutraceutical, cosmeceutical, medicinal and pharmaceutical products. They are characterized by bearing a wide spectrum of structures, such as sulfated, non-sulfated and acetylated glycosides. Over 700 triterpene glycosides have been reported from the Holothuroidea in which more than 145 are decorated with an acetoxy group having 38 different aglycones. The majority of sea cucumber triterpene glycosides are of the holostane type containing a C18 (20) lactone group and either Δ7(8) or Δ9(11) double bond in their genins. The acetoxy group is mainly connected to the C-16, C-22, C-23 and/or C-25 of their aglycone. Apparently, the presence of an acetoxy group, particularly at C-16 of the aglycone, plays a significant role in the bioactivity; including induction of caspase, apoptosis, cytotoxicity, anticancer, antifungal and antibacterial activities of these compounds. This manuscript highlights the structure of acetylated saponins, their biological activity, and their structure-activity relationships. PMID:27527190

Anti-Escherichia coli activity of extracts from Schinus terebinthifolius fruits and leaves.

PubMed

da Silva, Jessica H S; Simas, Naomi K; Alviano, Celuta S; Alviano, Daniela S; Ventura, José A; de Lima, Eliandro J; Seabra, Sergio H; Kuster, Ricardo M

2018-06-01

Ethanol extracts obtained from Schinus terebinthifolius Raddi fruits and leaves were active against Escherichia coli with MIC of 78 μg mL -1 for both extracts. Phytochemical analyses revealed a major presence of phenolic acids, tannins, fatty acids and acid triterpenes in the leaves and phenolic acids, fatty acids, acid triterpenes and biflavonoids in the fruits. Major compounds isolated from the plant, such as the acid triterpene schinol, the phenolic acid derivative ethyl gallate and the biflavonoids agathisflavone and tetrahydroamentoflavone, showed very little activity against E. coli. Bioautography of the ethanol extracts on silica gel plate showed inhibition zones for E. coli. They were removed from the plate and the compounds identified as a mixture of myristic, pentadecanoic, palmitic, heptadecanoic, stearic, nonadecanoic, eicosanoic, heneicosanoic and behenic fatty acids.

Triterpene esters from Uncaria rhynchophylla drive potent IL-12-dependent Th1 polarization.

PubMed

Umeyama, Akemi; Yahisa, Yoshinori; Okada, Minori; Okayama, Eriko; Uda, Ayaka; Shoji, Noboru; Lee, Je-Jung; Takei, Masao; Hashimoto, Toshihiro

2010-10-01

Dendritic cells (DC) are key antigen-presenting cells that link innate and adaptive immunity and ultimately activate antigen-specific T cells. In the current study, we demonstrated that two triterpene esters, uncarinic acid C (1) and uncarinic acid D (2), which are isolated from the hooks of Uncaria rhynchophylla, activate phenotypic and cytokine production alterations in DC. We also show that 1 and 2 modulate human DC function in a fashion that favors Th1 cell polarization. The effect of 1 (E configuration at the 2' position) was approximately 20 times more potent than that of 2 (Z configuration at 2'). These results indicated that the configuration of the 2' double bond greatly effects activity. Thus, 1 and 2 may prove useful as DC-based vaccines for cancer immunotherapy.

Methyl Jasmonate and Salicylic Acid Enhanced the Production of Ursolic and Oleanolic Acid in Callus Cultures of Lepechinia Caulescens

PubMed Central

Vergara Martínez, Víctor M.; Estrada-Soto, Samuel E.; Arellano-García, José de Jesús; Rivera-Leyva, Julio C.; Castillo-España, Patricia; Flores, Angélica Flores; Cardoso-Taketa, Alexandre T.; Perea-Arango, Irene

2017-01-01

Background: The production of triterpenes from plants for pharmacological purposes varies in concentration, due to genetic and environmental factors. In vitro culture enables the control and increase of these bioactive molecules. Objective: To evaluate the effect of plant growth regulators and elicitors in the induction of calli and the production of ursolic acid (UA) and oleanolic acid (OA) in Lepechinia caulescens. Materials and Methods: Leaf explants were exposed for the induction of calli at different concentrations and combinations of 2,4-dichlorophenoxyacetic acid (2,4-D) and 6-benzylaminopurine (BAP). Methyl jasmonate (MJ) and salicylic acid were used as elicitors. High-performance liquid chromatography method was used to quantify UA and OA content in each treatment. Results: Treatment with 3.0 mg/L of 2,4-D and 0.1 mg/L of BAP produced the best results for calli induction and production of UA (1.57 mg/g dry weight [DW]) and OA (1.13 mg/g DW). Both elicitors facilitated the accumulation of triterpenes. Conclusion: The combination of auxins and cytokinins showed favorable results for the induction of calli. Variation concerning the accumulation of UA and OA was observed between treatments. MJ increased the production of triterpenes five times after 8 h of exposure, compared to control treatment. There is a greater accumulation of UA (16.58 mg/g DW) and OA (1.94 mg/g DW) in leaves of wild plants. SUMMARY Callus cultures of Lepechinia caulescens were obtained from leaf explants treated with 2,4-dichlorophenoxyacetic acid and 6-bencylaminopurineResulting cultures were elicited with methyl jasmonate (MJ) and salicylic acid to increase the production of the triterpenes, ursolic acid (UA), and oleanolic acid (OA)The cultures elicited with MJ increased the production of UA and OA five times, as compared to the control. Abbreviations used: 2,4-D: 2,4-dichlorophenoxyacetic acid, BAP: 6-benzylaminopurine, DW: Dry weight, MJ: Methyl jasmonate, OA: Oleanolic acid, PGRs

DIOL Triterpenes Block Profibrotic Effects of Angiotensin II and Protect from Cardiac Hypertrophy

PubMed Central

Jurado-López, Raquel; Martínez-Martínez, Ernesto; Gómez-Hurtado, Nieves; Delgado, Carmen; Visitación Bartolomé, Maria; San Román, José Alberto; Cordova, Claudia; Lahera, Vicente; Nieto, Maria Luisa; Cachofeiro, Victoria

2012-01-01

Background The natural triterpenes, erythrodiol and uvaol, exert anti-inflammatory, vasorelaxing and anti-proliferative effects. Angiotensin II is a well-known profibrotic and proliferative agent that participates in the cardiac remodeling associated with different pathological situations through the stimulation and proliferation of cardiac fibroblasts. Therefore, the aim of the study was to investigate the preventive effects of the natural triterpenes erythrodiol and uvaol on the proliferation and collagen production induced by angiotensin II in cardiac myofibroblasts. Their actions on cardiac hypertrophy triggered by angiotensin II were also studied. Methodology/Principal Findings The effect of erythrodiol and uvaol on angiotensin II-induced proliferation was evaluated in cardiac myofibroblasts from adult rats in the presence or the absence of the inhibitors of PPAR-γ, GW9662 or JNK, SP600125. The effect on collagen levels induced by angiotensin II was evaluated in cardiac myofibroblasts and mouse heart. The presence of low doses of both triterpenes reduced the proliferation of cardiac myofibroblasts induced by angiotensin II. Pretreatment with GW9662 reversed the effect elicited by both triterpenes while SP600125 did not modify it. Both triterpenes at high doses produced an increase in annexing-V binding in the presence or absence of angiotensin II, which was reduced by either SP600125 or GW9662. Erythrodiol and uvaol decreased collagen I and galectin 3 levels induced by angiotensin II in cardiac myofribroblasts. Finally, cardiac hypertrophy, ventricular remodeling, fibrosis, and increases in myocyte area and brain natriuretic peptide levels observed in angiotensin II-infused mice were reduced in triterpene-treated animals. Conclusions/Significance Erythrodiol and uvaol reduce cardiac hypertrophy and left ventricle remodeling induced by angiotensin II in mice by diminishing fibrosis and myocyte area. They also modulate growth and survival of cardiac

Triterpene Esters and Biological Activities from Edible Fruits of Manilkara subsericea (Mart.) Dubard, Sapotaceae

PubMed Central

Fernandes, Caio P.; Corrêa, Arthur L.; Lobo, Jonathas F. R.; Caramel, Otávio P.; de Almeida, Fernanda B.; Castro, Elaine S.; Souza, Kauê F. C. S.; Burth, Patrícia; Amorim, Lidia M. F.; Santos, Marcelo G.; Ferreira, José Luiz P.; Falcão, Deborah Q.; Carvalho, José C. T.; Rocha, Leandro

2013-01-01

Manilkara subsericea (Mart.) Dubard (Sapotaceae) is popularly known in Brazil as “guracica.” Studies with Manilkara spp indicated the presence of triterpenes, saponins, and flavonoids. Several activities have been attributed to Manilkara spp such as antimicrobial, antiparasitic and antitumoral, which indicates the great biological potential of this genus. In all, 87.19% of the hexanic extract from fruits relative composition were evaluated, in which 72.81% were beta- and alpha-amyrin esters, suggesting that they may be chemical markers for M. subsericea. Hexadecanoic acid, hexadecanoic acid ethyl ester, (E)-9-octadecenoic acid ethyl ester, and octadecanoic acid ethyl ester were also identified. Ethanolic crude extracts from leaves, stems, and hexanic extract from fruits exhibited antimicrobial activity against Staphylococcus aureus ATCC25923. These extracts had high IC50 values against Vero cells, demonstrating weak cytotoxicity. This is the first time, to our knowledge, that beta- and alpha-amyrin caproates and caprylates are described for Manilkara subsericea. PMID:23509702

Study of isomeric pentacyclic triterpene acids in traditional Chinese medicine of Forsythiae Fructus and their binding constants with β-cyclodextrin by capillary electrophoresis.

PubMed

Ren, Tingjun; Xu, Zhongqi

2018-04-01

In this study, a capillary zone electrophoresis (CZE) method was first developed to identify three microconstituents of isomeric pentacyclic triterpene acids (PTAs including oleanolic acid (OA), ursolic acid (UA) and betulinic acid (BA)) in Forsythiae Fructus (FF). The baseline separation of PTAs by CZE were eventually achieved in a background electrolyte (BGE) containing 50.0 mmol/L borax and 0.5 mmol/L β-cyclodextrin (β-CD) at pH 9.5 within 13.0 min. Herein, it was not only the compositions of BGE were detail investigated for rapid and good separation, but also the binding ratio and the equilibrium constants (K) for OA, UA and BA with β-CD was estimated by double reciprocal equation to well understand the separation mechanism. The proposed method allowed the LODs of PTAs were averaged at 1.50 μg/mL with UV detection (at 200 nm). The interday RSD of migration time and peak area were around 2.0 and 4.7% (n = 5), respectively. Thus, the content of PTAs in 19 FF real samples distinguished from maturation stages and geographical areas in China was quantified with the proposed method. Depending on the amount of each PTA in FF, it was demonstrated these microconstituents might benefit to identify their harvested time even qualities. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The bHLH Transcription Factors TSAR1 and TSAR2 Regulate Triterpene Saponin Biosynthesis in Medicago truncatula.

PubMed

Mertens, Jan; Pollier, Jacob; Vanden Bossche, Robin; Lopez-Vidriero, Irene; Franco-Zorrilla, José Manuel; Goossens, Alain

2016-01-01

Plants respond to stresses by producing a broad spectrum of bioactive specialized metabolites. Hormonal elicitors, such as jasmonates, trigger a complex signaling circuit leading to the concerted activation of specific metabolic pathways. However, for many specialized metabolic pathways, the transcription factors involved remain unknown. Here, we report on two homologous jasmonate-inducible transcription factors of the basic helix-loop-helix family, TRITERPENE SAPONIN BIOSYNTHESIS ACTIVATING REGULATOR1 (TSAR1) and TSAR2, which direct triterpene saponin biosynthesis in Medicago truncatula. TSAR1 and TSAR2 are coregulated with and transactivate the genes encoding 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE1 (HMGR1) and MAKIBISHI1, the rate-limiting enzyme for triterpene biosynthesis and an E3 ubiquitin ligase that controls HMGR1 levels, respectively. Transactivation is mediated by direct binding of TSARs to the N-box in the promoter of HMGR1. In transient expression assays in tobacco (Nicotiana tabacum) protoplasts, TSAR1 and TSAR2 exhibit different patterns of transactivation of downstream triterpene saponin biosynthetic genes, hinting at distinct functionalities within the regulation of the pathway. Correspondingly, overexpression of TSAR1 or TSAR2 in M. truncatula hairy roots resulted in elevated transcript levels of known triterpene saponin biosynthetic genes and strongly increased the accumulation of triterpene saponins. TSAR2 overexpression specifically boosted hemolytic saponin biosynthesis, whereas TSAR1 overexpression primarily stimulated nonhemolytic soyasaponin biosynthesis. Both TSARs also activated all genes of the precursor mevalonate pathway but did not affect sterol biosynthetic genes, pointing to their specific role as regulators of specialized triterpene metabolism in M. truncatula. © 2016 American Society of Plant Biologists. All Rights Reserved.

Anti-AIDS agents 81. Design, synthesis, and structure-activity relationship study of betulinic acid and moronic acid derivatives as potent HIV maturation inhibitors.

PubMed

Qian, Keduo; Kuo, Reen-Yun; Chen, Chin-Ho; Huang, Li; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

2010-04-22

In our continuing study of triterpene derivatives as potent anti-HIV agents, different C-3 conformationally restricted betulinic acid (BA, 1) derivatives were designed and synthesized in order to explore the conformational space of the C-3 pharmacophore. 3-O-Monomethylsuccinyl-betulinic acid (MSB) analogues were also designed to better understand the contribution of the C-3' dimethyl group of bevirimat (2), the first-in-class HIV maturation inhibitor, which is currently in phase IIb clinical trials. In addition, another triterpene skeleton, moronic acid (MA, 3), was also employed to study the influence of the backbone and the C-3 modification toward the anti-HIV activity of this compound class. This study enabled us to better understand the structure-activity relationships (SAR) of triterpene-derived anti-HIV agents and led to the design and synthesis of compound 12 (EC(50): 0.0006 microM), which displayed slightly better activity than 2 as a HIV-1 maturation inhibitor.

Ganoderma lucidum total triterpenes induce apoptosis in MCF-7 cells and attenuate DMBA induced mammary and skin carcinomas in experimental animals.

PubMed

Smina, T P; Nitha, B; Devasagayam, T P A; Janardhanan, K K

2017-01-01

Ganoderma lucidum total triterpenes were evaluated for its apoptosis-inducing and anti-cancer activities. Cytotoxicity and pro-apoptotic effect of total triterpenes were evaluated in human breast adenocarcinoma (MCF-7) cell line using MTT assay and DNA fragmentation analysis. Total triterpenes induced apoptosis in MCF-7 cells by down-regulating the levels of cyclin D1, Bcl-2, Bcl-xL and also by up-regulating the levels of Bax and caspase-9. Anti-carcinogenicity of total triterpenes was analysed using dimethyl benz [a] anthracene (DMBA) induced skin papilloma and mammary adenocarcinoma in Swiss albino mice and Wistar rats respectively. Topical application of 5mg, 10mg and 20mg total triterpenes reduced the incidence of skin papilloma by 62.5, 37.5 and 12.5% respectively. Incidence of the mammary tumour was also reduced significantly by 33.33, 66.67 and 16.67% in 10, 50 and 100mg/kg b.wt. total triterpenes treated animals respectively. Total triterpenes were also found to reduce the average number of tumours per animal and extended the tumour latency period in both the models. The results indicate the potential cytotoxicity and anti-cancerous activity of total triterpenes, there by opens up a path to the development of a safe and successive chemo preventive agent of natural origin. Copyright © 2016 Elsevier B.V. All rights reserved.

Triterpene glycosides from the tubers of Anemone coronaria.

PubMed

Mimaki, Yoshihiro; Watanabe, Kazuki; Matsuo, Yukiko; Sakagami, Hiroshi

2009-07-01

Six new triterpene glycosides (1-6), together with 11 known ones (7-17), have been isolated from a glycoside-enriched fraction prepared from the tubers of Anemone coronaria L. (Ranunculaceae). On the basis of extensive spectroscopic analysis, including 2D NMR data, and the results of hydrolytic cleavage, the structures of 1-6 were determined to be 3beta-[(O-beta-D-glucopyranosyl-(1-->4)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-2beta,23-dihydroxyolean-12-en-28-oic acid (1), 3beta-[(O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid (2), 3beta-[(O-beta-D-glucopyranosyl-(1-->4)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (3), 3beta-[(O-beta-D-glucopyranosyl-(1-->4)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-2beta,23-dihydroxyolean-12-en-28-oic acid O-alpha-L-rhamnopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (4), 3beta-[(O-beta-D-glucopyranosyl-(1-->4)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-2beta-hydroxyolean-12-en-28-oic acid O-alpha-L-rhamnopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (5), and 3beta-[(O-beta-D-glucopyranosyl-(1-->4)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-23-hydroxyolean-18-en-28-oic acid O-alpha-L-rhamnopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (6), respectively. Furthermore, the isolated compounds were evaluated for their cytotoxic activity against HSC-2 cells.

Identification and structural characterisation of triterpene saponins from the root of Ardisia mamillata Hance by HPLC-ESI-QTOF-MS/MS.

PubMed

Zhang, Er-Fei; Ling, Yun; Yin, Zi; Zhang, Qing

2018-04-01

Triterpene saponins in medicinal plants attract scientific attentions for their structural diversity and significant bioactivities. In this work, a high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS/MS) method is used to rapidly separate and identify triterpene saponins from the extract of Ardisia mamillata Hance (AMH). In the full scan mass spectrum, the accurate determination of molecular formula is obtained by the predominant ion [M + HCOO] - in negative ion mode. As a result, 30 triterpene saponins are identified or tentatively identified in the plant extract. Of these, 17 triterpene saponins are new compounds. In conclusion, the HPLC-ESI-QTOF-MS/MS is an efficient technique to separate and identify triterpene saponins in complex matrices of medicinal plant.

Medicinal flowers. XXXVI.1) Acylated oleanane-type triterpene saponins with inhibitory effects on melanogenesis from the flower buds of Chinese Camellia japonica.

PubMed

Nakamura, Seikou; Fujimoto, Katsuyoshi; Nakashima, Souichi; Matsumoto, Takahiro; Miura, Tomoko; Uno, Kaoru; Matsuda, Hisashi; Yoshikawa, Masayuki

2012-01-01

Four acylated oleanane-type triterpene oligoglycosides, sanchakasaponins E-H, were isolated from the flower buds of Camellia japonica cultivated in Yunnan province, China, together with four known triterpene oligoglycosides. The chemical structures of the new triterpene oligoglycosides were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the triterpene oligoglycoside constituents on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells were investigated.

Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers

USDA-ARS?s Scientific Manuscript database

Rosmarinic acid (RA), a caffeic acid derivative found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be of benefit t...

Polyoxygenated ursane and oleanane triterpenes from Siphonodon celastrineus.

PubMed

Kaweetripob, Wirongrong; Mahidol, Chulabhorn; Thongnest, Sanit; Prawat, Hunsa; Ruchirawat, Somsak

2016-09-01

Twenty polyoxygenated triterpenes, including nineteen ursanes and one oleanane, were characterized from the stem material of Siphonodon celastrineus (Celastraceae) through the application of spectroscopic techniques and chemical transformation. Three of the ursane-type triterpenoids possessed the rare 13,27-cyclopropane ring skeleton. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rapid Determination of Major Compounds in the Ethanol Extract of Geopropolis from Malaysian Stingless Bees, Heterotrigona itama, by UHPLC-Q-TOF/MS and NMR.

PubMed

Zhao, Lingling; Yu, Mengjiao; Sun, Minghui; Xue, Xiaofeng; Wang, Tongtong; Cao, Wei; Sun, Liping

2017-11-10

A reliable, rapid analytical method was established for the characterization of constituents of the ethanol extract of geopropolis (EEGP) produced by Malaysian stingless bees- Heterotrigona itama -by combining ultra-high-performance liquid chromatography with quadruple time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Based on known standards, the online METLIN database, and published literature, 28 compounds were confirmed. Phenolic acids, flavones, triterpenes and phytosterol were identified or tentatively identified using characteristic diagnostic fragment ions. The results indicated that terpenoids were the main components of EEGP, accompanied by low levels of phenolic acids, flavonoids, and phytosterol. Two major components were further purified by preparative high-performance liquid chromatography (PHPLC) and identified by nuclear magnetic resonance (NMR) as 24( E )-cycloart-24-ene-26-ol-3-one and 20-hydroxy-24-dammaren-3-one. These two triterpenes, confirmed in this geopropolis for the first time, are potential chemical markers for the identification of geopropolis from Malaysian stingless bees, H. itama .

A sensitive liquid chromatography-mass spectrometry method for the simultaneous determination in plasma of pentacyclic triterpenes of Olea europaea L.

PubMed

Giménez, Estela; Juan, M Emília; Calvo-Melià, Sara; Planas, Joana M

2017-08-15

Table olives are especially rich in pentacyclic triterpenic compounds, which exert several biological activities. A crucial step in order to know if these compounds could contribute to the beneficial and healthy properties of this food is their measurement in blood. Therefore, the present study describes a simple and accurate liquid-liquid extraction followed by LC-QqQ-MS analysis for the simultaneous determination of the main pentacyclic triterpenes from Olea europaea L. in rat plasma. The method was validated by the analysis of blank plasma samples spiked with pure compounds, obtaining a linear correlation, adequate sensitivity with a limit of quantification ranging from 1nM for maslinic acid to 10nM for uvaol. Precision and accuracy were lower than 10% in all cases and recoveries were between 95 and 104%. The oral administration of olives to rats and its determination in plasma verified that the established methodology is appropriate for bioavailability studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibition of phospholipase cgamma1 and cancer cell proliferation by triterpene esters from Uncaria rhynchophylla.

PubMed

Lee, J S; Kim, J; Kim, B Y; Lee, H S; Ahn, J S; Chang, Y S

2000-06-01

Investigation of the hooks of Uncaria rhynchophylla resulted in isolation of six phospholipase Cgamma1 (PLCgamma1) inhibitors (1-6). The structures of these compounds were elucidated as pentacyclic triterpene esters by spectroscopic and chemical analysis. Three of them, namely uncarinic acids C (1), D (2), and E (3), are newly reported as natural products. All the compounds showed dose-dependent inhibitory activities against PLCgamma1 in vitro with IC(50) values of 9.5-44.6 microM and inhibited the proliferation of human cancer cells with IC(50) values of 0.5-6.5 microg/mL.

Triterpene saponins from Vietnamese ginseng (Panax vietnamensis) and their hepatocytoprotective activity.

PubMed

Tran, Q L; Adnyana, I K; Tezuka, Y; Nagaoka, T; Tran, Q K; Kadota, S

2001-04-01

The methanol extract of Vietnamese ginseng (Panax vietnamensis) was found to possess hepatocytoprotective effects on D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. Further chemical investigation of the extract afforded two new dammarane-type triterpene saponins, ginsenoside Rh(5) (1) and vina-ginsenoside R(25) (2), as well as eight known dammarane-type triterpene saponins, majonoside R(2) (3), pseudo-ginsenoside RT(4) (4), vina-ginsenosides R(1) (5), R(2) (6), and R(10) (7), ginsenosides Rg(1) (8), Rh(1) (9), and Rh(4) (10), and a known sapogenin protopanaxatriol oxide II (11). Their structures were elucidated on the basis of spectral analysis. In addition, by the using LC-electrospray ionization (ESI)-MS method, five known saponins, ginsenosides Rb(1), Rb(2), Rc, Rd, and Re (12--16), were also identified in the extract. Among the compounds isolated, majonoside R(2) (3), the main saponin in Vietnamese ginseng, showed strong protective activity against D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes. This demonstrates that the hepatocytoprotective effect of Vietnamese ginseng is due to dammarane-type triterpene saponins that have an ocotillol-type side chain, a characteristic constituent of Vietnamese ginseng.

Bioactive constituents of oleanane-type triterpene saponins from the roots of Glycyrrhiza glabra.

PubMed

Wei, Juan-Hua; Zheng, Yun-Feng; Li, Cun-Yu; Tang, Yu-Ping; Peng, Guo-Ping

2014-01-01

Three new oleanane-type triterpene saponins, namely licorice-saponin M3 (1), licorice-saponin N4 (2), and licorice-saponin O4 (3), an artificial product (4), as well as five known triterpene glucuronides (5-9), were isolated from the roots of Glycyrrhiza glabra L. Their structures were established using 1D and 2D NMR spectroscopy, mass spectrometry, and by comparison with spectroscopic data reported in the literature. The inhibitory effects of the selected compounds on neuraminidase were evaluated, and the preliminary structure-activity relationship was also predicted.

Antiprotozoal activity of quinonemethide triterpenes from Maytenus ilicifolia (Celastraceae).

PubMed

Dos Santos, Vania A F F M; Leite, Karoline M; da Costa Siqueira, Mariana; Regasini, Luis O; Martinez, Isabel; Nogueira, Camila T; Galuppo, Mariana Kolos; Stolf, Beatriz S; Pereira, Ana Maria Soares; Cicarelli, Regina M B; Furlan, Maysa; Graminha, Marcia A S

2013-01-15

The present study describes the leishmanicidal and trypanocidal activities of two quinonemethide triterpenes, maytenin (1) and pristimerin (2), isolated from Maytenus ilicifolia root barks (Celastraceae). The compounds were effective against the Trypanosomatidae Leishmania amazonensis and Leishmania chagasi and Trypanosoma cruzi, etiologic agents of leishmaniasis and Chagas' disease, respectively. The quinonemethide triterpenes 1 and 2 exhibited a marked in vitro leishmanicidal activity against promastigotes and amastigotes with 50% inhibitory concentration (IC(50)) values of less than 0.88 nM. Both compounds showed IC(50) lower than 0.3 nM against Trypanosoma cruzi epimastigotes. The selectivity indexes (SI) based on BALB/c macrophages for L. amazonensis and L. chagasi were 243.65 and 46.61 for (1) and 193.63 and 23.85 for (2) indicating that both compounds presented high selectivity for Leishmania sp. The data here presented suggests that these compounds should be considered in the development of new and more potent drugs for the treatment of leishmaniasis and Chagas' disease.

24-Methylenedammarenol: a new triterpene alcohol from shea butter.

PubMed

Itoh, T; Tamura, T; Matsumoto, T

1975-12-01

A new triterpene alcohol was isolated from shea butter and its structure was shown to be 24-methylenedammarenol (24-methylene-5alpha-dammar-20[21]-en-3beta-o1). Dammaradienol (5alpha-dammara-20[21],24-dien-3beta-o1) also was isolated from shea butter.

Engineering triterpene metabolism in tobacco

PubMed Central

Shuiqin, Wu; Zuodong, Jiang; Chase, Kempinski; Eric Nybo, S.; Husodo, Satrio; Williams, Robert

2013-01-01

Terpenes comprise a distinct class of natural products that serve a diverse range of physiological functions, provide for interactions between plants and their environment and represent a resource for many kinds of practical applications. To better appreciate the importance of terpenes to overall growth and development, and to create a production capacity for specific terpenes of industrial interest, we have pioneered the development of strategies for diverting carbon flow from the native terpene biosynthetic pathways operating in the cytosol and plastid compartments of tobacco for the generation of specific classes of terpenes. In the current work, we demonstrate how difficult it is to divert the 5-carbon intermediates DMAPP and IPP from the mevalonate pathway operating in the cytoplasm for triterpene biosynthesis, yet diversion of the same intermediates from the methylerythritol phosphate pathway operating in the plastid compartment leads to the accumulation of very high levels of the triterpene squalene. This was assessed by the co-expression of an avian farnesyl diphosphate synthase and yeast squalene synthase genes targeting metabolism in the cytoplasm or chloroplast. We also evaluated the possibility of directing this metabolism to the secretory trichomes of tobacco by comparing the effects of trichome-specific gene promoters to strong, constitutive viral promoters. Surprisingly, when transgene expression was directed to trichomes, high-level squalene accumulation was observed, but overall plant growth and physiology were reduced up to 80 % of the non-transgenic controls. Our results support the notion that the biosynthesis of a desired terpene can be dramatically improved by directing that metabolism to a non-native cellular compartment, thus avoiding regulatory mechanisms that might attenuate carbon flux within an engineered pathway. PMID:22729821

Structure Identification and Anti-Cancer Pharmacological Prediction of Triterpenes from Ganoderma lucidum.

PubMed

Shao, Yanyan; Qiao, Liansheng; Wu, Lingfang; Sun, Xuefei; Zhu, Dan; Yang, Guanghui; Zhang, Xiaoxue; Mao, Xin; Chen, Wenjing; Liang, Wenyi; Zhang, Yanling; Zhang, Lanzhen

2016-05-21

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. In the present study, systematic isolation, and in silico pharmacological prediction are implemented to discover potential anti-cancer active GTs from G. lucidum. Nineteen GTs, three steroids, one cerebroside, and one thymidine were isolated from G. lucidum. Six GTs were first isolated from the fruiting bodies of G. lucidum, including 3β,7β,15β-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid methyl ester (1), 3β,7β,15β-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (2), 3β,7β,15α,28-tetrahydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (3), ganotropic acid (4), 26-nor-11,23-dioxo-5α-lanost-8-en-3β,7β,15α,25-tetrol (5) and (3β,7α)-dihydroxy-lanosta-8,24-dien- 11-one (6). (4E,8E)-N-d-2'-hydroxypalmitoyl-l-O-β-d-glucopyranosyl-9-methyl-4,8-spingodienine (7), and stigmasta-7,22-dien-3β,5α,6α-triol (8) were first reported from the genus Ganodema. By using reverse pharmacophoric profiling of the six GTs, thirty potential anti-cancer therapeutic targets were identified and utilized to construct their ingredient-target interaction network. Then nineteen high frequency targets of GTs were selected from thirty potential targets to construct a protein interaction network (PIN). In order to cluster the pharmacological activity of GTs, twelve function modules were identified by molecular complex detection (MCODE) and gene ontology (GO) enrichment analysis. The results indicated that anti-cancer effect of GTs might be related to histone acetylation and interphase of mitotic cell cycle by regulating general control non-derepressible 5 (GCN5) and cyclin-dependent kinase-2 (CDK2), respectively. This research mode of extraction, isolation, pharmacological prediction, and PIN analysis might be beneficial to rapidly predict and discover pharmacological activities of novel compounds.

Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells

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

Choi, Solip; Nguyen, Van Thu; Tae, Nara

Ganoderma lucidum is a popular medicinal mushroom used in traditional medicine for preventing or treating a variety of diseases. In the present study, we investigated the anti-inflammatory and heme oxygenase (HO)-1 inducing effects of 12 lanostane triterpenes from G. lucidum in RAW264.7 cells. Of these, seven triterpenes, butyl lucidenateE{sub 2}, butyl lucidenateD{sub 2} (GT-2), butyl lucidenate P, butyl lucidenateQ, Ganoderiol F, methyl ganodenate J and butyl lucidenate N induced HO-1 expression and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Inhibiting HO-1 activity abrogated the inhibitory effects of these triterpenes on the production of NO in LPS-stimulated RAW264.7 cells, suggesting themore » involvement of HO-1 in the anti-inflammatory effects of these triterpenes. We further studied the anti-inflammatory and HO-1 inducing effects of GT-2. Mitogen-activated protein kinase inhibitors or N-acetylcysteine, an antioxidant, did not suppress GT-2-mediated HO-1 induction; however, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked GT-2-induced HO-1 mRNA and protein expression. GT-2 increased nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and knockdown of Nrf2 by small interfering RNA blocked GT-2-mediated HO-1 induction, suggesting that GT-2 induced HO-1 expression via the PI3K/AKT-Nrf2 pathway. Consistent with the notion that HO-1 has anti-inflammatory properties, GT-2 inhibited the production of tumor necrosis factor-α and interleukin-6, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression. These findings suggest that HO-1 inducing activities of these lanostane triterpenes may be important in the understanding of a novel mechanism for the anti-inflammatory activity of G. lucidum. - Highlights: • The anti-inflammatory effects of selected triterpenes from Ganoderma lucidum are demonstrated. • Heme oxygenase-1 induction is attributable to the anti-inflammatory properties of

Triterpene glycosides from the whole plant of Anemone hupehensis var. japonica and their cytotoxic activity.

PubMed

Yokosuka, Akihito; Sano, Tomoe; Hashimoto, Ken; Sakagami, Hiroshi; Mimaki, Yoshihiro

2009-12-01

Three new triterpene glycosides (1-3), together with eight known triterpene glycosides (4-11), were isolated from the whole plant of Anemone hupehensis var. japonica (Ranunculaceae). The structures of the new compounds were determined on the basis of spectroscopic analysis and the results of hydrolytic cleavage experiments. The isolated compounds were evaluated for their cytotoxic activities against HL-60 human leukemia cells, HSC-2 human oral squamous carcinoma cells, HSC-4 human oral squamous carcinoma cells, and A549 human lung adenocarcinoma cells.

Triterpene glycosides and other polar constituents of shea (Vitellaria paradoxa) kernels and their bioactivities.

PubMed

Zhang, Jie; Kurita, Masahiro; Shinozaki, Takuro; Ukiya, Motohiko; Yasukawa, Ken; Shimizu, Naoto; Tokuda, Harukuni; Masters, Eliot T; Akihisa, Momoko; Akihisa, Toshihiro

2014-12-01

The MeOH extract of defatted shea (Vitellaria paradoxa; Sapotaceae) kernels was investigated for its constituents, and fifteen oleanane-type triterpene acids and glycosides, two steroid glucosides, two pentane-2,4-diol glucosides, seven phenolic compounds, and three sugars, were isolated. The structures of five triterpene glycosides were elucidated on the basis of spectroscopic and chemical methods. Upon evaluation of the bioactivity of the isolated compounds, it was found that some or most of the compounds have potent or moderate inhibitory activities against the following: melanogenesis in B16 melanoma cells induced by α-melanocyte-stimulating hormone (α-MSH); generation of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, against Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-teradecanoylphorbol 13-acetate (TPA) in Raji cells; t TPA-induced inflammation in mice, and proliferation of one or more of HL-60, A549, AZ521, and SK-BR-3 human cancer cell lines, respectively. Western blot analysis established that paradoxoside E inhibits melanogenesis by regulation of expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein-1 (TRP-1) and TRP-2. In addition, tieghemelin A was demonstrated to exhibit cytotoxic activity against A549 cells (IC50 13.5 μM) mainly due to induction of apoptosis by flow cytometry. The extract of defatted shea kernels and its constituents may be, therefore, valuable as potential antioxidant, anti-inflammatory, skin-whitening, chemopreventive, and anticancer agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Two new triterpene saponins from the anti-inflammatory saponin fraction of Ilex pubescens root.

PubMed

Wang, Jing-Rong; Zhou, Hua; Jiang, Zhi-Hong; Liu, Liang

2008-07-01

The saponin fraction from the ethanolic extracts of the root of Ilex pubescens Hook. et Arn. (Ilexaceae) was found to exhibit potent anti-inflammatory effects on carrageenan-induced paw edema in rats. Two novel triterpene saponins, pubescenosides C and D (1 and 2, resp.), together with five known saponins were isolated from this saponin fraction. The structures of 1 and 2 were elucidated as (20beta)-3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl]ursa-12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester, and (20beta)-3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl]ursa- 12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester, respectively, on the basis of chemical and spectroscopic data. Five known saponins isolated from the saponin fraction were identified as ilexsaponin B(1), B(2), B(3), A(1), and chikusetsusaponin IV(a).

[Development of the devices for synthetic biology of triterpene saponins at an early stage: cloning and expression profiling of squalene epoxidase genes in panax notoginseng].

PubMed

Niu, Yun-Yun; Zhu, Xiao-Xuan; Luo, Hong-Mei; Sun, Chao; Huang, Lin-Fang; Chen, Shi-Lin

2013-02-01

Synthetic biology of traditional Chinese medicine (TCM) is a new and developing subject based on the research of secondary metabolite biosynthesis for nature products. The early development of synthetic biology focused on the screening and modification of parts or devices, and establishment of standardized device libraries. Panax notoginseng (Burk.) F.H.Chen is one of the most famous medicinal plants in Panax species. Triterpene saponins have important pharmacological activities in P. notoginseng. Squalene epoxidase (SE) has been considered as a key rate-limiting enzyme in biosynthetic pathways of triterpene saponins and phytosterols. SE acts as one of necessary devices for biosynthesis of triterpene saponins and phytosterols in vitro via synthetic biology approach. Here we cloned two genes encoding squalene epoxidase (PnSE1 and PnSE2) and analyzed the predict amino acid sequences by bioinformatic analysis. Further, we detected the gene expression profiling in different organs and the expression level of SEs in leaves elicited by methyl jasmonate (MeJA) treatment in 4-year-old P notoginseng using real-time quantitative PCR (real-time PCR). The study will provide a foundation for discovery and modification of devices in previous research by TCM synthetic biology. PnSE1 and PnSE2 encoded predicted proteins of 537 and 545 amino acids, respectively. Two amino acid sequences predicted from PnSEs shared strong similarity (79%), but were highly divergent in N-terminal regions (the first 70 amino acids). The genes expression profiling detected by real-time PCR, PnSE1 mRNA abundantly accumulated in all organs, especially in flower. PnSE2 was only weakly expressed and preferentially in flower. MeJA treatment enhanced the accumulation of PnSEI mRNA expression level in leaves, while there is no obvious enhancement of PnSE2 in same condition. Results indicated that the gene expressions of PnSE1 and PnSE2 were differently transcribed in four organs, and two PnSEs differently

Novel triterpene oxidizing activity of Arabidopsis thaliana CYP716A subfamily enzymes.

PubMed

Yasumoto, Shuhei; Fukushima, Ery O; Seki, Hikaru; Muranaka, Toshiya

2016-02-01

Triterpenoids have diverse chemical structures and bioactivities. Cytochrome P450 monooxygenases play a key role in their structural diversification. In higher plants, CYP716A subfamily enzymes are triterpene oxidases. In this study, Arabidopsis thaliana CYP716A1 and CYP716A2 were characterized by heterologously expressing them in simple triterpene-producing yeast strains. In contrast to the C-28 oxidative activity of CYP716A1 shown in several CYP716A subfamily enzymes, remarkably, CYP716A2 displayed 22α-hydroxylation activity against α-amyrin that has not been previously reported, which produces the cytotoxic triterpenoid, 22α-hydroxy-α-amyrin. Our results contribute to the enrichment of the molecular toolbox that allows for the combinatorial biosynthesis of diverse triterpenoids. © 2016 Federation of European Biochemical Societies.

Medicinal flowers. XVI. New dammarane-type triterpene tetraglycosides and gastroprotective principles from flower buds of Panax ginseng.

PubMed

Yoshikawa, Masayuki; Sugimoto, Sachiko; Nakamura, Seikou; Sakumae, Hayaka; Matsuda, Hisashi

2007-07-01

The oligoglycoside fraction from the flower buds of Panax ginseng C. A. MEYER (Araliaceae) was found to show protective effects on ethanol-induced gastric mucosal lesions in rats. From the oligoglycoside fraction, new dammarane-type triterpene tetraglycosides, floralginsenosides M, N, O, and P, were isolated together with the major oligoglycosides ginsenoside Rd and Re. The structures of the new floralginsenosides were elucidated on the basis of chemical and physicochemical evidence. Ginsenoside Rd (protopanaxadiol 3,20-O-bisdesmoside) exhibited inhibitory effects on ethanol- and indomethacin-induced gastric mucosal lesions in rats.

Metabolite Profiling of Triterpene Glycosides of the Far Eastern Sea Cucumber Eupentacta fraudatrix and Their Distribution in Various Body Components Using LC-ESI QTOF-MS.

PubMed

Popov, Roman S; Ivanchina, Natalia V; Silchenko, Alexandra S; Avilov, Sergey A; Kalinin, Vladimir I; Dolmatov, Igor Yu; Stonik, Valentin A; Dmitrenok, Pavel S

2017-10-02

The Far Eastern sea cucumber Eupentacta fraudatrix is an inhabitant of shallow waters of the south part of the Sea of Japan. This animal is an interesting and rich source of triterpene glycosides with unique chemical structures and various biological activities. The objective of this study was to investigate composition and distribution in various body components of triterpene glycosides of the sea cucumber E. fraudatrix . We applied LC-ESI MS (liquid chromatography-electrospray mass spectrometry) of whole body extract and extracts of various body components for metabolic profiling and structure elucidation of triterpene glycosides from the E. fraudatrix . Totally, 54 compounds, including 26 sulfated, 18 non-sulfated and 10 disulfated glycosides were detected and described. Triterpene glycosides from the body walls, gonads, aquapharyngeal bulbs, guts and respiratory trees were extracted separately and the distributions of the detected compounds in various body components were analyzed. Series of new glycosides with unusual structural features were described in E. fraudatrix , which allow clarifying the biosynthesis of these compounds. Comparison of the triterpene glycosides contents from the five different body components revealed that the profiles of triterpene glycosides were qualitatively similar, and only some quantitative variabilities for minor compounds were observed.

Antibacterial secotirucallane triterpenes from the stem bark of Pseudocedrela kotschyi.

PubMed

Mambou, Christèle Sorèle; Nono, Raymond Ngansop; Chouna, Jean Rodolphe; Tamokou, Jean-de-Dieu; Nkeng-Efouet-Alango, Pépin; Sewald, Norbert

2018-04-25

The antibacterial-guided investigation of the stem bark extract of Pseudocedrela kotschyi led to the isolation of a new secotirucallane triterpene derivative: 4-hydroxy-3,4-secotirucalla-7,24-dien-3,21-dioic acid (1), together with the known one: 3,4-secotirucalla-4(28),7,24-trien-3,21-dioic acid (2) and 3-methyl ester 3,4-secotirucalla-4(28),7,24-trien-3,21-dioic (3). The structures of the isolated compounds were elucidated on the basis of extensive 1D- and 2D-NMR spectroscopy. Extracts, fractions and compounds (1-3) were tested in vitro for antibacterial activity against two Gram positive bacteria (Bacillus subtilis and Staphylococcus aureus ATCC 25923), and two Gram negative bacteria (Escherichia coli S2(1) and Pseudomonas aeruginosa). The MeOH extract and the Hex/CH2Cl2 (70:30) fraction showed significant levels of activity (MIC=64- 256 μg/mL) compared with the two reference drugs [ciprofloxacin: MIC (0.5-1 μg/mL) and amoxicillin: MIC (1-128 μg/mL)]. Moreover, the compound 2 isolated from this Hex/CH2Cl2 (70:30) fraction had the greatest potential value against S. aureus, E. coli and P. aeruginosa, with minimum inhibitory concentrations (MIC) ranging from 4-16 μg/mL.

Simple and Reproducible Two-Stage Agitation Speed Control Strategy for Enhanced Triterpene Production by Lingzhi or Reishi Medicinal Mushrooms, Ganoderma lucidum ACCC G0119 (Higher Basidiomycetes) Based on Submerged Liquid Fermentation.

PubMed

Feng, Jie; Feng, Na; Yang, Yan; Liu, Fang; Zhang, Jingsong; Jia, Wei; Lin, Chi-Chung

2015-01-01

Triterpenes are important anticancer agents produced by batch submerged liquid fermentation, with the medicinal mushroom Ganoderma lucidum ACCC G0119, which was investigated under various dissolved oxygen levels by varying agitation speeds. Three kinetic parameters were analyzed: specific mycelial growth rate (μsmg), specific glucose consumption rate (qsgc), and specific triterpene production rate (qstp). High concentration, yield, and productivity of triterpenes were achieved by developing a simple and reproducible two-stage agitation speed control strategy. At the first 40 h, agitation speed was controlled at 150 rpm to obtain the quickest peak qstp for triterpene production, subsequently agitation speed was controlled at 100 rpm to maintain high qstp for high triterpene accumulation. The maximum concentration of triterpenes reached 0.086 g/l with the yield of 6.072 g/kg and the productivity of 6.532 × 10-4 g/(l·h), which were 39.61%, 36.48%, and 49.22%, respectively, better than the best results controlled by fixed agitation speeds. Conceivably, such a triterpene fermentation production strategy would be useful for industrial large-scale production of triterpenes with G. lucidum.

Genomic and Coexpression Analyses Predict Multiple Genes Involved in Triterpene Saponin Biosynthesis in Medicago truncatula[C][W

PubMed Central

Naoumkina, Marina A.; Modolo, Luzia V.; Huhman, David V.; Urbanczyk-Wochniak, Ewa; Tang, Yuhong; Sumner, Lloyd W.; Dixon, Richard A.

2010-01-01

Saponins, an important group of bioactive plant natural products, are glycosides of triterpenoid or steroidal aglycones (sapogenins). Saponins possess many biological activities, including conferring potential health benefits for humans. However, most of the steps specific for the biosynthesis of triterpene saponins remain uncharacterized at the molecular level. Here, we use comprehensive gene expression clustering analysis to identify candidate genes involved in the elaboration, hydroxylation, and glycosylation of the triterpene skeleton in the model legume Medicago truncatula. Four candidate uridine diphosphate glycosyltransferases were expressed in Escherichia coli, one of which (UGT73F3) showed specificity for multiple sapogenins and was confirmed to glucosylate hederagenin at the C28 position. Genetic loss-of-function studies in M. truncatula confirmed the in vivo function of UGT73F3 in saponin biosynthesis. This report provides a basis for future studies to define genetically the roles of multiple cytochromes P450 and glycosyltransferases in triterpene saponin biosynthesis in Medicago. PMID:20348429

Lanostane-Type Triterpenes from the Mushroom Astraeus pteridis with Antituberculosis Activity

USDA-ARS?s Scientific Manuscript database

Bioassay-guided fractionation of the EtOH extract of the Truffle-mimiking mushroom Astraeus pteridis led to the isolation and identification of three new (3-5) and two known (1, 2) lanostane triterpenes, and phenylalanine betaine (6). The structures of the isolates were elucidated based on 1D and 2D...

Anti-plasmodial activity of some Zulu medicinal plants and of some triterpenes isolated from them.

PubMed

Simelane, Mthokozisi B C; Shonhai, Addmore; Shode, Francis O; Smith, Peter; Singh, Mogie; Opoku, Andy R

2013-10-08

Mimusops caffra E. Mey. ex A.DC and Mimusops obtusifolia Lam (both members of the Sapotaceae family), and Hypoxis colchicifolia Bak (family Hypoxidaceae) are used by traditional healers in Zululand to manage malaria. Anti-plasmodial investigation of the crude extracts and some triterpenes isolated from the plants showed activity against a chloroquine sensitive (CQS) strain of Plasmodium falciparum (D10). Among the crude extracts the leaves of M. caffra exhibited the highest activity, with an IC₅₀ of 2.14 μg/mL. The pentacyclic tritepenoid ursolic acid (1), isolated from the leaves of M. caffra was the most active compound (IC₅₀ 6.8 μg/mL) as compared to taraxerol (2) and sawamilletin (3) isolated from the stem bark of M. obtusifolia (IC₅₀ > 100). Chemical modification of the ursolic acid (1) to 3β-acetylursolic acid (4) greatly enhanced its anti-plasmodial activity. Compound 4 reduced parasitaemia against Plasmodium berghei by 94.01% in in vivo studies in mice. The cytotoxicity of 3β-acetylursolic acid (IC₅₀) to two human cell lines (HEK293 and HepG2) was 366.00 μg/mL and 566.09 μg/mL, respectively. The results validate the use of these plants in folk medicine.

New cycloartane-type ester triterpenes from Euphorbia pterococca and biological evaluation.

PubMed

Benabdelaziz, Imane; Gómez-Ruiz, Santiago; Benkhaled, Mohammed; Carralero, Sandra; Schenker, Patricia; Salm, Andrea; Gertsch, Jürg; Haba, Hamada

2018-03-07

From acetonic extract of the whole plant Euphorbia pterococca Brot. (Euphorbiaceae), four new cycloartane-type ester triterpenes named cycloartenyl-2'E,4'E-decadienoate (1), cycloartenyl-2'E,4'Z-decadienoate (2), 24-methylenecycloartanyl-2'E,4'Z-tetradecadienoate (3), and 24-oxo-29-norcycloartanyl-2'E,4'Z-hexadecadienoate (4) were obtained along with nine known tetracyclic triterpenes (5-13). Their structures were established mainly by extensive use of spectroscopic techniques, including 1D ( 1 H and 13 C) and 2D homo- and heteronuclear NMR experiments (COSY, HSQC, HMBC and NOESY), and mass spectrometry (HRESIMS), and by comparison with data reported in the literature. In addition, the new compounds 1-3 have been tested for cytotoxicity, trypanocidal effects and on enzymes involved in endocannabinoid degradation. While inactive in all assays up to 100 μM, 1 showed selective inhibition of α/β-hydrolase 12 with an IC 50 of 11.6 ± 1.9 μM. Copyright © 2018 Elsevier B.V. All rights reserved.

Improving the fermentation production of the individual key triterpene ganoderic acid me by the medicinal fungus Ganoderma lucidum in submerged culture.

PubMed

Liu, Gao-Qiang; Wang, Xiao-Ling; Han, Wen-Jun; Lin, Qin-Lu

2012-10-24

Enhanced ganoderic acid Me (GA-Me, an important anti-tumor triterpene) yield was attained with the medicinal fungus Ganoderma lucidum using response surface methodology (RSM). Interactions were studied with three variables, viz. glucose, peptone and culture time using a Central Composite Design (CCD). The CCD contains a total of 20 experiments with the first 14 experiments organized in a fractional factorial design, with the experimental trails from 15 to 20 involving the replications of the central points. A polynomial model, describing the relationships between the yield of GA-Me and the three factors in a second-order equation, was developed. The model predicted the maximum GA-Me yield of 11.9 mg·L−1 for glucose, peptone, culture time values of 44.4 g·L−1, 5.0 g·L−1, 437.1 h, respectively, and a maximum GA-Me yield of 12.4 mg·L−1 was obtained in the validation experiment, which represented a 129.6% increase in titre compared to that of the non-optimized conditions. In addition, 11.4 mg·L−1 of GA-Me was obtained in a 30-L agitated fermenter under the optimized conditions, suggesting the submerged culture conditions optimized in the present study were also suitable for GA-Me production on a large scale.

Antimicrobial Activity of Oleanolic and Ursolic Acids: An Update

PubMed Central

Jesus, Jéssica A.; Lago, João Henrique G.; Laurenti, Márcia D.; Yamamoto, Eduardo S.; Passero, Luiz Felipe D.

2015-01-01

Triterpenoids are the most representative group of phytochemicals, as they comprise more than 20,000 recognized molecules. These compounds are biosynthesized in plants via squalene cyclization, a C30 hydrocarbon that is considered to be the precursor of all steroids. Due to their low hydrophilicity, triterpenes were considered to be inactive for a long period of time; however, evidence regarding their wide range of pharmacological activities is emerging, and elegant studies have highlighted these activities. Several triterpenic skeletons have been described, including some that have presented with pentacyclic features, such as oleanolic and ursolic acids. These compounds have displayed incontestable biological activity, such as antibacterial, antiviral, and antiprotozoal effects, which were not included in a single review until now. Thus, the present review investigates the potential use of these triterpenes against human pathogens, including their mechanisms of action, via in vivo studies, and the future perspectives about the use of compounds for human or even animal health are also discussed. PMID:25793002

Lanostane-type triterpenes from the mushroom Astraeus pteridis with Antituberculosis Activity

Treesearch

Rita Stanikunaite; Mohamed Radwan; James M. Trappe; Frank Fronczek; Samir A. Ross

2008-01-01

Bioassay-guided fractionation of an EtOH extract of the truffle-mimiking mushroom Astraeus pteridis led to the isolation and identification of three new (3-5) and two known (1, 2) lanostane triterpenes and phenylalanine betaine (6). The structures of the isolates were elucidated on the basis of 1D and 2D NMR spectroscopic data, HRESIMS results, and X...

The cloning, characterization, and functional analysis of a gene encoding an isopentenyl diphosphate isomerase involved in triterpene biosynthesis in the Lingzhi or reishi medicinal mushroom Ganoderma lucidum (higher Basidiomycetes).

PubMed

Wu, Feng-Li; Shi, Liang; Yao, Jian; Ren, Ang; Zhou, Chao; Mu, Da-Shuai; Zhao, Ming-Wen

2013-01-01

An isopentenyl diphosphate isomerase (IDI) gene, GlIDI, was isolated from Ganoderma lucidum, which produces triterpenes through the mevalonate pathway. The open reading frame of GlIDI encodes a 252 amino acid polypeptide with a theoretical molecular mass of 28.71 kDa and a theoretical isoelectric point of 5.36. GlIDI is highly homologous to other fungal IDIs and contains conserved active residues and nudix motifs shared by the IDI protein family. The color complementation assay indicated that GlIDI can accelerate the accumulation of β-carotene and confirmed that the cloned complementary DNA encoded a functional GlIDI protein. Gene expression analysis showed that the GlIDI transcription level was relatively low in the mycelia and reached a relatively high level in the mushroom primordia. In addition, its expression level could be up-regulated by 254 µM methyl jasmonate. Our results suggest that this enzyme may play an important role in triterpene biosynthesis.

ESI-MS2 and Anti-inflammatory Studies of Cyclopropanic Triterpenes. UPLC-ESI-MS and MS2 Search of Related Metabolites from Donella ubanguiensis.

PubMed

Sandjo, Louis P; Nascimento, Marcus V P Dos Santos; da Silva, Layzon A L; Munhoz, Antonio C M; Pollo, Luiz A E; Biavatti, Maique W; Ngadjui, Bonaventure T; Opatz, Till; Fröde, Tania S

2017-01-01

Triterpenes are one of the largest secondary metabolites groups spread in the plant kingdom with various skeletons. These metabolites have showed various bioactivities including anti-inflammatory activity. The study aims to explore the mass spectrometry fragmentation of donellanic acids A-C (DA A-C), three compounds identified from Donella ubanguiensis; in addition, the fragmentation behaviour of these metabolites will serve as a fingerprint to search and characterise triterpenes congeners in fruits, bark and wood crude extracts of D. ubanguiensis. This work was prompted by the anti-inflammatory activity on leukocyte migration, exudate concentrations and myeloperoxidase activity obtained for DA A-B. The bioactivity was performed on mouse model of pleurisy induced by carrageenan and the parameters were analysed by veterinarian automated cell counter and colorimetric assays. While the tandem mass analyses of DA A-C were carried out by a direct infusion ESI-QTOF-MS/MS, the extracts were studied by UPLC-ESI-QTOF-MS and UPLC-ESI-QTOF-MS/MS. DA A displayed interesting anti-inflammatory activity by inhibiting leukocyte migration, exudate concentrations and myeloperoxidase activity (p < 0.05) while DA B was weakly active (p > 0.05). Moreover, the diagnostic of the MS 2 behaviour of DA A-C in conjunction with the chromatograms and the obtained MS 2 data of the crude extract led to the characterisation of three cyclopropane triterpenes (T1-T3) and six saponins (T4-T9) from the fruits, the bark, and the wood extracts. Donella species deserve more investigation since metabolites related to the anti-inflammatory compound (DA A) could be identified. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Structure Identification of Triterpene from the Mushroom Pleurotus eryngii with Inhibitory Effects Against Breast Cancer.

PubMed

Xue, Zhaohui; Li, Jiaomei; Cheng, Aiqing; Yu, Wancong; Zhang, Zhijun; Kou, Xiaohong; Zhou, Fengjuan

2015-09-01

Breast cancer is the leading cause of death among women, with approximately 1 million diagnoses annually. Triterpenoids, which have cancer preventive or anti-tumour efficacy towards various tumour cells, may play a role in breast cancer prevention. In our previous study, an acetic ether (EtOAc) fraction from the sporocarp of the edible mushroom Pleurotus eryngii (P. eryngii) exhibited significant tumour cell growth inhibition both in vitro and in vivo. In this study, three pentacyclic triterpenoid compounds (1-3) were isolated from EtOAc extracts using chromatographic separation and were identified using nuclear magnetic resonance (NMR) and mass spectrometry (MS). The compounds were 2, 3, 6, 23-tetrahydroxy-urs-12-en-28 oic acid (1), 2,3,23-trihydroxy-urs-12-en-28 oic acid (2) and lupeol (3). All three purified triterpenes showed significant inhibitory activity against breast cancer MCF-7 cell lines in vitro, with the greatest activity exhibited by compound 1, followed by compound 2 and 3. The IC(50) values were 15.71, 48 and 66.89 μM, respectively. Our study may help elucidate the health benefits of P. eryngii mushroom consumption.

New cycloartane-type triterpenes from Marcetia latifolia (Melastomataceae) and in silico studies on Candida parapsilosis protease.

PubMed

Leite, Tonny C C; Leite, Franco H A; Vieira, Ivo J C; Braz Filho, Raimundo; Branco, Alexsandro

2013-08-01

We have previously reported the antimicrobial activity of the ethyl acetate extract of Marcetia latifolia, particularly against Candida parapsilosis. In this work we describe the isolation of two new cycloartane-type triterpenes, 28,29-bis-norcycloartan-3beta,4alpha-diol (1) and 28,29-bis-norcycloart-24-en-3beta,4alpha-diol (2) from the same extract. These compounds were mainly characterized by one- (1H, 13C and APT) and two-dimensional (1H-1H-COSY, 1H-1H-NOESY, HMQC and HMBC) NMR spectroscopy, mass spectrometry and comparison with published structural data. In addition, the activity of triterpenes 1 and 2 on the Candida protease target was investigated by in silico methods using molecular docking.

Lipophilic extracts of Cynara cardunculus L. var. altilis (DC): a source of valuable bioactive terpenic compounds.

PubMed

Ramos, Patrícia A B; Guerra, Ângela R; Guerreiro, Olinda; Freire, Carmen S R; Silva, Artur M S; Duarte, Maria F; Silvestre, Armando J D

2013-09-04

Lipophilic extracts of Cynara cardunculus L. var. altilis (DC) from the south of Portugal (Baixo Alentejo) were studied by gas chromatography-mass spectrometry. One sesquiterpene lactone, four pentacyclic triterpenes, and four sterols were reported for the first time as cultivated cardoon components, namely, deacylcynaropicrin, β- and α-amyrin, lupenyl and ψ-taraxasteryl acetates, stigmasterol, 24-methylenecholesterol, campesterol, and Δ(5)-avenasterol. In addition, other new compounds were identified: ten fatty acids, eight long-chain aliphatic alcohols, and six aromatic compounds. Four triterpenyl fatty acid esters were also detected. Sesquiterpene lactones and pentacyclic triterpenes were the major lipophilic families, representing respectively 2-46% and 10-89% of the detected compounds. Cynaropicrin was the most abundant sesquiterpene lactone, while taraxasteryl acetate was the main pentacyclic triterpene. Fatty acids and sterols, mainly hexadecanoic acid and β-sitosterol, were present at lower amounts (1-20% and 1-11% of the detected compounds). Long-chain aliphatic alcohols and aromatic compounds were detected at reduced abundances (1-6% of the detected compounds).

Medicinal foodstuffs. XXVII. Saponin constituents of gotu kola (2): structures of new ursane- and oleanane-type triterpene oligoglycosides, centellasaponins B, C, and D, from Centella asiatica cultivated in Sri Lanka.

PubMed

Matsuda, H; Morikawa, T; Ueda, H; Yoshikawa, M

2001-10-01

Ursane- and oleanane-type triterpene oligoglycosides, centellasaponins B, C, and D, were isolated from the aerial parts of Centella asiatica (L.) Urban cultivated in Sri Lanka together with madecassoside, asiaticoside, asiaticoside B, and sceffoleoside A. The chemical structures of centellasaponins B, C, and D were determined on the basis of chemical and physicochemical evidence to be madecassic acid 28-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, madasiatic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, and 3beta,6beta,23-trihydroxyolean-12-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, respectively.

Triterpene Functional Genomics in Licorice for Identification of CYP72A154 Involved in the Biosynthesis of Glycyrrhizin[C][W][OA

PubMed Central

Seki, Hikaru; Sawai, Satoru; Ohyama, Kiyoshi; Mizutani, Masaharu; Ohnishi, Toshiyuki; Sudo, Hiroshi; Fukushima, Ery Odette; Akashi, Tomoyoshi; Aoki, Toshio; Saito, Kazuki; Muranaka, Toshiya

2011-01-01

Glycyrrhizin, a triterpenoid saponin derived from the underground parts of Glycyrrhiza plants (licorice), has several pharmacological activities and is also used worldwide as a natural sweetener. The biosynthesis of glycyrrhizin involves the initial cyclization of 2,3-oxidosqualene to the triterpene skeleton β-amyrin, followed by a series of oxidative reactions at positions C-11 and C-30, and glycosyl transfers to the C-3 hydroxyl group. We previously reported the identification of a cytochrome P450 monooxygenase (P450) gene encoding β-amyrin 11-oxidase (CYP88D6) as the initial P450 gene in glycyrrhizin biosynthesis. In this study, a second relevant P450 (CYP72A154) was identified and shown to be responsible for C-30 oxidation in the glycyrrhizin pathway. CYP72A154 expressed in an engineered yeast strain that endogenously produces 11-oxo-β-amyrin (a possible biosynthetic intermediate between β-amyrin and glycyrrhizin) catalyzed three sequential oxidation steps at C-30 of 11-oxo-β-amyrin supplied in situ to produce glycyrrhetinic acid, a glycyrrhizin aglycone. Furthermore, CYP72A63 of Medicago truncatula, which has high sequence similarity to CYP72A154, was able to catalyze C-30 oxidation of β-amyrin. These results reveal a function of CYP72A subfamily proteins as triterpene-oxidizing enzymes and provide a genetic tool for engineering the production of glycyrrhizin. PMID:22128119

An improved HPLC-DAD method for quantitative comparisons of triterpenes in Ganoderma lucidum and its five related species originating from Vietnam.

PubMed

Ha, Do Thi; Loan, Le Thi; Hung, Tran Manh; Han, Le Vu Ngoc; Khoi, Nguyen Minh; Dung, Le Viet; Min, Byung Sun; Nguyen, Nguyen Phuong Dai

2015-01-09

An HPLC-DAD method for the quality control of wild and cultivated Ganoderma lucidum (Linhzhi) and related species samples was developed and validated. The quantitative determination of G. lucidum and its related species using 14 triterpene constituents, including nine ganoderma acids (compounds 4-12), four alcohols (compounds 13-16), and one sterol (ergosterol, 17) were reported. The standard curves were linear over the concentration range of 7.5-180 µg/mL. The LOD and LOQ values for the analyses varied from 0.34 to 1.41 µg/mL and from 1.01 to 4.23 µg/mL, respectively. The percentage recovery of each reference compound was found to be from 97.09% to 100.79%, and the RSD (%) was less than 2.35%. The precision and accuracy ranged from 0.81%-3.20% and 95.38%-102.19% for intra-day, and from 0.43%-3.67% and 96.63%-103.09% for inter-day, respectively. The study disclosed in detail significant differences between the quantities of analyzed compounds in different samples. The total triterpenes in wild Linhzhi samples were significantly higher than in cultivated ones. The total constituent contents of the five related Linhzhi samples were considerably lower than that in the G. lucidum specimens, except for G. australe as its constituent content outweighed wild Linhzhi's content by 4:1.

Schinus terebinthifolius scale-up countercurrent chromatography (Part I): High performance countercurrent chromatography fractionation of triterpene acids with off-line detection using atmospheric pressure chemical ionization mass spectrometry.

PubMed

Vieira, Mariana Neves; Costa, Fernanda das Neves; Leitão, Gilda Guimarães; Garrard, Ian; Hewitson, Peter; Ignatova, Svetlana; Winterhalter, Peter; Jerz, Gerold

2015-04-10

'Countercurrent chromatography' (CCC) is an ideal technique for the recovery, purification and isolation of bioactive natural products, due to the liquid nature of the stationary phase, process predictability and the possibility of scale-up from analytical to preparative scale. In this work, a method developed for the fractionation of Schinus terebinthifolius Raddi berries dichloromethane extract was thoroughly optimized to achieve maximal throughput with minimal solvent and time consumption per gram of processed crude extract, using analytical, semi-preparative and preparative 'high performance countercurrent chromatography' (HPCCC) instruments. The method using the biphasic solvent system composed of n-heptane-ethyl acetate-methanol-water (6:1:6:1, v/v/v/v) was volumetrically scaled up to increase sample throughput up to 120 times, while maintaining separation efficiency and time. As a fast and specific detection alternative, the fractions collected from the CCC-separations were injected to an 'atmospheric pressure chemical ionization mass-spectrometer' (APCI-MS/MS) and reconstituted molecular weight MS-chromatograms of the APCI-ionizable compounds from S. terebinthifolius were obtained. This procedure led to the direct isolation of tirucallane type triterpenes such as masticadienonic and 3β-masticadienolic acids. Also oleanonic and moronic acids have been identified for the first time in the species. In summary, this approach can be used for other CCC scale-up processes, enabling MS-target-guided isolation procedures. Copyright © 2015 Elsevier B.V. All rights reserved.

Structure-activity relationship of pentacylic triterpene esters from Uncaria rhynchophylla as inhibitors of phospholipase Cgamma1.

PubMed

Lee, Ji Suk; Yoo, Hunseung; Suh, Young Ger; Jung, Jae Kyung; Kim, Jinwoong

2008-10-01

A systematic structure-activity relationship of 3beta-hydroxy-27- P- E-coumaroyloxyurs-12-en-28-oic acid ( 7), a triterpene ester isolated from UNCARIA RHYNCHOPHYLLA as a phospholipase Cgamma1 inhibitor, was undertaken with a view toward elucidating its chemical mode of action on PLCgamma1. Related derivatives and analogues of 7 were synthesized and their inhibitory activities against PLCgamma1 were evaluated IN VITRO. The results indicate that 3-OH and 27-esterification may be essential, and that 28-COOH and the 2' double bond appear to be important for activity. Furthermore, the compound possessing a P-coumaroyloxy at position 27 rather than at the 3 and 28 positions shows the greatest inhibitory activity against PLCgamma1. Therefore, this inhibitor will be providing a chemical lead for the further development of cancer chemopreventive or cancer chemotherapeutic agents that have lower toxicity against normal tissues.

Use of topical tranexamic acid or aminocaproic acid to prevent bleeding after major surgical procedures.

PubMed

Ipema, Heather J; Tanzi, Maria G

2012-01-01

To evaluate the literature describing topical use of tranexamic acid or aminocaproic acid for prevention of postoperative bleeding after major surgical procedures. Literature was retrieved through MEDLINE (1946-September 2011) and International Pharmaceutical Abstracts (1970-September 2011) using the terms tranexamic acid, aminocaproic acid, antifibrinolytic, topical, and surgical. In addition, reference citations from publications identified were reviewed. All identified articles in English were evaluated. Clinical trials, case reports, and meta-analyses describing topical use of tranexamic acid or aminocaproic acid to prevent postoperative bleeding were included. A total of 16 publications in the setting of major surgical procedures were included; the majority of data were for tranexamic acid. For cardiac surgery, 4 trials used solutions containing tranexamic acid (1-2.5 g in 100-250 mL of 0.9% NaCl), and 1 trial assessed a solution containing aminocaproic acid (24 g in 250 mL of 0.9% NaCl). These solutions were poured into the chest cavity before sternotomy closure. For orthopedic procedures, all of the data were for topical irrigation solutions containing tranexamic acid (500 mg-3 g in 50-100 mL of 0.9% NaCl) or for intraarticular injections of tranexamic acid (250 mg to 2 g in 20-50 mL of 0.9% sodium chloride, with or without carbazochrome sodium sulfate). Overall, use of topical tranexamic acid or aminocaproic acid reduced postoperative blood loss; however, few studies reported a significant reduction in the number of packed red blood cell transfusions or units given, intensive care unit stay, or length of hospitalization. Topical application of tranexamic acid and aminocaproic acid to decrease postsurgical bleeding after major surgical procedures is a promising strategy. Further data are needed regarding the safety of this hemostatic approach.

Anti-Helicobacter pylori activity of anacardic acids from Amphipterygium adstringens.

PubMed

Castillo-Juárez, Israel; Rivero-Cruz, Fausto; Celis, Heliodoro; Romero, Irma

2007-10-08

Amphipterygium adstringens (Schltdl.) Standl. (Anacardiaceae) is widely used in traditional Mexican medicine for the treatment of gastritis and ulcers. In this work, we studied the anti-Helicobacter pylori activity of its bark, this Gram-negative bacterium is considered the major etiological agent of chronic active gastritis and peptic ulcer disease, and it is linked to gastric carcinoma. From a bio-guided assay of the fractions obtained form a continuous Soxhlet extraction of the bark, we identified that petroleum ether fraction had significant antimicrobial activity against Helicobacter pylori. From this fraction, we isolated an anacardic acids mixture and three known triterpenes: masticadienonic acid; 3alpha-hydroxymasticadienonic acid; 3-epi-oleanolic; as well as the sterol beta-sitosterol. Only the anacardic acids mixture exhibits a potent dose-dependent antibacterial activity (MIC=10 microg/ml in broth cultures). It is enriched in saturated alkyl phenolic acids (C15:0, C16:0, C17:0 C19:0) which represents a novel source of these compounds with potent anti-Helicobacter pylori activity. The promising use of anacardic acids and Amphipterygium adstringens bark in the development of an integral treatment of Helicobacter pylori diseases is discussed.

Shea Nut Oil Triterpene Concentrate Attenuates Knee Osteoarthritis Development in Rats: Evidence from Knee Joint Histology.

PubMed

Kao, Jen-Hsin; Lin, Sheng-Hsiung; Lai, Chun-Fu; Lin, Yu-Chieh; Kong, Zwe-Ling; Wong, Chih-Shung

2016-01-01

Shea nut oil triterpene concentrate is considered to have anti-inflammatory and antioxidant properties. Traditionally, it has been used to treat arthritic conditions in humans. This study aimed to investigate the effect of attenuating osteoarthritis (OA)-induced pain and joint destruction in rats by administering shea nut oil triterpene concentrate (SheaFlex75, which is more than 50% triterpenes). An anterior cruciate ligament transaction (ACLT) with medial meniscectomy (MMx) was used to induce OA in male Wistar rats. Different doses of SheaFlex75 (111.6 mg/kg, 223.2 mg/kg, and 446.4 mg/kg) were then intragastrically administered daily for 12 weeks after surgery. Body weight and the width of the knee joint were measured weekly. Additionally, incapacitance tests were performed at weeks 2, 4, 6, 8, 10 and 12 to measure the weight bearing of the hind limbs, and the morphology and histopathology of the medial femoral condyles were examined and were evaluated using the Osteoarthritis Research Society International (OARSI) scoring system. This study showed that SheaFlex75 reduced the swelling of the knee joint with OA and rectified its weight bearing after ACLT plus MMx surgery in rats. Treatment with SheaFlex75 also decreased ACLT plus MMx surgery-induced knee joint matrix loss and cartilage degeneration. SheaFlex75 relieves the symptoms of OA and protects cartilage from degeneration. SheaFlex75 thus has the potential to be an ideal nutraceutical supplement for joint protection, particularly for injured knee joints.

Enhanced triterpene accumulation in Panax ginseng hairy roots overexpressing mevalonate-5-pyrophosphate decarboxylase and farnesyl pyrophosphate synthase.

PubMed

Kim, Yong-Kyoung; Kim, Yeon Bok; Uddin, Md Romij; Lee, Sanghyun; Kim, Soo-Un; Park, Sang Un

2014-10-17

To elucidate the function of mevalonate-5-pyrophosphate decarboxylase (MVD) and farnesyl pyrophosphate synthase (FPS) in triterpene biosynthesis, the genes governing the expression of these enzymes were transformed into Panax ginseng hairy roots. All the transgenic lines showed higher expression levels of PgMVD and PgFPS than that by the wild-type control. Among the hairy root lines transformed with PgMVD, M18 showed the highest level of transcription compared to the control (14.5-fold higher). Transcriptions of F11 and F20 transformed with PgFPS showed 11.1-fold higher level compared with control. In triterpene analysis, M25 of PgMVD produced 4.4-fold higher stigmasterol content (138.95 μg/100 mg, dry weight [DW]) than that by the control; F17 of PgFPS showed the highest total ginsenoside (36.42 mg/g DW) content, which was 2.4-fold higher compared with control. Our results indicate that metabolic engineering in P. ginseng was successfully achieved through Agrobacterium rhizogenes-mediated transformation and that the accumulation of phytosterols and ginsenosides was enhanced by introducing the PgMVD and PgFPS genes into the hairy roots of the plant. Our results suggest that PgMVD and PgFPS play an important role in the triterpene biosynthesis of P. ginseng.

Alkaline phosphatase activity-guided isolation of active compounds and new dammarane-type triterpenes from Cissus quadrangularis hexane extract.

PubMed

Pathomwichaiwat, Thanika; Ochareon, Pannee; Soonthornchareonnon, Noppamas; Ali, Zulfiqar; Khan, Ikhlas A; Prathanturarug, Sompop

2015-02-03

The stem of Cissus quadrangularis L. (CQ) is used in traditional medicine to treat bone fractures and swelling. Anti-osteoporotic activity of CQ hexane extract has been reported, but the active compounds in this extract remain unknown. Thus, we aimed to identify the active compounds in CQ hexane extract using bioassay-guided isolation. The CQ hexane extract was fractionated sequentially with benzene, dichloromethane, ethyl acetate, and methanol. The examination of CQ extract and its fractions was guided by bioassays for alkaline phosphatase (ALP) activity during the differentiation of MC3T3-E1 osteoblastic cells. The cells were treated with or without the CQ extract and its fractions for a period of time, and then the stimulatory effect of the alkaline phosphatase enzyme, a bone differentiation marker, was investigated. The compounds obtained were structurally elucidated using spectroscopic techniques and re-evaluated for activity during bone differentiation. A total of 29 compounds were isolated, viz., triterpenes, fatty acid methyl esters, glycerolipids, steroids, phytols, and cerebrosides. Four new dammarane-type triterpenes were isolated for the first time from nature, and this report is the first to identify this group of compounds from the Vitaceae family. Seven compounds, viz., glycerolipids and squalene, stimulated ALP activity at a dose of 10μg/mL. Moreover, the synergistic effect of these compounds on bone formation was demonstrated. This report describes, for the first time, the isolation of active compounds from CQ hexane extract; these active compounds will be useful for the quality control of extracts from this plant used to treat osteoporosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Shea Nut Oil Triterpene Concentrate Attenuates Knee Osteoarthritis Development in Rats: Evidence from Knee Joint Histology

PubMed Central

Lin, Sheng-Hsiung; Lai, Chun-Fu; Lin, Yu-Chieh; Kong, Zwe-Ling; Wong, Chih-Shung

2016-01-01

Background Shea nut oil triterpene concentrate is considered to have anti-inflammatory and antioxidant properties. Traditionally, it has been used to treat arthritic conditions in humans. This study aimed to investigate the effect of attenuating osteoarthritis (OA)-induced pain and joint destruction in rats by administering shea nut oil triterpene concentrate (SheaFlex75, which is more than 50% triterpenes). Methods An anterior cruciate ligament transaction (ACLT) with medial meniscectomy (MMx) was used to induce OA in male Wistar rats. Different doses of SheaFlex75 (111.6 mg/kg, 223.2 mg/kg, and 446.4 mg/kg) were then intragastrically administered daily for 12 weeks after surgery. Body weight and the width of the knee joint were measured weekly. Additionally, incapacitance tests were performed at weeks 2, 4, 6, 8, 10 and 12 to measure the weight bearing of the hind limbs, and the morphology and histopathology of the medial femoral condyles were examined and were evaluated using the Osteoarthritis Research Society International (OARSI) scoring system. Results This study showed that SheaFlex75 reduced the swelling of the knee joint with OA and rectified its weight bearing after ACLT plus MMx surgery in rats. Treatment with SheaFlex75 also decreased ACLT plus MMx surgery-induced knee joint matrix loss and cartilage degeneration. Conclusion SheaFlex75 relieves the symptoms of OA and protects cartilage from degeneration. SheaFlex75 thus has the potential to be an ideal nutraceutical supplement for joint protection, particularly for injured knee joints. PMID:27583436

Three new multiflorane-type triterpenes from pumpkin (Cucurbita maxima) seeds.

PubMed

Kikuchi, Takashi; Takebayashi, Mika; Shinto, Mayumi; Yamada, Takeshi; Tanaka, Reiko

2013-05-14

Three new multiflorane-type triterpenes; 7a-methoxymultiflor-8-ene-3a,29-diol 3-acetate-29-benzoate (1), 7-oxomultiflor-8-ene-3a,29-diol 3-acetate-29-benzoate (2), and multiflora-7,9(11)-diene-3a,29-diol 3-p-hydroxybenzoate-29-benzoate (3), were isolated from seeds of Cucurbita maxima, along with three known compounds. Compound 3 and multiflora-7,9(11)-diene-3a-29-diol 3-benzoate (5) exhibited potent inhibitory effects on melanogenesis, with low cytotoxicities, and 2 exhibited single-digit micromolar cytotoxicity against HL-60 and P388 cells.

Quantification of bioactive compounds in Picual and Arbequina olive leaves and fruit.

PubMed

Romero, Concepción; Medina, Eduardo; Mateo, Mª Antonia; Brenes, Manuel

2017-04-01

Olive leaves and fruit possess bioactive substances such as phenolic compounds and triterpenic acids that can be obtained from olive by-products generated during olive oil extraction. The aim of the present study was the characterization and quantification of these compounds in Picual and Arbequina cultivars from different locations and throughout two seasons in both olive leaves and fruit. The major phenolic compound identified in the leaves was oleuropein, and the total content of phenolic compounds in this material reached 70 g kg -1 fresh weight. The leaves were also rich in triterpenic acids (20 g kg -1 fresh weight), with oleanolic acid being the most concentrated among them. With regard to olives, oleuropein and demethyloleuropein were the main phenolic compounds in the pulp of Picual and Arbequina cultivars, and the total concentration of these phenolic compounds reached 3.5% fresh weight. Olives can also be an important source of triterpenic acids, although this is mainly the skin part, where the maslinic and oleanolic acids are concentrated. Olive leaves can contain up to 70 g kg -1 phenolic compounds and 20 g kg -1 triterpenic acids, and olive fruit can contain up to 35 g kg -1 of the former and 3 g kg -1 of the latter. It must also be noted that this level was constant both between seasons and orchard locations. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Three new triterpene esters from pumpkin (Cucurbita maxima) seeds.

PubMed

Kikuchi, Takashi; Ueda, Shinsuke; Kanazawa, Jokaku; Naoe, Hiroki; Yamada, Takeshi; Tanaka, Reiko

2014-04-16

Three new multiflorane-type triterpene esters, i.e. 7α-hydroxymultiflor-8-ene-3α,29-diol 3-acetate-29-benzoate (1), 7α-methoxymultiflor-8-ene-3α,29-diol 3,29-dibenzoate (2), and 7β-methoxymultiflor-8-ene-3α,29-diol 3,29-dibenzoate (3), were isolated from seeds of Cucurbita maxima, along with the known compound, multiflora-7,9(11)-diene-3α,29-diol 3,29-dibenzoate (4). Compound 1 exhibited melanogenesis inhibitory activities comparable with those of arbutin. In cytotoxicity assays, compounds 1 and 3 exhibited weak cytotoxicity, with IC50 values of 34.5-93.7 μM against HL-60 and P388 cells.

Functional Analysis of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Encoding Genes in Triterpene Saponin-Producing Ginseng1[C][W

PubMed Central

Kim, Yu-Jin; Lee, Ok Ran; Oh, Ji Yeon; Jang, Moon-Gi; Yang, Deok-Chun

2014-01-01

Ginsenosides are glycosylated triterpenes that are considered to be important pharmaceutically active components of the ginseng (Panax ginseng ‘Meyer’) plant, which is known as an adaptogenic herb. However, the regulatory mechanism underlying the biosynthesis of triterpene saponin through the mevalonate pathway in ginseng remains unclear. In this study, we characterized the role of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) concerning ginsenoside biosynthesis. Through analysis of full-length complementary DNA, two forms of ginseng HMGR (PgHMGR1 and PgHMGR2) were identified as showing high sequence identity. The steady-state mRNA expression patterns of PgHMGR1 and PgHMGR2 are relatively low in seed, leaf, stem, and flower, but stronger in the petiole of seedling and root. The transcripts of PgHMGR1 were relatively constant in 3- and 6-year-old ginseng roots. However, PgHMGR2 was increased five times in the 6-year-old ginseng roots compared with the 3-year-old ginseng roots, which indicates that HMGRs have constant and specific roles in the accumulation of ginsenosides in roots. Competitive inhibition of HMGR by mevinolin caused a significant reduction of total ginsenoside in ginseng adventitious roots. Moreover, continuous dark exposure for 2 to 3 d increased the total ginsenosides content in 3-year-old ginseng after the dark-induced activity of PgHMGR1. These results suggest that PgHMGR1 is associated with the dark-dependent promotion of ginsenoside biosynthesis. We also observed that the PgHMGR1 can complement Arabidopsis (Arabidopsis thaliana) hmgr1-1 and that the overexpression of PgHMGR1 enhanced the production of sterols and triterpenes in Arabidopsis and ginseng. Overall, this finding suggests that ginseng HMGRs play a regulatory role in triterpene ginsenoside biosynthesis. PMID:24569845

A novel melanin inhibitor: hydroperoxy traxastane-type triterpene from flowers of Arnica montana.

PubMed

Maeda, Kazuhisa; Naitou, Tomoko; Umishio, Kenichi; Fukuhara, Tadao; Motoyama, Akira

2007-05-01

We isolated a novel inhibitor of melanin biosynthesis from the flowers of Arnica montana L. (Compositae), and identified it as a traxastane-type triterpene (3beta,16beta-dihydroxy-21alpha-hydroperoxy-20(30)-taraxastene) [1] by means of 1D or 2D-NMR and liquid chromatography/high-resolution mass spectrometry (LC-HR-MS). Compound [1] at the concentration of 0.53 muM completely inhibited melanin accumulation in cultured B16 melanoma cells. It is one of the most potent among known plant inhibitors of melanin biosynthesis in cultured cells, being 50 times more potent than 4-methoxyphenol, which is used as an anti-pigmentation agent. Its mechanism of action is considered to involve inhibition of transcriptional factor MITF-M (melanocyte-type isoform of microphthalmia-associated transcription factor), which would lead to a decrease of tyrosinase and related genes. We confirmed that compound [1] decreased the protein levels of tyrosinase and its related proteins in B16 melanoma cells. Further study revealed that a similar hydroperoxy triterpene also suppressed the melanin pigment accumulation of B16 melanoma cells. These results indicate that the hydroperoxy group may play an important role in the suppression of the melanin accumulation by compound [1].

[Studies on the triterpenoids of Cyclocarya paliurus (Batal.) Iljinsk].

PubMed

Shu, Rengeng; Liu, Yufeng; Chen, Jie; Shu, Jicheng

2005-07-01

Three triterpenes (I-II) were obtained from the leaves of Cyclocarya paliurus (Batal.) Iljinsk. By means of physicochemical and spectral methods, the structures of the three triterpenes were identified as oleanolic acid (I), ursolic acid (II) and epikatonic acid (III) respectively. All of the three triterpenes were isolated for the first time from the plant of Cyclocarya paliurus (Batal.) Iljinsk.

Uncarinic acids: phospholipase Cgamma1 inhibitors from hooks of Uncaria rhynchophylla.

PubMed

Lee, J S; Yang, M Y; Yeo, H; Kim, J; Lee, H S; Ahn, J S

1999-05-17

Bioactivity-guided fractionation of the CHCl3 extract from hooks of Uncaria rhynchophylla led to the isolation of two triterpene esters, namely uncarinic acids A (1) and B (2). Their structures were established by spectroscopic and chemical methods. These compounds inhibited phospholipase Cgamma1 with IC50 values of 35.66 and 44.55 microM, respectively.

Pistagremic acid as a broad spectrum natural inhibitor from Pistacia integerrima Stewart.

PubMed

Rauf, Abdur; Patel, Seema

2017-02-01

Pistagremic acid (PA) is a bioactive tri-terpene isolated in bulk quantity from the galls of Pistacia integerrima. PA has been documented for a broad range of in vitro and in vivo biological properties. This letter documented the bioloigical potential of PA, which directed the researcher to re-isolate this compound and enhanced their biological potential.

Synergy between Ursolic and Oleanolic Acids from Vitellaria paradoxa Leaf Extract and β-Lactams against Methicillin-Resistant Staphylococcus aureus: In Vitro and In Vivo Activity and Underlying Mechanisms.

PubMed

Catteau, Lucy; Reichmann, Nathalie T; Olson, Joshua; Pinho, Mariana G; Nizet, Victor; Van Bambeke, Françoise; Quetin-Leclercq, Joëlle

2017-12-16

Combining antibiotics with resistance reversing agents is a key strategy to overcome bacterial resistance. Upon screening antimicrobial activities of plants used in traditional medicine, we found that a leaf dichloromethane extract from the shea butter tree ( Vitellaria paradoxa ) had antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) with further evidence of synergy when combined with β-lactams. Using HPLC-MS, we identified ursolic (UA) and oleanolic acids (OA) in leaves and twigs of this species, and quantified them by HPLC-UV as the major constituents in leaf extracts (21% and 6% respectively). Both pure triterpenic acids showed antimicrobial activity against reference and clinical strains of MRSA, with MICs ranging from 8-16 mg/L for UA to 32-128 mg/L for OA. They were highly synergistic with β-lactams (ampicillin and oxacillin) at subMIC concentrations. Reversion of MRSA phenotype was attributed to their capacity to delocalize PBP2 from the septal division site, as observed by fluorescence microscopy, and to disturb thereby peptidoglycan synthesis. Moreover, both compounds also inhibited β-lactamases activity of living bacteria (as assessed by inhibition of nitrocefin hydrolysis), but not in bacterial lysates, suggesting an indirect mechanism for this inhibition. In a murine model of subcutaneous MRSA infection, local administration of UA was synergistic with nafcillin to reduce lesion size and inflammatory cytokine (IL-1β) production. Thus, these data highlight the potential interest of triterpenic acids as resistance reversing agents in combination with β-lactams against MRSA.

Triterpene tetraglycosides from the sea cucumber Stichopus horrens.

PubMed

Vien, Le Thi; Hoang, Le; Hanh, Tran Thi Hong; Thanh, Nguyen Van; Cuong, Nguyen Xuan; Nam, Nguyen Hoai; Thung, Do Cong; Kiem, Phan Van; Minh, Chau Van

2018-05-01

Using various chromatographic separations, three triterpene tetraglycosides (1-3), including one new compound, namely stichorrenoside E (1) along with thelenotoside B (2) and deacetyl thelenotoside B (3), were isolated from the MeOH extract of the Vietnamese sea cucumber Stichopus horrens. Their structures were confirmed by spectroscopic experiments, such as 1D and 2D NMR and HR-ESI-MS. Deacetylated thelenotoside B (3) is firstly isolated as a natural product. Among these compounds, thelenotoside B (2) showed strong cytotoxicities against five human cancer cell lines as HepG2, KB, LNCaP, MCF7 and SK-Mel2 with the IC 50 values from 0.95 ± 0.08 to 1.90 ± 0.13 μM, whereas stichorrenoside E (1) and deacetyl thelenotoside B (3) exhibited significant activities with the IC 50 values from 6.87 ± 0.25 to 11.62 ± 1.05 μM.

Identification of 4-oxo-13-cis-retinoic acid as the major metabolite of 13-cis-retinoic acid in human blood.

PubMed

Vane, F M; Buggé, C J

1981-01-01

The metabolites of 13-cis-retinoic acid (Accutane) were investigated in blood samples from human volunteers on chronic treatment for dermatological disorders. The major metabolite was isolated by reverse-phase high-pressure liquid chromatography and identified as 4-oxo-13-cis-retinoic acid by comparison of its mass and NMR spectra to the spectra of the reference compound. 4-Oxo-all-trans-retinoic acid was also identified, but the extent to which this compound was a metabolite of 13-cis-retinoic acid or an artifactual isomerization product of the major metabolite is unknown. Chromatographic data suggested that small amounts of 13-cis-retinoic acid, 4-hydroxy-13-cis-retinoic acid, and dioxygenated metabolites of 13-cis-retinoic acid may also be present in the blood. This study indicates that a major metabolic pathway of 13-cis-retinoic acid in humans is oxidation at C4 of the cyclohexenyl group.

New isomalabaricane triterpenes from the marine sponge Stelletta globostellata that induce morphological changes in rat fibroblasts.

PubMed

Oku, N; Matsunaga, S; Wada, S i; Watabe, S; Fusetani, N

2000-02-01

Three new isomalabaricane triterpenes, 29-hydroxystelliferin D (2), 3-epi-29-hydroxystelliferin E (3), and 3-epi-29-hydroxystelliferin A (4), were isolated from the marine sponge Stelletta globostellata. Their structures, including absolute stereochemistry, were determined on the basis of spectral data and chemical methods. Rat fibroblasts treated with 0.2 microM of 2-4 exhibited unusual morphological characteristics, followed by death in 5 days.

Triterpene alcohols and sterols from rice bran reduce postprandial hyperglycemia in rodents and humans.

PubMed

Okahara, Fumiaki; Suzuki, Junko; Hashizume, Kohjiro; Osaki, Noriko; Shimotoyodome, Akira

2016-07-01

Hyperglycemia is a major public health problem worldwide and there is increasing demand for prevention of postprandial hyperglycemia in diabetic, prediabetic, and healthy humans. We investigated whether rice bran and triterpene alcohol and sterol preparation (TASP) lowered hyperglycemia in mice and humans. Brown rice and white rice supplemented with TASP lowered the postprandial hyperglycemia in humans. TASP and its components (cycloartenol [CA], 24-methylene cycloartanol, β-sitosterol, and campesterol) decreased postprandial hyperglycemia in C57BL/6J mice. Glucose transport into everted rat intestinal sacs and human HuTu80 cells transfected with sodium-glucose cotransporter-1 (SGLT1) was significantly reduced by the addition of CA. Intracellular localization analysis suggested that SGLT1 translocation to the apical plasma membrane was inhibited when the cells were treated with CA. We demonstrated for the first time that TASP from rice bran lowered postprandial hyperglycemia in mice and humans. The smaller increase in blood glucose following TASP consumption may be due to the CA-induced decrease in glucose absorption from the intestine, which may be related to decreased membrane translocation of SGLT1. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dammarane-type triterpenes from the Brazilian medicinal plant Cordia multispicata.

PubMed

Kuroyanagi, Masanori; Kawahara, Nobuo; Sekita, Setsuko; Satake, Motoyoshi; Hayashi, Tatsuo; Takase, Yoichi; Masuda, Kazuo

2003-10-01

From the Brazilian medicinal plant Carucaá (Cordia multispicata), oleanane- and ursane-type triterpenoids were previously reported as anti-androgenic constituents of the plant. In this study, purification of the polar elements of the EtOAc-soluble fraction of the plant revealed nine novel dammarane-type triterpenes, named cordianols A-I (1-9) along with the known compound cordialin A (10). The structures of these new compounds were elucidated by means of spectral methods including HRFABMS, (1)H NMR, (13)C NMR, and 2D NMR (HMQC, HMBC, NOESY). Absolute configuration at C-23 of compound 7 was determined by an excitone chirality method. Some of these new compounds revealed a hemiketal structure on the A ring and a hydroxylated or epoxidated 20(22)-(E)-ene side chain and showed weak anti-androgenic activity.

Plasma Nervonic Acid Is a Potential Biomarker for Major Depressive Disorder: A Pilot Study.

PubMed

Kageyama, Yuki; Kasahara, Takaoki; Nakamura, Takemichi; Hattori, Kotaro; Deguchi, Yasuhiko; Tani, Munehide; Kuroda, Kenji; Yoshida, Sumiko; Goto, Yu-Ichi; Inoue, Koki; Kato, Tadafumi

2018-03-01

Diagnostic biomarkers of major depressive disorder, bipolar disorder, and schizophrenia are urgently needed, because none are currently available. We performed a comprehensive metabolome analysis of plasma samples from drug-free patients with major depressive disorder (n=9), bipolar disorder (n=6), schizophrenia (n=17), and matched healthy controls (n=19) (cohort 1) using liquid chromatography time-of-flight mass spectrometry. A significant effect of diagnosis was found for 2 metabolites: nervonic acid and cortisone, with nervonic acid being the most significantly altered. The reproducibility of the results and effects of psychotropic medication on nervonic acid were verified in cohort 2, an independent sample set of medicated patients [major depressive disorder (n=45), bipolar disorder (n=71), schizophrenia (n=115)], and controls (n=90) using gas chromatography time-of-flight mass spectrometry. The increased levels of nervonic acid in patients with major depressive disorder compared with controls and patients with bipolar disorder in cohort 1 were replicated in the independent sample set (cohort 2). In cohort 2, plasma nervonic acid levels were also increased in the patients with major depressive disorder compared with the patients with schizophrenia. In cohort 2, nervonic acid levels were increased in the depressive state in patients with major depressive disorder compared with the levels in the remission state in patients with major depressive disorder and the depressive state in patients with bipolar disorder. These results suggested that plasma nervonic acid is a good candidate biomarker for the depressive state of major depressive disorder. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Cytotoxic triterpene diglycosides from the sea cucumber Stichopus horrens.

PubMed

Cuong, Nguyen Xuan; Vien, Le Thi; Hoang, Le; Hanh, Tran Thi Hong; Thao, Do Thi; Thanh, Nguyen Van; Nam, Nguyen Hoai; Thung, Do Cong; Kiem, Phan Van; Minh, Chau Van

2017-07-01

Using various chromatographic separation techniques, eight triterpene diglycosides (1-8), including four new compounds namely stichorrenosides A-D (1-4), were isolated from a methanol extract of the Vietnamese sea cucumber S. horrens. Their structures were elucidated based on spectroscopic analyses, including HR ESI MS, 1D and 2D NMR. Their in vitro cytotoxic activity against five human cancer cell lines, Hep-G2 (hepatoma cancer), KB (epidermoid carcinoma), LNCaP (prostate cancer), MCF7 (breast cancer), and SK-Mel2 (melanoma), was evaluated using SRB methods. Stichorrenoside D (4), stichoposide A (5), and 3β-O-[β-d-xylopyranosyl-(1→2)-β-d-xylopyranosyl]-23S-acetoxyholost-7-ene (7) showed strong cytotoxicity on all five tested cancer cell lines, whereas significant effect was observed for stichorrenoside C (3) and stichoposide B (6). Copyright © 2017 Elsevier Ltd. All rights reserved.

Targeting Inflammatory Pathways by Triterpenoids for Prevention and Treatment of Cancer

PubMed Central

Yadav, Vivek R.; Prasad, Sahdeo; Sung, Bokyung; Kannappan, Ramaswamy; Aggarwal, Bharat B.

2010-01-01

Traditional medicine and diet has served mankind through the ages for prevention and treatment of most chronic diseases. Mounting evidence suggests that chronic inflammation mediates most chronic diseases, including cancer. More than other transcription factors, nuclear factor-kappaB (NF-κB) and STAT3 have emerged as major regulators of inflammation, cellular transformation, and tumor cell survival, proliferation, invasion, angiogenesis, and metastasis. Thus, agents that can inhibit NF-κB and STAT3 activation pathways have the potential to both prevent and treat cancer. In this review, we examine the potential of one group of compounds called triterpenes, derived from traditional medicine and diet for their ability to suppress inflammatory pathways linked to tumorigenesis. These triterpenes include avicins, betulinic acid, boswellic acid, celastrol, diosgenin, madecassic acid, maslinic acid, momordin, saikosaponins, platycodon, pristimerin, ursolic acid, and withanolide. This review thus supports the famous adage of Hippocrates, “Let food be thy medicine and medicine be thy food”. PMID:22069560

Accumulation of Rutin and Betulinic Acid and Expression of Phenylpropanoid and Triterpenoid Biosynthetic Genes in Mulberry (Morus alba L.).

PubMed

Zhao, Shicheng; Park, Chang Ha; Li, Xiaohua; Kim, Yeon Bok; Yang, Jingli; Sung, Gyoo Byung; Park, Nam Il; Kim, Soonok; Park, Sang Un

2015-09-30

Mulberry (Morus alba L.) is used in traditional Chinese medicine and is the sole food source of the silkworm. Here, 21 cDNAs encoding phenylpropanoid biosynthetic genes and 21 cDNAs encoding triterpene biosynthetic genes were isolated from mulberry. The expression levels of genes involved in these biosynthetic pathways and the accumulation of rutin, betulin, and betulinic acid, important secondary metabolites, were investigated in different plant organs. Most phenylpropanoid and triterpene biosynthetic genes were highly expressed in leaves and/or fruit, and most genes were downregulated during fruit ripening. The accumulation of rutin was more than fivefold higher in leaves than in other organs, and higher levels of betulin and betulinic acid were found in roots and leaves than in fruit. By comparing the contents of these compounds with gene expression levels, we speculate that MaUGT78D1 and MaLUS play important regulatory roles in the rutin and betulin biosynthetic pathways.

Identification of gut-derived metabolites of maslinic acid, a bioactive compound from Olea europaea L.

PubMed

Lozano-Mena, Glòria; Sánchez-González, Marta; Parra, Andrés; Juan, M Emília; Planas, Joana M

2016-09-01

Maslinic acid has been described to exert a chemopreventive activity in colon cancer. Hereby, we determined maslinic acid and its metabolites in the rat intestine previous oral administration as a first step in elucidating whether this triterpene might be used as a nutraceutical. Maslinic acid was orally administered at 1, 2, and 5 mg/kg to male Sprague-Dawley for 2 days. At 24 h after the last administration, the content of the duodenum and jejunum, ileum, cecum, and colon was collected and extracted with methanol 80% prior to LC-APCI-MS analysis. The developed method was validated providing suitable sensitivity (LOQ of 5 nM), good recovery (97.8 ± 3.6%), linear correlation, and appropriate precision (< 9%). Maslinic acid was detected in all the segments with higher concentrations in the distal part of the intestine. LC-APCI-LTQ-ORBITRAP-MS allowed the identification of 11 gut-derived metabolites that were formed by mono-, dihydroxylation, and dehydrogenation reactions. Maslinic acid undergoes phase I reactions resulting in a majority of monohydroxylated metabolites without the presence of phase II derivatives. The high concentration of maslinic acid achieved in the intestine suggests that it could exert a beneficial effect in the prevention of colon cancer. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modulation of K(Ca)3.1 channels by eicosanoids, omega-3 fatty acids, and molecular determinants.

PubMed

Kacik, Michael; Oliván-Viguera, Aida; Köhler, Ralf

2014-01-01

Cytochrome P450- and ω-hydrolase products (epoxyeicosatrienoic acids (EETs), hydroxyeicosatetraeonic acid (20-HETE)), natural omega-3 fatty acids (ω3), and pentacyclic triterpenes have been proposed to contribute to a wide range of vaso-protective and anti-fibrotic/anti-cancer signaling pathways including the modulation of membrane ion channels. Here we studied the modulation of intermediate-conductance Ca(2+)/calmodulin-regulated K(+) channels (K(Ca)3.1) by EETs, 20-HETE, ω3, and pentacyclic triterpenes and the structural requirements of these fatty acids to exert channel blockade. We studied modulation of cloned human hK(Ca)3.1 and the mutant hK(Ca)3.1(V275A) in HEK-293 cells, of rK(Ca)3.1 in aortic endothelial cells, and of mK(Ca)3.1 in 3T3-fibroblasts by inside-out and whole-cell patch-clamp experiments, respectively. In inside-out patches, Ca(2+)-activated hK(Ca)3.1 were inhibited by the ω3, DHA and α-LA, and the ω6, AA, in the lower µmolar range and with similar potencies. 5,6-EET, 8,9-EET, 5,6-DiHETE, and saturated arachidic acid, had no appreciable effects. In contrast, 14,15-EET, its stable derivative, 14,15-EEZE, and 20-HETE produced channel inhibition. 11,12-EET displayed less inhibitory activity. The K(Ca)3.1(V275A) mutant channel was insensitive to any of the blocking EETs. Non-blocking 5,6-EET antagonized the inhibition caused by AA and augmented cloned hK(Ca)3.1 and rK(Ca)3.1 whole-cell currents. Pentacyclic triterpenes did not modulate K(Ca)3.1 currents. Inhibition of K(Ca)3.1 by EETs (14,15-EET), 20-HETE, and ω3 critically depended on the presence of electron double bonds and hydrophobicity within the 10 carbons preceding the carboxyl-head of the molecules. From the physiological perspective, metabolism of AA to non-blocking 5,6,- and 8,9-EET may cause AA-de-blockade and contribute to cellular signal transduction processes influenced by these fatty acids.

The influence of major dietary fatty acids on insulin secretion and action.

PubMed

López, Sergio; Bermúdez, Beatriz; Abia, Rocío; Muriana, Francisco J G

2010-02-01

To briefly summarize recent advances towards understanding the influence of major dietary fatty acids on beta-cell function and evaluate their implications for insulin resistance. Studies in humans have shown that beta-cell function and insulin sensitivity improve progressively in the postprandial period as the proportion of monounsaturated fatty acids (MUFAs) with respect to saturated fatty acids (SFAs) in dietary fats increases. However, cell-culture experiments have revealed a dichotomy in the ability of fatty acids to moderate hyperactivity of, and induce lipotoxicity in, beta-cells. There are also some novel findings regarding the ability of HDL to protect beta-cells against oxidized LDL-induced apoptosis in vitro and of reconstituted HDL to attenuate insulin resistance in vivo. These findings raise new questions regarding the contribution of dietary fatty acids to insulin secretion and action. These new findings point to a critical role for major dietary fatty acids in the etiology and pathogenesis of diabetes, which appears to be of particular relevance during postprandial periods and mainly depends on the fatty acid type. This underscores the importance of dietary fatty acids in standard diabetes management.

Characterization and function of the 3-hydroxy-3-methylglutaryl-CoA reductase gene in Alisma orientale (Sam.) Juz. and its relationship with protostane triterpene production.

PubMed

Gu, Wei; Geng, Chao; Xue, Wenda; Wu, Qinan; Chao, Jianguo; Xu, Fei; Sun, Hongmei; Jiang, Ling; Han, Yun; Zhang, Shuangquan

2015-12-01

Protostane triterpenes from Alisma orientale (Sam.) Juz. have exhibited distinct pharmacological properties that are currently in high demand. 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) is considered the first rate-limiting enzyme in isoprenoid biosynthesis via the mevalonic acid (MVA) pathway. In this study, we cloned a full-length cDNA of A. orientale (Sam.) Juz. HMGR (AoHMGR; 2252 bp; GenBank accession no. KP342318) with an open reading frame (ORF) of 1809 bp. The deduced protein sequence contained four conserved motifs and exhibited homology with HMGR proteins from other plants. We next expressed the cloned gene in Escherichia coli BL21 (Rosetta) cells, collected the expressed products, and incubated those with 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to determine enzymatic activity. GC/MS analysis revealed that the products were able to catalyze HMG-CoA and NADPH to form MVA. The purified protein was used to immunize New Zealand rabbits and prepare an antibody against AoHMGR. Western blot results demonstrated that the antibodies specifically recognized AoHMGR protein in A. orientale (Sam.) Juz. We then established a rapid test to detect AoHMGR protein in the plant, and found the tuber to be the most AoHMGR protein-abundant organ in A. orientale (Sam.) Juz. Furthermore, we detected the expression level of AoHMGR and contents of the main active component, Alisol B 23-acetate, at different growth phases of A. orientale (Sam.) Juz. A significant positive correlation was identified, indicating that AoHMGR represents a key enzyme in the synthetic pathway of protostane triterpenes. Copyright © 2015. Published by Elsevier Masson SAS.

Activity of cycloartane-type triterpenes and sterols isolated from Musa paradisiaca fruit peel against Leishmania infantum chagasi.

PubMed

Silva, A A S; Morais, S M; Falcão, M J C; Vieira, I G P; Ribeiro, L M; Viana, S M; Teixeira, M J; Barreto, F S; Carvalho, C A; Cardoso, R P A; Andrade-Junior, H F

2014-09-25

The aim of the study was to evaluate in vitro the antileishmanial activity of triterpenes and sterols isolated from Musa paradisiaca (banana) fruit peel used traditionally to treat leishmaniasis. The compounds were isolated from the ethanolic extract of the peel of the banana fruit by column chromatography. The chemical structure of compounds was determined by (1)H and (13)C - nuclear magnetic resonance spectroscopy. The cytotoxicity was measured in RAW 264.7 cells and LLC-MK2. Leishmanicidal activity against L. infantum chagasi promastigotes was performed by the MTT colorimetric method and activity against amastigotes was assayed in mammalian cells using in situ ELISA method. Five compounds were identified, consisting of three triterpenes: cycloeucalenone, 31-norcyclolaudenone and 24-methylene-cicloartanol and a mixture of two sterols: beta-sitosterol and stigmasterol. With the exception of cycloeucalenone, all compounds showed statistically similar activity against promastigote to pentamidine. While, acting against amastigotes, excluding 31-norcyclolaudenone, other compounds showed activity similar to amphotericin B. All compounds showed low cytotoxicity in mammalian cells. This study partially confirms the use of Musa paradisiaca in folk medicine against leishmaniasis. Further in vivo studies are necessary to evaluate the efficacy. Copyright © 2014 Elsevier GmbH. All rights reserved.

Separation and purification of triterpene saponins from roots of Radix phytolaccae by high-speed countercurrent chromatography coupled with evaporative light scattering detection

PubMed Central

Ma, Jie; Chen, Qianliang; Lai, Daowan; Sun, Wenji; Zhang, Tianyou; Ito, Yoichiro

2009-01-01

Coupled with evaporative light scattering detection, high-speed countercurrent chromatography was successfully applied for the first time to separation and purification of four triterpene saponins including esculentoside A, B, C and D from roots of Radix Phytolaccae. The separation was performed with an optimized two-phase solvent system composed of chloroform-methanol-water (4:4:2, v/v) using the lower phase as the mobile phase at a flow rate of 1.5 ml/min,. From 150 mg of crude extract 46.3 mg of esculentoside A, 21.8 mg of esculentoside B, 7.3 mg of esculentoside C, and 13.6 mg of esculentoside D were obtained at purities of 96.7%, 99.2%, 96.5% and 97.8%, respectively, as determined by HPLC analysis. The structures of the four triterpene saponins were identified by ESI-MS,1H NMR and 13C NMR. PMID:20454595

Bioassay-guided supercritical fluid extraction of cyclooxygenase-2 inhibiting substances in Plantago major L.

PubMed

Stenholm, A; Göransson, U; Bohlin, L

2013-02-01

Selective extraction of plant materials is advantageous for obtaining extracts enriched with desired constituents, thereby reducing the need for subsequent chromatography purification. Such compounds include three cyclooxygenase-2 (COX-2) inhibitory substances in Plantago major L. targeted in this investigation: α-linolenic acid (α-LNA) (18:3 ω-3) and the triterpenic acids ursolic acid and oleanolic acid. To investigate the scope for tuning the selectivity of supercritical fluid extraction (SFE) using bioassay guidance, and Soxhlet extraction with dichloromethane as solvent as a reference technique, to optimise yields of these substances. Extraction parameters were varied to optimise extracts' COX-2/COX-1 inhibitory effect ratios. The crude extracts were purified initially using a solid phase extraction (SPE) clean-up procedure and the target compounds were identified with GC-MS, LC-ESI-MS and LC-ESI-MS² using GC-FID for quantification. α-LNA was preferentially extracted in dynamic mode using unmodified carbon dioxide at 40°C and 172 bar, at a 0.04% (w/w) yield with a COX-2/COX-1 inhibitory effect ratio of 1.5. Ursolic and oleanolic acids were dynamically extracted at 0.25% and 0.06% yields, respectively, with no traces of (α-LNA) and a COX-2/COX-1-inhibitory effect ratio of 1.1 using 10% (v/v) ethanol as polar modifier at 75°C and 483 bar. The Soxhlet extracts had ursolic acid, oleanolic acid and αLNA yields up to 1.36%, 0.34% and 0.15%, respectively, with a COX-2/COX-1 inhibitory effect ratio of 1.2. The target substances can be extracted selectively by bioassay guided optimisation of SFE conditions. Copyright © 2012 John Wiley & Sons, Ltd.

The Lupane-type Triterpene 30-Oxo-calenduladiol Is a CCR5 Antagonist with Anti-HIV-1 and Anti-chemotactic Activities*

PubMed Central

Barroso-González, Jonathan; El Jaber-Vazdekis, Nabil; García-Expósito, Laura; Machado, José-David; Zárate, Rafael; Ravelo, Ángel G.; Estévez-Braun, Ana; Valenzuela-Fernández, Agustín

2009-01-01

The existence of drug-resistant human immunodeficiency virus (HIV) viruses in patients receiving antiretroviral treatment urgently requires the characterization and development of new antiretroviral drugs designed to inhibit resistant viruses and to complement the existing antiretroviral strategies against AIDS. We assayed several natural or semi-synthetic lupane-type pentacyclic triterpenes in their ability to inhibit HIV-1 infection in permissive cells. We observed that the 30-oxo-calenduladiol triterpene, compound 1, specifically impaired R5-tropic HIV-1 envelope-mediated viral infection and cell fusion in permissive cells, without affecting X4-tropic virus. This lupane derivative competed for the binding of a specific anti-CCR5 monoclonal antibody or the natural CCL5 chemokine to the CCR5 viral coreceptor with high affinity. 30-Oxo-calenduladiol seems not to interact with the CD4 antigen, the main HIV receptor, or the CXCR4 viral coreceptor. Our results suggest that compound 1 is a specific CCR5 antagonist, because it binds to the CCR5 receptor without triggering cell signaling or receptor internalization, and inhibits RANTES (regulated on activation normal T cell expressed and secreted)-mediated CCR5 internalization, intracellular calcium mobilization, and cell chemotaxis. Furthermore, compound 1 appeared not to interact with β-chemokine receptors CCR1, CCR2b, CCR3, or CCR4. Thereby, the 30-oxo-calenduladiol-associated anti-HIV-1 activity against R5-tropic virus appears to rely on the selective occupancy of the CCR5 receptor to inhibit CCR5-mediated HIV-1 infection. Therefore, it is plausible that the chemical structure of 30-oxo-calenduladiol or other related dihydroxylated lupane-type triterpenes could represent a good model to develop more potent anti-HIV-1 molecules to inhibit viral infection by interfering with early fusion and entry steps in the HIV life cycle. PMID:19386595

Antitrypanosomal compounds from the essential oil and extracts of Keetia leucantha leaves with inhibitor activity on Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase.

PubMed

Bero, J; Beaufay, C; Hannaert, V; Hérent, M-F; Michels, P A; Quetin-Leclercq, J

2013-02-15

Keetia leucantha is a West African tree used in traditional medicine to treat several diseases among which parasitic infections. The dichloromethane extract of leaves was previously shown to possess growth-inhibitory activities on Plasmodium falciparum, Trypanosoma brucei brucei and Leishmania mexicana mexicana with low or no cytotoxicity (>100 μg/ml on human normal fibroblasts) (Bero et al. 2009, 2011). In continuation of our investigations on the antitrypanosomal compounds from this dichloromethane extract, we analyzed by GC-FID and GC-MS the essential oil of its leaves obtained by hydrodistillation and the major triterpenic acids in this extract by LC-MS. Twenty-seven compounds were identified in the oil whose percentages were calculated using the normalization method. The essential oil, seven of its constituents and the three triterpenic acids were evaluated for their antitrypanosomal activity on Trypanosoma brucei brucei bloodstream forms (Tbb BSF) and procyclic forms (Tbb PF) to identify an activity on the glycolytic process of trypanosomes. The oil showed an IC(50) of 20.9 μg/ml on Tbb BSF and no activity was observed on Tbb PF. The best antitrypanosomal activity was observed for ursolic acid with IC(50) of 2.5 and 6.5 μg/ml respectively on Tbb BSF and Tbb PF. The inhibitory activity on a glycolytic enzyme of T. brucei, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was also evaluated for betulinic acid, olenaolic acid, ursolic acid, phytol, α-ionone and β-ionone. The three triterpenic acids and β-ionone showed inhibitory activities on GAPDH with oleanolic acid being the most active with an inhibition of 72.63% at 20 μg/ml. This paper reports for the first time the composition and antitrypanosomal activity of the essential oil of Keetia leucantha. Several of its constituents and three triterpenic acids present in the dichloromethane leaves extract showed a higher antitrypanosomal activity on bloodstream forms of Tbb as compared to procyclic forms

One new and six known triterpene xylosides from Cimicifuga racemosa: FT-IR, Raman and NMR studies and DFT calculations

NASA Astrophysics Data System (ADS)

Jamróz, Marta K.; Jamróz, Michał H.; Cz. Dobrowolski, Jan; Gliński, Jan A.; Gleńsk, Michał

One new and six known triterpene xylosides were isolated from Cimicifuga racemosa (black cohosh, Actaea racemosa). The structure of a new compound, designated as isocimipodocarpaside (1), was established to be (24S)-3β-hydroxy-24,25-oxiirane-16,23-dione-9,10-seco-9,19-cyclolanost-1(10),7(8),9(11)-trien 3-O-β-D-xylopyranoside, by means of 1H and 13C NMR, IR and Raman spectroscopies and Mass Spectrometry. The six known compounds are: 23-epi-26-deoxycimicifugoside (2), 23-epi-26-deoxyactein (3), 25-anhydrocimigenol xyloside (4), 23-O-acetylshengmanol xyloside (5), 25-O-acetylcimigenol xyloside (6) and 3'-O-acetylcimicifugoside H-1 (7). On the basis of NMR data supported by DFT calculations of NMR shielding constants of (2), its structure, previously described as 26-deoxycimicifugoside was corrected and determined as 23-epi-26-deoxycimicifugoside. The 13C CPMAS NMR spectra of the studied compounds (1)-(7) provided data on their solid-state interactions. The IR and Raman spectra in the Cdbnd O, Cdbnd C, and Csbnd H stretching vibration regions clearly discriminate different triterpenes found in C. racemosa.

One new and six known triterpene xylosides from Cimicifuga racemosa: FT-IR, Raman and NMR studies and DFT calculations.

PubMed

Jamróz, Marta K; Jamróz, Michał H; Cz Dobrowolski, Jan; Gliński, Jan A; Gleńsk, Michał

2012-07-01

One new and six known triterpene xylosides were isolated from Cimicifuga racemosa (black cohosh, Actaea racemosa). The structure of a new compound, designated as isocimipodocarpaside (1), was established to be (24S)-3β-hydroxy-24,25-oxiirane-16,23-dione-9,10-seco-9,19-cyclolanost-1(10),7(8),9(11)-trien 3-O-β-d-xylopyranoside, by means of (1)H and (13)C NMR, IR and Raman spectroscopies and Mass Spectrometry. The six known compounds are: 23-epi-26-deoxycimicifugoside (2), 23-epi-26-deoxyactein (3), 25-anhydrocimigenol xyloside (4), 23-O-acetylshengmanol xyloside (5), 25-O-acetylcimigenol xyloside (6) and 3'-O-acetylcimicifugoside H-1 (7). On the basis of NMR data supported by DFT calculations of NMR shielding constants of (2), its structure, previously described as 26-deoxycimicifugoside was corrected and determined as 23-epi-26-deoxycimicifugoside. The (13)C CPMAS NMR spectra of the studied compounds (1)-(7) provided data on their solid-state interactions. The IR and Raman spectra in the CO, CC, and CH stretching vibration regions clearly discriminate different triterpenes found in C. racemosa. Copyright © 2012 Elsevier B.V. All rights reserved.

Can Tranexamic Acid Reduce Blood Loss during Major Cardiac Surgery? A Pilot Study.

PubMed

Compton, Frances; Wahed, Amer; Gregoric, Igor; Kar, Biswajit; Dasgupta, Amitava; Tint, Hlaing

2017-09-01

We examined the effectiveness of tranexamic acid in preventing intraoperative blood loss during major cardiac surgery. Out of initial 81 patients undergoing major cardiac surgery (both coronary artery bypass and valve repair procedures) at our teaching hospital, sixty-seven patients were selected for this study. We compared estimated blood loss, decrease in percent hemoglobin and hematocrit following surgery between two groups of patients (none of them received any blood product during surgery), one group receiving no tranexamic acid (n=17) and another group receiving tranexamic acid (n=25). In the second study, we combined these patients with patients receiving modest amounts of blood products (1-2 unit) and compared these parameters between two groups of patients (25 patients received no tranexamic acid, 42 patients received tranexamic acid). In patients who received no blood product during surgery, those who received no tranexamic acid showed statistically significant (independent t-test two tailed at p <0.05) reduced estimated blood loss (mean: 713.5 mL, SD: 351.6, n=17) compared to those who received tranexamic acid (mean: 987.2 mL, SD: 459.9, n=25). We observed similar results when the patients receiving no blood products and patients receiving modest amount of blood products were combined based on the use of tranexamic acid or not. No statistically significant difference was observed in percent reduced hemoglobin or hematocrit following surgery in any group of patients. We conclude that intraoperative antifibrinolytic therapy with tranexamic acid does not reduce intraoperative blood loss during major cardiac surgery which contradicts popular belief. © 2017 by the Association of Clinical Scientists, Inc.

Isolation and analysis of a multifunctional triterpene synthase KcMS promoter region from mangrove plant kandelia candel

NASA Astrophysics Data System (ADS)

Basyuni, M.; Wati, R.; Sulistiyono, N.; Sumardi; Oku, H.; Baba, S.; Sagami, H.

2018-03-01

Molecular cloning of Kandelia candel KcMS gene has previously been cloned and encoded a multifunctional triterpene synthase. In this study, the KcMS gene promoter was cloned through Genome walking, sequenced, and analyzed. A 1,358 bp genomic DNA fragment of KcMS promoter was obtained. PLACE and PlantCARE analysis of the KcMS promoter revealed that there was some regulatory elements in response to environmental signals and involved in the regulation of gene expression. Results showed that four kinds of elements are regulated by hormone binding, namely 2 MeJA-responsiveness elements (CGTCA-motif and TGACG-motif), the ABRE (TACGTG) involved in abscisic acid responsiveness, gibberellin-related GARE-motif (AAACAGA), and the TGA-element (AACGAC) as an auxin-responsive element. Several elements in the KcMS have been shown in other plants to be responsive to abiotic stress. These motifs were MBS (CAACTG), TC-rich repeats, and eight light responsive elements. The KcMS promoter was also involved in the activation of defense genes in plants such as HSE (AAAAAATTC) and four circadian control elements (CAANNNNATC). The presence of multipotential regulatory motifs suggested that KcMS may be involved in regulation of plant tolerance to several types of stresses.

Uric acid in major depressive and anxiety disorders.

PubMed

Black, Catherine N; Bot, Mariska; Scheffer, Peter G; Snieder, Harold; Penninx, Brenda W J H

2018-01-01

Uric acid has neuroprotective effects, owing to its antioxidant properties. Lowered antioxidant capacity, causing increased oxidative stress, may be involved in affective disorders and might be altered by antidepressants. This study investigated the association of plasma uric acid, the greatest contributor to blood antioxidant capacity, with major depressive disorder (MDD) and anxiety disorders. Data were from the Netherlands Study of Depression and Anxiety including patients with current (N = 1648), remitted (N = 609) MDD and/or anxiety disorders (of which N = 710 antidepressant users) and 618 controls. Diagnoses were established with the Composite International Diagnostic Interview. Symptom severity was assessed with the Inventory of Depressive Symptoms-Self Report, Beck Anxiety Inventory and Fear Questionnaire. Uric acid was measured in plasma. Analyses were adjusted for sociodemographic, health and lifestyle variables. Plasma uric acid adjusted mean levels were lower in current MDD and/or anxiety disorder(s) (289μmol/l) compared to remitted disorders (298μmol/l, p < .001) and controls (299μmol/l, p < .001; Cohen's d .10). This finding was independent of antidepressant use. Depressive (β-.05, p = .0012), anxiety (β-.04, p = .009) and phobic (β-.03, p = .036) symptom severity, and symptom duration (β-.04, p = .009) were negatively associated with uric acid. Limitations include the lack of data on dietary intake which could be a potential confounding factor. From these cross-sectional findings, the association between uric acid and psychopathology cannot be inferred to be causal. This large scale study finds plasma uric acid levels are lower in current, but not remitted, MDD and/or anxiety disorders, according to a dose-response gradient. This suggests the involvement of decreased antioxidant status in affective disorders, and points to their potential as an avenue for treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Triterpene glycosides with stimulatory activity on melanogenesis from the aerial parts of Weigela subsessilis.

PubMed

Won, Yu-Mi; Seong, Zuh-Kyung; Kim, Jae-Lim; Kim, Hui-Seong; Song, Hyuk-Hwan; Kim, Doo-Young; Kim, Jung-Hee; Oh, Sei-Ryang; Cho, Hyun-Woo; Cho, Jung-Hee; Lee, Hyeong-Kyu

2015-08-01

Three new triterpene glycosides (Lonicerosides K, L and M) and 11 known compounds were isolated from the aerial parts of Weigela subsessilis. Among the known isolated compounds, loniceroside A, sweroside, kaempferol-3-O-glucopyranoside 6″-(3-hydroxy-3-methylglutarate), kaempferol-3-O-acetylglucoside and grandifloroside were reported for the first time in a Weigela genus plant. Their chemical structures were identified using extensive spectroscopic analysis including two-dimensional (2D)-NMR experiments, HR-ESI-QTOF-MS and comparison with reported data. Among these compounds, lonicerosides A and L had potent melanogenesis stimulatory activity in murine B16F0 melanoma cells. The structural relationship of active compounds was discussed.

[Triterpenes and triterpene glycosides from aerial part of Paraboea glutinosa].

PubMed

Wang, Xiaoqin; Peng, Yong; Xu, Lijia; Xiao, Wei; Xiao, Peigen; Liu, Yong

2009-05-01

To investigate the chemical constituents from aerial part of Paraboea glutinosa. The compounds were isolated with silica gel, Sephadex LH-20 column chromatography and their structures were elucidated by means of spectral data analysis. Five compounds were isolated and identified as 2alpha, 3beta, 19alpha, 24-tetrahydroxyurs-12-en-28-oate(24-hydroxytormentic acid,1), glucosyl-2alpha, 3beta, 19alpha, 24-tetrahydroxyurs-12-en-28-oate (24-hydroxytormentic acid ester glucoside,2), 28-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl-24-hydroxytormentic acid (3), beta-sitosterol (4), daucosterol (5). All these compounds were isolated from the genus Paraboea for the first time.

Immunochromatographic strip assay for detection of bioactive Ganoderma triterpenoid, ganoderic acid A in Ganoderma lingzhi.

PubMed

Sakamoto, Seiichi; Kikkawa, Nao; Kohno, Toshitaka; Shimizu, Kuniyoshi; Tanaka, Hiroyuki; Morimoto, Satoshi

2016-10-01

Ganoderic acid A (GAA) is one of the major Ganoderma triterpenes produced by medicinal mushroom belonging to the genus Ganoderma (Ganodermataceae). Due to its interesting pharmacological activities, Ganoderma species have been traditionally used in China for the treatment of various diseases. Herein, we developed a colloidal gold-based immunochromatographic strip assay (ICA) for the rapid detection of GAA using highly specific monoclonal antibody against GAA (MAb 12A) conjugated with gold nanoparticles. Using the developed ICA, the detection of GAA can be completed within 15min after dipping the test strip into an analyte solution with the limit of detection (LOD) for GAA of ~500ng/mL. In addition, this system makes it possible to perform a semi-quantitative analysis of GAA in Ganoderma lingzhi, where high reliability was evaluated by enzyme-linked immunosorbent assay (ELISA). The newly developed ICA can potentially be applied to the standardization of Ganoderma using GAA as an index because GAA is major triterpenoid present much in the mushroom. Copyright © 2016. Published by Elsevier B.V.

HPLC method for the simultaneous quantification of the major organic acids in Angeleno plum fruit

NASA Astrophysics Data System (ADS)

Wang, Yanwei; Wang, Jing; Cheng, Wei; Zhao, Zhilei; Cao, Jiankang

2014-08-01

A method was developed to profile major organic acids in Angeleno fruit by high performance liquid chromatography. Organic acids in plum were extracted by water with ultra- sonication at 50°C for 30 min. The extracts were chromatographed on Waters Atlantis T3 C18 column (4.6 mm×250 mm, 5 μm) with 0.01mol/L sulfuric acid and water as mobile phase, and flow rate was 0.5 ml/min. The column temperature was 40C, and chromatography was monitored by a diode array detector at 210 nm. The result showed that malic acid, citric acid, tartaric acid, oxalic acid, pyruvic acid, acetic acid, succinic acid in Angeleno plum, and the malic acid was the major organic acids. The coefficient of determination of the standard calibration curve is R2 > 0.999. The organic acids recovery ranged from 99.11% for Malic acid to 106.70% for Oxalic acid, and CV (n=6) ranged from 0.95% for Malic acid to 6.23% for Oxalic acid, respectively. The method was accurate, sensitive and feasible in analyzing the organic acids in Angeleno plum.

Preparative purification of the major anti-inflammatory triterpenoid esters from Marigold (Calendula officinalis).

PubMed

Hamburger, M; Adler, S; Baumann, D; Förg, A; Weinreich, B

2003-06-01

A method for the efficient preparative purification of faradiol 3-O-laurate, palmitate and myristate, the major anti-inflammatory triterpenoid esters in the flower heads of the medicinal plant Calendula officinalis has been developed. Gram quantities of the individual compounds were obtained with 96 to 98% purity by a combination of supercritical fluid extraction (SFE), normal-phase and reversed-phase column chromatography. During the work-up of the faradiol esters, accompanying minor compounds of the triterpene ester fraction were purified and identified by spectroscopic means as maniladiol 3-O-laurate and myristate.

Antimicrobial activity and cytotoxicity of triterpenes isolated from leaves of Maytenus undata (Celastraceae)

PubMed Central

2013-01-01

Background Plants of the genus Maytenus belong to the family Celastraceae and are widely used in folk medicine as anti-tumour, anti-asthmatic, analgesic, anti-inflammatory, antimicrobial and anti-ulcer agents, and as a treatment for stomach problems. The aim of this study was to isolate and identify active compounds with antifungal activity from Maytenus undata after a preliminary study highlighted promising activity in crude extracts. Methods Sequential extracts of M. undata leaves prepared using hexane, dichloromethane (DCM), acetone and methanol (MeOH) were tested for activity against Cryptococcus neoformans, a fungal organism implicated in opportunistic infections. Bioassay-guided fractionation of the hexane extract using C. neoformans as test organism was carried out to isolate antifungal compounds. The cytotoxicity of compounds isolated in sufficient quantities was evaluated using a tetrazolium-based colorimetric cellular assay (MTT) and a haemagglutination assay (HA). Results The hexane extract was most active with an MIC of 20 μg/ml against C. neoformans. The triterpene compounds friedelin (1), epifriedelanol (2), taraxerol (3), 3-oxo-11α-methoxyolean-12-ene-30-oic acid (4), 3-oxo-11α-hydroxyolean-12-ene-30-oic acid (5) and 3,11-dihydroxyolean-12-ene-30-oic acid (6) were isolated. Compound 6 was isolated for the first time from a plant species. The antimicrobial activity of compounds 1, 3, 5 and 6 was determined against a range of bacteria and fungi implicated in opportunistic and nosocomial infections. Compounds 5 and 6 were the most active against all the tested microorganisms with MIC values ranging between 24 and 63 μg/ml, except against Staphylococcus aureus which was relatively resistant. Compounds 1 and 3 had a low toxicity with an LC50 > 200 μg/ml towards Vero cells in the MTT assay. Compounds 5 and 6 were toxic with LC50 values of 6.03±0.02 and 2.98±0.01 μg/ml, respectively. Compounds 1 and 3 similarly were not toxic to the red blood cells

Antimicrobial activity and cytotoxicity of triterpenes isolated from leaves of Maytenus undata (Celastraceae).

PubMed

Mokoka, Tsholofelo Abednego; McGaw, Lyndy Joy; Mdee, Ladislaus Kakore; Bagla, Victor Patrick; Iwalewa, Ezekiel Olugbenga; Eloff, Jacobus Nicolaas

2013-05-20

Plants of the genus Maytenus belong to the family Celastraceae and are widely used in folk medicine as anti-tumour, anti-asthmatic, analgesic, anti-inflammatory, antimicrobial and anti-ulcer agents, and as a treatment for stomach problems. The aim of this study was to isolate and identify active compounds with antifungal activity from Maytenus undata after a preliminary study highlighted promising activity in crude extracts. Sequential extracts of M. undata leaves prepared using hexane, dichloromethane (DCM), acetone and methanol (MeOH) were tested for activity against Cryptococcus neoformans, a fungal organism implicated in opportunistic infections. Bioassay-guided fractionation of the hexane extract using C. neoformans as test organism was carried out to isolate antifungal compounds. The cytotoxicity of compounds isolated in sufficient quantities was evaluated using a tetrazolium-based colorimetric cellular assay (MTT) and a haemagglutination assay (HA). The hexane extract was most active with an MIC of 20 μg/ml against C. neoformans. The triterpene compounds friedelin (1), epifriedelanol (2), taraxerol (3), 3-oxo-11α-methoxyolean-12-ene-30-oic acid (4), 3-oxo-11α-hydroxyolean-12-ene-30-oic acid (5) and 3,11-dihydroxyolean-12-ene-30-oic acid (6) were isolated. Compound 6 was isolated for the first time from a plant species. The antimicrobial activity of compounds 1, 3, 5 and 6 was determined against a range of bacteria and fungi implicated in opportunistic and nosocomial infections. Compounds 5 and 6 were the most active against all the tested microorganisms with MIC values ranging between 24 and 63 μg/ml, except against Staphylococcus aureus which was relatively resistant. Compounds 1 and 3 had a low toxicity with an LC50 > 200 μg/ml towards Vero cells in the MTT assay. Compounds 5 and 6 were toxic with LC50 values of 6.03±0.02 and 2.98±0.01 μg/ml, respectively. Compounds 1 and 3 similarly were not toxic to the red blood cells (RBCs) but compounds 5 and

In Planta Variation of Volatile Biosynthesis: An Alternative Biosynthetic Route to the Formation of the Pathogen-Induced Volatile Homoterpene DMNT via Triterpene Degradation in Arabidopsis Roots

PubMed Central

Sohrabi, Reza; Huh, Jung-Hyun; Badieyan, Somayesadat; Rakotondraibe, Liva Harinantenaina; Kliebenstein, Daniel J.; Sobrado, Pablo; Tholl, Dorothea

2015-01-01

Plant-derived volatile compounds such as terpenes exhibit substantial structural variation and serve multiple ecological functions. Despite their structural diversity, volatile terpenes are generally produced from a small number of core 5- to 20-carbon intermediates. Here, we present unexpected plasticity in volatile terpene biosynthesis by showing that irregular homo/norterpenes can arise from different biosynthetic routes in a tissue specific manner. While Arabidopsis thaliana and other angiosperms are known to produce the homoterpene (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) or its C16-analog (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene by the breakdown of sesquiterpene and diterpene tertiary alcohols in aboveground tissues, we demonstrate that Arabidopsis roots biosynthesize DMNT by the degradation of the C30 triterpene diol, arabidiol. The reaction is catalyzed by the Brassicaceae-specific cytochrome P450 monooxygenase CYP705A1 and is transiently induced in a jasmonate-dependent manner by infection with the root-rot pathogen Pythium irregulare. CYP705A1 clusters with the arabidiol synthase gene ABDS, and both genes are coexpressed constitutively in the root stele and meristematic tissue. We further provide in vitro and in vivo evidence for the role of the DMNT biosynthetic pathway in resistance against P. irregulare. Our results show biosynthetic plasticity in DMNT biosynthesis in land plants via the assembly of triterpene gene clusters and present biochemical and genetic evidence for volatile compound formation via triterpene degradation in plants. PMID:25724638

Complexation of phospholipids and cholesterol by triterpenic saponins in bulk and in monolayers.

PubMed

Wojciechowski, Kamil; Orczyk, Marta; Gutberlet, Thomas; Geue, Thomas

2016-02-01

The interactions between three triterpene saponins: α-hederin, hederacoside C and ammonium glycyrrhizate with model lipids: cholesterol and dipalmitoylphosphatidylcholine (DPPC) are described. The oleanolic acid-type saponins (α-hederin and hederacoside C) were shown to form 1:1 complexes with lipids in bulk, characterized by stability constants in the range (4.0±0.2)·10(3)-(5.0±0.4)·10(4) M(-1). The complexes with cholesterol are generally stronger than those with DPPC. On the contrary, ammonium glycyrrhizate does not form complexes with any of the lipids in solution. The saponin-lipid interactions were also studied in a confined environment of Langmuir monolayers of DPPC and DPPC/cholesterol with the saponins present in the subphase. A combined monolayer relaxation, surface dilational rheology, fluorescence microscopy and neutron reflectivity (NR) study showed that all three saponins are able to penetrate pure DPPC and mixed DPPC/cholesterol monolayers. Overall, the effect of the saponins on the model lipid monolayers does not fully correlate with the lipid-saponin complex formation in the homogeneous solution. The best correlation was found for α-hederin, for which even the preference for cholesterol over DPPC observed in bulk is well reflected in the monolayer studies and the literature data on its membranolytic activity. Similarly, the lack of interaction of ammonium glycyrrhizate with both lipids is evident equally in bulk and monolayer experiments, as well as in its weak membranolytic activity. The combined bulk and monolayer results are discussed in view of the role of confinement in modulating the saponin-lipid interactions and possible mechanism of membranolytic activity of saponins. Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical Composition and Bioactivities of Two Common Chaenomeles Fruits in China: Chaenomeles speciosa and Chaenomeles sinensis.

PubMed

Miao, Jing; Zhao, Chengcheng; Li, Xia; Chen, Xuetao; Mao, Xinhui; Huang, Hanhan; Wang, Tingting; Gao, Wenyuan

2016-08-01

Contents of total flavonoids, total phenolics, total triterpenes, total condensed tannin and total saponins in peels, flesh and endocarps of Chaenomeles speciosa (CSP) and Chaenomeles sinensis (CSS) were determined by colorimetric method, while 5 phenolics (vanillic, gallic, chlorogenic, ferulic and p-coumaric acids), 2 triterpenes (oleanolic and ursolic acids), and 3 flavonoids (rutin, catechin and epicatechin) were identified and quantified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and HPLC, and antioxidant and α-glucosidase inhibitory activities of them also were evaluated as well as their digestive characteristics. In the correlation analysis, total phenolics, vanillic acid, catechin, ursolic acid and oleanolic acid all contribute to DPPH(·) scavenge capacity, gallic acid contributes to total ferric reducing antioxidant power, while total triterpenes, total saponins, chlorogenic acid and ferullic acid contribute to α-glucosidase inhibitory activity. In the principal component analysis, endocarps of CSP and CSS both show better quality than their peels and flesh, respectively. In vitro digestion can increase contents of total flavonoids, total condensed tannin and total saponins, while contents of total phenolics and total triterpenes decreased greatly. Our study would contribute to the full use of discarded parts of the 2 Chaenomeles and be helpful to establish a good foundation for further research of CSP and CSS. © 2016 Institute of Food Technologists®

Hillasides A and B, two new cytotoxic triterpene glycosides from the sea cucumber Holothuria hilla Lesson.

PubMed

Wu, Jun; Yi, Yang-Hua; Tang, Hai-Feng; Wu, Hou-Ming; Zhou, Zhen-Rong

2007-01-01

Two new triterpene glycosides, hillasides A (1) and B (2), were isolated from the sea cucumber H. hilla Lesson, together with one known glycoside holothuria B (3). Their structures were deduced by extensive spectral analysis and chemical evidences. The presence of conjugated double bonds [22E,24-diene] in the aglycone of 1 is a rare structural feature among sea cucumber glycosides. The two glycosides showed significant cytotoxicity against eight human tumour cell lines (A-549, MCF-7, IA9, CAKI-1, PC-3, KB, KB-VIN and HCT-8) with IC(50) in the range of 0.1-3.8 microg/ml.

Antileishmanial activity of the hydroalcoholic extract of Miconia langsdorffii, isolated compounds, and semi-synthetic derivatives.

PubMed

Peixoto, Juliana A; Andrade E Silva, Márcio Luis; Crotti, Antônio E M; Cassio Sola Veneziani, Rodrigo; Gimenez, Valéria M M; Januário, Ana H; Groppo, Milton; Magalhães, Lizandra G; Dos Santos, Fransérgio F; Albuquerque, Sérgio; da Silva Filho, Ademar A; Cunha, Wilson R

2011-02-22

The in vitro activity of the crude hydroalcoholic extract of the aerial parts of Miconia langsdorffii Cogn. was evaluated against the promastigote forms of L. amazonensis, the causative agent of cutaneous leishmaniasis in humans. The bioassay-guided fractionation of this extract led to identification of the triterpenes ursolic acid and oleanolic acid as the major compounds in the fraction that displayed the highest activity. Several ursolic acid semi-synthetic derivatives were prepared, to find out whether more active compounds could be obtained. Among these ursolic acid-derived substances, the C-28 methyl ester derivative exhibited the best antileishmanial activity.

Chemical constituents of radix Ranunculus ternati.

PubMed

Zhao, Yun; Ruan, Jin-Lan; Wang, Jin-Hui; Cong, Yue; Song, Shuang; Cai, Ya-Ling; Fang, Wei; Zhou, Dao-Nian

2008-02-15

3 Beta-acetoxy-(20S, 22E)-dammaran-22-en-25-ol, a new triterpene, was isolated along with five known triterpenes (ursolic acid, oleanolic acid, betulinic acid, 3-epiocotillol acetate, and dimmarenediol II acetate), and alpha-D-glc and sucrose from Radix Ranunculus ternati All of them, except oleanolic acid and alpha-D-glc, were isolated from the family of Ranunculaceae for the very first time, and the NMR data of sucrose was first described. In addition, the absolute configurations of alpha-D-glc and the glucose component of sucrose were determined.

Anticancer effect of triterpenes from Ganoderma lucidum in human prostate cancer cells.

PubMed

Qu, Lijun; Li, Sumei; Zhuo, Yumin; Chen, Jianfan; Qin, Xiaoping; Guo, Guoqing

2017-12-01

Ganoderma lucidum , within the Polyporaceae family of Basidiomycota, is a popular traditional remedy medicine used in Asia to promote health and longevity. Compounds extracted from G. lucidum have revealed anticancer, antioxidant and liver protective effects. G. lucidum has been associated with prostate cancer cells. G. lucidum extracts contain numerous bioactive components; however, the exact functional monomer is unknown and the role of triterpenes from G. lucidum (GLT) in prostate cancer remain obscure. The present study investigated the effects of GLT on cell viability, migration, invasion and apoptosis in DU-145 human prostate cancer cells. The results demonstrated that a high dose (2 mg/ml) of GLT inhibits cell viability in a dose- and time-dependent manner by the regulation of matrix metalloproteases. Furthermore, GLT induced apoptosis of DU-145 cells. In general, GLT exerts its effect on cancer cells via numerous mechanisms and may have potential therapeutic use for the prevention and treatment of cancer.

Lucidumol C, a new cytotoxic lanostanoid triterpene from Ganoderma lingzhi against human cancer cells.

PubMed

Amen, Yhiya M; Zhu, Qinchang; Tran, Hai-Bang; Afifi, Mohamed S; Halim, Ahmed F; Ashour, Ahmed; Mira, Amira; Shimizu, Kuniyoshi

2016-07-01

A new oxygenated lanostane-type triterpene, named lucidumol C, together with six known compounds, was isolated from the chloroform extract of the fruiting bodies of Ganoderma lingzhi. Structures were established based on extensive spectroscopic and chemical studies. Potential cytotoxic activities of the isolated compounds were evaluated against human colorectal carcinoma (HCT-116, Caco-2), human liver carcinoma (HepG2), and human cervical carcinoma (HeLa) cell lines using WST-1 reagent. Selectivity was evaluated using normal human fibroblast cells (TIG-1 and HF19). Among the compounds, lucidumol C showed potent selective cytotoxicity against HCT-116 cells with an IC50 value of 7.86 ± 4.56 µM and selectivity index (SI) >10 with remarkable cytotoxic activities against Caco-2, HepG2 and HeLa cell lines.

New by-products rich in bioactive substances from the olive oil mill processing.

PubMed

Romero, Concepción; Medina, Eduardo; Mateo, Maria Antonia; Brenes, Manuel

2018-01-01

Olive oil extraction generates a large amount of residue consisting mainly of the pomace and leaves when using a two-phase centrifugation system. The aim of this study was to assess the content of phenolic and triterpene compounds in the by-products produced in Spanish olive oil mills. Olive pomace had concentrations of phenolic and triterpene substances lower than 2 and 3 g kg -1 , respectively. The leaves contained a high concentration of these substances, although those collected from ground-picked olives had lost most of their phenolic compounds. Moreover, the sediment from the bottom of the olive oil storage tanks did not have a significant amount of these substances. By contrast, a new by-product called olive pomace skin has been revealed as a very rich source of triterpenic acids, the content of which can reach up to 120 g kg -1 in this waste product, maslinic acid comprising around 70% of total triterpenics. Among the by-products generated during extraction of olive oil, olive pomace skin has been discovered to be a very rich source of triterpenic acids, which can reach up to 120 g kg -1 of the waste. These results will contribute to the valorization of olive oil by-products. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Apoptosis caused by triterpenes and phytosterols and antioxidant activity of an enriched flavonoid extract and from Passiflora mucronata.

PubMed

da Silva, Isabel Cristina Vieira; Kaluderovic, Goran; de Oliveira, Pollyana Felix; Guimaraes, Denise Oliveira; Quaresma, Carla Holandino; Porzel, Andrea; Muzitano, Michelle Frazao; Wessjohann, Ludger A; Leal, Ivana Correa Ramos

2018-03-14

The genus Passiflora is knew for food consumption mainly and it extracts present a variety of methabolites, including flavones, alkaloids and triterpenes usually correlated with their antioxidant and antitumoral activities. P. mucronata (Pm) is from Brazil South America and is characterized as "Maracujá de Restinga", being used in the folk medicine for treating insomnia and soothing. The present study evaluated in the first time, the antioxidant and cytotoxicity of the hydroalcoholic leaves extract and fractions from Pm. Their cytotoxic effects were against human prostate cancer (PC3) and mouse malignant melanoma (B16F10) cell lines, by the MTT and CV assays. β-Amyrin, oleanolic acid, β-sitosterol and stigmasterol were isolated as the main components of the most active hexane fraction. These substances were tested individually against the tumor cell lines, whereby β-sitosterol and stigmasterol showed the most relevant activity to PC3 in CV assay and, oleanolic acid to B16F10 by the MTT assay. In addition, these compounds were analysed to cell cycle arrest, and stigmasterol decreased the number of cells in B16F10 line in the G1/G0 phase and subsequently, increased the cell number in sub-G1 phase, presumably indicating apoptosis as possible mode of cell death.The antioxidant activity by the DPPH method showed that the hydroalcoholic extract from the leaves presented higher antioxidant activity (EC50= 133.3 µg/mL) compared to the flowers (EC50= 152.3 µg/mL) and fruits (EC50=207.9 µg/mL) extracts. By the HPLC-MS it was possible to identify the main flavones present in the leaf extract (isoschaftoside, schaftoside, isovitexin, vitexin, isoorientin, orientin). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pedunculoside, a novel triterpene saponin extracted from Ilex rotunda, ameliorates high-fat diet induced hyperlipidemia in rats.

PubMed

Liu, Chang; Shen, Yan-Jun; Tu, Qing-Bo; Zhao, Yan-Ran; Guo, Hao; Wang, Juan; Zhang, Li; Shi, Hua-Wei; Sun, Yun

2018-05-01

Pedunculoside (PE) is a novel triterpene saponin extracted from the dried barks of Ilex rotunda Thunb. The present study aims to explore lipid-lowering effects of PE on hyperlipidemia rat induced by high-fat diet. The rats were fed with the high-fat diet and subjected to intragastric administration of PE at doses of 30, 15, or 5 mg/kg daily for 7 weeks. The results demonstrated that treatment with PE for 7-week dramatically decreased serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and reduced liver TC in hyperlipidemia rat induced by high-fat diet. Furthermore, the results also showed that PE modulated the expression of enzymes involved in lipid metabolism including peroxisome proliferator-activated receptor α (PPAR-α), sterol regulatory element-binding protein 1 (SREBP-1), fatty acid synthase (FAS) and stearoyl CoA desaturase-1 (SCD-1) mRNA in liver. Besides, PE-treated group decreased weights and diameters of epididymal adipose hyperlipidemia rat. Mechanism study demonstrated that PE regulated PPAR-γ, CCAAT/Enhancer-binding Protein α (C/EBPα)、and SREBP-1 expression as well as inhibited phosphorylation of AMPK in MDI (methylisobutylxanthine, dexamethasone, insulin) induced-3T3L1 cells. Molecular Docking confirmed interaction between PE with proteins involving PPAR-γ, C/EBPα and SREBP-1. In summary, these findings may support that PE is a novel lipid-lowering drug candidate. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

In vitro Inhibitory Effect of Gymnema sylvestre Extracts and Total Gymnemic Acids Fraction on Select Cytochrome P450 Activities in Rat Liver Microsomes.

PubMed

Vaghela, Madhuri; Iyer, Krishna; Pandita, Nancy

2018-04-01

Gymnema sylvestre R. Br. is a well-known Indian medicinal herb. Gymnemic acids are pentacyclic triterpenes saponins and active phytoconstituents of Gymnema sylvestre. The study aimed at evaluation of the in vitro rat liver cytochrome P450 (CYP) inhibition potential of extracts and total gymnemic acid (TA)-enriched fractions from G. sylvestre. Standardization of G. sylvestre [ethanolic (EL), hydroethanolic (HE), total acid of ethanolic (TAE), total acid of hydroethanolic (TAHE) and total acid of aqueous (TAAQ) extract] was done with respect to deacyl gymnemic acid (DAGA), using reverse phase-high performance liquid chromatography (RP-HPLC). Total triterpenoid content was determined by vanillin perchloric acid assay. Total triterpene content was found to be the highest in TAAQ (59.86 ± 0.005% w/w) and TAE (49.77 ± 0.009% w/w). TAAQ showed IC 50  ≤ 50 µg/ml for all selected CYP activities. Testosterone 6β-hydroxylation was strongly inhibited by TAE (IC 50 : 15.48 ± 2.13 µg/ml) and was moderately by TAAQ and EL with IC 50  ≥ 50 µg/ml. Flurbiprofen 4'-hydroxylation was subject to strong, weak and moderate inhibition by TAAQ (IC 50 : 34.67 ± 1.38 µg/ml), TAE (IC 50 : ≥ 50 µg/ml) and EL (IC 50 : > 50 µg/ml), respectively. Dextromethorphan O-demethylation was inhibited by TAHE and TAAQ. In vitro inhibition studies suggested that TA strongly inhibits activity of selected CYP. This inhibition may possibly be due to triterpenoids and gymnemic acids that have been reported to be present in it. Data also suggest a potential for possible in vivo herb-drug interactions involving G. sylvestre and other medications that are metabolized by the same CYP.

Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review

PubMed Central

Li, Jian-yuan; Cao, Hong-yan; Cheng, Gen-hong; Sun, Ming-yu

2014-01-01

Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra). GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions. PMID:24963489

Profile of preoperative fecal organic acids closely predicts the incidence of postoperative infectious complications after major hepatectomy with extrahepatic bile duct resection: Importance of fecal acetic acid plus butyric acid minus lactic acid gap.

PubMed

Yokoyama, Yukihiro; Mizuno, Takashi; Sugawara, Gen; Asahara, Takashi; Nomoto, Koji; Igami, Tsuyoshi; Ebata, Tomoki; Nagino, Masato

2017-10-01

To investigate the association between preoperative fecal organic acid concentrations and the incidence of postoperative infectious complications in patients undergoing major hepatectomy with extrahepatic bile duct resection for biliary malignancies. The fecal samples of 44 patients were collected before undergoing hepatectomy with bile duct resection for biliary malignancies. The concentrations of fecal organic acids, including acetic acid, butyric acid, and lactic acid, and representative fecal bacteria were measured. The perioperative clinical characteristics and the concentrations of fecal organic acids were compared between patients with and without postoperative infectious complications. Among 44 patients, 13 (30%) developed postoperative infectious complications. Patient age and intraoperative bleeding were significantly greater in patients with postoperative infectious complications compared with those without postoperative infectious complications. The concentrations of fecal acetic acid and butyric acid were significantly less, whereas the concentration of fecal lactic acid tended to be greater in the patients with postoperative infectious complications. The calculated gap between the concentrations of fecal acetic acid plus butyric acid minus lactic acid gap was less in the patients with postoperative infectious complications (median 43.5 vs 76.1 μmol/g of feces, P = .011). Multivariate analysis revealed that an acetic acid plus butyric acid minus lactic acid gap <60 μmol/g was an independent risk factor for postoperative infectious complications with an odds ratio of 15.6; 95% confidence interval 1.8-384.1. The preoperative fecal organic acid profile (especially low acetic acid, low butyric acid, and high lactic acid) had a clinically important impact on the incidence of postoperative infectious complications in patients undergoing major hepatectomy with extrahepatic bile duct resection. Copyright © 2017. Published by Elsevier Inc.

Occurrence ofCis-6-hexadecenoic acid as the major component ofThunbergia alata seed oil.

PubMed

Spencer, G F; Kleiman, R; Miller, R W; Earle, F R

1971-10-01

An unusual series of monoenoic fatty acids constitutes about 85% of the total acids in seed oil fromThunbergia alata. The major component in the oil,cis-6-hexadecenoic acid (82%), is accompanied by the homologous 4-tetradecenoic (ca. 0.2%) and 8-octadecenoic (1.8%) acids. Another homologous series is represented by 5-tetradecenoic (ca. 0.2%), 7-hexadecenoic (1.8%) and the familiar 9-octadecenoic (4.4%) acids. Traces (<0.1%) of three other acids, 6-tetradecenoic and 10- and 11-octadecenoic, are also present along with palmitic (5.8%), stearic (0.6%) and linoleic (2.2%) acids. Some of the monoenoic acids have not previously been known to occur in seed oils.

Annual trends in use of periconceptional folic acid and birth prevalence of major congenital malformations.

PubMed

Richard-Tremblay, Audrey-Ann; Sheehy, Odile; Bérard, Anick

2013-07-01

Recent evidence suggests that periconceptional folic acid use could not only prevent neural tube defects but also other malformations. The objectives of this study were to assess trends in dispensed high dose periconceptional folic acid (5 mg) and birth prevalence of major congenital malformations. The Quebec Pregnancy Registry, an administrative database with information on periconceptional prescribed medication and diagnostic codes was used to conduct this study. All pregnant women insured by the Quebec public drug plan between January 1(st) 1998 and December 31(st) 2008 were included. The exposure was defined as the use of high dose periconceptional folic acid 30 days before, and during the first 70 days of pregnancy. The outcome measured was the birth prevalence of major congenital malformations among live births. We identified 152,392 pregnancies and babies. The annual prevalence of high dose periconceptional folic acid use increased from 0.17% to 0.80% (p<0.05) during the study period; birth prevalence of congenital malformations increased by 15% (3.35% to 3.87%, p<0.05). More specifically, a 23% increase in the prevalence of cardiac malformation and 23% increase in musculoskeletal defects were observed, whereas there was no change in the prevalence of malformations of the nervous system. Although there was an increase in the use of periconceptional high dose folic acid over the past decade, there was no decrease in the prevalence of major congenital malformations. A limitation of this study is the absence of data on low dose folic acid use, available over the counter, in our administrative database.

Evaluation of antioxidant capacity and synergistic associations of quinonemethide triterpenes and phenolic substances from Maytenus ilicifolia (Celastraceae).

PubMed

Dos Santos, Vânia Aparecida de Freitas Formenton Macedo; Dos Santos, Daniela Pereira; Castro-Gamboa, Ian; Zanoni, Maria Valnice Boldrin; Furlan, Maysa

2010-10-11

This work describes the isolation of the secondary metabolites identified as the quinonemethides maytenin (1) and pristimerin (2) from Maytenus ilicifolia extracts obtained from root barks of adult plants and roots of seedlings and their quantification by high performance liquid chromatography coupled to a diode array detector. The electrochemical profiles obtained from cyclic voltammetry and a coulometric detector coupled to high-performance liquid chromatography contributed to the evaluation of their antioxidant capacity. The antioxidant properties of individual components and the crude extracts of the root barks of Maytenus ilicifolia were compared and the possible synergistic associations of quinonemethide triterpenes and phenolic substances were investigated by using rutin as a model phenolic compound.

Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

PubMed

Zaki, Ahmed; Ashour, Ahmed; Mira, Amira; Kishikawa, Asuka; Nakagawa, Toshinori; Zhu, Qinchang; Shimizu, Kuniyoshi

2016-05-01

Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-β-D-glucopyranosyl-oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The effect of aprotinin, tranexamic acid, and aminocaproic acid on blood loss and use of blood products in major pediatric surgery: a meta-analysis.

PubMed

Schouten, Esther S; van de Pol, Alma C; Schouten, Anton N J; Turner, Nigel M; Jansen, Nicolaas J G; Bollen, Casper W

2009-03-01

Aprotinin reduces the blood loss and transfusion of blood products in children undergoing major surgery. Aprotinin has been associated with severe side effects in adults, and tranexamic acid and aminocaproic acid have been found to be safer alternatives in adults. This systematic review addresses the question of whether tranexamic acid and aminocaproic acid are equally effective as aprotinin for reducing blood loss and transfusion in children undergoing major surgery. A systematic review of the literature was conducted to identify all randomized controlled trials of aprotinin, tranexamic acid, and aminocaproic acid involving children undergoing cardiac or scoliosis surgery. Twenty-three cardiac studies, totaling 1893 patients, met the inclusion criteria. None of the studies directly compared aprotinin to an alternative antifibrinolytic. Five scoliosis studies, totaling 207 patients, met the inclusion criteria. Data on blood loss and use of blood products in the first 24 postoperative hours were extracted. Only homogenously distributed outcomes were pooled. Tranexamic acid showed a homogeneously distributed reduction of blood loss by 11 mL/kg (95% confidence interval [CI] 9-13 mL/kg). Outcomes of blood loss reduction by aprotinin and aminocaproic acid were too heterogeneously distributed to be pooled, so the effect on blood loss could not be evaluated. Both aprotinin and tranexamic acid significantly reduced packed red cell transfusion (4 mL/kg, 95% CI 2-7 mL/kg and 7 mL/kg, 95% CI 5-10 mL/kg, respectively). Type of antifibrinolytic was not a determining factor that explained differences in outcome among trials in a meta-regression analysis. In the scoliosis studies, aprotinin and tranexamic acid significantly reduced blood loss compared with placebo (385 mL, 95% CI 727-42 mL and 682 mL, 95% CI 1149-214 mL, respectively). There is no evidence that suggests that, compared with aprotinin, alternative antifibrinolytics such as tranexamic acid were less effective in

Production of Gymnemic Acid from Cell Suspension Cultures of Gymnema sylvestre.

PubMed

Nagella, Praveen; Dandin, Vijayalaxmi S; Murthy, Hosakatte Niranjana

2016-01-01

Gymnema sylvestre R. Br. is a popular herbal medicine. It has been used in ayurvedic system of medicine for thousands of years. It is popularly called as "Gur-mar" for its distinctive property of temporarily destroying the taste of sweetness and is used in the treatment of diabetes. The leaves of gymnema possess antidiabetic, antimicrobial, anti-hypercholesterolemic, anti-sweetener, anti-inflammatory, and hepatoprotective properties and have traditional uses in the treatment of asthma, eye complaints, and snake bite. The leaves contain triterpene saponins such as gymnemic acid which is an active ingredient of Gymnema. Since the cultivation of G. sylvestre is a very slow process and the content of gymnemic acid depends on the environmental factors, cell suspension culture is sought as an alternative means for the production of Gymnema biomass and to enhance the gymnemic acid content. In this chapter, the methods employed for the induction of callus and subsequent establishment of cell suspension cultures for the production of biomass and analysis of gymnemic acid using high performance liquid chromatography are described.

Identification of oxalic acid and tartaric acid as major persistent pain-inducing toxins in the stinging hairs of the nettle, Urtica thunbergiana.

PubMed

Fu, Han Yi; Chen, Shiang Jiuun; Chen, Ruei Feng; Ding, Wang Hsien; Kuo-Huang, Ling Long; Huang, Rong Nan

2006-07-01

Once human skin contacts stinging hairs of Urtica spp. (stinging nettles), the irritant is released and produces pain, wheals or a stinging sensation which may last for >12 h. However, the existence of pain-inducing toxins in the stinging hairs of Urtica thunbergiana has never been systematically demonstrated. Experiments were therefore conducted to identify the persistent pain-inducing agents in the stinging hairs of U. thunbergiana. The stinging hairs of U. thunbergiana were removed and immersed in deionized water. After centrifugation, the clear supernatants were then subjected to high-performance liquid chromatography (HPLC), enzymatic analysis and/or behavioural bioassays. The HPLC results showed that the major constituents in the stinging hairs of U. thunbergiana were histamine, oxalic acid and tartaric acid. However, the well-recognized pain-inducing agents, serotonin and formic acid, existed at a low concentration as estimated by HPLC and/or enzymatic analyses. The behavioural tests showed that 2% oxalic acid and 10% tartaric acid dramatically elicited persistent pain sensations in rats. In contrast, 10% formic acid and 2% serotonin only elicited moderate pain sensation in the first 10 min. Moreover, no significant pain-related behavioural response was observed after injecting 10% acetylcholine and histamine in rats. Oxalic acid and tartaric acid were identified, for the first time, as major long-lasting pain-inducing toxins in the stinging hairs of U. thunbergiana. The general view that formic acid, histamine and serotonin are the pain-inducing agents in the stinging hairs of U. dioica may require updating, since their concentrations in U. thunbergiana were too low to induce significant pain sensation in behavioural bioassays.

Chemical composition and antioxidant and anti-inflammatory potential of peels and flesh from 10 different pear varieties (Pyrus spp.).

PubMed

Li, Xia; Wang, Tingting; Zhou, Bin; Gao, Wenyuan; Cao, Jingguo; Huang, Luqi

2014-01-01

This study was performed to compare the contents of total phenolics, total flavonoids, and total triterpenes between peel and flesh of ten different pear cultivars. The monomeric compounds were analyzed by HPLC, their antioxidant and anti-inflammatory activities were also measured. Peel and flesh from Yaguang, Hongpi, Qingpi and Guifei varieties contained relatively more total phenolic, total flavonoids and total triterpene, and showed stronger antioxidant and anti-inflammatory activities, while Lvbaoshi and Youran appeared to be weakest among them. All the chemical components found in the pear peel were approximately 6-20 times higher than those in the flesh of pear. For the monomeric compounds, arbutin, oleanolic acid, ursolic acid, chlorogenic acid, epicatechin, and rutin were the dominant components contained in the ten pear cultivars both in peel and in flesh. All of the analyses suggested that the peel of pear might be an excellent polyphenol and triterpenes source. Copyright © 2013 Elsevier Ltd. All rights reserved.

Muscle Fiber Characteristics and Fatty Acid Compositions of the Four Major Muscles in Korean Native Black Goat.

PubMed

Hwang, Young-Hwa; Joo, Sung-Hyun; Bakhsh, Allah; Ismail, Ishamri; Joo, Seon-Tea

2017-01-01

The objective of this study was to investigate the relationship between muscle fiber characteristics and fatty acid composition of four major muscles in Korean native black goat (KNBG). Longissimus lumborum (LL), psoas major (PM), semimembranosus (SM), and gluteus medius (GM) were obtained from five male KNBGs of 36 mon of age and subjected to histochemical analysis and to determine fatty acid composition and meat quality traits. There were significant ( p <0.05) differences in fiber number percentage (FNP) and fiber area percentage (FAP) of fiber types among these four muscles. PM had the highest FNP of type I and the lowest FNP of type IIB, while SM had the highest FNP of type IIB. The highest fat content was observed in LL while SM had the lowest fat content. The proportions of SFA and MUFA were significantly ( p <0.05) different among four muscles due to differences in the majority of fatty acids such as oleic (C18:1) and palmitic (C16:0) acids. The PUFA/SFA ratio was significantly ( p <0.05) different among four muscles, and the highest PUFA/SFA ratio was observed in PM. Results suggested that LL and PM might be healthful because of higher desirable fatty acid value and PUFA/SFA ratio, respectively. Also, data showed that correlations between muscle fiber types and fatty acids proportion of goat muscles were reversed with those of cattle muscles.

Medicinal Flowers. XXXII. Structures of oleanane-type triterpene saponins, perennisosides VIII, IX, X, XI, and XII, from the flowers of Bellis perennis.

PubMed

Morikawa, Toshio; Li, Xuezheng; Nishida, Eriko; Nakamura, Seikou; Ninomiya, Kiyofumi; Matsuda, Hisashi; Hamao, Makoto; Muraoka, Osamu; Hayakawa, Takao; Yoshikawa, Masayuki

2011-01-01

Five new triterpene saponins perennisosides VIII (1), IX (2), X (3), XI (4), and XII (5) were isolated from the MeOH-eluated fraction of the methanolic extract from the flowers of Bellis perennis. The MeOH-eluted fraction of the methanolic extract from the flowers of B. perennis was found to inhibit gastric emptying in olive oil-loaded mice at a dose of 200 mg/kg, per os (p.o.). The stereostructures of 1-5 were elucidated on the basis of chemical and spectroscopic evidence.

Triacylglycerol and triterpene ester composition of shea nuts from seven African countries.

PubMed

Akihisa, Toshihiro; Kojima, Nobuo; Katoh, Naoko; Kikuchi, Takashi; Fukatsu, Makoto; Shimizu, Naoto; Masters, Eliot T

2011-01-01

The compositions of the triacylglycerol (TAG) and triterpene ester (TE) fractions of the kernel fats (n-hexane extracts; shea butter) of the shea tree (Vitellaria paradoxa; Sapotaceae) were determined for 36 samples from seven sub-Saharan countries, i.e., Cote d' Ivoire, Ghana, Nigeria, Cameroun, Chad, Sudan, and Uganda. The principal TAGs are stearic-oleic-stearic (SOS; mean 31.2%), SOO (27.7%), and OOO (10.8%). The TE fractions contents are in the range of 0.5-6.5%, and contain α-amyrin cinnamate (1c; mean 29.3%) as the predominant TE followed by butyrospermol cinnamate (4c; 14.8%), α-amyrin acetate (1a; 14.1%), lupeol cinnamate (3c; 9.0%), β-amyrin cinnamate (2c; 7.6%), lupeol acetate (3a; 7.2%), butyrospermol acetate (4a; 5.8%), and β-amyrin acetate (2a; 4.9%). Shea kernel fats from West African provenances contained, in general, higher levels of high-melting TAGs such as SOS, and higher amount of TEs than those from East African provenances. No striking regional difference in the composition of the TE fractions was observed. Copyright © 2011 by Japan Oil Chemists' Society

Forensic issues in suicide due to acid ingestion in a case of major depressive disorder.

PubMed

Vijayanath, V; Nagaraja Rao, K; Raju, G M; Anitha, M R

2012-06-01

Although rare, suicide using caustic substances in psychiatric practice is not infrequent. Such circumstances involve important forensic and psychiatric issues. In this case report, death due to sulfuric acid ingestion in a patient with major depressive disorder is reported. The legal issues concerning suicide in a patient with mental illness, autopsy findings, forensic issues, and pathophysiology concerning death by acid ingestion have been discussed.

Phytotoxicity of triterpenes and limonoids from the Rutaceae and Meliaceae. 5α,6β,8α,12α-Tetrahydro-28-norisotoonafolin--a potent phytotoxin from Toona ciliata.

PubMed

Nebo, Liliane; Varela, Rosa M; Molinillo, José M G; Severino, Vanessa G P; Sarria, André L F; Cazal, Cristiane M; Fernandes, Maria Fátima das Graças; Fernandes, João B; Macías, Francisco A

2015-01-01

Limonoids and triterpenes are the largest groups of secondary metabolites and have notable biological activities. Meliaceae and Rutaceae are known for their high diversity of metabolites, including limonoids, and are distinguished from other families due to the frequent occurrence of such compounds. The increased interest in crop protection associated with the diverse bioactivity of these compounds has made these families attractive in the search for new allelopathic compounds. In the study reported here we evaluated the bioactivity profiles of four triterpenes (1-4) and six limonoids (5-10) from Meliaceae and Rutaceae. The compounds were assessed in a wheat coleoptile bioassay and those that had the highest activities were tested on the standard target species Lepidinum sativum (cress), Lactuca sativa (lettuce), Lycopersicon esculentum (tomato) and Allium cepa (onion). Limonoids showed phytotoxic activity and 5α,6β,8α, 12α- tetrahydro-28-norisotoonafolin (10) and gedunin (5) were the most active, with bioactivity levels similar to, and in some cases better than, those of the commercial herbicide Logran. The results indicate that these products could also be allelochemicals involved in the ecological interactions of these plant species.

Inhibition of Nuclear Transcription Factor-κB and Activation of Peroxisome Proliferator-Activated Receptors in HepG2 Cells by Cucurbitane-Type Triterpene Glycosides from Momordica charantia

PubMed Central

Nhiem, Nguyen Xuan; Yen, Pham Hai; Ngan, Nguyen Thi Thanh; Quang, Tran Hong; Kiem, Phan Van; Minh, Chau Van; Tai, Bui Huu; Cuong, Nguyen Xuan; Song, Seok Bean

2012-01-01

Abstract Momordica charantia: is used to treat various diseases, including inflammatory conditions. Previous reports indicated that the extract of this plant inhibits activation of nuclear transcription factor-κB (NF-κB) but activates peroxisome proliferator-activated receptor (PPAR). Additionally, cucurbitane-type triterpene glycosides are the main bioactive components of the fruit of M. charantia. Therefore, we investigated the anti-inflammatory activity of 17 cucurbitane-type triterpene glycosides (1–17) isolated from this plant. Their inhibition of NF-κB and activation of PPAR activities in HepG2 cells were measured using luciferase reporter and PPAR subtype transactivation assays. Compounds 6 and 8 were found to inhibit NF-κB activation stimulated by tumor necrosis factor-α (TNFα) in a dose-dependent manner. With 50% inhibition concentration (IC50) values of 0.4 μM, compounds 6 and 8 were more potent inhibitors than the positive control, sulfasalazine (IC50=0.9 μM). Compounds 4, 6, and 8 also inhibited TNFα-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 mRNA. However, only compound 13 significantly increased PPARγ transactivation. PMID:22248180

Novel and unusual triterpene from Black Cohosh. Determination of structure of 9,10- seco-9,19-cyclolanostane xyloside (cimipodocarpaside) by NMR, IR and Raman spectroscopy and DFT calculations

NASA Astrophysics Data System (ADS)

Jamróz, Marta K.; Jamróz, Michał H.; Dobrowolski, Jan Cz.; Gliński, Jan A.; Davey, Matthew H.; Wawer, Iwona

2011-01-01

A new triterpene xyloside, designated cimipodocarpaside was isolated from a Black Cohosh ( Actea racemosa L.) extract and its structure was elucidated by means of 1H, 13C NMR, IR and Raman spectroscopy supported by B3LYP/6-31G** calculations. The vibrational spectra were interpreted using the PED analysis of 273 fundamentals. Its structure comprises four condensed rings A-D which are 6, 7, 6, and 5-membered, respectively. An oxiirane ring is located in the side chain and a xylose moiety is attached to the A-ring. Comparison of the experimental 13C NMR data with the theoretical chemical shifts of 24 S- and 24 R-cimipodocarpaside isomers revealed that the isolated compound has the 24 S-configuration. Combined spectroscopic and computational studies enabled the determination of the structure of cimipodocarpaside as (24 S)-3β-hydroxy-24,25-oxiirane-16,23-dione-9,10- seco-9,19-cyclolanost-7(8),9(11),10(19)-trien-3-O-β- D-xylopyranoside. Triterpenes with 7-membered ring were thus far isolated from only Actea podocarpa DC. plants. This is the first report on the isolation of such a compound from Black Cohosh.

Therapeutic potential of glycyrrhetinic acids: a patent review (2010-2017).

PubMed

Hussain, Hidayat; Green, Ivan R; Shamraiz, Umair; Saleem, Muhammad; Badshah, Amin; Abbas, Ghulam; Rehman, Najeeb Ur; Irshad, Muhammad

2018-05-01

Glycyrrhetinic acids (GAs) viz., 18β-glycyrrhetinic acid and 18α-glycyrrhetinic acid, are oleanane-type triterpenes having a carboxylic acid group at C-30, and are extracted from the Chines herbal medicine licorice (Glycyrrhiza uralensis). Although the pharmacological properties of GAs have long been known, attention to them has greatly increased in recent times due to their cytotoxic activity. Areas covered: This review represents the patents granted about natural and synthetic glycyrrhetinic acid analogs from January 2010 to December 2017, the advances made by research groups in conjunction with pharmaceutical companies in the discovery of new natural or synthetic glycyrrhetinic acid analogs. Expert opinion: GAs demonstrate excellent cytotoxic, antimicrobial, enzyme inhibitory, antiinflammatory, antioxidant, analgesic, and antiviral effects. It is interesting to note that the C- 3 (OH) and C 30- CO 2 H functional groups make GAs very attractive lead structures for medicinal scientists since these functionalities allow the generation of further chemical diversity for improved pharmacological effects. Moreover, various GA analogues have been prepared via modification of the C 30- CO 2 H. It is noteworthy that the C-30 amide of GA demonstrated better cytotoxic effects compared to the parent compounds. In addition, GAs have the capability to conjugate with other anticancer drugs or be converted into their halo or amino analogs which is expected to stimulate medicinal chemist to synthesize new lead compounds in cancer drug discovery.

Method for the routine quantitative gas chromatographic analysis of major free fatty acids in butter and cream.

PubMed

Woo, A H; Lindsay, R C

1980-07-01

A rapid quantiative method was developed for routine analysis of the major, even carbon-numbered free fatty acids in butter and cream. Free fatty acids were isolated directly from intact samples by a modified silicic acid-potassium hydroxide arrestant column and were separated by gas chromatography with a 1.8 m x 2 mm inner diameter glass column packed with 10% neopentyl glycol adipate on 80/100 Chromosorb W. Purified, formic acid-saturated carrier gas was required for minimal peak tailing and extended column life. The accuracy and reproducibility of the mmethod was established through quantitative recovery studies of free fatty acid mixtures, free fatty acids added to butter, and replicate analysis of butter and cream samples.

Synthesis and antiplasmodial activity of betulinic acid and ursolic acid analogues.

PubMed

Innocente, Adrine M; Silva, Gloria N S; Cruz, Laura Nogueira; Moraes, Miriam S; Nakabashi, Myna; Sonnet, Pascal; Gosmann, Grace; Garcia, Célia R S; Gnoatto, Simone C B

2012-10-12

More than 40% of the World population is at risk of contracting malaria, which affects primarily poor populations in tropical and subtropical areas. Antimalarial pharmacotherapy has utilised plant-derived products such as quinine and artemisinin as well as their derivatives. However, worldwide use of these antimalarials has caused the spread of resistant parasites, resulting in increased malaria morbidity and mortality. Considering that the literature has demonstrated the antimalarial potential of triterpenes, specially betulinic acid (1) and ursolic acid (2), this study investigated the antimalarial activity against P. falciparum chloroquine-sensitive 3D7 strain of some new derivatives of 1 and 2 with modifications at C-3 and C-28. The antiplasmodial study employed flow cytometry and spectrofluorimetric analyses using YOYO-1, dihydroethidium and Fluo4/AM for staining. Among the six analogues obtained, compounds 1c and 2c showed excellent activity (IC₅₀ = 220 and 175 nM, respectively) while 1a and b demonstrated good activity (IC₅₀ = 4 and 5 μM, respectively). After cytotoxicity evaluation against HEK293T cells, 1a was not toxic, while 1c and 2c showed IC₅₀ of 4 μM and a selectivity index (SI) value of 18 and 23, respectively. Moreover, compound 2c, which presents the best antiplasmodial activity, is involved in the calcium-regulated pathway(s).

Anti-Trichomonas vaginalis activity of ursolic acid derivative: a promising alternative.

PubMed

Bitencourt, Fernanda Gobbi; de Brum Vieira, Patrícia; Meirelles, Lucia Collares; Rigo, Graziela Vargas; da Silva, Elenilson Figueiredo; Gnoatto, Simone Cristina Baggio; Tasca, Tiana

2018-05-01

Trichomonas vaginalis is an extracellular parasite that binds to the epithelium of the human urogenital tract and causes the sexually transmitted infection, trichomoniasis. In view of increased resistance to drugs belonging to the 5-nitroimidazole class, new treatment alternatives are urgently needed. In this study, eight semisynthetized triterpene derivatives were evaluated for in vitro anti-T. vaginalis activity. Ursolic acid and its derivative, 3-oxime-urs-12-en-28-oic-ursolic acid (9), presented the best anti-T. vaginalis activity when compared to other derivatives, with minimum inhibitory concentration (MIC) at 25 μM. Moreover, 9 was active against several T. vaginalis fresh clinical isolates. Hemolysis assay demonstrated that 9 presented a low hemolytic effect. Importantly, 25 μM 9 was not cytotoxic against the Vero cell lineage. Finally, we demonstrated that compound 9 acts synergistically with metronidazole against a T. vaginalis metronidazole-resistant isolate. This report reveals the high potential of the triterpenoid derivative 9 as trichomonicidal agent.

Anxiety in major depression and cerebrospinal fluid free gamma-aminobutyric acid.

PubMed

Mann, J John; Oquendo, Maria A; Watson, Kalycia Trishana; Boldrini, Maura; Malone, Kevin M; Ellis, Steven P; Sullivan, Gregory; Cooper, Thomas B; Xie, Shan; Currier, Dianne

2014-10-01

Low gamma-aminobutyric acid (GABA) is implicated in both anxiety and depression pathophysiology. They are often comorbid, but most clinical studies have not examined these relationships separately. We investigated the relationship of cerebrospinal fluid (CSF) free GABA to the anxiety and depression components of a major depressive episode (MDE) and to monoamine systems. Patients with a DSM-IV major depressive episode (N = 167: 130 major depressive disorder; 37 bipolar disorder) and healthy volunteers (N = 38) had CSF free GABA measured by gas chromatography mass spectroscopy. Monoamine metabolites were assayed by high performance liquid chromatography. Symptomatology was assessed by Hamilton depression rating scale. Psychic anxiety severity increased with age and correlated with lower CSF free GABA, controlling for age. CSF free GABA declined with age but was not related to depression severity. Other monoamine metabolites correlated positively with CSF GABA but not with psychic anxiety or depression severity. CSF free GABA was lower in MDD compared with bipolar disorder and healthy volunteers. GABA levels did not differ based on a suicide attempt history in mood disorders. Recent exposure to benzodiazepines, but not alcohol or past alcoholism, was associated with a statistical trend for more severe anxiety and lower CSF GABA. Lower CSF GABA may explain increasing severity of psychic anxiety in major depression with increasing age. This relationship is not seen with monoamine metabolites, suggesting treatments targeting the GABAergic system should be evaluated in treatment-resistant anxious major depression and in older patients. © 2014 Wiley Periodicals, Inc.

Microtropins Q-W, ent-Labdane Glucosides: Microtropiosides G-I, Ursane-Type Triterpene Diglucoside and Flavonol Glycoside from the Leaves of Microtropis japonica.

PubMed

Terazawa, Saori; Uemura, Yuka; Koyama, Yuka; Kawakami, Susumu; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki; Shinzato, Takakazu; Kawahata, Masatoshi; Yamaguchi, Kentaro

2017-01-01

Microtropins Q-W, (2S,3R)-2-ethyl-2,3-dihydroxybutyrate of various glucosides and glucose, as well as three ent-labdane diterpenoid glucosides, named microtropiosides G, H and I, an ursane-type triterpene diglucoside and a flavonoid glycoside were isolated from the MeOH extract of the leaves of Microtropis japonica. The structure of microtropioside A, also isolated from the branches of M. japonica, was elucidated spectroscopically in a previous experiment and was found to possess a rare seven-membered oxyrane ring. Its structure was confirmed by X-ray crystallographic analysis of its pentaacetate.

A new, major C27 biliary bile acid in the Red-winged tinamou (Rhynchotus rufescens):(25R)-1β,3α,7α-trihydroxy-5β-cholestan-27-oic acid*

PubMed Central

Hagey, Lee R.; Kakiyama, Genta; Muto, Akina; Iida, Takashi; Mushiake, Kumiko; Goto, Takaaki; Mano, Nariyasu; Goto, Junichi; Oliveira, Cleida A.; Hofmann, Alan F.

2009-01-01

The chemical structures of the three major bile acids present in the gallbladder bile of the Red-winged tinamou (Rhynchotus rufescens), an early evolving, ground-living bird related to ratites, were determined. Bile acids were isolated by preparative reversed-phase HPLC. Two of the compounds were identified as the taurine N-acylamidates of (25R)-3α,7α-dihydroxy-5β-cholestan-27-oic acid (constituting 22% of biliary bile acids) and (25R)-3α,7α,12α-trihydroxy-5β-cholestan-27-oic acid (constituting 51%). The remaining compound, constituting 21% of biliary bile acids, was an unknown C27 bile acid. Its structure was elucidated by LC/ESI-MS/MS and NMR and shown to be the taurine conjugate of (25R)-1β,3α,7α-trihydroxy-5β-cholestan-27-oic acid, a C27 trihydroxy bile acid not previously reported. Although C27 bile acids with a 1β-hydroxyl group have been identified as trace bile acids in the alligator, this is the first report of a major biliary C27 bile acid possessing a 1β-hydroxyl group. PMID:19011113

[Study on triterpenes of Microtropis tiflora].

PubMed

Wang, Kui-wu; Hu, Xin-ling; Shen, Lian-qing; Pan, Yuan-jiang

2007-08-01

To study the chemical constituents of Microtropis triflora. The compounds were isolated by chromatography on silica gel and Sephadex LH-20. There structures were elucidatedby by chemical methods and spectral analysis. Five triterpenoids were isolated and elucidated as friedelin (1), 3-oxo-28-friedelanoic acid (2), 29-hydroxy-3-friedelanone (3), salaspermic acid (4), orthosphenic acid (5). Compounds 1-5 are all isolated from M. triflora for the first time.

Identification of rosmarinic acid as the major active constituent in Cordia americana.

PubMed

Geller, F; Schmidt, C; Göttert, M; Fronza, M; Schattel, V; Heinzmann, B; Werz, O; Flores, E M M; Merfort, I; Laufer, S

2010-04-21

Preparation from leaves of Cordia americana have been widely used in traditional medicine in South Brazil to treat wounds and various inflammations. The objective of this work was to identify the effective compounds in the ethanolic extract prepared from the leaves of Cordia americana, which is used in traditional South Brazilian medicine as anti-inflammatory and wound healing remedy. Isolation and structure elucidation techniques were performed in order to identify the compounds of Cordia americana and HPLC analysis was used for the quantification. The major constituent and the ethanolic extract were investigated for inhibition of 5-lipoxygenase, p38alpha MAPK, TNFalpha release and NF-kappaB as well as in the fibroblast scratch assay. Rosmarinic acid (1) was identified as the major compound with an amount of 8.44% in the ethanolic extract of the leaves of Cordia americana. The ethanolic extract as well as (1) exhibited the highest inhibitory effects on 5-lipoxygenase (IC(50)=0.69 and 0.97microg/mL, resp., IC50 of BWA4C as reference: 0.3microM) and p38alpha (IC50=3.25 and 1.16microg/mL, resp., IC50 of SB203580 as reference: 0.046microM) and moderate inhibitory effects on TNFalpha release. Slight effects were observed in the fibroblast scratch assay. This study increases our knowledge on the effective compound in Cordia americana and supports its use in traditional medicine. We demonstrated for the first time pharmacological effects of Cordia americana and we provide evidences for a crucial role of rosmarinic acid as the major key player. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

ANXIETY IN MAJOR DEPRESSION AND CEREBROSPINAL FLUID FREE GAMMA-AMINOBUTYRIC ACID

PubMed Central

Mann, J. John; Oquendo, Maria A.; Watson, Kalycia Trishana; Boldrini, Maura; Malone, Kevin M.; Ellis, Steven P.; Sullivan, Gregory; Cooper, Thomas B.; Xie, Shan; Currier, Dianne

2016-01-01

Background Low gamma-aminobutyric acid (GABA) is implicated in both anxiety and depression pathophysiology. They are often comorbid, but most clinical studies have not examined these relationships separately. We investigated the relationship of cerebrospinal fluid (CSF) free GABA to the anxiety and depression components of a major depressive episode (MDE) and to monoamine systems. Methods and Materials Patients with a DSM-IV major depressive episode (N = 167: 130 major depressive disorder; 37 bipolar disorder) and healthy volunteers (N = 38) had CSF free GABA measured by gas chromatography mass spectroscopy. Monoamine metabolites were assayed by high performance liquid chromatography. Symptomatology was assessed by Hamilton depression rating scale. Results Psychic anxiety severity increased with age and correlated with lower CSF free GABA, controlling for age. CSF free GABA declined with age but was not related to depression severity. Other monoamine metabolites correlated positively with CSF GABA but not with psychic anxiety or depression severity. CSF free GABA was lower in MDD compared with bipolar disorder and healthy volunteers. GABA levels did not differ based on a suicide attempt history in mood disorders. Recent exposure to benzodiazepines, but not alcohol or past alcoholism, was associated with a statistical trend for more severe anxiety and lower CSF GABA. Conclusions Lower CSF GABA may explain increasing severity of psychic anxiety in major depression with increasing age. This relationship is not seen with monoamine metabolites, suggesting treatments targeting the GABAergic system should be evaluated in treatment-resistant anxious major depression and in older patients. PMID:24865448

Ursolic acid in health and disease.

PubMed

Seo, Dae Yun; Lee, Sung Ryul; Heo, Jun-Won; No, Mi-Hyun; Rhee, Byoung Doo; Ko, Kyung Soo; Kwak, Hyo-Bum; Han, Jin

2018-05-01

Ursolic acid (UA) is a natural triterpene compound found in various fruits and vegetables. There is a growing interest in UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects. It exerts these effects in various tissues and organs: by suppressing nuclear factor-kappa B signaling in cancer cells, improving insulin signaling in adipose tissues, reducing the expression of markers of cardiac damage in the heart, decreasing inflammation and increasing the level of anti-oxidants in the brain, reducing apoptotic signaling and the level of oxidants in the liver, and reducing atrophy and increasing the expression levels of adenosine monophosphate-activated protein kinase and irisin in skeletal muscles. Moreover, UA can be used as an alternative medicine for the treatment and prevention of cancer, obesity/diabetes, cardiovascular disease, brain disease, liver disease, and muscle wasting (sarcopenia). In this review, we have summarized recent data on the beneficial effects and possible uses of UA in health and disease managements.

Molecular Mechanisms for Sweet-suppressing Effect of Gymnemic Acids*

PubMed Central

Sanematsu, Keisuke; Kusakabe, Yuko; Shigemura, Noriatsu; Hirokawa, Takatsugu; Nakamura, Seiji; Imoto, Toshiaki; Ninomiya, Yuzo

2014-01-01

Gymnemic acids are triterpene glycosides that selectively suppress taste responses to various sweet substances in humans but not in mice. This sweet-suppressing effect of gymnemic acids is diminished by rinsing the tongue with γ-cyclodextrin (γ-CD). However, little is known about the molecular mechanisms underlying the sweet-suppressing effect of gymnemic acids and the interaction between gymnemic acids versus sweet taste receptor and/or γ-CD. To investigate whether gymnemic acids directly interact with human (h) sweet receptor hT1R2 + hT1R3, we used the sweet receptor T1R2 + T1R3 assay in transiently transfected HEK293 cells. Similar to previous studies in humans and mice, gymnemic acids (100 μg/ml) inhibited the [Ca2+]i responses to sweet compounds in HEK293 cells heterologously expressing hT1R2 + hT1R3 but not in those expressing the mouse (m) sweet receptor mT1R2 + mT1R3. The effect of gymnemic acids rapidly disappeared after rinsing the HEK293 cells with γ-CD. Using mixed species pairings of human and mouse sweet receptor subunits and chimeras, we determined that the transmembrane domain of hT1R3 was mainly required for the sweet-suppressing effect of gymnemic acids. Directed mutagenesis in the transmembrane domain of hT1R3 revealed that the interaction site for gymnemic acids shared the amino acid residues that determined the sensitivity to another sweet antagonist, lactisole. Glucuronic acid, which is the common structure of gymnemic acids, also reduced sensitivity to sweet compounds. In our models, gymnemic acids were predicted to dock to a binding pocket within the transmembrane domain of hT1R3. PMID:25056955

Tannins and terpenoids as major precursors of Suwannee River fulvic acid

USGS Publications Warehouse

Leenheer, Jerry A.; Rostad, Colleen E.

2004-01-01

Suwannee River fulvic acid (SRFA) was fractionated into 7 fractions by normal-phase chromatography on silica gel followed by reverse-phase fractionation on XAD-8 resin that produced 18 subfractions. Selected major subfractions were characterized by 13C-nuclear magnetic resonance (NMR), infrared spectrometry, and elemental analyses. 13C-NMR spectra of the subfractions were more indicative of precursor structures than unfractionated SRFA, and gave spectral profiles that indicated SRFA mass was about equally split between tannin precursors and terpenoid precursors. Lignin precursors were minor components. Synthesis of 13C-NMR data with elemental data for subfractions derived from both tannin and terpenoid precursors revealed high ring contents and low numbers of carbon per rings which is indicative of fused ring structures that are extensively substituted with carboxyl and methyl groups. These results ruled out extended chain structures for SRFA. This information is useful for determining sources and properties of fulvic acid in drinking water supplies as tannins are more reactive with chlorine to produce undesirable disinfection by-products than are terpenoids.

Novel and unusual triterpene from Black Cohosh. Determination of structure of 9,10-seco-9,19-cyclolanostane xyloside (cimipodocarpaside) by NMR, IR and Raman spectroscopy and DFT calculations.

PubMed

Jamróz, Marta K; Jamróz, Michał H; Dobrowolski, Jan Cz; Gliński, Jan A; Davey, Matthew H; Wawer, Iwona

2011-01-01

A new triterpene xyloside, designated cimipodocarpaside was isolated from a Black Cohosh (Actea racemosa L.) extract and its structure was elucidated by means of 1H, 13C NMR, IR and Raman spectroscopy supported by B3LYP/6-31G** calculations. The vibrational spectra were interpreted using the PED analysis of 273 fundamentals. Its structure comprises four condensed rings A-D which are 6, 7, 6, and 5-membered, respectively. An oxiirane ring is located in the side chain and a xylose moiety is attached to the A-ring. Comparison of the experimental 13C NMR data with the theoretical chemical shifts of 24S- and 24R-cimipodocarpaside isomers revealed that the isolated compound has the 24S-configuration. Combined spectroscopic and computational studies enabled the determination of the structure of cimipodocarpaside as (24S)-3β-hydroxy-24,25-oxiirane-16,23-dione-9,10-seco-9,19-cyclolanost-7(8),9(11),10(19)-trien-3-O-β-D-xylopyranoside. Triterpenes with 7-membered ring were thus far isolated from only Actea podocarpa DC. plants. This is the first report on the isolation of such a compound from Black Cohosh. Copyright © 2010 Elsevier B.V. All rights reserved.

An Overview of Structurally Modified Glycyrrhetinic Acid Derivatives as Antitumor Agents.

PubMed

Xu, Bing; Wu, Gao-Rong; Zhang, Xin-Yu; Yan, Meng-Meng; Zhao, Rui; Xue, Nan-Nan; Fang, Kang; Wang, Hui; Chen, Meng; Guo, Wen-Bo; Wang, Peng-Long; Lei, Hai-Min

2017-06-02

Glycyrrhetinic Acid ( GA ), a triterpenoid aglycone component of the natural product glycyrrhizinic acid, was found to possess remarkable anti-proliferative and apoptosis-inducing activity in various cancer cell lines. Though GA was not as active as other triterpenes, such as betulinic acid and oleanolic acid, it could trigger apoptosis in tumor cells and it can be obtained easily and cheaply, which has stimulated scientific interest in using GA as a scaffold to synthesize new antitumor agents. The structural modifications of GA reported in recent decades can be divided into four groups, which include structural modifications on ring-A, ring-C, ring-E and multiple ring modifications. The lack of a comprehensive and recent review on this topic prompted us to gather more new information. This overview is dedicated to summarizing and updating the structural modification of GA to improve its antitumor activity published between 2005 and 2016. We reviewed a total of 210 GA derivatives that we encountered and compiled the most active GA derivatives along with their activity profile in different series. Furthermore, the structure activity relationships of these derivatives are briefly discussed. The included information is expected to be of benefit to further studies of structural modifications of GA to enhance its antitumor activity.

Triterpene derivatives as inhibitors of protein involved in the inflammatory process: molecules interfering with phospholipase A2, cycloxygenase, and lipoxygenase.

PubMed

Braca, Alessandra; Dal Piaz, Fabrizio; Marzocco, Stefania; Autore, Giuseppina; Vassallo, Antonio; De Tommasi, Nunziatina

2011-03-01

Over the past years, there was an explosion in the knowledge of the protein target and molecular mechanism associated with various disease types and in the new research of drugs of natural origin. The key idea is to evaluate bioactive natural products interacting with protein domains of different genetic origin but structurally preserved to develop libraries of compounds biologically validated and selected from an evolutionistic point of view. Compared with synthetic compounds, natural products have a major number of unused scaffolds and not comparable to the libraries of synthetic compounds, and could represent a promising starting points for the discovery of new bioactive compounds. Many natural products are reported to interact with proteins involved in serious diseases, such as inflammation and cancer. Recently various chemical classes of plant secondary metabolites have emerged as potential therapeutic compounds in several inflammatory diseases. Owing to the findings that triterpenoids, a common class of plant secondary metabolites, have anti-inflammatory and anti-cancer effects on humans, the interest in their potential application in human health and disease is increasing. The present review describes anti-inflammatory triterpenes derivatives from plant and fungi reported during the last two decades in order to provide an account of this field of investigation, sorting compounds according to their targets, phospholipase A(2) (PLA(2)), cycloxygenase (COX), and lipoxygenase (LOX). The attempt is also being made to enumerate the possible leads for further synthetic and drug discovery program development.

13C CPMAS NMR studies and DFT calculations of triterpene xylosides isolated from Actaea racemosa

NASA Astrophysics Data System (ADS)

Jamróz, Marta K.; Paradowska, Katarzyna; Gliński, Jan A.; Wawer, Iwona

2011-05-01

13C CPMAS NMR spectra of four triterpene glycosides: cimigenol xyloside ( 1), 26-deoxyactein ( 2), cimicifugoside H-1 ( 3) and 24-acethylhydroshengmanol xyloside ( 4) were recorded and analyzed to characterize their solid-state structure. Experimental data were supported by theoretical calculations of NMR shielding constants with the GIAO/6-31G**-su1 approach. A number of methods for the conformational search and a number of functionals for the DFT calculations were applied to ( 1). The best method was proven to be MMFF or MMFFAQ for the conformational search and the PBE1PBE functional for the DFT calculations. Extra calculations simulating C16 dbnd O⋯HOH hydrogen bond yield the isotropic shielding closer to the experimental solid-state value. For all the compounds CP kinetics parameters were calculated using either the I-S or the I-I*-S model. The analysis of CP kinetics data for methyl groups revealed differences in the T2 time constant for two methyl groups (C29 and C30) linked at C4.

The position of the acid pocket as a major risk factor for acidic reflux in healthy subjects and patients with GORD.

PubMed

Beaumont, Hanneke; Bennink, Roelof J; de Jong, Jan; Boeckxstaens, Guy E

2010-04-01

Gastro-oesophageal reflux occurs twice as much during transient lower oesophageal sphincter relaxations (TLOSRs) in patients with gastro-oesophageal reflux disease (GORD) compared to healthy volunteers (HVs). Our aim was to assess whether the localisation of the postprandial acid pocket and its interaction with a hiatal hernia (HH) play a role in the occurrence of acidic reflux during TLOSRs. Ten HVs and 22 patients with GORD (12 with HH<3 cm (s-HH), 10 with HH > or =3 cm (l-HH)) were studied. The squamocolumnar junction and diaphragmatic impression were marked with a radioactively labelled clip. To visualise the acid pocket, (99m)Tc-pertechnetate was injected intravenously and images were acquired up to 2 h postprandial. Concurrently, combined manometry/impedance and four-channel pH-metry were performed, with pH pull-through at multiple time-points. The rate of TLOSRs and the per cent associated with reflux was comparable between all groups. However, acidic reflux was significantly increased in patients, especially in patients with l-HH. Acid pocket length was significantly enlarged in patients. Moreover, immediately before a TLOSR, the acid pocket was more frequently located within the hiatus or above the diaphragm in patients with GORD (s-HH, 54%; l-HH, 77%) compared to HVs (22% of TLOSRs). Acidic reflux was significantly increased when the acid pocket was located above the diaphragm in all groups compared to a sub-diaphragmatic localisation. The position of the acid pocket is largely determined by the presence of a HH. Entrapment of the pocket above the diaphragm, especially in patients with l-HH, is a major risk factor underlying the increased occurrence of acidic reflux during a TLOSR in patients with GORD.

An economical approach for d-lactic acid production utilizing unpolished rice from aging paddy as major nutrient source.

PubMed

Lu, Zhengdong; Lu, Mingbo; He, Feng; Yu, Longjiang

2009-03-01

In order to reduce the raw material cost of d-lactic acid fermentation, the unpolished rice from aging paddy was used as major nutrient source in this study. The unpolished rice saccharificate, wheat bran powder and yeast extract were employed as carbon source, nitrogen source and growth factors, respectively. Response surface methodology (RSM) was applied to optimize the dosages of medium compositions. As a result, when the fermentation was carried out under the optimal conditions for wheat bran powder (29.10g/l) and yeast extract (2.50g/l), the d-lactic acid yield reached 731.50g/kg unpolished rice with a volumetric production rate of 1.50g/(lh). In comparison with fresh corn and polished rice, the d-lactic acid yield increased by 5.79% and 8.71%, and the raw material cost decreased by 65% and 52%, respectively, when the unpolished rice was used as a major nutrient source. These results might provide a reference for the industrial production of d-lactic acid.

Anti-Gastric Ulcer Effect of Betulinic Acid in Male Albino Rats.

PubMed

Onwuchekwa, C; Oluwole, F S

2015-12-20

Betulinic acid (BA) is a lupane-type triterpene that has been identified and isolated from various plant species used in ethnomedicine in various cultures across the world. This study was undertaken to elucidate the mechanisms underlying the anti-ulcer effect of Betulinic acid. The effect of BA on indomethacin-induced ulcer, gastric mucus secretion, gastric mucus cells count, basal and histamine-induced gastric acid secretion and levels of malondialdehyde formation were studied using dose of 0.5, 1.5, and 3.0 mg/kg. The results showed that BA reduced indomethacin-induced ulceration significantly and significantly increased  gastric mucus secretion in the 1.5 mg/kg and 3.0 mg/kg BA treated rats compared to the control rats. There was a significant increase  in the mucus cells count in all the treated groups which is in a dose- dependent manner compared to the control group. There was significant decrease  in gastric acid secretion in each of the BA treated groups compared to the control. Malondialdehyde concentration significantly decrease in all the treated groups compared to the control. The anti-gastric ulcer effect of BA may be mediated via decreasing gastric acid secretion, increasing gastric mucus secretions, increasing the number of gastric mucus cells and also by reducing the level of MDA concentration.

Associations between Proportion of Plasma Phospholipid Fatty Acids, Depressive Symptoms and Major Depressive Disorder. Cross-Sectional Analyses from the AGES Reykjavik Study.

PubMed

Imai, C M; Halldorsson, T I; Aspelund, T; Eiriksdottir, G; Launer, L J; Thorsdottir, I; Harris, T B; Gudnason, V; Brouwer, I A; Gunnarsdottir, I

2018-01-01

Deficits in n-3 fatty acids may be associated with depression. However, data are scarce from older adults who are at greater risk of poor dietary intake and of developing depression. To investigate proportion of plasma phospholipid fatty acids with respect to depressive symptoms and major depressive disorder in community dwelling older adults. Cross-sectional analyses of 1571 participants in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study aged 67-93 years. Depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS-15). Major depressive disorder was assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria using the Mini-International Neuropsychiatric Interview (MINI). Depressive symptoms were observed in 195 (12.4%) subjects and there were 27 (1.7%) cases of major depressive disorder. Participants with depressive symptoms were less educated, more likely to be smokers, less physically active and consumed cod liver oil less frequently. Difference in GDS-15 scores by tertiles of n-3 fatty acid proportion was not significant. Proportion of long chain n-3 fatty acids (Eicosapentaenoic- + Docosahexaenoic acid) were inversely related to major depressive disorder, (tertile 2 vs. tertile 1) OR: 0.31 (95% CI: 0.11, 0.86); tertile 3 vs. tertile 1, OR: 0.45 (95% CI: 0.17, 1.21). In our cross sectional analyses low proportions of long chain n-3 fatty acids in plasma phospholipids appear to be associated with increased risk of major depressive disorder. However, the results from this study warrant further investigation in prospective setting with sufficiently long follow-up.

Fatty acid composition of the postmortem prefrontal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Hamazaki, Kei; Maekawa, Motoko; Toyota, Tomoko; Dean, Brian; Hamazaki, Tomohito; Yoshikawa, Takeo

2015-06-30

Postmortem brain studies have shown abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, in the frontal cortex (particularly the orbitofrontal cortex) of patients with depression, schizophrenia, or bipolar disorder. However, the results from regions in the frontal cortex other than the orbitofrontal cortex are inconsistent. In this study we investigated whether patients with schizophrenia, bipolar disorder, or major depressive disorder have abnormalities in PUFA levels in the prefrontal cortex [Brodmann area (BA) 8]. In postmortem studies, fatty acids in the phospholipids of the prefrontal cortex (BA8) were evaluated by thin layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). In contrast to previous studies, we found no significant differences in the levels of PUFAs or other fatty acids in the prefrontal cortex (BA8) between patients and controls. Subanalysis by sex also showed no significant differences. No significant differences were found in any individual fatty acids between suicide and non-suicide cases. These psychiatric disorders might be characterized by very specific fatty acid compositions in certain areas of the brain, and BA8 might not be involved in abnormalities of PUFA metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ultrasound-assisted Extraction of Ursolic Acid from the Flowers of Ixora coccinia Linn (Rubiaceae) and Antiproliferative Activity of Ursolic Acid and Synthesized Derivatives

PubMed Central

Alves Monteath, Silvana Amadeu Ferreira; Maciel, Maria Aparecida M.; Vega, Raquel Garcia; de Mello, Heloisa; de Araújo Martins, Carollina; Esteves-Souza, Andressa; Gattass, Cerli Rocha; Echevarria, Aurea

2017-01-01

Background: Ixora coccinea Linn (Rubiaceae) is an evergreen shrub with bright scarlet colored flowers found in several tropical and subtropical countries. It is used as an ornamental and medicinal plant. Phytochemical studies revealed that its major special metabolites are triterpene acids, such as ursolic and oleanolic acid. Objective: To evaluate the isolation of ursolic acid (UA) (1) from methanol extracts of I. coccinea flowers through two methodologies, to prepare four derivatives, and to evaluate the cytotoxic effect against six cancer cell lines. Materials and Methods: The UA was isolated from vegetal material by percolation at room temperature and by ultrasound-assisted extraction. The preparation of derivatives was performed according to literature methods, and the cytotoxic effects were evaluated using the MTT (3,4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) assay. Results: The most efficient extraction was achieved through ultrasound irradiation with a yield of 35% after KOH-impregnated silica in chromatography column. Furthermore, four derivatives (3, 5, 6, 7) of UA were prepared and evaluated, including 1, against two lung cancer (A549 and H460) and four leukemia (K562, Lucena, HL60, and Jurkat) cell lines. Generally, results showed that 1 and 7 were the most active compounds against the assayed cell lines. Also, the cytotoxic effects observed on terpenes 1 and 7 were higher when compared with cisplatin, used as positive control, with the exception of Jurkat cell line. Conclusion: The efficiency of such an alternative extraction method led to the principal and abundant active component, 1, of I. coccinea, thus representing a considerable contribution for promising triterpenoid in cancer chemotherapy. SUMMARY The ultrasound-assisted extraction of Ixora coccinea flowers improved of the ursolic acid isolationMethanolic extract from flowers of I. coccinea provided, by ultrasound irradiation, after KOH-impregnated silica in chromatography column

Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain

PubMed Central

Chen, Chuck T.; Kitson, Alex P.; Hopperton, Kathryn E.; Domenichiello, Anthony F.; Trépanier, Marc-Olivier; Lin, Lauren E.; Ermini, Leonardo; Post, Martin; Thies, Frank; Bazinet, Richard P.

2015-01-01

Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to the brain are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate that DHA uptake from the plasma non-esterified fatty acid (NEFA) pool predicts brain uptake of DHA upon oral administration, which enters the plasma NEFA pool as well as multiple plasma esterified pools. The rate of DHA loss by the brain is similar to the uptake from the plasma NEFA pool. Furthermore, upon acute iv administration, although more radiolabeled lysophosphatidylcholine (LPC)-DHA enters the brain than NEFA-DHA, this is due to the longer plasma half-life and exposure to the brain. Direct comparison of the uptake rate of LPC-DHA and NEFA-DHA demonstrates that uptake of NEFA-DHA into the brain is 10-fold greater than LPC-DHA. In conclusion, plasma NEFA-DHA is the major plasma pool supplying the brain. PMID:26511533

Amino acids rather than glucose account for the majority of cell mass in proliferating mammalian cells

PubMed Central

Hosios, Aaron M.; Hecht, Vivian C.; Danai, Laura V.; Johnson, Marc O.; Rathmell, Jeffrey C.; Steinhauser, Matthew L.; Manalis, Scott R.; Vander Heiden, Matthew G.

2016-01-01

Cells must duplicate their mass in order to proliferate. Glucose and glutamine are the major nutrients consumed by proliferating mammalian cells, but the extent to which these and other nutrients contribute to cell mass is unknown. We quantified the fraction of cell mass derived from different nutrients and find that the majority of carbon mass in cells is derived from other amino acids, which are consumed at much lower rates than glucose and glutamine. While glucose carbon has diverse fates, glutamine contributes most to protein, and this suggests that glutamine’s ability to replenish TCA cycle intermediates (anaplerosis) is primarily used for amino acid biosynthesis. These findings demonstrate that rates of nutrient consumption are indirectly associated with mass accumulation and suggest that high rates of glucose and glutamine consumption support rapid cell proliferation beyond providing carbon for biosynthesis. PMID:26954548

Investigation of cytochrome P450 inhibitory properties of maslinic acid, a bioactive compound from Olea europaea L., and its structure-activity relationship.

PubMed

Sun, Min; Tang, Yu; Ding, Tonggui; Liu, Mingyao; Wang, Xin

2015-01-15

Maslinic acid (MA), the main pentacyclic triterpene of Olea europaea L. fruit, possesses a variety of pharmacological actions, including hypoglycemic, antioxidant, cardioprotective and antitumoral activities. Despite its importance, little is known about its effects on the cytochrome P450 (CYP) activity in both humans and animals. Therefore, the aim of this study was to investigate the effects of MA on the CYP 1A2, 2C9/11, 2D1/6, 2E1 and 3A2/4 activities by human and rat liver microsomes and specific CYP isoforms. In humans, MA only weakly inhibited CYP3A4 activity in human liver microsomes and specific CYP3A4 isoform with IC50 value at 46.1 and 62.3µM, respectively. In rats, MA also exhibited weak inhibition on CYP2C11, CYP2E1 and CYP3A2 activities with IC50 values more than 100µM. Enzyme kinetic studies showed that the MA was not only a competitive inhibitor of CYP3A4 in humans, but also a competitive inhibitor of CYP2C11 and 3A2 in rats, with Ki of 18.4, 98.7 and 66.3µM, respectively. Moreover, the presence of hydroxyl group at C-2 position of triterpenic acid in MA compared with oleanolic acid could magnify its competitive inhibition on human CYP3A4 activity. The relatively high Ki values of MA would have a low potential to cause the possible toxicity and drug interactions involving CYP enzymes, thus suggesting a sufficient safety for its putative use as a nutraceutical taken together with drugs. Copyright © 2014 Elsevier GmbH. All rights reserved.

Plasma Phosphatidylethanolamine and Triacylglycerol Fatty Acid Concentrations are Altered in Major Depressive Disorder Patients with Seasonal Pattern.

PubMed

Otoki, Yurika; Hennebelle, Marie; Levitt, Anthony J; Nakagawa, Kiyotaka; Swardfager, Walter; Taha, Ameer Y

2017-06-01

Disturbances in peripheral and brain lipid metabolism, including the omega-3 fatty acid docosahexaenoic acid (DHA), have been reported in major depressive disorder (MDD). However, these changes have yet to be confirmed in MDD with seasonal pattern (MDD-s), a subtype of recurrent MDD. The present exploratory study quantified plasma plasmalogen and diacyl-phospholipid species, and fatty acids within total phospholipids, cholesteryl esters, triacylglycerols and free fatty acids in non-medicated MDD-s participants (n = 9) during euthymia in summer or fall, and during depression in winter in order to screen for potential high sensitivity lipid biomarkers. Triacylglycerol alpha-linolenic acid concentration was significantly decreased, and myristoleic acid concentration was significantly increased, during winter depression compared to summer-fall euthymia. 1-stearyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine, a diacyl-phospholipid containing stearic acid and DHA, was significantly decreased in winter depression. Concentrations of cholesteryl ester oleic acid and several polyunsaturated fatty acids between summer/fall and winter increased in proportion to the increase in depressive symptoms. The observed changes in lipid metabolic pathways in winter-type MDD-s offer new promise for lipid biomarker development.

Metabolic profiling of roots of liquorice (Glycyrrhiza glabra) from different geographical areas by ESI/MS/MS and determination of major metabolites by LC-ESI/MS and LC-ESI/MS/MS.

PubMed

Montoro, Paola; Maldini, Mariateresa; Russo, Mariateresa; Postorino, Santo; Piacente, Sonia; Pizza, Cosimo

2011-02-20

Liquid chromatography electrospray mass spectrometry (LC-ESI/MS) has been applied to the full characterization of saponins and phenolics in hydroalcoholic extracts of roots of liquorice (Glycyrrhiza glabra). Relative quantitative analyses of the samples with respect to the phenolic constituents and to a group of saponins related to glycyrrhizic acid were performed using LC-ESI/MS. For the saponin constituents, full scan LC-MS/MS fragmentation of the protonated (positive ion mode) or deprotonated (negative ion mode) molecular species generated diagnostic fragment ions that provided information concerning the triterpene skeleton and the number and nature of the substituents. On the basis of the specific fragmentation of glycyrrhizic acid, an LC-MS/MS method was developed in order to quantify the analyte in the liquorice root samples. Chinese G. glabra roots contained the highest levels of glycyrrhizic acid, followed by those from Italy (Calabria). Copyright © 2010 Elsevier B.V. All rights reserved.

Ursolic acid isolated from Uncaria rhynchophylla activates human dendritic cells via TLR2 and/or TLR4 and induces the production of IFN-gamma by CD4+ naïve T cells.

PubMed

Jung, Tae-Young; Pham, Thanh Nhan Nguyen; Umeyama, Akemi; Shoji, Noboru; Hashimoto, Toshihiro; Lee, Je-Jung; Takei, Masao

2010-09-25

Ursolic acid is triterpene isolated from Uncaria rhynchophylla and is a pharmacologically active substance. The induction of dendritic cell maturation is critical for the induction of Ag-specific T-lymphocyte response and may be essential for the development of human vaccine relying on T cell immunity. In this study, we investigated that the effect of Ursolic acid on the phenotypic and functional maturation of human monocyte-derived dendritic cells in vitro. Dendritic cells harvested on day 8 were examined using functional assay. The expression levels of CD1a, CD80, CD83, CD86, HLA-DR and CCR7 on Ursolic acid-primed dendritic cells was slightly enhanced. Ursolic acid dose-dependently enhanced the T cell stimulatory capacity in an allogeneic mixed lymphocyte reaction, as measured by T cell proliferation. The production of IL-12p70 induced by Ursolic acid-primed dendritic cells was inhibited by the anti-Toll-like receptor-2 (TLR2) mAb and anti-TLR4 mAb. Moreover, Ursolic acid-primed dendritic cells expressed levels of mRNA coding for both TLR2 and TLR4. The majority of cells produced considerable interferon-gamma (IFN-gamma), but also small amounts of interleukin (IL-4)-4. Ursolic acid-primed dendritic cells have an intermediate migratory capacity towards CCL19 and CCL21. These results suggest that Ursolic acid modulates human dendritic cells function in a fashion that favors Th1 polarization via the activation of IL-12p70 dependent on TLR2 and/or TLR4, and may be used on dendritic cells-based vaccines for cancer immunotherapy. 2010 Elsevier B.V. All rights reserved.

Quantitative analysis of acylated oleanane-type triterpene saponins, chakasaponins I-III and floratheasaponins A-F, in the flower buds of Camellia sinensis from different regional origins.

PubMed

Morikawa, Toshio; Miyake, Sohachiro; Miki, Yoshinobu; Ninomiya, Kiyofumi; Yoshikawa, Masayuki; Muraoka, Osamu

2012-10-01

A quantitative analytical method was developed for the determination of acylated oleanane-type triterpene saponins, chakasaponins I-III (1-3) and floratheasaponins A-F (4-9), found in Camellia sinensis (Theaceae). The practical conditions for separation and detection of these saponins were established on an ODS column with methanol containing 5 mM trifluoroacetic acid as a mobile phase, and the detection and quantitation limits of the method were estimated to be 1.1-3.8 and 3.5-12.5 ng, respectively. The relative standard deviation values of intra- and interday precision were lower than 2.35 and 6.12%, respectively, overall mean recoveries of all saponins being 94.7-108.8%, and the correlation coefficients of all the calibration curves showed good linearity within the test ranges. To approve the validity of the protocol, extracts of 13 kinds of C. sinensis collected in China, Taiwan, Japan, and India were evaluated. The results indicated that the assay was reproducible and precise, and could be readily utilized for the quality evaluation of tea flowers. It was noteworthy that the distinct regional difference was observed with respect to the content of chakasaponins and floratheasaponins, more chakasaponins being contained in the extracts of tea flowers from Fujian and Sichuan provinces, China than those from Japan, Taiwan, and India. Optimum conditions for the extraction process were also established.

Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers.

PubMed

Qiang, Zhiyi; Ye, Zhong; Hauck, Cathy; Murphy, Patricia A; McCoy, Joe-Ann; Widrlechner, Mark P; Reddy, Manju B; Hendrich, Suzanne

2011-10-11

Rosmarinic acid (RA), a caffeic acid-related compound found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be beneficial for gastrointestinal health in general. To investigate the permeabilities of RA and UA as pure compounds and in Prunella vulgaris and Salvia officinalis ethanol extracts across human intestinal epithelial Caco-2 cell monolayers. The permeabilities and phase II biotransformation of RA and UA as pure compounds and in herbal extracts were compared using Caco-2 cells with HPLC detection. The apparent permeability coefficient (P(app)) for RA and RA in Prunella vulgaris extracts was 0.2 ± 0.05 × 10(-6)cm/s, significantly increased to 0.9 ± 0.2 × 10(-6)cm/s after β-glucuronidase/sulfatase treatment. P(app) for UA and UA in Salvia officinalis extract was 2.7 ± 0.3 × 10(-6)cm/s and 2.3 ± 0.5 × 10(-6)cm/s before and after β-glucuronidase/sulfatase treatment, respectively. Neither compound was affected in permeability by the herbal extract matrix. RA and UA in herbal extracts had similar uptake as that found using the pure compounds, which may simplify the prediction of compound efficacy, but the apparent lack of intestinal glucuronidation/sulfation of UA is likely to further enhance the bioavailability of that compound compared with RA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Permeability of Rosmarinic acid in Prunella vulgaris and Ursolic acid in Salvia officinalis Extracts across Caco-2 Cell Monolayers

PubMed Central

Qiang, Zhiyi; Ye, Zhong; Hauck, Cathy; Murphy, Patricia A.; McCoy, Joe-Ann; Widrlechner, Mark P.; Reddy, Manju B.; Hendrich, Suzanne

2011-01-01

Ethnopharmacological relevance Rosmarinic acid (RA), a caffeic acid-related compound found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be beneficial for gastrointestinal health in general. Aim of the study To investigate the permeabilities of RA and UA as pure compounds and in P. vulgaris and S. officinalis ethanol extracts across human intestinal epithelial Caco-2 cell monolayers. Materials and methods The permeabilities and Phase II biotransformation of RA and UA as pure compounds and in herbal extracts were compared using Caco-2 cells with HPLC detection. Results The apparent permeability coefficient (Papp) for RA and RA in P. vulgaris extracts was 0.2 ± 0.05 × 10−6 cm/s, significantly increased to 0.9 ± 0.2 × 10−6 cm/s after β-glucuronidase/sulfatase treatment. Papp for UA and UA in S. officinalis extract was 2.7 ± 0.3 × 10−6 cm/s and 2.3 ± 0.5 × 10−6 cm/s before and after β-glucuronidase/sulfatase treatment, respectively. Neither compound was affected in permeability by the herbal extract matrix. Conclusion RA and UA in herbal extracts had similar uptake as that found using the pure compounds, which may simplify the prediction of compound efficacy, but the apparent lack of intestinal glucuronidation/sulfation of UA is likely to further enhance the bioavailability of that compound compared with RA. PMID:21798330

Proteomic analysis of the molecular response of Raji cells to maslinic acid treatment.

PubMed

Yap, W H; Khoo, K S; Lim, S H; Yeo, C C; Lim, Y M

2012-01-15

Maslinic acid, a natural pentacyclic triterpene has been shown to inhibit growth and induce apoptosis in some tumour cell lines. We studied the molecular response of Raji cells towards maslinic acid treatment. A proteomics approach was employed to identify the target proteins. Seventeen differentially expressed proteins including those involved in DNA replication, microtubule filament assembly, nucleo-cytoplasmic trafficking, cell signaling, energy metabolism and cytoskeletal organization were identified by MALDI TOF-TOF MS. The down-regulation of stathmin, Ran GTPase activating protein-1 (RanBP1), and microtubule associated protein RP/EB family member 1 (EB1) were confirmed by Western blotting. The study of the effect of maslinic acid on Raji cell cycle regulation showed that it induced a G1 cell cycle arrest. The differential proteomic changes in maslinic acid-treated Raji cells demonstrated that it also inhibited expression of dUTPase and stathmin which are known to induce early S and G2 cell cycle arrests. The mechanism of maslinic acid-induced cell cycle arrest may be mediated by inhibiting cyclin D1 expression and enhancing the levels of cell cycle-dependent kinase (CDK) inhibitor p21 protein. Maslinic acid suppressed nuclear factor-kappa B (NF-κB) activity which is known to stimulate expression of anti-apoptotic and cell cycle regulatory gene products. These results suggest that maslinic acid affects multiple signaling molecules and inhibits fundamental pathways regulating cell growth and survival in Raji cells. Copyright © 2011 Elsevier GmbH. All rights reserved.

Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial.

PubMed

Smith, Deidre J; Sarris, Jerome; Dowling, Nathan; O'Connor, Manjula; Ng, Chee H

2018-04-01

Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD). A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted. Primary outcomes of depression, clinical severity, and daytime sleepiness were measured. After 8 weeks, 54% of patients had a ≥50% reduction on the HAM-D, and 45% were in remission (HAM-D ≤ 7). The eta-squared statistic (0.59) indicated a large effect size for the reduction of depression (equivalent to Cohen's d of 2.4). However confidence in this effect size is tempered due to the lack of a placebo. The mean score for the Clinical Global Impression Severity Scale was significantly improved by 1.28 points (P < 0.05). Despite a significant reduction in the HAM-D score for middle insomnia (P = 0.02), the reduction in excessive daytime somnolence on the total Epworth Sleepiness Scale (ESS) did not reach significance. No significant adverse reactions to DHA were found. Within the major limits of this open-label pilot study, the results suggest that DHA may provide additional adjunctive benefits in patients with mild- to -moderate depression.

Sources and formation processes of water-soluble dicarboxylic acids, ω-oxocarboxylic acids, α-dicarbonyls, and major ions in summer aerosols from eastern central India

NASA Astrophysics Data System (ADS)

Deshmukh, Dhananjay K.; Kawamura, Kimitaka; Deb, Manas K.; Boreddy, Suresh K. R.

2017-03-01

The sources and formation processes of dicarboxylic acids are still under investigation. Size-segregated aerosol (nine-size) samples collected in the urban site (Raipur: 21.2°N and 82.3°E) in eastern central India during summer of 2013 were measured for water-soluble diacids (C2-C12), ω-oxoacids (ωC2-ωC9), α-dicarbonyls (C2-C3), and inorganic ions to better understand their sources and formation processes. Diacids showed the predominance of oxalic acid (C2), whereas ω-oxoacids showed the predominance of glyoxylic acid (ωC2), and glyoxal (Gly) was a major α-dicarbonyl in all the sizes. Diacids, ω-oxoacids, and α-dicarbonyls as well as SO42

Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer

PubMed Central

Gai, Wen-Tao; Yu, Da-Peng; Wang, Xin-Sheng; Wang, Pei-Tao

2016-01-01

Ursolic acid is a type of pentacyclic triterpene compound with multiple pharmacological activities including cancer resistance, protection from liver injury, antisepsis, anti-inflammation and antiviral activity. The present study aimed to investigate the anticancer effect of ursolic acid. Ursolic acid activates cell apoptosis and its pro-apoptotic mechanism remains to be fully elucidated. Cell Counting kit-8 assays, flow cytometric analysis and analysis of caspase-3 and caspase-9 activity were used to estimate the anticancer effect of ursolic acid on DU145 prostate cancer cells. The protein expression of cytochrome c, rho-associated protein kinase (ROCK), phosphatase and tensin homolog (PTEN) and cofilin-1 were examined using western blot analysis. In the present study, ursolic acid significantly suppressed cell growth and induced apoptosis, as well as increasing caspase-3 and caspase-9 activities of DU145 cells. Furthermore, cytoplasmic and mitochondrial cytochrome c protein expression was significantly activated and suppressed, respectively, by ursolic acid. Ursolic acid significantly suppressed the ROCK/PTEN signaling pathway and inhibited cofilin-1 protein expression in DU145 cells. The results of the present study indicate that the anticancer effect of ursolic acid activates cell apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer. PMID:27698874

Ursolic acid in health and disease

PubMed Central

Seo, Dae Yun; Lee, Sung Ryul; Heo, Jun-Won; No, Mi-Hyun; Rhee, Byoung Doo; Ko, Kyung Soo

2018-01-01

Ursolic acid (UA) is a natural triterpene compound found in various fruits and vegetables. There is a growing interest in UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects. It exerts these effects in various tissues and organs: by suppressing nuclear factor-kappa B signaling in cancer cells, improving insulin signaling in adipose tissues, reducing the expression of markers of cardiac damage in the heart, decreasing inflammation and increasing the level of anti-oxidants in the brain, reducing apoptotic signaling and the level of oxidants in the liver, and reducing atrophy and increasing the expression levels of adenosine monophosphate-activated protein kinase and irisin in skeletal muscles. Moreover, UA can be used as an alternative medicine for the treatment and prevention of cancer, obesity/diabetes, cardiovascular disease, brain disease, liver disease, and muscle wasting (sarcopenia). In this review, we have summarized recent data on the beneficial effects and possible uses of UA in health and disease managements. PMID:29719446

Chemical constituents of gold-red apple and their α-glucosidase inhibitory activities.

PubMed

He, Qian-Qian; Yang, Liu; Zhang, Jia-Yu; Ma, Jian-Nan; Ma, Chao-Mei

2014-10-01

Ten compounds were isolated and purified from the peels of gold-red apple (Malus domestica) for the 1st time. The identified compounds are 3β, 20β-dihydroxyursan-28-oic acid (1), 2α-hydroxyoleanolic acid (2), euscaphic acid (3), 3-O-p-coumaroyl tormentic acid (4), ursolic acid (5), 2α-hydroxyursolic acid (6), oleanolic acid (7), betulinic acid (8), linolic acid (9), and α-linolenic acid (10). Their structures were determined by interpreting their nuclear magnetic resonance and mass spectrometry (MS) spectra, and by comparison with literature data. Compound 1 is new, and compound 2 is herein reported for the 1st time for the genus Malus. α-Glucosidase inhibition assay revealed 6 of the triterpenoid isolates as remarkable α-glucosidase inhibitors, with betulinic acid showing the strongest inhibition (IC50 = 15.19 μM). Ultra-performance liquid chromatography-electrospray ionization MS analysis of the fruit peels, pomace, flesh, and juice revealed that the peels and pomace contained high levels of triterpenes, suggesting that wastes from the fruit juice industry could serve as rich sources of bioactive triterpenes. © 2014 Institute of Food Technologists®

Evaluation of antimicrobial activity of extracts of Tibouchina candolleana (melastomataceae), isolated compounds and semi-synthetic derivatives against endodontic bacteria.

PubMed

Dos Santos, Fernanda M; de Souza, Maria Gorete; Crotti, Antônio E Miller; Martins, Carlos H G; Ambrósio, Sérgio R; Veneziani, Rodrigo C S; E Silva, Márcio L Andrade; Cunha, Wilson R

2012-04-01

This work describes the phytochemical study of the extracts from aerial parts of Tibouchina candolleana as well as the evaluation of the antimicrobial activity of extracts, isolated compounds, and semi-synthetic derivatives of ursolic acid against endodontic bacteria. HRGC analysis of the n-hexane extract of T. candolleana allowed identification of β-amyrin, α-amyrin, and β-sitosterol as major constituents. The triterpenes ursolic acid and oleanolic acid were isolated from the methylene chloride extract and identified. In addition, the flavonoids luteolin and genistein were isolated from the ethanol extract and identified. The antimicrobial activity was investigated via determination of the minimum inhibitory concentration (MIC) using the broth microdilution method. Amongst the isolated compounds, ursolic acid was the most effective against the selected endodontic bacteria. As for the semi-synthetic ursolic acid derivatives, only the methyl ester derivative potentiated the activity against Bacteroides fragilis.

Evaluation of antimicrobial activity of extracts of Tibouchina candolleana (melastomataceae), isolated compounds and semi-synthetic derivatives against endodontic bacteria

PubMed Central

dos Santos, Fernanda M.; de Souza, Maria Gorete; Crotti, Antônio E. Miller; Martins, Carlos H. G.; Ambrósio, Sérgio R.; Veneziani, Rodrigo C. S.; e Silva, Márcio L. Andrade; Cunha, Wilson R.

2012-01-01

This work describes the phytochemical study of the extracts from aerial parts of Tibouchina candolleana as well as the evaluation of the antimicrobial activity of extracts, isolated compounds, and semi-synthetic derivatives of ursolic acid against endodontic bacteria. HRGC analysis of the n-hexane extract of T. candolleana allowed identification of β-amyrin, α-amyrin, and β-sitosterol as major constituents. The triterpenes ursolic acid and oleanolic acid were isolated from the methylene chloride extract and identified. In addition, the flavonoids luteolin and genistein were isolated from the ethanol extract and identified. The antimicrobial activity was investigated via determination of the minimum inhibitory concentration (MIC) using the broth microdilution method. Amongst the isolated compounds, ursolic acid was the most effective against the selected endodontic bacteria. As for the semi-synthetic ursolic acid derivatives, only the methyl ester derivative potentiated the activity against Bacteroides fragilis. PMID:24031892

An efficient approach to finding Siraitia grosvenorii triterpene biosynthetic genes by RNA-seq and digital gene expression analysis.

PubMed

Tang, Qi; Ma, Xiaojun; Mo, Changming; Wilson, Iain W; Song, Cai; Zhao, Huan; Yang, Yanfang; Fu, Wei; Qiu, Deyou

2011-07-05

Siraitia grosvenorii (Luohanguo) is an herbaceous perennial plant native to southern China and most prevalent in Guilin city. Its fruit contains a sweet, fleshy, edible pulp that is widely used in traditional Chinese medicine. The major bioactive constituents in the fruit extract are the cucurbitane-type triterpene saponins known as mogrosides. Among them, mogroside V is nearly 300 times sweeter than sucrose. However, little is known about mogrosides biosynthesis in S. grosvenorii, especially the late steps of the pathway. In this study, a cDNA library generated from of equal amount of RNA taken from S. grosvenorii fruit at 50 days after flowering (DAF) and 70 DAF were sequenced using Illumina/Solexa platform. More than 48,755,516 high-quality reads from a cDNA library were generated that was assembled into 43,891 unigenes. De novo assembly and gap-filling generated 43,891 unigenes with an average sequence length of 668 base pairs. A total of 26,308 (59.9%) unique sequences were annotated and 11,476 of the unique sequences were assigned to specific metabolic pathways by the Kyoto Encyclopedia of Genes and Genomes. cDNA sequences for all of the known enzymes involved in mogrosides backbone synthesis were identified from our library. Additionally, a total of eighty-five cytochrome P450 (CYP450) and ninety UDP-glucosyltransferase (UDPG) unigenes were identified, some of which appear to encode enzymes responsible for the conversion of the mogroside backbone into the various mogrosides. Digital gene expression profile (DGE) analysis using Solexa sequencing was performed on three important stages of fruit development, and based on their expression pattern, seven CYP450s and five UDPGs were selected as the candidates most likely to be involved in mogrosides biosynthesis. A combination of RNA-seq and DGE analysis based on the next generation sequencing technology was shown to be a powerful method for identifying candidate genes encoding enzymes responsible for the

Oleanolic acid liposomes with polyethylene glycol modification: promising antitumor drug delivery

PubMed Central

Gao, Dawei; Tang, Shengnan; Tong, Qi

2012-01-01

Background Oleanolic acid is a pentacyclic triterpene present in many fruits and vegetables, and has received much attention on account of its biological properties. However, its poor solubility and low bioavailability limit its use. The objective of this study was to encapsulate oleanolic acid into nanoliposomes using the modified ethanol injection method. Methods The liposomes contain a hydrophobic oleanolic acid core, an amphiphilic soybean lecithin monolayer, and a protective hydrophilic polyethylene glycol (PEG) coating. During the preparation process, the formulations described were investigated by designing 34 orthogonal experiments as well as considering the effects of different physical characteristics. The four factors were the ratios of drug to soybean phosphatidylcholine (w/w), cholesterol (w/w), PEG-2000 (w/w), and temperature of phosphate-buffered saline at three different levels. We identified the optimized formulation which showed the most satisfactory lipid stability and particle formation. The morphology of the liposomes obtained was determined by transmission electron microscopy and atomic force microscopy. The existence of PEG in the liposome component was validated by Fourier transform infrared spectrum analysis. Results The PEGylated liposomes dispersed individually and had diameters of around 110–200 nm. Encapsulation efficiency was more than 85%, as calculated by high-performance liquid chromatography and Sephadex® gel filtration. Furthermore, when compared with native oleanolic acid, the liposomal formulations showed better stability in vitro. Finally, the cytotoxicity of the oleanolic acid liposomes was evaluated using a microtiter tetrazolium assay. Conclusion These results suggest that PEGylated liposomes would serve as a potent delivery vehicle for oleanolic acid in future cancer therapy. PMID:22848175

Oleanane-type triterpene saponins from Calendula stellata.

PubMed

Lehbili, Meryem; Alabdul Magid, Abdulmagid; Kabouche, Ahmed; Voutquenne-Nazabadioko, Laurence; Abedini, Amin; Morjani, Hamid; Sarazin, Thomas; Gangloff, Sophie C; Kabouche, Zahia

2017-12-01

Five previously undescribed bisdesmosidic triterpenoid saponins named calendustellatosides A-E, along with fifteen known compounds were isolated from the 70% ethanol whole plant extract of Calendula stellata Cav. (Asteraceae). Their structures were determined by 1D- and 2D-NMR spectroscopy as well as high resolution mass spectrometry and acid hydrolysis. The saponins comprised oleanolic acid, echinocystic acid, morolic acid or mesembryanthemoidigenic acid as the aglycones and saccharide moieties at C-3 and C-28. Like most Calendula saponins, the sugar moiety linked at C-3 was either β-d-glucose or β-d-glucuronic acid which could be substituted at C-3 by a β-d-galactose and/or C-2 by a supplementary β-d-galactose or a β-d-glucose. The sugar moiety linked to C-28 was determined as β-d-glucose. The antibacterial evaluation of compounds 1-20 by bioautography on Staphylococcus aureus followed by the determination of MIC values of active compounds by serial dilution technique against 5 bacteria revealed that; calendustellatoside D was the most active against Enterococcus faecalis with an antibacterial effect comparable to antibiotics. The cytotoxic activities of isolated compounds were evaluated against fibrosarcoma cell line (HT1080) and human lung cancer cell line (A549). Calendustellatosides B and D exhibited a low cytotoxic activity against HT1080 cell line with IC 50 values of 47 ± 0.6 and 39 ± 0.5 μM, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

18β-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents.

PubMed

Huang, Li-Rong; Hao, Xiao-Jiang; Li, Qi-Ji; Wang, Dao-Ping; Zhang, Jian-Xin; Luo, Heng; Yang, Xiao-Sheng

2016-04-22

The oleanane-type triterpene 18β-glycyrrhetinic acid (1) was modified chemically through the introduction of a trihydroxylated A ring and an ester moiety at C-20 to enhance its antibacterial activity. Compounds 22, 23, 25, 28, 29, 31, and 32 showed more potent inhibitory activity against Streptomyces scabies than the positive control, streptomycin. Additionally, the inhibitory activity of the most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined through a quantitative real-time reverse transcriptase PCR assay.

Identification, quantification, spatiotemporal distribution and genetic variation of major latex secondary metabolites in the common dandelion (Taraxacum officinale agg.).

PubMed

Huber, Meret; Triebwasser-Freese, Daniella; Reichelt, Michael; Heiling, Sven; Paetz, Christian; Chandran, Jima N; Bartram, Stefan; Schneider, Bernd; Gershenzon, Jonathan; Erb, Matthias

2015-07-01

The secondary metabolites in the roots, leaves and flowers of the common dandelion (Taraxacum officinale agg.) have been studied in detail. However, little is known about the specific constituents of the plant's highly specialized laticifer cells. Using a combination of liquid and gas chromatography, mass spectrometry and nuclear magnetic resonance spectrometry, we identified and quantified the major secondary metabolites in the latex of different organs across different growth stages in three genotypes, and tested the activity of the metabolites against the generalist root herbivore Diabrotica balteata. We found that common dandelion latex is dominated by three classes of secondary metabolites: phenolic inositol esters (PIEs), triterpene acetates (TritAc) and the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G). Purification and absolute quantification revealed concentrations in the upper mgg(-1) range for all compound classes with up to 6% PIEs, 5% TritAc and 7% TA-G per gram latex fresh weight. Contrary to typical secondary metabolite patterns, concentrations of all three classes increased with plant age. The highest concentrations were measured in the main root. PIE profiles differed both quantitatively and qualitatively between plant genotypes, whereas TritAc and TA-G differed only quantitatively. Metabolite concentrations were positively correlated within and between the different compound classes, indicating tight biosynthetic co-regulation. Latex metabolite extracts strongly repelled D. balteata larvae, suggesting that the latex constituents are biologically active. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oleanolic and maslinic acid sensitize soft tissue sarcoma cells to doxorubicin by inhibiting the multidrug resistance protein MRP-1, but not P-glycoprotein.

PubMed

Villar, Victor Hugo; Vögler, Oliver; Barceló, Francisca; Gómez-Florit, Manuel; Martínez-Serra, Jordi; Obrador-Hevia, Antònia; Martín-Broto, Javier; Ruiz-Gutiérrez, Valentina; Alemany, Regina

2014-04-01

The pentacyclic triterpenes oleanolic acid (OLA) and maslinic acid (MLA) are natural compounds present in many plants and dietary products consumed in the Mediterranean diet (e.g., pomace and virgin olive oils). Several nutraceutical activities have been attributed to OLA and MLA, whose antitumoral effects have been extensively evaluated in human adenocarcinomas, but little is known regarding their effectiveness in soft tissue sarcomas (STS). We assessed efficacy and molecular mechanisms involved in the antiproliferative effects of OLA and MLA as single agents or in combination with doxorubicin (DXR) in human synovial sarcoma SW982 and leiomyosarcoma SK-UT-1 cells. As single compound, MLA (10-100 μM) was more potent than OLA, inhibiting the growth of SW982 and SK-UT-1 cells by 70.3 ± 1.11% and 68.8 ± 1.52% at 80 μM, respectively. Importantly, OLA (80 μM) or MLA (30 μM) enhanced the antitumoral effect of DXR (0.5-10 μM) by up to 2.3-fold. On the molecular level, efflux activity of the multidrug resistance protein MRP-1, but not of the P-glycoprotein, was inhibited. Most probably as a consequence, DXR accumulated in these cells. Kinetic studies showed that OLA behaved as a competitive inhibitor of substrate-mediated MRP-1 transport, whereas MLA acted as a non-competitive one. Moreover, none of both triterpenes induced a compensatory increase in MRP-1 expression. In summary, OLA or MLA sensitized cellular models of STS to DXR and selectively inhibited MRP-1 activity, but not its expression, leading to a higher antitumoral effect possibly relevant for clinical treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Antiproliferative triterpene saponins from Entada africana.

PubMed

Cioffi, Giuseppina; Dal Piaz, Fabrizio; De Caprariis, Paolo; Sanogo, Rokia; Marzocco, Stefania; Autore, Giuseppina; De Tommasi, Nunziatina

2006-09-01

Nine new ester saponins (1-9) were isolated from the roots of Entada africana. Their structures were elucidated by 1D and 2D NMR experiments including 1D and 2D TOCSY, DQF-COSY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis, and chemical methods. The aglycon moieties were found to be echinocystic acid for compounds 1, 2, 4-6, 8, and 9 and acacic acid for 3 and 7. All isolated compounds were tested for their antiproliferative activity against the J774.A1, HEK-293, and WEHI-164 cell lines. Moderate to high cytotoxic potency was found for almost all compounds tested.

Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer.

PubMed

Liu, Can; Dai, Longhai; Liu, Yueping; Rong, Long; Dou, Dequan; Sun, Yuanxia; Ma, Lanqing

2016-06-13

Colorectal cancer and throat cancer are the world's most prevalent neoplastic diseases, and a serious threat to human health. Plant triterpene glycosides have demonstrated antitumor activity. In this study, we investigated potential anticancer effects of mogroside IVe, a triterpenoid glycoside from monk fruit, using in vitro and in vivo models of colorectal and laryngeal cancer. The effects of mogroside IVe on the proliferation of colorectal cancer HT29 cells and throat cancer Hep-2 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the expression levels of p53, phosphorylated ERK1/2, and MMP-9 were analyzed by western blotting and immunohistochemistry. The results indicated that mogroside IVe inhibited, in a dose-dependent manner, the proliferation of HT29 and Hep-2 cells in culture and in xenografted mice, which was accompanied by the upregulation of tumor suppressor p53, and downregulation of matrix metallopeptidase 9 (MMP-9) and phosphorylated extracellular signal-regulated kinases (ERK)1/2. This study revealed the suppressive activity of mogroside IVe towards colorectal and throat cancers and identified the underlying mechanisms, suggesting that mogroside IVe may be potentially used as a biologically-active phytochemical supplement for treating colorectal and throat cancers.

Isolation of two triterpenoids and a biflavanone with anti-Inflammatory activity from Schinus molle fruits.

PubMed

Yueqin, Zeng; Recio, M Carmen; Máñez, Salvador; Giner, Rosa M; Cerdá-Nicolás, M; Ríos, José-Luis

2003-10-01

Three compounds with anti-inflammatory activity were isolated from Schinus molle fruits. Two of the compounds were identified as 3- epi-isomasticadienolalic acid ( 1), isomasticadienonalic acid ( 2) and chamaejasmin ( 3). Triterpenes 1 and 2, and biflavanone 3 were tested on two models of mice paw inflammation: one of acute inflammation, induced by subcutaneous injection of either phospholipase A (2) (PLA (2)) or carrageenan in the paws of mice, and one of chronic inflammation in the form of eczema, provoked by repeated administration of TPA to the ears of mice. On the PLA (2)-induced mouse paw oedema, only 2 was active (30 mg/kg, 66 % inhibition at 60 min), whereas all compounds reduced the chronic model of inflammation (48 to 26 % of swelling reduction), but only triterpenes reduced the leukocyte infiltration, measured as tissue peroxidase activity. In the case of the carrageenan-induced mouse paw oedema, only 3 led to a reduction of the swelling 3 h after challenge (50 mg/kg, 46 % oedema inhibition). In addition, 3 inhibited the LTB (4) production in rat peritoneal polymorphonuclear leukocytes with an IC (50) value of 29.8 microM, while triterpenes showed toxicity against cells at 100 microM.

Abnormalities in the fatty acid composition of the postmortem entorhinal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Hamazaki, Kei; Hamazaki, Tomohito; Inadera, Hidekuni

2013-11-30

Previous studies of postmortem orbitofrontal cortex have shown abnormalities in levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), in individuals with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We have previously measured PUFA levels in the postmortem hippocampus from patients with schizophrenia or bipolar disorder and control subjects; however, we found no significant differences between the groups except for small changes in n-6 PUFAs. Furthermore, our study of the postmortem amygdala showed no significant differences in major PUFAs in individuals with schizophrenia, bipolar disorder, or MDD in comparison with controls. In the present study, we investigated whether there were any changes in PUFAs in the entorhinal cortexes of patients with schizophrenia (n=15), bipolar disorder (n=15), or MDD (n=15) compared with unaffected controls (n=15) matched for characteristics including age and sex. In contrast to previous studies of the orbitofrontal cortex and hippocampus, we found no significant differences in major PUFAs. However, we found a 34.3% decrease in docosapentaenoic acid (DPA) (22:5n-3) in patients with MDD and an 8.7% decrease in docosatetraenoic acid (22:4n-6) in those with schizophrenia, compared with controls. Changes in PUFAs in patients with these psychiatric disorders may be specific to certain brain regions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

13-cis-retinoic acid metabolism in vivo. The major tissue metabolites in the rat have the all-trans configuration.

PubMed

McCormick, A M; Kroll, K D; Napoli, J L

1983-08-02

The liver and intestinal metabolites of orally dosed 13-cis-[11-3H]retinoic acid were analyzed in normal and 13-cis-retinoic acid treated rats 3 h after administration of the radiolabeled retinoid. all-trans-Retinoic acid was identified as a liver and intestinal mucosa metabolite in normal rats given physiological doses of 13-cis-[3H]retinoic acid. all-trans-Retinoyl glucuronide was identified as the most abundant radiolabeled metabolite in mucosa and a prominent liver metabolite under the same conditions. Thus, the major 13-cis-retinoic acid metabolites retained in liver and mucosa, two retinoid target tissues, had the all-trans configuration. These data indicate that the isomerization of 13-cis-retinoic acid to all-trans-retinoic acid and the subsequent conversion to all-trans-retinoyl glucuronide are central events in the in vivo metabolism of 13-cis-retinoic acid in the rat. Moreover, the all-trans-retinoic acid detected in vivo could account for a significant fraction of the physiological activity of 13-cis-retinoic acid. The tissue disposition and metabolism of orally dosed 13-cis-[3H]retinoic acid are modulated by retinoid treatment. Chronic 13-cis-retinoic acid treatment apparently increased the intestinal accumulation of all-trans-retinoic acid, all-trans-retinoyl glucuronide, and 13-cis-retinoyl glucuronide. The liver concentrations of tritiated all-trans-retinoic acid and all-trans-retinoyl glucuronide were also elevated in 13-cis-retinoic acid treated rats.

Strong-acid, carboxyl-group structures in fulvic acid from the Suwannee River, Georgia. 2. Major structures

USGS Publications Warehouse

Leenheer, J.A.; Wershaw, R. L.; Reddy, M.M.

1995-01-01

Polycarboxylic acid structures that account for the strong-acid characteristics (pKa1 near 2.0) were examined for fulvic acid from the Suwannee River. Studies of model compounds demonstrated that pKa values near 2.0 occur only if the ??-ether or ??-ester groups were in cyclic structures with two to three additional electronegative functional groups (carboxyl, ester, ketone, aromatic groups) at adjacent positions on the ring. Ester linkage removal by alkaline hydrolysis and destruction of ether linkages through cleavage and reduction with hydriodic acid confirmed that the strong carboxyl acidity in fulvic acid was associated with polycarboxylic ??-ether and ??-ester structures. Studies of hypothetical structural models of fulvic acid indicated possible relation of these polycarboxylic structures with the amphiphilic and metal-binding properties of fulvic acid.

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.

Differential Lipid Composition and Gene Expression in the Semi-Russeted “Cox Orange Pippin” Apple Variety

PubMed Central

Legay, Sylvain; Cocco, Emmanuelle; André, Christelle M.; Guignard, Cédric; Hausman, Jean-Francois; Guerriero, Gea

2017-01-01

Russeting is characterized by a particular rough and brown phenotype, which is mainly due to the accumulation of suberin in the inner part of the epidermal cell walls. In our previous bulk transcriptomic analysis, comparing fully russeted, and waxy apple varieties, showed, in apple fruit skin, a massive decreased expression of cutin, wax and some pentacyclic triterpene biosynthesis genes in the russeted varieties, with an expected concomitant enhanced expression of the suberin biosynthetic genes. In the present work, we performed a deep investigation of the aliphatic composition of the cutin, suberin, waxes, and triterpenes in the waxy and russeted patches of the semi-russeted apple variety “Cox Orange Pippin.” A targeted gene expression profiling was performed to validate candidate genes which were identified in our previous work and might be involved in the respective metabolic pathways. Our results showed that a decrease of cuticular waxes, ursolic acid and oleanolic acid, accompanied by an accumulation of alkyl-hydroxycinamates and betulinic acid, occurs in the russeted patches. The suberin monomer composition is characterized by specific occurrence of 20, 22, and 24 carbon aliphatic chains, whereas cutin is mainly represented by common C16 and C18 aliphatic chains. This work depicts, for the first time in apple, the complex composition of suberin, cutin, waxes and triterpenes, and confirms the strong interplay between these epidermal polymers in apple fruit skin. PMID:29018466

Differential Lipid Composition and Gene Expression in the Semi-Russeted "Cox Orange Pippin" Apple Variety.

PubMed

Legay, Sylvain; Cocco, Emmanuelle; André, Christelle M; Guignard, Cédric; Hausman, Jean-Francois; Guerriero, Gea

2017-01-01

Russeting is characterized by a particular rough and brown phenotype, which is mainly due to the accumulation of suberin in the inner part of the epidermal cell walls. In our previous bulk transcriptomic analysis, comparing fully russeted, and waxy apple varieties, showed, in apple fruit skin, a massive decreased expression of cutin, wax and some pentacyclic triterpene biosynthesis genes in the russeted varieties, with an expected concomitant enhanced expression of the suberin biosynthetic genes. In the present work, we performed a deep investigation of the aliphatic composition of the cutin, suberin, waxes, and triterpenes in the waxy and russeted patches of the semi-russeted apple variety "Cox Orange Pippin." A targeted gene expression profiling was performed to validate candidate genes which were identified in our previous work and might be involved in the respective metabolic pathways. Our results showed that a decrease of cuticular waxes, ursolic acid and oleanolic acid, accompanied by an accumulation of alkyl-hydroxycinamates and betulinic acid, occurs in the russeted patches. The suberin monomer composition is characterized by specific occurrence of 20, 22, and 24 carbon aliphatic chains, whereas cutin is mainly represented by common C16 and C18 aliphatic chains. This work depicts, for the first time in apple, the complex composition of suberin, cutin, waxes and triterpenes, and confirms the strong interplay between these epidermal polymers in apple fruit skin.

Prediction of anticancer property of bowsellic acid derivatives by quantitative structure activity relationship analysis and molecular docking study.

PubMed

Satpathy, Raghunath; Guru, R K; Behera, R; Nayak, B

2015-01-01

Boswellic acid consists of a series of pentacyclic triterpene molecules that are produced by the plant Boswellia serrata. The potential applications of Bowsellic acid for treatment of cancer have been focused here. To predict the property of the bowsellic acid derivatives as anticancer compounds by various computational approaches. In this work, all total 65 derivatives of bowsellic acids from the PubChem database were considered for the study. After energy minimization of the ligands various types of molecular descriptors were computed and corresponding two-dimensional quantitative structure activity relationship (QSAR) models were obtained by taking Andrews coefficient as the dependent variable. Different types of comparative analysis were used for QSAR study are multiple linear regression, partial least squares, support vector machines and artificial neural network. From the study geometrical descriptors shows the highest correlation coefficient, which indicates the binding factor of the compound. To evaluate the anticancer property molecular docking study of six selected ligands based on Andrews affinity were performed with nuclear factor-kappa protein kinase (Protein Data Bank ID 4G3D), which is an established therapeutic target for cancers. Along with QSAR study and docking result, it was predicted that bowsellic acid can also be treated as a potential anticancer compound. Along with QSAR study and docking result, it was predicted that bowsellic acid can also be treated as a potential anticancer compound.

Determination of oleanolic acid in human plasma and its association with olive oil intake in healthy Spanish adults within the EPIC Spain cohort study.

PubMed

Buckland, Genevieve; Pastor, Antoni; Lujan-Barroso, Leila; Gonzalez, Carlos Alberto; Travier, Noemie; Amiano, Pilar; Huerta, José María; Agudo, Antonio; Navarro, Carmen; Chirlaque, María Dolores; Sánchez, Maria-José; Rodríguez-Barranco, Miguel; Barricarte, Aurelio; Ardanaz, Eva; Dorronsoro, Miren; Molinuevo, Amaia; Quirós, José Ramón; de la Torre, Rafael

2017-08-01

Oleanolic acid (OA) is an important triterpenic compound found in olive oil, however little is known about its concentrations in human plasma. We aimed to determine plasma OA levels in a healthy Spanish population and compare them with estimates of dietary olive oil intake. The final study sample included 141 individuals randomly selected from the European Prospective Investigation into Cancer and Nutrition Spanish cohort. Dietary olive oil intake was estimated using validated dietary history questionnaires. OA concentrations were determined in plasma (from the participants' stored blood samples) using a HPLC-MS method. Correlation coefficients between OA and olive oil intake were calculated, adjusting for center; sex; age; consumption of olives, apples, grapes, and red wine; and fasting state. The mean OA concentration in olive oil nonconsumers was 0.72 ng/mL (SD 0.82), while in the high olive oil intake group it was 1.32 ng/mL (SD 1.14). The fully adjusted partial Spearman correlations coefficients reached 0.36 (p-value < 0.001) overall, varying minimally by sex and fasting state. This is the first study providing steady-state concentrations of triterpenes in humans. The results show that there was low-to-moderate correlation between OA concentrations and olive oil intake in this population. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ursolic Acid, a Natural Pentacylcic Triterpene from Ochrosia elliptica and Its Role in The Management of Certain Neglected Tropical Diseases

PubMed Central

Labib, Rola M.; Ebada, Sherif S.; Youssef, Fadia S.; Ashour, Mohamed L.; Ross, Samir A.

2016-01-01

Background: Leishmaniasis and African trypanosomiasis are recognized as the leading causes of mortality and morbidity with the greatest prevalence in the developing countries. They affect more than one billion of the poorest people on the globe. Objective: To find a cheap, affordable, safe, and efficacious antileshmanial and antitrypanosomal natural drug and to elucidate its probable mode of action. Materials and Methods: Phytochemical investigation of the non-polar fraction of the methanol extract of leaves of Ochrosia elliptica Labill. (Apocyanaceae) resulted in the isolation of ursolic acid, which was unambiguously determined based on HR-ESI-FTMS, extensive 1D and 2D NMR spectroscopy. It was further tested for its cytotoxicity, antimicrobial, antimalarial, antileishmanial, and trypanocidal potency. in-silico molecular modeling studies were conducted on six vital parasitic enzymes including farnesyl diphosphate synthase, N-myristoyl transferase, pteridine reductase 1, trypanothione reductase, methionyl-tRNA synthetase, and inosine–adenosine–guanosine nucleoside hydrolase to discover its potential mode of action as antitrypanosomal and antileishmanial agent. Results: Ursolic acid displayed considerable antitrypanosomal and antileishmanial activities with IC50 values ranging between 1.53 and 8.79 μg/mL. It showed superior antitrypanosomal activity as compared to the standard drug difluoromethylornithine (DFMO), with higher binding affinities towards trypanothione reductase and pteridine reductase 1. It displayed free binding energy of -30.73 and -50.08 kcal/mole towards the previously mentioned enzymes, respectively. In addition, ursolic acid exhibited considerable affinities to farnesyl diphosphate synthase, N-myristoyl transferase and methionyl-tRNA synthetase with free binding energies ranging from -42.54 to -63.93 kcal/mole. Conclusion: Ursolic acid offers a safe, effective and cheap antitrypanosomal and antileishmanial candidate acting on several key

Dammarane triterpene saponin from Bacopa monniera as the superoxide inhibitor in polymorphonuclear cells.

PubMed

Pawar, R; Gopalakrishnan, C; Bhutani, K K

2001-11-01

The hydroalcoholic extract of the whole plant of Bacopa monniera Wettst. (Scrophulariaceae), exhibited an inhibitory effect on superoxide released from polymorphonuclear (PMN) cells in the nitroblue tetrazolium (NBT) assay. The major saponin bacoside A(3) was found to be responsible for this effect in the herb. This compound showed 85, 91.66, 91.66, and 83 % inhibitions of NBT reduction at the concentrations of 200, 100, 50, and 25 microg/ml, respectively, with an IC(50) value of 10.22 microg/ml. These inhibitory effects were compared with those of the standard positive controls, quercetin and ascorbic acid with IC(50) of 111 and 14.16 microg/ml, respectively. Another major saponin bacopasaponin C was found to be much less potent as compared to bacoside A(3) whereas the remaining two mixtures of saponins were found to be inactive.

Antioxidant capacity and amino acid profile of millet bran wine and the synergistic interaction between major polyphenols.

PubMed

Guo, XiaoXuan; Sha, XiaoHong; Rahman, Ebeydulla; Wang, Yong; Ji, BaoPing; Wu, Wei; Zhou, Feng

2018-03-01

Millet bran, the by-product of millet processing industry, contains an abundance of phytochemicals, especially polyphenols. The main objective of this study was brewing antioxidant wine from millet bran, as well as the nutritional evaluation. The total polyphenol content of wine samples was determined by Folin-Ciocalteu colorimetric method, and the antioxidant capacity was evaluated by DPPH radical-scavenging capacity, Trolox equivalent antioxidant capacity (TEAC), and ferric reducing antioxidant power (FRAP). Results showed that millet bran wine (MBW) contained as much as six times of total polyphenols compared with millet wine (MW), and performed considerably stronger antioxidant activity in DPPH, TEAC and FRAP assays. More than sixfold of total amino acids (AA) were found in MBW than in MW. Moreover, the indispensable AA and functional AA were also abundant in MBW. The major polyphenol compounds in MBW were identified using HPLC, including vanillic acid, syringic acid (SA), p -coumaric acid (CA) and ferulic acid (FA). They exhibited synergism in the antioxidant assays, especially the combinations of SA and CA, SA and FA. This study not only provides evidence for MBW as a nutraceutical with antioxidant activity, but also opens new avenues in the area of making comprehensive utilization of agricultural by-products.

Retrobiosynthetic nuclear magnetic resonance analysis of amino acid biosynthesis and intermediary metabolism. Metabolic flux in developing maize kernels.

PubMed

Glawischnig, E; Gierl, A; Tomas, A; Bacher, A; Eisenreich, W

2001-03-01

Information on metabolic networks could provide the basis for the design of targets for metabolic engineering. To study metabolic flux in cereals, developing maize (Zea mays) kernels were grown in sterile culture on medium containing [U-(13)C(6)]glucose or [1,2-(13)C(2)]acetate. After growth, amino acids, lipids, and sitosterol were isolated from kernels as well as from the cobs, and their (13)C isotopomer compositions were determined by quantitative nuclear magnetic resonance spectroscopy. The highly specific labeling patterns were used to analyze the metabolic pathways leading to amino acids and the triterpene on a quantitative basis. The data show that serine is generated from phosphoglycerate, as well as from glycine. Lysine is formed entirely via the diaminopimelate pathway and sitosterol is synthesized entirely via the mevalonate route. The labeling data of amino acids and sitosterol were used to reconstruct the labeling patterns of key metabolic intermediates (e.g. acetyl-coenzyme A, pyruvate, phosphoenolpyruvate, erythrose 4-phosphate, and Rib 5-phosphate) that revealed quantitative information about carbon flux in the intermediary metabolism of developing maize kernels. Exogenous acetate served as an efficient precursor of sitosterol, as well as of amino acids of the aspartate and glutamate family; in comparison, metabolites formed in the plastidic compartments showed low acetate incorporation.

Laticifer-specific cis-prenyltransferase silencing affects the rubber, triterpene, and inulin content of Taraxacum brevicorniculatum.

PubMed

Post, Janina; van Deenen, Nicole; Fricke, Julia; Kowalski, Natalie; Wurbs, David; Schaller, Hubert; Eisenreich, Wolfgang; Huber, Claudia; Twyman, Richard M; Prüfer, Dirk; Gronover, Christian Schulze

2012-03-01

Certain Taraxacum species, such as Taraxacum koksaghyz and Taraxacum brevicorniculatum, produce large amounts of high-quality natural rubber in their latex, the milky cytoplasm of specialized cells known as laticifers. This high-molecular mass biopolymer consists mainly of poly(cis-1,4-isoprene) and is deposited in rubber particles by particle-bound enzymes that carry out the stereospecific condensation of isopentenyl diphosphate units. The polymer configuration suggests that the chain-elongating enzyme (rubber transferase; EC 2.5.1.20) is a cis-prenyltransferase (CPT). Here, we present a comprehensive analysis of transgenic T. brevicorniculatum plants in which the expression of three recently isolated CPTs known to be associated with rubber particles (TbCPT1 to -3) was heavily depleted by laticifer-specific RNA interference (RNAi). Analysis of the CPT-RNAi plants by nuclear magnetic resonance, size-exclusion chromatography, and gas chromatography-mass spectrometry indicated a significant reduction in rubber biosynthesis and a corresponding 50% increase in the levels of triterpenes and the main storage carbohydrate, inulin. Transmission electron microscopy revealed that the laticifers in CPT-RNAi plants contained fewer and smaller rubber particles than wild-type laticifers. We also observed lower activity of hydroxymethylglutaryl-coenzyme A reductase, the key enzyme in the mevalonate pathway, reflecting homeostatic control of the isopentenyl diphosphate pool. To our knowledge, this is the first in planta demonstration of latex-specific CPT activity in rubber biosynthesis.

Phosphatidic acid is a major phospholipid class in reproductive organs of Arabidopsis thaliana.

PubMed

Yunus, Ian Sofian; Cazenave-Gassiot, Amaury; Liu, Yu-Chi; Lin, Ying-Chen; Wenk, Markus R; Nakamura, Yuki

2015-01-01

Phospholipids are the crucial components of biological membranes and signal transduction. Among different tissues, flower phospholipids are one of the least characterized features of plant lipidome. Here, we report that floral reproductive organs of Arabidopsis thaliana contain high levels of phosphatidic acid (PA), a known lipid second messenger. By using floral homeotic mutants enriched with specific floral organs, lipidomics study showed increased levels of PA species in ap3-3 mutant with enriched pistils. Accompanied gene expression study for 7 diacylglycerol kinases and 11 PA phosphatases revealed distinct floral organ specificity, suggesting an active phosphorylation/dephosphorylation between PA and diacylglycerol in flowers. Our results suggest that PA is a major phospholipid class in floral reproductive organs of A. thaliana.

Protective effects of glycyrrhizic acid against non-alcoholic fatty liver disease in mice.

PubMed

Sun, Xue; Duan, Xingping; Wang, Changyuan; Liu, Zhihao; Sun, Pengyuan; Huo, Xiaokui; Ma, Xiaodong; Sun, Huijun; Liu, Kexin; Meng, Qiang

2017-07-05

Non-alcoholic fatty liver disease (NAFLD) has become a predictive factor of death from many diseases. The purpose of the present study is to investigate the protective effect of glycyrrhizic acid (GA), a natural triterpene glycoside, on NAFLD induced by a high-fat diet (HFD) in mice, and further to elucidate the mechanisms underlying GA protection. GA treatment significantly reduced the relative liver weight, serum ALT, AST activities, levels of serum lipid, blood glucose and insulin. GA suppressed lipid accumulation in liver. Further mechanism investigation indicated that GA reduced hepatic lipogenesis via downregulating SREBP-1c, FAS and SCD1 expression, increased fatty acids β-oxidation via an increase in PPARα, CPT1α and ACADS, and promoted triglyceride metabolism through inducing LPL activity. Furthermore, GA reduced gluconeogenesis through repressing PEPCK and G6Pase, and increased glycogen synthesis through an induction in gene expression of PDase and GSK3β. In addition, GA increased insulin sensitivity through upregulating phosphorylation of IRS-1 and IRS-2. In conclusion, GA produces protective effect against NAFLD, due to regulation of genes involved in lipid, glucose homeostasis and insulin sensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Lipophilic extracts from banana fruit residues: a source of valuable phytosterols.

PubMed

Oliveira, Lúcia; Freire, Carmen S R; Silvestre, Armando J D; Cordeiro, Nereida

2008-10-22

The chemical composition of the lipophilic extracts of unripe pulp and peel of banana fruit 'Dwarf Cavendish' was studied by gas chromatography-mass spectrometry. Fatty acids, sterols, and steryl esters are the major families of lipophilic components present in banana tissues, followed by diacylglycerols, steryl glucosides, long chain fatty alcohols, and aromatic compounds. Fatty acids are more abundant in the banana pulp (29-90% of the total amount of lipophilic extract), with linoleic, linolenic, and oleic acids as the major compounds of this family. In banana peel, sterols represent about 49-71% of the lipophilic extract with two triterpenic ketones (31-norcyclolaudenone and cycloeucalenone) as the major components. The detection of high amounts of steryl esters (469-24405 mg/kg) and diacylglycerols (119-878 mg/kg), mainly present in the banana peel extract, explains the increase in the abundance of fatty acids and sterols after alkaline hydrolysis. Several steryl glucosides were also found in significative amounts (273-888 mg/kg), particularly in banana pulp (888 mg/kg). The high content of sterols (and their derivatives) in the 'Dwarf Cavendish' fruit can open new strategies for the valorization of the banana residues as a potential source of high-value phytochemicals with nutraceutical and functional food additive applications.

Fatty acid composition of the postmortem corpus callosum of patients with schizophrenia, bipolar disorder, or major depressive disorder.

PubMed

Hamazaki, K; Maekawa, M; Toyota, T; Dean, B; Hamazaki, T; Yoshikawa, T

2017-01-01

Studies investigating the relationship between n-3 polyunsaturated fatty acid (PUFA) levels and psychiatric disorders have thus far focused mainly on analyzing gray matter, rather than white matter, in the postmortem brain. In this study, we investigated whether PUFA levels showed abnormalities in the corpus callosum, the largest area of white matter, in the postmortem brain tissue of patients with schizophrenia, bipolar disorder, or major depressive disorder. Fatty acids in the phospholipids of the postmortem corpus callosum were evaluated by thin-layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). In contrast to some previous studies, no significant differences were found in the levels of PUFAs or other fatty acids in the corpus callosum between patients and controls. A subanalysis by sex gave the same results. No significant differences were found in any PUFAs between suicide completers and non-suicide cases regardless of psychiatric disorder diagnosis. Patients with psychiatric disorders did not exhibit n-3 PUFAs deficits in the postmortem corpus callosum relative to the unaffected controls, and the corpus callosum might not be involved in abnormalities of PUFA metabolism. This area of research is still at an early stage and requires further investigation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Modulation by glycyrrhetinic acid derivatives of TPA-induced mouse ear oedema.

PubMed Central

Inoue, H.; Mori, T.; Shibata, S.; Koshihara, Y.

1989-01-01

1. The anti-inflammatory effects of glycyrrhetinic acid and its derivatives on TPA (12-O-tetradecanoylphorbol-13-acetate)-induced mouse ear oedema were studied. The mechanisms of TPA-induced ear oedema were first investigated with respect to the chemical mediators. 2. The formation of ear oedema reached a maximum 5 h after TPA application (2 micrograms per ear) and the prostaglandin E2 (PGE2) production of mouse ear increased with the oedema formation. 3. TPA-induced ear oedema was prevented by actinomycin D and cycloheximide (0.1 mg per ear, respectively) when applied during 60 min after TPA treatment. 4. Of glycyrrhetinic acid derivatives examined, dihemiphthalate derivatives (IIe, IIe', IIIa, IIIa', IVa, IVa') most strongly inhibited ear oedema on both topical (ID50, 1.6 mg per ear for IIe, 2.0 mg per ear for IIIa and 1.6 mg per ear for IVa) and oral (ID50, 88 mg kg-1 for IIe', 130 mg kg-1 for IIIa' and 92 mg kg-1 for IVa') administration. 5. Glycyrrhetinic acid (Ia) and its derivatives applied 30 min before TPA treatment were much more effective in inhibiting oedema than when applied 30 min after TPA. A dihemiphthalate of triterpenoid compound IVa completely inhibited oedema, even when applied 3 h before TPA treatment. 6. Glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the parent compounds, produced little inhibition by oral administration at less than 200 mg kg-1. 7. These results suggest that the dihemiphthalate derivatives of triterpenes derived from glycyrrhetinic acid by chemical modification are useful for the treatment of skin inflammation by both topical and oral application. PMID:2924072

Phenolic acids of the two major blueberry species in the US Market and their antioxidant and anti-inflammatory activities.

PubMed

Kang, Jie; Thakali, Keshari M; Jensen, Gitte S; Wu, Xianli

2015-03-01

Highbush (cultivated) and lowbush (wild) are the two major blueberry species in the US market. Eight phenolic acids were detected and quantified from these two species by HPLC-MS. Chlorogenic acid was found to be the predominant phenolic acid in both species, with 0.44 mg/g fresh weight in lowbush blueberries and 0.13 mg/g fresh weight in highbush blueberries. Total phenolic content in lowbush blueberries is over three times higher than that of highbush blueberries. The phenolic acid mixtures representing those in the two species were prepared by using authentic standards to assess their contribution to total antioxidant and anti-inflammatory activities of the whole berries. Neither lowbush nor highbush blueberry phenolic acid mixture contributed significantly to the total antioxidant capacity of their relevant whole berries measured by oxygen radical absorbance capacity (ORAC). Both phenolic acid mixtures were able to enter the cell and showed in cell antioxidant activities from the cell based antioxidant protection of erythrocytes (CAP-e) assay. Lowbush blueberry phenolic acid mixture was found to show anti-inflammatory activities by inhibiting the nuclear factor-κB (NF-κB) activation and the production of inflammatory cytokines (TNF-α and IL-6) at the high dose.

Prediction of intramuscular fat content and major fatty acid groups of lamb M. longissimus lumborum using Raman spectroscopy.

PubMed

Fowler, Stephanie M; Ponnampalam, Eric N; Schmidt, Heinar; Wynn, Peter; Hopkins, David L

2015-12-01

A hand held Raman spectroscopic device was used to predict intramuscular fat (IMF) levels and the major fatty acid (FA) groups of fresh intact ovine M. longissimus lumborum (LL). IMF levels were determined using the Soxhlet method, while FA analysis was conducted using a rapid (KOH in water, methanol and sulphuric acid in water) extraction procedure. IMF levels and FA values were regressed against Raman spectra using partial least squares regression and against each other using linear regression. The results indicate that there is potential to predict PUFA (R(2)=0.93) and MUFA (R(2)=0.54) as well as SFA values that had been adjusted for IMF content (R(2)=0.54). However, this potential was significantly reduced when correlations between predicted and observed values were determined by cross validation (R(2)cv=0.21-0.00). Overall, the prediction of major FA groups using Raman spectra was more precise (relative reductions in error of 0.3-40.8%) compared to the null models. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of Uric Acid on the Alterations of White Matter Connectivity in Patients with Major Depression.

PubMed

Sohn, Hoyoung; Kwon, Min-Soo; Lee, Sun-Woo; Oh, Jongsoo; Kim, Min-Kyoung; Lee, Sang-Hyuk; Lee, Kang Soo; Kim, Borah

2018-06-07

Uric acid is a non-enzymatic antioxidant associated with depression. Despite its known protective role in other brain disorders, little is known about its influence on the structural characteristics of brains of patients with major depressive disorder (MDD). This study explored the association between uric acid and characteristics of white matter (WM) in patients with MDD. A total of 32 patients with MDD and 23 healthy controls (HCs) were examined. All participants were scored based on the Beck Depression Inventory and Beck Anxiety Inventory at baseline. All patients were also rated with the Hamilton Depression Rating Scale. We collected blood samples from all participants immediately after their enrollment and before the initiation of antidepressants in case of patients. Tract-based spatial statistics were used for all imaging analyses. Lower fractional anisotropy (FA) and higher radial diffusivity (RD) values were found in the MDD group than in the HC group. Voxelwise correlation analysis revealed that the serum uric acid levels positively correlated with the FA and negatively with the RD in WM regions that previously showed significant group differences in the MDD group. The correlated areas were located in the left anterior corona radiata, left frontal lobe WM, and left anterior cingulate cortex WM. The present study suggests a significant association between altered WM connectivity and serum uric acid levels in patients with MDD, possibly through demyelination.

Antiulcerogenic activity of crude extract, fractions and populnoic acid isolated from Austroplenckia populnea (Celastraceae).

PubMed

Andrade, Sérgio F; Antoniolli, Daiane; Comunello, Eros; Cardoso, Luis G V; Carvalho, José C T; Bastos, Jairo K

2006-01-01

Many plant crude extracts and their isolated compounds are the most attractive sources of new drugs and show promising results for the treatment of gastric ulcers. Austroplenckia populnea is commonly known as "marmelinho-do campo, mangabeira-brava, mangabarana and vime" and it has been used in folk medicine as anti-dysenteric and anti-rheumatic. Powdered bark wood (3.25 kg) was macerated with aqueous ethanol (96%) and the extract was concentrated under reduced pressure to yield 406 g of crude hydralcoholic extract. The hydralcoholic extract was suspended in aqueous methanol and partitioned with hexane, chloroform and ethyl acetate (EtOAc) in sequence, yielding 8.0 g, 9.5 g and 98.17 g of crude extracts, respectively. Chromatography of the hexane extract over a silica gel column led to the isolation of the triterpene populnoic acid. The oral administration of hydralcoholic, hexane, chloroform and EtOAc extracts (200 mg/kg) decreased the ulcer lesion index (ULI) by 83.15%, 46.87%, 32.2%, 68.12%, respectively. Oral administration of populnoic acid (100 mg/kg) diminished the ULI by 55.29%. All the obtained results were significant in comparison with the negative control, with exception of the chloroform extract.

Phytochemical analysis and biological evaluation of selected African propolis samples from Cameroon and Congo.

PubMed

Papachroni, Danai; Graikou, Konstantia; Kosalec, Ivan; Damianakos, Harilaos; Ingram, Verina; Chinou, Ioanna

2015-01-01

The objective of this study was the chemical analysis of four selected samples of African propolis (Congo and Cameroon) and their biological evaluation. Twenty-one secondary metabolites belonging to four different chemical groups were isolated from the 70% ethanolic extracts of propolis and their structures were elucidated on the basis of spectral evidence. Three triterpenes and two diprenyl-flavonoids were identified from Congo propolis, which has been investigated for the first time, while thirteen triterpenes, three diprenyl-flavonoids, two monoterpenic alcohols and one fatty acid ester have been identified from Cameroon propolis samples. To our knowledge, the identified diprenyl-flavonoids, as well as five of the isolated and determined triterpenes, are reported for the first time in propolis. Moreover, the total polyphenol content was estimated in all extracts and the antimicrobial activities of all four extracts were studied against six Gram-positive and -negative bacteria and three pathogenic fungi, showing an interesting antibacterial profile.

Antibacterial, anti-inflammatory and anti-oxidatant activities of various isolated compounds from Cratoxylum species.

PubMed

Rodanant, Pirasut; Boonnak, Nawong; Surarit, Rudee; Kuvatanasuchati, Jintakorn; Lertsooksawat, Wannee

2017-05-01

The objective of this study was to investigate the bioactivity of twenty-nine known isolated compounds from Cratoxylum species including three anthraquinones, four triterpenes, and twenty-two xanthones. All isolated compounds were subjected to antibacterial, anti-inflammatory and anti-oxidant activities. Cytotoxicity evaluations were performed by MTT assay. The anti-oxidatant activity was performed using DPPH assay. The anti-inflammatory activity was evaluated from the production of cytokines TNF-α and IL1-β using ELISA assay. Human gingival fibroblasts and monocytes could tolerate both anthraquinones and triterpenes. All isolated anthraquinones showed moderate-to-high antibacterial efficacy while compound A3 also demonstrated moderate anti-inflammatory effect. None of the isolated triterpenes, except for T1, inhibited the expression of TNF-α. A number of isolated xanthones was toxic to HGFs and monocytes. Compound X5, X14 and a 1:1 mixture of X5 and X6 showed comparative anti-inflammatory activity to dexamethasone. Several triterpene and xanthone compounds also expressed antibacterial effect against P. gingivalis. Some isolated xanthones exerted anti-oxidant activity comparable to ascorbic acid. Accordingly, selected pure compounds from plants of Cratoxylum genus might be of benefit in developing medications that are important in treating periodontal diseases.

Isolation and quantification of major chlorogenic acids in three major instant coffee brands and their potential effects on H2O2-induced mitochondrial membrane depolarization and apoptosis in PC-12 cells

USDA-ARS?s Scientific Manuscript database

Coffee is a most consumed drink worldwide. In this paper, from three commercially available instant coffees, major chlorogenic acids were isolated and quantified using HPLC and NMR spectroscopic methods. Also, their anti-oxidant and anti-inflammatory activities were determined using DPPH-radical sca...

The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer's disease: Acting separately or synergistically?

PubMed

Song, Cai; Shieh, Chu-Hsin; Wu, Yi-Shyuan; Kalueff, Allan; Gaikwad, Siddharth; Su, Kuan-Pin

2016-04-01

Omega-3 polyunsaturated fatty acids (n-3-PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may improve or prevent some psychiatric and neurodegenerative diseases in both experimental and clinical studies. As important membrane components, these PUFAs benefit brain health by modulating neuroimmune and apoptotic pathways, changing membrane function and/or competing with n-6 PUFAs, the precursors of inflammatory mediators. However, the exact role of each fatty acid in neuroimmune modulation and neurogenesis, the interaction between EPA and DHA, and the best EPA:DHA ratios for improving brain disorders, remain unclear. It is also unknown whether EPA, as a DHA precursor, acts directly or via DHA. Here, we discuss recent evidence of EPA and DHA effects in the treatment of major depression and Alzheimer's disease, as well as their potential synergistic action on anti-inflammatory, antioxidant and neurotrophic processes in the brain. We further analyze the cellular and molecular mechanisms by which EPA, DHA or their combination may benefit these diseases. We also outline the limitations of current studies and suggest new genetic models and novel approaches to overcome these limitations. Finally, we summarize future strategies for translational research in this field. Copyright © 2016 Elsevier B.V. All rights reserved.

Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach.

PubMed

Taylor, Sophie; Spugnini, Enrico Pierluigi; Assaraf, Yehuda G; Azzarito, Tommaso; Rauch, Cyril; Fais, Stefano

2015-11-01

Despite the major progresses in biomedical research and the development of novel therapeutics and treatment strategies, cancer is still among the dominant causes of death worldwide. One of the crucial challenges in the clinical management of cancer is primary (intrinsic) and secondary (acquired) resistance to both conventional and targeted chemotherapeutics. Multiple mechanisms have been identifiedthat underlie intrinsic and acquired chemoresistance: these include impaired drug uptake, increased drug efflux, deletion of receptors, altered drug metabolism, quantitative and qualitative alterations in drug targets, increased DNA damage repair and various mechanisms of anti-apoptosis. The fast efflux of anticancer drugs mediated by multidrug efflux pumps and the partial or complete reversibility of chemoresistance combined with the absence of genetic mutations suggests a multifactorial process. However, a growing body of recent evidence suggests that chemoresistance is often triggered by the highly acidic microenvironment of tumors. The vast majority of drugs, including conventional chemotherapeutics and more recent biological agents, are weak bases that are quickly protonated and neutralized in acidic environments, such as the extracellular microenvironment and the acidic organelles of tumor cells. It is therefore essential to develop new strategies to overcome the entrapment and neutralization of weak base drugs. One such strategy is the use of proton pump inhibitors which can enhance tumor chemosensitivity by increasing the pH of the tumor microenvironment. Recent clinical trials in animals with spontaneous tumors have indicated that patient alkalization is capable of reversing acquired chemoresistance in a large percentage of tumors that are refractory to chemotherapy. Of particular interest was the benefit of alkalization for patients undergoing metronomic regimens which are becoming more widely used in veterinary medicine. Overall, these results provide

Evaluation of the mechanism of gelation of an oleogel based on a triterpene extract from the outer bark of birch.

PubMed

Grysko, M; Daniels, R

2013-07-01

Oleogels are known for their high physical, chemical, and mechanical stability and good in vivo efficacy, which make them appropriate vehicles for dermal drug delivery and skin care for very dry skin. Modern formulation research focusses on well tolerated and sustainable formulation concepts. This paper deals with an innovative oleogel, which is based on a triterpene dry extract from the outer bark of birch (TE). In this formulation TE does not only act as an excipient but provides interesting pharmacological properties at the same time. The oleogel was formulated using solely Simmondsia Chinensis seed oil (jojoba oil) and TE. Fluorescence microscopy and confocal Raman microscopy showed that suspended TE particles arrange in a three-dimensional gel network. Infrared spectroscopy revealed that the formation of hydrogen bonds between TE particles is responsible for the self-assembly of TE in oil. Moreover, the influence of TE concentration and morphology of the TE particles on the viscoelasticity of the resulting oleogels was analyzed. Gel strength increased with TE concentration and was critical to the specific surface area of the TE particles.

Isolation of a new anti-inflammatory 20, 21, 22, 23, 24, 25, 26, 27-octanorcucurbitacin-type triterpene from Ibervillea sonorae.

PubMed

Jardón-Delgado, Angel; Magos-Guerrero, Gil Alfonso; Martínez-Vázquez, Mariano

2014-01-01

A new cucurbitane-type triterpene, 20, 21, 22, 23, 24, 25, 26, 27-octanorcucurbita-5-ene-3, 11, 16-trione (1), named kinoin D, was isolated from the roots of the medicinal plant Ibervillea sonorae, (wereque). The structure of 1 was established on the basis of extensive NMR and MS studies. In addition, the known kinoins B (3) and C (5) were isolated, as were 16alpha-20,25-trihydroxy-3alpha-(2-O-alpha-L-rhamnopyranosiyl-D-glucopyranosyloxy)-(10alpha)-cucurbit-5-en-11,22-dione (6), (22S)-16alpha,22-diacetoxy-20,25-dihydroxy-3alpha-[3,4,6-tri-O-acetyl-2-O-(2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl)-beta-glucopyranosyl]-(10alpha)-cucurbita-5,23t-dien-11-one (7) and 16alpha-acetoxy-20,25-dihydroxy-3alpha-[3,4,6-tri-O-acetyl-2-O-(2,3,4,-tri-O-acetyl-alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-(10alpha)-cucurbita-5-ene-11,22-dione (8). Compound 1 exhibited anti-inflammatory activity in TPA-induced edema in mice.

Cellular uptake mechanism and clearance kinetics of fluorescence-labeled glycyrrhetinic acid and glycyrrhetinic acid-modified liposome in hepatocellular carcinoma cells.

PubMed

Sun, Yuqi; Lu, Jinghua; Yan, Dongxue; Shen, Liping; Hu, Haiyang; Chen, Dawei

2017-07-01

Glycyrrhetinic acid (GA) is a natural pentacyclic triterpene derivative that exerts significant effects in the suppression of liver cancer. The receptors of GA on liver cells and hepatocellular carcinoma (HCC) cells have drawn broad attention. The effects of GA might depend on its transport into and out of cells. However, the question has not been previously addressed despite its obvious and fundamental importance. In this paper, GA and GA-modified liposome (GA-Lip) were labeled with fluorescein isothiocyanate (FITC) or coumarin 6 (Cou6) using chemical or pharmaceutical techniques. The transport courses of FITC-GA and GA-Cou6-Lip were studied in HepG2 cells in vitro. We found that the fluorescence labeled GA and GA-Lip uptake and clearance were time-dependent. FITC-GA uptake involved passive diffusion and active transport, and the receptors were in the cytomembrane proteins. GA-Cou6-Lip uptake was mediated by caveolae-dependent endocytosis. In addition, FITC-GA and GA-Cou6-Lip clearance of the HCC cells fitted exponential decay and second-order processes, respectively. These findings provide new insights into the anti-HCC actions of GA. Copyright © 2017. Published by Elsevier B.V.

Determination of 5-caffeoylquinic acid (5-CQA) as one of the major classes of chlorogenic acid in commercial tea and coffee samples.

PubMed

Nevena, Grujić-Letić; Branislava, Rakić; Emilia, Sefer; Dusica, Rakić; Ivan, Nedeljković; Nebojsa, Kladar; Biljana, Božin

2015-11-01

Tea and coffee are one of the most widely consumed beverages in the world due to their beneficial health effects which are largely associated with their phenolic compounds composition, including chlorogenic acid. The main aim of this study was to determine 5-caffeoylquinic acid (5-CQA), as one of the major classes of chlorogenic acid, in various commercial tea and coffee samples present at the Serbian market. A high-performance liquid chromatography (HPLC) method for determination of 5-CQA in plant extracts was applied to determine the content of this active compound in commercial tea and coffee samples. Mobile phase was aqueous 1.5% acetic acid-methanol (80:20, v/v) with the flow rate of 0.8 mL/min. Run time was 15 min and column temperature 25°C. The detection was performed at 240 nm. The HPLC method was modified and revalidated. The 5-CQA content varied depending on the type of tea (white, green, black tea and mate) and the processing technology. Green tea had the highest 5-CQA content (16 mg/100 mL) among the analyzed tea samples. The content of 5-CQA in coffee samples ranged 0-36.20 mg/g of coffee and 0-46.98 mg/100 mL of beverage, showing that the content varied depending on the type of coffee, coffee processing technology and the formulation. The modified and revalidated HPLC method showed a good accuracy, repeatability, selectivity and robustness. The highest amount of 5-CQA was determined in green tea in comparison to white, black and mate tea because the increased oxidation level decreases the amount of 5-CQA. The obtained results for commercial coffee samples indicated that the formulation was the most important factor determining the amount of 5-CQA. It can be concluded that plant material selection, processing conditions and formulation have great influence on the amount of chlorogenic acid (5-CQA) in the final tea and coffee products.

Medicinal flowers. III. Marigold. (1): hypoglycemic, gastric emptying inhibitory, and gastroprotective principles and new oleanane-type triterpene oligoglycosides, calendasaponins A, B, C, and D, from Egyptian Calendula officinalis.

PubMed

Yoshikawa, M; Murakami, T; Kishi, A; Kageura, T; Matsuda, H

2001-07-01

The methanolic extract and its 1-butanol-soluble fraction from the flowers of Calendula officinalis were found to show a hypoglycemic effect, inhibitory activity of gastric emptying, and gastroprotective effect. From the 1-butanol-soluble fraction, four new triterpene oligoglycosides, calendasaponins A, B, C, and D, were isolated, together with eight known saponins, seven known flavonol glycosides, and a known sesquiterpene glucoside. Their structures were elucidated on the basis of chemical and physicochemical evidence. The principal saponin constituents, glycosides A, B, C, D, and F, exhibited potent inhibitory effects on an increase in serum glucose levels in glucose-loaded rats, gastric emptying in mice, and ethanol- and indomethacin-induced gastric lesions in rats. Some structure-activity relationships are discussed.

Pistacia lentiscus Oleoresin: Virtual Screening and Identification of Masticadienonic and Isomasticadienonic Acids as Inhibitors of 11β-Hydroxysteroid Dehydrogenase 1.

PubMed

Vuorinen, Anna; Seibert, Julia; Papageorgiou, Vassilios P; Rollinger, Judith M; Odermatt, Alex; Schuster, Daniela; Assimopoulou, Andreana N

2015-04-01

In traditional medicine, the oleoresinous gum of Pistacia lentiscus var. chia, so-called mastic gum, has been used to treat multiple conditions such as coughs, sore throats, eczema, dyslipidemia, and diabetes. Mastic gum is rich in triterpenes, which have been postulated to exert antidiabetic effects and improve lipid metabolism. In fact, there is evidence of oleanonic acid, a constituent of mastic gum, acting as a peroxisome proliferator-activated receptor γ agonist, and mastic gum being antidiabetic in mice in vivo. Despite these findings, the exact antidiabetic mechanism of mastic gum remains unknown. Glucocorticoids play a key role in regulating glucose and fatty acid metabolism, and inhibition of 11β-hydroxysteroid dehydrogenase 1 that converts inactive cortisone to active cortisol has been proposed as a promising approach to combat metabolic disturbances including diabetes. In this study, a pharmacophore-based virtual screening was applied to filter a natural product database for possible 11β-hydroxysteroid dehydrogenase 1 inhibitors. The hit list analysis was especially focused on the triterpenoids present in Pistacia species. Multiple triterpenoids, such as masticadienonic acid and isomasticadienonic acid, main constituents of mastic gum, were identified. Indeed, masticadienonic acid and isomasticadienonic acid selectively inhibited 11β-hydroxysteroid dehydrogenase 1 over 11β-hydroxysteroid dehydrogenase 2 at low micromolar concentrations. These findings suggest that inhibition of 11β-hydroxysteroid dehydrogenase 1 contributes to the antidiabetic activity of mastic gum. Georg Thieme Verlag KG Stuttgart · New York.

Major perfluoroalkyl acid (PFAA) concentrations and influence of food consumption among the general population of Daegu, Korea.

PubMed

Ji, Kyunghee; Kim, Sunmi; Kho, Younglim; Sakong, Joon; Paek, Domyung; Choi, Kyungho

2012-11-01

Perfluoroalkyl acids (PFAAs) have been used in various industrial and consumer products for decades, and have consequently been detected in human blood worldwide. In the present study, general adult population in Daegu, Korea (n=140, >20 years of old) was recruited, collected for serum, and analyzed for 13 major PFAAs. The influence of dietary and water consumption on serum PFAA levels was also evaluated. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS) were frequently detected with relatively higher concentrations in blood serum. Most PFAA concentrations except for PFOA were detected in higher concentrations among males, and were positively correlated with age and body mass index (BMI). PFOA concentrations were relatively higher among the female of childbearing age, e.g., 20-49years old, raising concerns on potential impacts on fetus through transplacental transfer or lactation. In addition, the concentrations of PFOA in Daegu population were higher than other areas of Korea, suggesting a presence of distinctive sources in the area. Among food items, potato consumption was identified to be significant contributor to serum PFOA. For PFUnDA and PFTrDA levels, intake of fish/shellfish was positively associated. The results of this study will be useful in developing public health management options for PFAAs. Copyright © 2012 Elsevier B.V. All rights reserved.

Ursane-type nortriterpenes with a five-membered A-ring from Rubus innominatus.

PubMed

Chen, Zhenzhong; Tong, Ling; Feng, Yuanli; Wu, Jizhou; Zhao, Xiaoya; Ruan, Hanli; Pi, Huifang; Zhang, Peng

2015-08-01

Two nortriterpenes (rubuminatus A and B), which contain a distinctive contracted a five-membered A-ring ursane-type skeleton, and six triterpenes along with 17 known triterpenes were isolated from the roots of Rubus innominatus S. Moore. These structures were determined to be 19α-hydroxy-2-oxo-nor- A(3)-urs-12-en-28-oic acid, 1β,19α-dihydroxy-2-oxo-nor-A(3)-urs-12-en-28-oic acid, 1β,2α,3α,19α-tetrahy droxyurs-12-en-23-formyl-28-oic acid, 1β,2α,3α,19α,23- pentahydroxyurs-11-en-28-oic acid, 1-oxo-siaresinolic acid, 2α,3α-dihydroxyolean-11,13(18)-dien-19β,28-olide, 1β,2α,3α-trihydroxy-19-oxo- 18,19-seco-urs-11,13(18)-dien-28-oic acid, and 2-O-benzoyl alphitolic acid based on extensive spectroscopic analyses. In vitro anti-inflammatory abilities to modulate the production of TNF-α, IL-1β, and IL-6 in LPS-induced RAW 264.7 macrophages of the compounds were determined. Rubuminatus A and B, as well as 1-oxo-siaresinolic acid and 2α,3α-dihydroxyolean-11,13(18)-dien-19β,28-olide, exhibited significant inhibitory effects on these cytokines. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Psychoneuroimmunological Role of Omega-3 Polyunsaturated Fatty Acids in Major Depressive Disorder and Bipolar Disorder.

PubMed

Rutkofsky, Ian Hunter; Khan, Anser Saeed; Sahito, Sindhu; Kumar, Vikram

2017-01-01

Context • Psychoneuroimmunology is the interdisciplinary study that links behavioral health with the neuroendocrinal system and investigates that link's bidirectional impact on the human immune system. Mechanistic studies have shown how omega-3 polyunsaturated fatty acids (PUFAs), like those found in fish oil, can modulate key pathways involved in inflammation, sympathetic activity, oxidative stress, transcription factors, and inflammatory cytokine production. Objective • The research team intended to investigate the effects that PUFAs have on the brain and the immune system, including the effects of proinflammatory cytokines and oxidative stress, and their therapeutic benefits in major depressive disorder (MDD) and bipolar disorder, either as an alternative monotherapy or a complementary adjunct treatment. Design • A literature search was conducted through PubMed and Google Scholar, with no restrictions on the publication dates or geographically. Setting • The research occurred at research facilities in Washington, DC, and Davis, California. Results • Well-described links between inflammation and MDD and bipolar disorder have been established. Similarly, a highly inflammatory state is a contributing factor to many significant health complications, and omega-3 PUFAs can help treat those issues. Conclusions • The research team concluded that omega-3 fatty acids have therapeutic benefits in the treatment of both MDD and bipolar disorder and are effective as a monotherapy and, particularly, as an adjunct therapy. The efficacy of omega-3 supplementation is clearly useful in promoting better health overall and supplementation should be encouraged in the primary care setting. A meta-analysis exploring an adjunct treatment of supplemental eicosapentaenoic acid or docosahexaenoic acid is likely to yield the greatest benefits to psychiatric conditions and provide an answer to proper dosing regimens. The team also created a chart of the supplements' salient

Design, Synthesis and Biological Evaluation of Betulinic Acid Derivatives as New Antitumor Agents for Leukemia.

PubMed

Waechter, Fernanda; da Silva, Gloria N S; Willig, Julia B; de Oliveira, Cristiane B; Vieira, Bruna D; Trivella, Daniela B B; Zimmer, Aline R; Buffon, Andreia; Pilger, Diogo A; Gnoatto, Simone C B

2017-01-01

Chronic myeloid leukemia (CML) is currently treated with imatinib, a Bcr-Abl inhibitor. However, resistance to this drug usually develops over time. Triptolide, a diterpenoid triepoxide, has been shown active against CML cells resistant to imatinib, acting mainly on the level of Bcr-Abl transcription inhibition. Here, we used the triterpene betulinic acid, a known proteasome inhibitor with potential antileukemic activity, as a scaffold for the generation of analogues with predicted triptolide biological activity. Betulinic acid derivatives were designed based on the structure-activity relationship of triptolide and evaluated for their cytotoxic effects in CML cells, lymphocytes and human keratinocytes (HaCaT), as well as against the proteasome complex. The main modification performed on betulinic acid was fluorination at C-28 and epoxidation, both of which are responsible for enhancing activity of triptolide. A total of 10 compounds were obtained: 6 previously described and 4 novel compounds. The cytotoxic activity over a CML cell line (K562) was assessed using flow cytometry and compared to lymphocytes and HaCaT. The results show that betulinic acid was the most cytotoxic compound against CML cells, showing a good selectivity index for cancer over normal cells. The most important trend for the activity in betulinic acid derivatives is the presence of a free hydroxyl group at C-3 and a carboxyl group at C-28. Results also indicated that the epoxide is important for enhancing the activity, while modification at C-28 worsens the activity. Proteasome inhibition assays suggest that proteasome is the main target for betulinic acid and its derivatives. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine

PubMed Central

Weerachayaphorn, Jittima; Mennone, Albert; Soroka, Carol J.; Harry, Kathy; Hagey, Lee R.; Kensler, Thomas W.

2012-01-01

The transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a key regulator for induction of hepatic detoxification and antioxidant mechanisms, as well as for certain hepatobiliary transporters. To examine the role of Nrf2 in bile acid homeostasis and cholestasis, we assessed the determinants of bile secretion and bile acid synthesis and transport before and after bile duct ligation (BDL) in Nrf2−/− mice. Our findings indicate reduced rates of biliary bile acid and GSH excretion, higher levels of intrahepatic bile acids, and decreased expression of regulators of bile acid synthesis, Cyp7a1 and Cyp8b1, in Nrf2−/− compared with wild-type control mice. The mRNA expression of the bile acid transporters bile salt export pump (Bsep) and organic solute transporter (Ostα) were increased in the face of impaired expression of the multidrug resistance-associated proteins Mrp3 and Mrp4. Deletion of Nrf2 also decreased ileal apical sodium-dependent bile acid transporter (Asbt) expression, leading to reduced bile acid reabsorption and increased loss of bile acid in feces. Finally, when cholestasis is induced by BDL, liver injury was not different from that in wild-type BDL mice. These Nrf2−/− mice also had increased pregnane X receptor (Pxr) and Cyp3a11 mRNA expression in association with enhanced hepatic bile acid hydroxylation. In conclusion, this study finds that Nrf2 plays a major role in the regulation of bile acid homeostasis in the liver and intestine. Deletion of Nrf2 results in a cholestatic phenotype but does not augment liver injury following BDL. PMID:22345550

Effect of tocopherols on the anti-polymerization activity of oryzanol and corn steryl ferulates in soybean oil

USDA-ARS?s Scientific Manuscript database

Steryl ferulates (SF) are ferulic acid esters of phytosterols and/or triterpene alcohols which have potential as frying oil antioxidants. The objective of this study was to evaluate the anti-polymerization and antioxidant activity at frying temperatures of corn steryl ferulates (CSF), rice steryl f...

Characterization of the major dehydrogenase related to d-lactic acid synthesis in Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293.

PubMed

Li, Ling; Eom, Hyun-Ju; Park, Jung-Mi; Seo, Eunyoung; Ahn, Ji Eun; Kim, Tae-Jip; Kim, Jeong Hwan; Han, Nam Soo

2012-10-10

Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 is a lactic acid bacterium that converts pyruvate mainly to d-(-)-lactic acid by using d-(-)-lactate dehydrogenase (ldhD). The aim of this study was to identify the gene responsible for d-lactic acid formation in this organism and to characterize the enzyme to facilitate the production of optically pure d-lactic acid. A genomic analysis of L. mesenteroides ATCC 8293 revealed that 7 genes encode lactate-related dehydrogenase. According to transcriptomic, proteomic, and phylogenetic analyses, LEUM_1756 was the major gene responsible for the production of d-lactic acid. The LEUM_1756 gene, of 996bp and encoding 332 amino acids (36.5kDa), was cloned and overexpressed in Escherichia coli BL21(DE3) Star from an inducible pET-21a(+) vector. The enzyme was purified by Ni-NTA column chromatography and showed a specific activity of 4450U/mg, significantly higher than those of other previously reported ldhDs. The gel permeation chromatography analysis showed that the purified enzyme exists as tetramers in solution and this was the first report among lactic acid bacteria. The pH and temperature optima were pH 8.0 and 30°C, respectively, for the pyruvate reduction reaction, and pH 11.0 and 20°C, respectively, for the lactate oxidation reaction. The K(m) kinetic parameters for pyruvate and lactate were 0.58mM and 260mM, respectively. In addition, the k(cat) values for pyruvate and lactate were 2900s(-1) and 2280s(-1), respectively. The enzyme was not inhibited by Ca(2+), Co(2+), Cu(2+), Mg(2+), Mn(2+), Na(+), or urea, but was inhibited by 1mM Zn(2+) and 1mM SDS. Copyright © 2012 Elsevier Inc. All rights reserved.

PgLOX6 encoding a lipoxygenase contributes to jasmonic acid biosynthesis and ginsenoside production in Panax ginseng

PubMed Central

Rahimi, Shadi; Kim, Yu-Jin; Sukweenadhi, Johan; Zhang, Dabing; Yang, Deok-Chun

2016-01-01

Ginsenosides, the valuable pharmaceutical compounds in Panax ginseng, are triterpene saponins that occur mainly in ginseng plants. It was shown that in vitro treatment with the phytohormone jasmonic acid (JA) is able to increase ginsenoside production in ginseng plants. To understand the molecular link between JA biosynthesis and ginsenoside biosynthesis, we identified a JA biosynthetic 13-lipoxygenase gene (PgLOX6) in P. ginseng that promotes ginsenoside production. The expression of PgLOX6 was high in vascular bundles, which corresponds with expression of ginsenoside biosynthetic genes. Consistent with the role of PgLOX6 in synthesizing JA and promoting ginsenoside synthesis, transgenic plants overexpressing PgLOX6 in Arabidopsis had increased amounts of JA and methyl jasmonate (MJ), increased expression of triterpene biosynthetic genes such as squalene synthase (AtSS1) and squalene epoxidase (AtSE1), and increased squalene content. Moreover, transgenic ginseng roots overexpressing PgLOX6 had around 1.4-fold increased ginsenoside content and upregulation of ginsenoside biosynthesis-related genes including PgSS1, PgSE1, and dammarenediol synthase (PgDDS), which is similar to that of treatment with MJ. However, MJ treatment of transgenic ginseng significantly enhanced JA and MJ, associated with a 2.8-fold increase of ginsenoside content compared with the non-treated, non-transgenic control plant, which was 1.4 times higher than the MJ treatment effect on non-transgenic plants. These results demonstrate that PgLOX6 is responsible for the biosynthesis of JA and promotion of the production of triterpenoid saponin through up-regulating the expression of ginsenoside biosynthetic genes. This work provides insight into the role of JA in biosynthesizing secondary metabolites and provides a molecular tool for increasing ginsenoside production. PMID:27811076

PgLOX6 encoding a lipoxygenase contributes to jasmonic acid biosynthesis and ginsenoside production in Panax ginseng.

PubMed

Rahimi, Shadi; Kim, Yu-Jin; Sukweenadhi, Johan; Zhang, Dabing; Yang, Deok-Chun

2016-11-01

Ginsenosides, the valuable pharmaceutical compounds in Panax ginseng, are triterpene saponins that occur mainly in ginseng plants. It was shown that in vitro treatment with the phytohormone jasmonic acid (JA) is able to increase ginsenoside production in ginseng plants. To understand the molecular link between JA biosynthesis and ginsenoside biosynthesis, we identified a JA biosynthetic 13-lipoxygenase gene (PgLOX6) in P. ginseng that promotes ginsenoside production. The expression of PgLOX6 was high in vascular bundles, which corresponds with expression of ginsenoside biosynthetic genes. Consistent with the role of PgLOX6 in synthesizing JA and promoting ginsenoside synthesis, transgenic plants overexpressing PgLOX6 in Arabidopsis had increased amounts of JA and methyl jasmonate (MJ), increased expression of triterpene biosynthetic genes such as squalene synthase (AtSS1) and squalene epoxidase (AtSE1), and increased squalene content. Moreover, transgenic ginseng roots overexpressing PgLOX6 had around 1.4-fold increased ginsenoside content and upregulation of ginsenoside biosynthesis-related genes including PgSS1, PgSE1, and dammarenediol synthase (PgDDS), which is similar to that of treatment with MJ. However, MJ treatment of transgenic ginseng significantly enhanced JA and MJ, associated with a 2.8-fold increase of ginsenoside content compared with the non-treated, non-transgenic control plant, which was 1.4 times higher than the MJ treatment effect on non-transgenic plants. These results demonstrate that PgLOX6 is responsible for the biosynthesis of JA and promotion of the production of triterpenoid saponin through up-regulating the expression of ginsenoside biosynthetic genes. This work provides insight into the role of JA in biosynthesizing secondary metabolites and provides a molecular tool for increasing ginsenoside production. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Structural basis for 18-β-glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor.

PubMed

Zhang, Hong; Huang, Qiang; Zhai, Jing; Zhao, Yi-ning; Zhang, Li-ping; Chen, Yun-yun; Zhang, Ren-wei; Li, Qing; Hu, Xiao-peng

2015-09-01

Glyoxalase I (GLOI), a glutathione (GSH)-dependent enzyme, is overexpressed in tumor cells and related to multi-drug resistance in chemotherapy, making GLOI inhibitors as potential anti-tumor agents. But the most studied GSH analogs exhibit poor pharmacokinetic properties. The aim of this study was to discover novel non-GSH analog GLOI inhibitors and analyze their binding mechanisms. Mouse GLOI (mGLOI) was expressed in BL21 (DE3) pLysS after induction with isopropyl-β-D-1-thiogalactopyranoside and purified using AKTA FPLC system. An in vitro mGLOI enzyme assay was used to screen a small pool of compounds containing carboxyl groups. Crystal structure of the mGLOI-inhibitor complex was determined at 2.3 Å resolution. Molecular docking study was performed using Discovery Studio 2.5 software package. A natural compound 18-β-glycyrrhetinic acid (GA) and its derivative carbenoxolone were identified as potent competitive non-GSH analog mGLOI inhibitors with Ki values of 0.29 μmol/L and 0.93 μmol/L, respectively. Four pentacyclic triterpenes (ursolic acid, oleanolic acid, betulic acid and tripterine) showed weak activities (mGLOI inhibition ratio <25% at 10 μmol/L) and other three (maslinic acid, corosolic acid and madecassic acid) were inactive. The crystal structure of the mGLOI-GA complex showed that the carboxyl group of GA mimicked the γ-glutamyl residue of GSH by hydrogen bonding to the glutamyl sites (residues Arg38B, Asn104B and Arg123A) in the GSH binding site of mGLOI. The extensive van der Waals interactions between GA and the surrounding residues also contributed greatly to the binding of GA and mGLOI. This work demonstrates a carboxyl group to be an important functional feature of non-GSH analog GLOI inhibitors.

Four new triterpene saponins from the seeds of Aesculus chinensis.

PubMed

Zhao, Jing; Yang, Xiu-Wei

2003-09-01

Two pairs of new geometrically isomeric triterpenoid saponins were isolated from the seeds of Aesculus chinensis and characterized as 28-acetyl-21-tigloylprotoaescigenin 3-O-[beta-D-xylopyranosyl (1 --> 2)] [beta-D-glucopyranosyl (1 --> 4)] [beta-D-glucopyranosiduronic acid (isoescin IIa, 1) and 28-acetyl-21-angeloylprotoaescigenin 3-O-[-beta-D-xylopyranosyl (1 --> 2)] [beta-D-glucopyranosyl (1 --> 4)] beta-D-glucopyranosiduronic acid (isoescin IIb, 2); 28-acetyl-21-tigloylbarringtogenol C 3-O-[beta-D-galactopyranosyl (1 --> 2)] [beta-D-glucopyranosyl (1 --> 4)] beta-D-glucopyranosiduronic acid (isoescin IIIa, 3) and 28-acetyl-21-angeloylbarringtogenol C 3-O-[beta-D-galactopyranosyl (1 --> 2)] [beta-D-glucopyranosyl (1 --> 4)] beta-D-glucopyranosiduronic acid (isoescin IIIb, 4). Their structures were established on the basis of spectroscopic and chemical evidence.

Erythrocyte membrane modifying agents and the inhibition of Plasmodium falciparum growth: structure-activity relationships for betulinic acid analogues.

PubMed

Ziegler, Hanne L; Franzyk, Henrik; Sairafianpour, Majid; Tabatabai, Mehrnoush; Tehrani, Mahboubeh D; Bagherzadeh, Karim; Hägerstrand, Henry; Staerk, Dan; Jaroszewski, Jerzy W

2004-01-02

The natural triterpene betulinic acid and its analogues (betulinic aldehyde, lupeol, betulin, methyl betulinate and betulinic acid amide) caused concentration-dependent alterations of erythrocyte membrane shape towards stomatocytes or echinocytes according to their hydrogen bonding properties. Thus, the analogues with a functional group having a capacity of donating a hydrogen bond (COOH, CH(2)OH, CONH(2)) caused formation of echinocytes, whereas those lacking this ability (CH(3), CHO, COOCH(3)) induced formation of stomatocytes. Both kinds of erythrocyte alterations were prohibitive with respect to Plasmodium falciparum invasion and growth; all compounds were inhibitory with IC(50) values in the range 7-28 microM, and the growth inhibition correlated well with the extent of membrane curvature changes assessed by transmission electron microscopy. Erythrocytes pre-loaded with betulinic acid or its analogues and extensively washed in order to remove excess of the chemicals could not serve as hosts for P. falciparum parasites. Betulinic acid and congeners can be responsible for in vitro antiplasmodial activity of plant extracts, as shown for Zataria multiflora Boiss. (Labiatae) and Zizyphus vulgaris Lam. (Rhamnaceae). The activity is evidently due to the incorporation of the compounds into the lipid bilayer of erythrocytes, and may be caused by modifications of cholesterol-rich membrane rafts, recently shown to play an important role in parasite vacuolization. The established link between erythrocyte membrane modifications and antiplasmodial activity may provide a novel target for potential antimalarial drugs.

Diterpenoids from Salvia ceratophylla.

PubMed

Gören, Ahmet C; Topçu, Gülaçti; Oksüz, Sevil; Kökdil, Gamze; Voelter, Wolfgang; Ulubelen, Ayhan

2002-02-01

Salvia ceratophylla L. has yielded four known and two new diterpenoids together with two triterpenic acids, a steroid and a flavone. The structures of the compounds were established by spectroscopic analyses. One of the known compounds candidissiol exhibited a high antibacterial activity against Staphylococcus epidermidis and Proteus mirabilis.

Pachymic acid inhibits growth and induces apoptosis of pancreatic cancer in vitro and in vivo by targeting ER stress.

PubMed

Cheng, Shujie; Swanson, Kristen; Eliaz, Isaac; McClintick, Jeanette N; Sandusky, George E; Sliva, Daniel

2015-01-01

Pachymic acid (PA) is a purified triterpene extracted from medicinal fungus Poria cocos. In this paper, we investigated the anticancer effect of PA on human chemotherapy resistant pancreatic cancer. PA triggered apoptosis in gemcitabine-resistant pancreatic cancer cells PANC-1 and MIA PaCa-2. Comparative gene expression array analysis demonstrated that endoplasmic reticulum (ER) stress was induced by PA through activation of heat shock response and unfolded protein response related genes. Induced ER stress was confirmed by increasing expression of XBP-1s, ATF4, Hsp70, CHOP and phospho-eIF2α. Moreover, ER stress inhibitor tauroursodeoxycholic acid (TUDCA) blocked PA induced apoptosis. In addition, 25 mg kg-1 of PA significantly suppressed MIA PaCa-2 tumor growth in vivo without toxicity, which correlated with induction of apoptosis and expression of ER stress related proteins in tumor tissues. Taken together, growth inhibition and induction of apoptosis by PA in gemcitabine-resistant pancreatic cancer cells were associated with ER stress activation both in vitro and in vivo. PA may be potentially exploited for the use in treatment of chemotherapy resistant pancreatic cancer.

Discovery and Development of Therapeutic Drugs against Lethal Human RNA Viruses: a Multidisciplinary Assault.

DTIC Science & Technology

1991-07-16

germacranolides, they also identified the two pentacyclic trzterpenes, lupeol and lupenone. In the present study, we found betulinic and ursolic acids as...O07 . tFurther elution with the same solvents yielded another minor product (22 mg), which proved to be ursolic acid , mp 26G-265’. Both triterpene...performed with ceric sulfate-sulfuric acid spray alcohol 5b (1.0 mg) in pyridine (0.2 mL) was added thionyl chloride reagent (heated at approximately 150 0 C

Back to Acid Soil Fields: The Citrate Transporter SbMATE Is a Major Asset for Sustainable Grain Yield for Sorghum Cultivated on Acid Soils.

PubMed

Carvalho, Geraldo; Schaffert, Robert Eugene; Malosetti, Marcos; Viana, Joao Herbert Moreira; Menezes, Cicero Bezerra; Silva, Lidianne Assis; Guimaraes, Claudia Teixeira; Coelho, Antonio Marcos; Kochian, Leon V; van Eeuwijk, Fred A; Magalhaes, Jurandir Vieira

2015-12-17

Aluminum (Al) toxicity damages plant roots and limits crop production on acid soils, which comprise up to 50% of the world's arable lands. A major Al tolerance locus on chromosome 3, AltSB, controls aluminum tolerance in sorghum [Sorghum bicolor (L.) Moench] via SbMATE, an Al-activated plasma membrane transporter that mediates Al exclusion from sensitive regions in the root apex. As is the case with other known Al tolerance genes, SbMATE was cloned based on studies conducted under controlled environmental conditions, in nutrient solution. Therefore, its impact on grain yield on acid soils remains undetermined. To determine the real world impact of SbMATE, multi-trait quantitative trait loci (QTL) mapping in hydroponics, and, in the field, revealed a large-effect QTL colocalized with the Al tolerance locus AltSB, where SbMATE lies, conferring a 0.6 ton ha(-1) grain yield increase on acid soils. A second QTL for Al tolerance in hydroponics, where the positive allele was also donated by the Al tolerant parent, SC283, was found on chromosome 9, indicating the presence of distinct Al tolerance genes in the sorghum genome, or genes acting in the SbMATE pathway leading to Al-activated citrate release. There was no yield penalty for AltSB, consistent with the highly localized Al regulated SbMATE expression in the root tip, and Al-dependent transport activity. A female effect of 0.5 ton ha(-1) independently demonstrated the effectiveness of AltSB in hybrids. Al tolerance conferred by AltSB is thus an indispensable asset for sorghum production and food security on acid soils, many of which are located in developing countries. Copyright © 2016 Carvalho et al.

Four new dammarane-type triterpene saponins from the stems and leaves of Panax ginseng and their cytotoxicity on HL-60 cells.

PubMed

Li, Ke-Ke; Yao, Chun-Mei; Yang, Xiu-Wei

2012-01-01

Four new triterpene saponins, ginsenosides Rh(14)-Rh(17)(1- 4), along with two known compounds, 20(S)-ginsenoside Rg₂ and dammar-(E)-20(22),24-diene-3 β,6 α,12 β-triol, were isolated from the stems and leaves of Panax ginseng. The structures of the new compounds were elucidated as 3 β,6 α,12 β,24 ξ-tetrahydroxy-dammar-(E)-20(22),25-diene 6- O- α- L-rhamnopyranosyl-(1 → 2)- β-D-glucopyranoside (1), 3 β,12 β,24 ξ-trihydroxy-dammar-(E)-20(22),25-diene 3- O- β- D-glucopyranosyl-(1 → 2)- β-D-glucopyranoside (2), 3 β,6 α,12 β-trihydroxy-dammar-(E)-20(22),24-diene 3-O-β-D-glucopyranoside (3), and 3-oxo-6 α,12 β,20(S)-trihydroxy-dammar-24-ene 6-O-α-L-rhamnopyranosyl-(1 → 2)-β-D-glucopyranoside (4) by means of extensive spectroscopic and chemical methods, respectively. The isolated compounds were tested for IN VITRO cytotoxicity against HL-60 cells. © Georg Thieme Verlag KG Stuttgart · New York.

Acid Earth--The Global Threat of Acid Pollution.

ERIC Educational Resources Information Center

McCormick, John

Acid pollution is a major international problem, but the debate it has elicited has often clouded the distinction between myth and facts. This publication attempts to concerning the acid pollution situation. This publication attempts to identify available facts. It is the first global review of the problem of acid pollution and the first to…

Assessing chemical constituents of Mimosa caesalpiniifolia stem bark: possible bioactive components accountable for the cytotoxic effect of M. caesalpiniifolia on human tumour cell lines.

PubMed

Monção, Nayana Bruna Nery; Araújo, Bruno Quirino; Silva, Jurandy do Nascimento; Lima, Daisy Jereissati Barbosa; Ferreira, Paulo Michel Pinheiro; Airoldi, Flavia Pereira da Silva; Pessoa, Cláudia; Citó, Antonia Maria das Graças Lopes

2015-03-05

Mimosa caesalpiniifolia is a native plant of the Brazilian northeast, and few studies have investigated its chemical composition and biological significance. This work describes the identification of the first chemical constituents in the ethanolic extract and fractions of M. caesalpiniifolia stem bark based on NMR, GC-qMS and HRMS analyses, as well as an assessment of their cytotoxic activity. GC-qMS analysis showed fatty acid derivatives, triterpenes and steroid substances and confirmed the identity of the chemical compounds isolated from the hexane fraction. Metabolite biodiversity in M. caesalpiniifolia stem bark revealed the differentiated accumulation of pentacyclic triterpenic acids, with a high content of betulinic acid and minor amounts of 3-oxo and 3β-acetoxy derivatives. Bioactive analysis based on total phenolic and flavonoid content showed a high amount of these compounds in the ethanolic extract, and ESI-(-)-LTQ-Orbitrap-MS identified caffeoyl hexose at high intensity, as well as the presence of phenolic acids and flavonoids. Furthermore, the evaluation of the ethanolic extract and fractions, including betulinic acid, against colon (HCT-116), ovarian (OVCAR-8) and glioblastoma (SF-295) tumour cell lines showed that the crude extract, hexane and dichloromethane fractions possessed moderate to high inhibitory activity, which may be related to the abundance of betulinic acid. The phytochemical and biological study of M. caesalpiniifolia stem bark thus revealed a new alternative source of antitumour compounds, possibly made effective by the presence of betulinic acid and by chemical co-synergism with other compounds.

A Structural Basis for the Biosynthesis of the Major Chlorogenic Acids Found in Coffee1[W][OA

PubMed Central

Lallemand, Laura A.; Zubieta, Chloe; Lee, Soon Goo; Wang, Yechun; Acajjaoui, Samira; Timmins, Joanna; McSweeney, Sean; Jez, Joseph M.; McCarthy, James G.; McCarthy, Andrew A.

2012-01-01

Chlorogenic acids (CGAs) are a group of phenolic secondary metabolites produced by certain plant species and an important component of coffee (Coffea spp.). The CGAs have been implicated in biotic and abiotic stress responses, while the related shikimate esters are key intermediates for lignin biosynthesis. Here, two hydroxycinnamoyl-coenzyme A shikimate/quinate hydroxycinnamoyl transferases (HCT/HQT) from coffee were biochemically characterized. We show, to our knowledge for the first time, that in vitro, HCT is capable of synthesizing the 3,5-O-dicaffeoylquinic acid diester, a major constituent of the immature coffee grain. In order to further understand the substrate specificity and catalytic mechanism of the HCT/HQT, we performed structural and mutagenesis studies of HCT. The three-dimensional structure of a native HCT and a proteolytically stable lysine mutant enabled the identification of important residues involved in substrate specificity and catalysis. Site-directed mutagenesis confirmed the role of residues leucine-400 and phenylalanine-402 in substrate specificity and of histidine-153 and the valine-31 to proline-37 loop in catalysis. In addition, the histidine-154-asparagine mutant was observed to produce 4-fold more dichlorogenic acids compared with the native protein. These data provide, to our knowledge, the first structural characterization of a HCT and, in conjunction with the biochemical and mutagenesis studies presented here, delineate the underlying molecular-level determinants for substrate specificity and catalysis. This work has potential applications in fine-tuning the levels of shikimate and quinate esters (CGAs including dichlorogenic acids) in different plant species in order to generate reduced or elevated levels of the desired target compounds. PMID:22822210

Influence of gastrointestinal digestion and edible plant combination on oral bioavailability of triterpene saponins, using a biomimetic digestion and absorption system and determination by HPLC.

PubMed

Li, Shun-Xing; Mu, Yang; Zheng, Feng-Ying

2013-11-06

Saponins have many biological activities, but their overload could cause toxicity to the human body. Bionic gastrointestinal digestion and monolayer liposome extraction were used for oral bioavailability assessment of triterpene saponins (notoginsenoside R1, ginsenosides Rb1 and Rd1) in an edible herb (San-Chi) and its compound herbal medicine (Pien Tze Huang, PZH). The concentrations of affinity-monolayer liposome saponins in the chyme were determined by HPLC and used for oral bioavailability assessment. With the digestion of San-Chi and PZH from the stomach to the intestine, the release of saponins in their chyme was increased. The intestinal absorption ratios of N-R1, G-Rb1, G-Rd1, and total saponins from San-Chi were 86.57, 18.56, 73.30, and 40.20%, respectively, which were more than those from PZH (i.e., 19.56, 10.11, 30.11, and 16.08%). The oral bioavailability of saponins was controlled by saponin species, gastrointestinal digestion, and edible plants combination.

Maternal and Fetal Acid-Base Chemistry: A Major Determinant of Perinatal Outcome

PubMed Central

Omo-Aghoja, L

2014-01-01

Very small changes in pH may significantly affect the function of various fetal organ systems, such as the central nervous system, and the cardiovascular system with associated fetal distress and poor Apgar score. Review of existing data on maternal-fetal acid-base balance in pregnancy highlight the factors that are associated with derangements of the acid-base status and the impact of the derangements on fetal outcome. Extensive search of electronic databases and manual search of journals for relevant literature on maternal and fetal acid chemistry, clinical studies and case studies were undertaken. There is a substantial reduction in the partial pressure of carbon dioxide (pCO2) in pregnancy. Adequate buffering prevents significant changes in maternal arterial pH. Normal fetal metabolism results in the production of acids which are buffered to maintain extracellular pH within a critical range. Fetal hypoxia can occur when maternal oxygenation is compromised, maternal perfusion of the placenta is reduced, or delivery of oxygenated blood from the placenta to the fetus is impeded. When adequate fetal oxygenation does not occur, metabolisms proceed along with an anaerobic pathway with production of organic acids, such as lactic acid. Accumulation of lactic acid can deplete the buffer system and result in metabolic acidosis with associated low fetal pH, fetal distress and poor Apgar score. There is a significant reduction in pCO2 in pregnancy. This change, however, does not result in a corresponding significant reduction in maternal arterial pH, because of adequate buffering. Very small changes in pH may cause significant derangement in fetal function and outcome. PMID:24669324

Maternal and fetal Acid-base chemistry: a major determinant of perinatal outcome.

PubMed

Omo-Aghoja, L

2014-01-01

Very small changes in pH may significantly affect the function of various fetal organ systems, such as the central nervous system, and the cardiovascular system with associated fetal distress and poor Apgar score. Review of existing data on maternal-fetal acid-base balance in pregnancy highlight the factors that are associated with derangements of the acid-base status and the impact of the derangements on fetal outcome. Extensive search of electronic databases and manual search of journals for relevant literature on maternal and fetal acid chemistry, clinical studies and case studies were undertaken. There is a substantial reduction in the partial pressure of carbon dioxide (pCO2) in pregnancy. Adequate buffering prevents significant changes in maternal arterial pH. Normal fetal metabolism results in the production of acids which are buffered to maintain extracellular pH within a critical range. Fetal hypoxia can occur when maternal oxygenation is compromised, maternal perfusion of the placenta is reduced, or delivery of oxygenated blood from the placenta to the fetus is impeded. When adequate fetal oxygenation does not occur, metabolisms proceed along with an anaerobic pathway with production of organic acids, such as lactic acid. Accumulation of lactic acid can deplete the buffer system and result in metabolic acidosis with associated low fetal pH, fetal distress and poor Apgar score. There is a significant reduction in pCO2 in pregnancy. This change, however, does not result in a corresponding significant reduction in maternal arterial pH, because of adequate buffering. Very small changes in pH may cause significant derangement in fetal function and outcome.

Acidic Residues Control the Dimerization of the N-terminal Domain of Black Widow Spiders’ Major Ampullate Spidroin 1

NASA Astrophysics Data System (ADS)

Bauer, Joschka; Schaal, Daniel; Eisoldt, Lukas; Schweimer, Kristian; Schwarzinger, Stephan; Scheibel, Thomas

2016-09-01

Dragline silk is the most prominent amongst spider silks and comprises two types of major ampullate spidroins (MaSp) differing in their proline content. In the natural spinning process, the conversion of soluble MaSp into a tough fiber is, amongst other factors, triggered by dimerization and conformational switching of their helical amino-terminal domains (NRN). Both processes are induced by protonation of acidic residues upon acidification along the spinning duct. Here, the structure and monomer-dimer-equilibrium of the domain NRN1 of Latrodectus hesperus MaSp1 and variants thereof have been investigated, and the key residues for both could be identified. Changes in ionic composition and strength within the spinning duct enable electrostatic interactions between the acidic and basic pole of two monomers which prearrange into an antiparallel dimer. Upon naturally occurring acidification this dimer is stabilized by protonation of residue E114. A conformational change is independently triggered by protonation of clustered acidic residues (D39, E76, E81). Such step-by-step mechanism allows a controlled spidroin assembly in a pH- and salt sensitive manner, preventing premature aggregation of spider silk proteins in the gland and at the same time ensuring fast and efficient dimer formation and stabilization on demand in the spinning duct.

Growth, fatty acid profile in major lipid classes and lipid fluidity of Aurantiochytrium mangrovei SK-02 As a function of growth temperature.

PubMed

Chodchoey, Kanokwan; Verduyn, Cornelis

2012-01-01

Aurantiochytrium mangrovei Sk-02 was grown in a medium containing glucose (40 g/l), yeast extract (10 g/L) and sea salts (15 g/L) at temperatures ranging from 12 to 35°C. The fastest growth (µmax= 0.15 h(-1)) and highest fatty acid content of 415 mg/g-dry cell weight were found in the cells grown at 30°C. However, the cells grown at 12°C showed the highest percentage of polyunsaturated fatty acid (PUFA) (48.6% of total fatty acid). The percentage of docosahexaenoic acid (DHA) and pentadecanoic acid (C15:0) decreased with an increase in the growth temperature, whereas, palmitic acid (C16:0), stearic acid (C18:0) and DPA (C22:5n6) increased with an increase in the growth temperature. The composition of the major lipid class (%w/w) was slightly affected by the growth temperature. The fluidity of the organelle membrane or intracellular lipid (by DPH measurement) decreased with an increase in the growth temperatures, while the plasma membrane fluidity (by TMA-DPH measurement) could still maintain its fluidity in a wide range of temperatures (15 - 37°C). Furthermore, the distribution of DHA was found to be higher (36 - 54%) in phospholipid (PL) as compared to neutral lipid (NL) (20 - 41%).

Terminalia laxiflora and Terminalia brownii contain a broad spectrum of antimycobacterial compounds including ellagitannins, ellagic acid derivatives, triterpenes, fatty acids and fatty alcohols.

PubMed

Salih, Enass Y A; Julkunen-Tiitto, Riitta; Lampi, Anna-Maija; Kanninen, Markku; Luukkanen, Olavi; Sipi, Marketta; Lehtonen, Mari; Vuorela, Heikki; Fyhrquist, Pia

2018-05-04

LH- 20 acetone fraction, while ellagic acid xyloside and methyl ellagic acid xyloside are suggested to give good antimycobacterial activity in the Sephadex LH-20 ethanol fraction. RP-18 TLC purifications of an ethyl acetate extract of T. laxiflora roots resulted in the enrichment of punicalagin in one of the fractions (Fr5). This fraction gave a five times smaller MIC (500µg/ml) than the crude ethyl acetate extract (2500µg/ml) and this improved activity is suggested to be mostly due to punicalagin. 1,18-octadec-9-ene-dioate, stigmast-4-en-3-one, 5α-stigmastan-3,6-dione, triacontanol, sitostenone and β-sitosterol were found in antimycobacterial hexane extracts of the stem bark of both studied species. Of these compounds, 1,18-octadec-9-ene-dioate, stigmast-4-en-3-one, 5α-stigmastan-3,6-dione, triacontanol, sitostenone have not been previously identified in T. brownii and T. laxiflora. Moreover, both plant species contained friedelin, betulinic acid, β-amyrine and two unknown oleanane-type triterpenoids. Of the listed compounds, friedelin, triacontanol and sitostenone gave a MIC of 250µg/ml against M. smegmatis, whereas stigmasterol and β-sitosterol gave MIC values of 500µg/ml. Our results show that T. laxiflora and T. brownii contain antimycobacterial compounds of diverse polarities and support the traditional uses of various parts of T. laxiflora and T.brownii as decoctions for treatment of tuberculosis. Further investigations are warranted to explore additional (new) antimycobacterial compounds in the active extracts of T. laxiflora and T. brownii. Copyright © 2018. Published by Elsevier B.V.

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) and the major constituent, xylopic acid in murine models.

PubMed

Woode, Eric; Ameyaw, Elvis O; Boakye-Gyasi, Eric; Abotsi, Wonder K M

2012-10-01

Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE) and xylopic acid (XA), in murine models. XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (Tail-flick and Hargreaves thermal hyperalgesia tests), and mechanical (Randall-Selitto paw pressure test) pain models. XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg(-1), p.o.) and XA (10-100 mg kg(-1), p.o.) inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg(-1), i.p.) and diclofenac (1-10 mg kg(-1), i.p.), used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid.

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) and the major constituent, xylopic acid in murine models

PubMed Central

Woode, Eric; Ameyaw, Elvis O.; Boakye-Gyasi, Eric; Abotsi, Wonder K. M.

2012-01-01

Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE) and xylopic acid (XA), in murine models. Materials and Methods: XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (Tail-flick and Hargreaves thermal hyperalgesia tests), and mechanical (Randall-Selitto paw pressure test) pain models. Results: XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg-1, p.o.) and XA (10-100 mg kg-1, p.o.) inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg-1, i.p.) and diclofenac (1-10 mg kg-1, i.p.), used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. Conclusions: These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid. PMID:23248562

Preparation of the 3-monosulphates of cholic acid, chenodeoxycholic acid and deoxycholic acid.

PubMed Central

Haslewood, E S; Haslewood, G A

1976-01-01

1. The 3-sulphates of cholic, chenodeoxycholic and deoxycholic acids were prepared as crystalline disodium salts. 2. The method described shows that it is possible to prepare specific sulphate esters of polyhydroxy bile acids and to remove protecting acyl groups without removing the sulphate. 3. A study of bile acid sulphate solvolysis showed that none of the usual methods give the original bile acid in major yield in a single step. 4. An understanding of the preparation, properties and methods of solvolysis of bile acid sulphates is basic for investigations of cholestasis and liver disease. PMID:938488

Screening of analgesic activity of Tunisian Urtica dioica and analysis of its major bioactive compounds by GCMS.

PubMed

Dhouibi, Raouia; Moalla, Dorsaf; Ksouda, Kamilia; Ben Salem, Maryem; Hammami, Serria; Sahnoun, Zouheir; Zeghal, Khaled Mounir; Affes, Hanen

2017-11-20

The present study was aimed to evaluate the analgesic properties of Urtica dioica (UD) and to profile phytochemicals by gas chromatography-mass spectrometry (GC-MS). The ethanolic extracts were prepared by maceration method and extraction using rotary evaporator. The analgesic activity was analysed by hot plate method, formalin test, acetic acid-induced writhing test and the tail-flick test with different doses of the ethanolic extract. In all tests, the leaf's ethanolic extract exhibited significant analgesic activity (p < .001) at a dose of 400 mg/kg. Even with a low dose, we noticed an analgesic activity with many tests. The GC-MS analysis of the ethanol extract of leaf revealed many compounds; 2-methyltetradecane dodecane, 2,6,11-trimethyl-; 2,6,11-trimethyldodecane, and trimethylhexane which are pharmaceutically the most important. These findings justify that UD can be a valuable natural analgesic source which seemed to provide potential phototherapeutics against various ailments. The analysis of ethanolic extract of UD by GCMS revealed the presence of several compounds including polyphenols, flavonoids, triterpenes which can explain the analgesic effect of UD and its mechanism of action. Hence, UD could be another therapeutic alternative for relieving pain and for minimising the use of drugs that have long-term secondary effects.

Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial.

PubMed

Armitage, Jane M; Bowman, Louise; Clarke, Robert J; Wallendszus, Karl; Bulbulia, Richard; Rahimi, Kazem; Haynes, Richard; Parish, Sarah; Sleight, Peter; Peto, Richard; Collins, Rory

2010-06-23

Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal. To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12) on vascular and nonvascular outcomes. Double-blind randomized controlled trial of 12,064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008. 2 mg folic acid plus 1 mg vitamin B(12) daily vs matching placebo. First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization. Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B(12) vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]). Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence. isrctn.org Identifier: ISRCTN74348595.

Antioxidants in Greek Virgin Olive Oils

PubMed Central

Kalogeropoulos, Nick; Tsimidou, Maria Z.

2014-01-01

Greece is ranked third after Spain and Italy in virgin olive oil production. The number of Greek olive cultivars—excluding clonal selections—is greater than 40; however, more than 90% of the acreage is cultivated with 20 cultivars, adapted to a wide range of environmental conditions. Greek virgin olive oils, produced mainly with traditional, non-intensive cultivation practices, are mostly of exceptional quality. The benefits of consuming virgin olive oil, originally attributed to its high oleic acid content, are now considered to be the combined result of several nutrient and non-nutrient phytochemicals. The present work summarizes available data regarding natural antioxidants in Greek virgin olive oils (VOO) namely, polar phenolic compounds, tocopherols, squalene, and triterpenic acids. The literature survey indicated gaps in information, which should be filled in the near future so that the intrinsic properties of this major agricultural product of Greece will be substantiated on a solid scientific basis. PMID:26784878

Laticifer-Specific cis-Prenyltransferase Silencing Affects the Rubber, Triterpene, and Inulin Content of Taraxacum brevicorniculatum12[C][W

PubMed Central

Post, Janina; van Deenen, Nicole; Fricke, Julia; Kowalski, Natalie; Wurbs, David; Schaller, Hubert; Eisenreich, Wolfgang; Huber, Claudia; Twyman, Richard M.; Prüfer, Dirk; Gronover, Christian Schulze

2012-01-01

Certain Taraxacum species, such as Taraxacum koksaghyz and Taraxacum brevicorniculatum, produce large amounts of high-quality natural rubber in their latex, the milky cytoplasm of specialized cells known as laticifers. This high-molecular mass biopolymer consists mainly of poly(cis-1,4-isoprene) and is deposited in rubber particles by particle-bound enzymes that carry out the stereospecific condensation of isopentenyl diphosphate units. The polymer configuration suggests that the chain-elongating enzyme (rubber transferase; EC 2.5.1.20) is a cis-prenyltransferase (CPT). Here, we present a comprehensive analysis of transgenic T. brevicorniculatum plants in which the expression of three recently isolated CPTs known to be associated with rubber particles (TbCPT1 to -3) was heavily depleted by laticifer-specific RNA interference (RNAi). Analysis of the CPT-RNAi plants by nuclear magnetic resonance, size-exclusion chromatography, and gas chromatography-mass spectrometry indicated a significant reduction in rubber biosynthesis and a corresponding 50% increase in the levels of triterpenes and the main storage carbohydrate, inulin. Transmission electron microscopy revealed that the laticifers in CPT-RNAi plants contained fewer and smaller rubber particles than wild-type laticifers. We also observed lower activity of hydroxymethylglutaryl-coenzyme A reductase, the key enzyme in the mevalonate pathway, reflecting homeostatic control of the isopentenyl diphosphate pool. To our knowledge, this is the first in planta demonstration of latex-specific CPT activity in rubber biosynthesis. PMID:22238421

Extraction, Identification and Biological Activities of Saponins in Sea Cucumber Pearsonothuria graeffei.

PubMed

Khattab, Rafat Afifi; Elbandy, Mohamed; Lawrence, Andrew; Paget, Tim; Rae-Rho, Jung; Binnaser, Yaser S; Ali, Imran

2018-01-01

Secondary metabolism in marine organisms produces a diversity of biologically important natural compounds that are not present in terrestrial species. Sea cucumbers belong to the invertebrate Echinodermata and are famous for their nutraceutical, medical and food values. They are known for possession triterpenoid glycosides (saponins) with various ecological roles. The current work aimed to separate, identify and test various biological activities (antibacterial, antifungal, antileishmanial and anticancer properties) of saponins produced by the holothurian Pearsonothuria graeffei from the Red Sea, Egypt. The structures were identified by 1D and 2D NMR (1H, 13C, TOCSY, COSY, HSQC, HMBC, and ROESY) experiments and acid hydrolysis. The crude and purified fractions was analyzed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)/MS to identify saponins and characterize their molecular structures. Partially purified fraction, mainly containing compounds 1 and 2, was screened for its antifungal activity against three clinical isolates of Candida albicans (Candida 580 (1), Candida 581(2) and Candida MEO47228. Antileishmanial activity against Leishmania major and toxicity on colon cell-line were also evaluated. Two lanostane type sulfated triterpene monoglycosides were isolated from the Holothurian Pearsonothuria graeffei from the Red Sea, Egypt. Holothurin A (1) and echinoside A (2) triterpene saponins were separated by reversed phase semi-preparative HPLC. LC50 values (µg/mL); calculated for the fraction containing saponins 1 and 2 as major constituents; against Candida albicans, Leishmania major and colon cell-line were 10, 20 and 0.50, respectively. Consequently, this study demonstrated the potential use of sea cucumber Pearsonothuria graeffei not only as appreciated functional food or nutraceuticals but also as the source of functional ingredients for pharmaceutical products with antifungal, antileishmanial and anticancer properties

Chemical composition of South American Burseraceae non-volatile oleoresins and preliminary solubility assessment of their commercial blend.

PubMed

Siani, A C; Nakamura, M J; Tappin, M R R; Monteiro, S S; Guimarães, A C; Ramos, M F S

2012-01-01

Non-volatile oleoresins from neotropical Burseraceae are traditionally used for craft, technological and medicinal purposes. The crude resin is usually sold in popular markets of the forest communities. Adding value to this rainforest raw material requires establishing its composition. To analyse the resin composition from different Burseraceae species and establish a minimally reproducible profile by gas chromatography, in order to parameterise its quality control. Crude oleoresin samples of 10 Protium and Trattinnickia species and a commercial blend were subjected to hydrodistillation to remove volatile compounds. The chloroform-soluble residues were methylated, analysed by GC-FID (flame ionisation detection), and individual components were identified by analysing their mass fragmentation pattern in GC-MS and comparison with data from the literature. The blend solubility was assayed in 30 non-chlorinated solvents at three different proportions. The resins consisted exclusively of triterpenes, showing a common predominance of four major compounds in all the samples, corresponding to α-amyrin, β-amyrin, α-amyrenone and β-amyrenone. This profile was complemented with minor amounts of the tetracyclic β-elemolic and α-elemolic acids, maniladiol, brein and other oxidised trace compounds. The better solvents for the resin were those chemically bearing more than four carbon atoms, as n-butyl acetate, 2-ethoxyethanol and isopropanol. The crude resin blend sold contained around 10% of insoluble material that was constituted by up to 70% inorganic residues mixed with humic acid derivatives, as attested by ash analysis and IR spectroscopy, respectively. The experimental results, complemented by a general inspection of the literature, demonstrated a systematically reproducible triterpene profile in Protium and Trattinnickia species. Copyright © 2012 John Wiley & Sons, Ltd.

Determination of 13-cis-retinoic acid and its major metabolite, 4-oxo-13-cis-retinoic acid, in human blood by reversed-phase high-performance liquid chromatography.

PubMed

Vane, F M; Stoltenborg, J K; Buggé, C J

1982-02-12

A high-performance liquid chromatography (HPLC) method for the quantitation of 13-cis-retinoic acid (13-cis-RA) and its major metabolite, 4-oxo-13-cis-RA, in human blood has been developed. The method includes extraction of 1 ml of blood with diethyl ether at pH 6 and the analysis of the extract by reversed-phase HPLC with solvent programming and detection at 365 nm. The quantitation ranges for 13-cis-RA and 4-oxo-13-cis-RA are 10--2000 and 50--2000 ng/ml of blood, respectively. The method also provides estimates of the concentrations of all-trans-RA and 4-oxo-all-trans-RA. The mean intra- and inter-assay variabilities for all four compounds were 6% or less. The method separates 13-cis-RA and 4-oxo-13-cis-RA from 9-cis-RA, all-trans-RA, 4-oxo-all-trans-RA, and some other possible metabolites, such as hydroxy and epoxy retinoic acids. The method has been successfully applied to the analyses of over 1200 blood samples from four 13-cis-RA clinical studies.

Methyl jasmonate and yeast elicitor induce differential transcriptional and metabolic re-programming in cell suspension cultures of the model legume Medicago truncatula.

PubMed

Suzuki, Hideyuki; Reddy, M S Srinivasa; Naoumkina, Marina; Aziz, Naveed; May, Gregory D; Huhman, David V; Sumner, Lloyd W; Blount, Jack W; Mendes, Pedro; Dixon, Richard A

2005-03-01

Exposure of cell suspension cultures of Medicago truncatula Gaerth. to methyl jasmonate (MeJA) resulted in up to 50-fold induction of transcripts encoding the key triterpene biosynthetic enzyme beta-amyrin synthase (betaAS; EC 5.4.99.-). Transcripts reached maximum levels at 24 h post-elicitation with 0.5 mM MeJA. The entry point enzymes into the phenylpropanoid and flavonoid pathways, L: -phenylalanine ammonia-lyase (PAL; EC 4.3.1.5) and chalcone synthase (CHS; EC 2.3.1.74), respectively, were not induced by MeJA. In contrast, exposure of cells to yeast elicitor (YE) resulted in up to 45- and 14-fold induction of PAL and CHS transcripts, respectively, at only 2 h post-elicitation. betaAS transcripts were weakly induced at 12 h after exposure to YE. Over 30 different triterpene saponins were identified in the cultures, many of which were strongly induced by MeJA, but not by YE. In contrast, cinnamic acids, benzoic acids and isoflavone-derived compounds accumulated following exposure of cultures to YE, but few changes in phenylpropanoid levels were observed in response to MeJA. DNA microarray analysis confirmed the strong differential transcriptional re-programming of the cell cultures for multiple genes in the phenylpropanoid and triterpene pathways in response to MeJA and YE, and indicated different responses of individual members of gene families. This work establishes Medicago cell cultures as an excellent model for future genomics approaches to understand the regulation of legume secondary metabolism.

Lanostane Triterpenes from the Tibetan Medicinal Mushroom Ganoderma leucocontextum and Their Inhibitory Effects on HMG-CoA Reductase and α-Glucosidase.

PubMed

Wang, Kai; Bao, Li; Xiong, Weiping; Ma, Ke; Han, Junjie; Wang, Wenzhao; Yin, Wenbing; Liu, Hongwei

2015-08-28

Sixteen new lanostane triterpenes, ganoleucoins A-P (1-16), together with 10 known tripterpenes (17-26), were isolated from the cultivated fruiting bodies of Ganoderma leucocontextum, a new member of the Ganoderma lucidum complex. The structures of the new compounds were elucidated by extensive spectroscopic analysis and chemical transformation. The inhibitory effects of 1-26 on HMG-CoA reductase and α-glucosidase were tested in vitro. Compounds 1, 3, 6, 10-14, 17, 18, 23, 25, and 26 showed much stronger inhibitory activity against HMG-CoA reductase than the positive control atorvastatin. Compounds 13, 14, and 16 presented potent inhibitory activity against α-glucosidase from yeast with IC₅₀ values of 13.6, 2.5, and 5.9 μM, respectively. In addition, the cytotoxicity of 1-26 was evaluated against the K562 and PC-3 cell lines by the MTT assay. Compounds 1, 2, 6, 7, 10, 12, 16, 18, and 25 exhibited cytotoxicity against K562 cells with IC₅₀ values in the range 10-20 μM. Paclitaxel was used as the positive control with an IC₅₀ value of 0.9 μM. This is the first report of secondary metabolites from this medicinal mushroom.

Reversed electrogenic sodium bicarbonate cotransporter 1 is the major acid loader during recovery from cytosolic alkalosis in mouse cortical astrocytes

PubMed Central

Theparambil, Shefeeq M; Naoshin, Zinnia; Thyssen, Anne; Deitmer, Joachim W

2015-01-01

Recovery of intracellular pH from cytosolic alkalosis has been attributed primarily to Cl– coupled acid loaders/base extruders such as Cl–/HCO3– or Cl–/OH– exchangers. We have studied this process in cortical astrocytes from wild-type and transgenic mouse models with gene deletion for the electrogenic sodium bicarbonate cotransporter 1 (NBCe1) and for carbonic anhydrase (CA) isoform II. An acute cytosolic alkalosis was induced by the removal of either CO2/HCO3– or butyric acid, and the subsequent acid loading was analysed by monitoring changes in cytosolic H+ or Na+ using ion-sensitive fluorescent dyes. We have identified that NBCe1 reverses during alkalosis and contributes more than 70% to the rate of recovery from alkalosis by extruding Na+ and HCO3–. After CA inhibition or in CAII-knockout (KO) cells, the rate of recovery was reduced by 40%, and even by 70% in the nominal absence of CO2/HCO3–. Increasing the extracellular K+ concentration modulated the rate of acid loading in wild-type cells, but not in NBCe1-KO cells. Removing chloride had only a minor effect on the recovery from alkalosis. Reversal of NBCe1 by reducing pH/[HCO3–] was demonstrated in astrocytes and in Xenopus oocytes, in which human NBCe1 was heterologously expressed. The results obtained suggest that reversed NBCe1, supported by CAII activity, plays a major role in acid-loading cortical astrocytes to support recovery from cytosolic alkalosis. PMID:25990710

The design, synthesis and structure-activity relationships associated with C28 amine-based betulinic acid derivatives as inhibitors of HIV-1 maturation.

PubMed

Chen, Yan; Sit, Sing-Yuen; Chen, Jie; Swidorski, Jacob J; Liu, Zheng; Sin, Ny; Venables, Brian L; Parker, Dawn D; Nowicka-Sans, Beata; Lin, Zeyu; Li, Zhufang; Terry, Brian J; Protack, Tricia; Rahematpura, Sandhya; Hanumegowda, Umesh; Jenkins, Susan; Krystal, Mark; Dicker, Ira D; Meanwell, Nicholas A; Regueiro-Ren, Alicia

2018-05-15

The design and synthesis of a series of C28 amine-based betulinic acid derivatives as HIV-1 maturation inhibitors is described. This series represents a continuation of efforts following on from previous studies of C-3 benzoic acid-substituted betulinic acid derivatives as HIV-1 maturation inhibitors (MIs) that were explored in the context of C-28 amide substituents. Compared to the C-28 amide series, the C-28 amine derivatives exhibited further improvements in HIV-1 inhibitory activity toward polymorphisms in the Gag polyprotein as well as improved activity in the presence of human serum. However, plasma exposure of basic amines following oral administration to rats was generally low, leading to a focus on moderating the basicity of the amine moiety distal from the triterpene core. The thiomorpholine dioxide (TMD) 20 emerged from this study as a compound with the optimal antiviral activity and an acceptable pharmacokinetic profile in the C-28 amine series. Compared to the C-28 amide 3, 20 offers a 2- to 4-fold improvement in potency towards the screening viruses, exhibits low shifts in the EC 50 values toward the V370A and ΔV370 viruses in the presence of human serum or human serum albumin, and demonstrates improved potency towards the polymorphic T371A and V362I virus variants. Copyright © 2018 Elsevier Ltd. All rights reserved.

In vivo activity of ursolic and oleanolic acids during the acute phase of Trypanosoma cruzi infection.

PubMed

da Silva Ferreira, Daniele; Esperandim, Viviane Rodrigues; Toldo, Miriam Paula Alonso; Kuehn, Christian Collins; do Prado Júnior, José Clóvis; Cunha, Wilson Roberto; e Silva, Márcio Luís Andrade; de Albuquerque, Sérgio

2013-08-01

Reduction in the parasitemic levels of the Y strain of Trypanosoma cruzi in mice treated with oral or intraperitoneal ursolic (UA) and oleanolic (OA) acids was evaluated during the acute phase of Chagas' disease. Oral administration of UA and OA (50mg/kg/day) provided the most significant reduction in the parasitemic peak, while intraperitoneal administration of UA and OA did not significantly affect the biological activity of the Y strain of T. cruzi. Interleukin levels in mice treated by the intraperitoneal route were compared to untreated chagasic mice. Reduced γ-IFN levels and enhanced IL-10 concentrations potentially explain the exacerbated parasitemia. Our data suggests an immunosuppressive effect for UA and OA, which could interfere with host control of parasitemia. Optimal results were achieved with oral administration. This observation may be explained by the low intestinal absorption of UA and OA, could cause a reduced immune response and promote parasite control. Taken together, these data demonstrate that triterpenes could be interesting compounds to develop therapeutically for the treatment of Chagas' disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Elevated striatal γ-aminobutyric acid in youth with major depressive disorder.

PubMed

Bradley, Kailyn A; Alonso, Carmen M; Mehra, Lushna M; Xu, Junqian; Gabbay, Vilma

2018-06-08

Alterations in γ-aminobutyric acid (GABA) have been hypothesized to play a role in the pathogenesis of psychiatric illness. Our previous work has specifically linked anterior cingulate cortex (ACC) GABA deficits with anhedonia in youth with major depressive disorder (MDD). As anhedonia reflects alterations within the reward circuitry, we sought to extend this investigation and examine GABA levels in another key reward-related region, the striatum, in the same adolescent population. Thirty-six youth [20 with MDD and 16 healthy controls; (HC)], ages 12 to 21 years old, underwent J-edited proton magnetic resonance spectroscopy ( 1 H MRS) whereby GABA levels were measured in striatal and ACC voxels. GABA levels were compared between groups and between voxel positions and were examined in relation to clinical symptomatology, such as depression severity, anhedonia, anxiety, and suicidality. Depressed youth had unexpectedly higher GABA levels in the striatum compared to HC. In both depressed and healthy youth, GABA levels were higher in the striatum than in the ACC, while the differences in depressed youth were greater. Moreover, in depressed youth, higher striatal GABA above the mean of HCs was correlated with lower ACC GABA below the mean of HCs. Striatal GABA was not correlated with clinical symptomatology in this small sample. Together, these findings suggest that higher striatal GABA levels may serve some compensatory function as a result of lower ACC GABA in depressed adolescents. It is also possible that, like lower ACC GABA, higher striatal GABA might simply be another pathological feature of adolescent depression. Copyright © 2018 Elsevier Inc. All rights reserved.

Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder.

PubMed

Mocking, R J T; Harmsen, I; Assies, J; Koeter, M W J; Ruhé, H G; Schene, A H

2016-03-15

Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114-0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I(2)=73.36, P<0.001), meta-regression showed that higher EPA dose (β=0.00037 (0.00009-0.00065), P=0.009), higher percentage antidepressant users (β=0.0058 (0.00017-0.01144), P=0.044) and earlier publication year (β=-0.0735 (-0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential

The effect of 12-wk ω-3 fatty acid supplementation on in vivo thalamus glutathione concentration in patients "at risk" for major depression.

PubMed

Duffy, Shantel L; Lagopoulos, Jim; Cockayne, Nicole; Lewis, Simon J G; Hickie, Ian B; Hermens, Daniel F; Naismith, Sharon L

2015-10-01

As life expectancy increases, the need to prevent major health disorders is clear. Depressive symptoms are common in older adults and are associated with cognitive decline and greater risk for transitioning to major depression. Oxidative stress may be implicated in the pathophysiology of major depression and can be measured in vivo using proton magnetic resonance spectroscopy via the neurometabolite glutathione (GSH). Evidence suggests ω-3 fatty acid (FA) supplementation may prevent depression and directly affect GSH concentration. The aim of this study was to examine the effect of ω-3 FA supplementation on in vivo GSH concentration in older adults at risk for depression. Fifty-one older adults at risk for depression were randomized to receive either four 1000-mg ω-3 FA supplements daily (containing eicosapentaenoic acid 1200 mg plus docosahexaenoic acid 800 mg) or placebo (four 1000-mg paraffin oil placebo capsules daily) for 12 wk. Participants underwent magnetic resonance spectroscopy, as well as medical, neuropsychological, and self-report assessments at baseline and after 12 wk of supplementation. GSH was measured in the thalamus and calculated as a ratio to creatine. Depressive symptoms were measured using the Patient Health Questionnaire. Compared with the group given the ω-3 FA supplements, the placebo group had greater change in the GSH-to-creatine ratio in the thalamus (t = 2.00; P = 0.049) after the 12 wk intervention. This increase was in turn associated with a worsening of depressive symptoms (r = 0.43; P = 0.043). Depressive symptom severity in older adults appears to be associated with increased brain levels of GSH, a key marker of oxidative stress. Importantly, ω-3 FA supplementation may attenuate oxidative stress mechanisms, thereby offering benefits for depression prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical composition of barks from Quercus faginea trees and characterization of their lipophilic and polar extracts.

PubMed

Ferreira, Joana P A; Miranda, Isabel; Sousa, Vicelina B; Pereira, Helena

2018-01-01

The bark from Quercus faginea mature trees from two sites was chemically characterized for the first time. The barks showed the following composition: ash 14.6%, total extractives 13.2%, suberin 2.9% and lignin 28.2%. The polysaccharides were composed mainly of glucose and xylose (50.3% and 35.1% of all monosaccharides respectively) with 4.8% of uronic acids. The suberin composition was: ω-hydroxyacids 46.3% of total compounds, ɑ,ω-alkanoic diacids 22.3%, alkanoic acids 5.9%, alkanols 6.7% and aromatics 6.9% (ferulic acid 4.0%). Polar extracts (ethanol-water) had a high phenolic content of 630.3 mg of gallic acid equivalents (GAE)/g of extract, condensed tannins 220.7 mg of catechin equivalents (CE)/g extract, and flavonoids 207.7 mg CE/g of extract. The antioxidant activity was very high corresponding to 1567 mg Trolox equivalents/g of extract, and an IC50 of 2.63 μg extract/ml. The lipophilic extracts were constituted mainly by glycerol and its derivatives (12.3% of all compounds), alkanoic acids (27.8%), sterols (11.5%) and triterpenes (17.8%). In view of an integrated valorization, Quercus faginea barks are interesting sources of polar compounds including phenols and polyphenols with possible interesting bioactivities, while the sterols and triterpenes contained in the lipophilic extracts are also valuable bioactive compounds or chemical intermediates for specific high-value market niches, such as cosmetics, pharmaceuticals and biomedicine.

Chemical composition of barks from Quercus faginea trees and characterization of their lipophilic and polar extracts

PubMed Central

2018-01-01

The bark from Quercus faginea mature trees from two sites was chemically characterized for the first time. The barks showed the following composition: ash 14.6%, total extractives 13.2%, suberin 2.9% and lignin 28.2%. The polysaccharides were composed mainly of glucose and xylose (50.3% and 35.1% of all monosaccharides respectively) with 4.8% of uronic acids. The suberin composition was: ω-hydroxyacids 46.3% of total compounds, ɑ,ω-alkanoic diacids 22.3%, alkanoic acids 5.9%, alkanols 6.7% and aromatics 6.9% (ferulic acid 4.0%). Polar extracts (ethanol-water) had a high phenolic content of 630.3 mg of gallic acid equivalents (GAE)/g of extract, condensed tannins 220.7 mg of catechin equivalents (CE)/g extract, and flavonoids 207.7 mg CE/g of extract. The antioxidant activity was very high corresponding to 1567 mg Trolox equivalents/g of extract, and an IC50 of 2.63 μg extract/ml. The lipophilic extracts were constituted mainly by glycerol and its derivatives (12.3% of all compounds), alkanoic acids (27.8%), sterols (11.5%) and triterpenes (17.8%). In view of an integrated valorization, Quercus faginea barks are interesting sources of polar compounds including phenols and polyphenols with possible interesting bioactivities, while the sterols and triterpenes contained in the lipophilic extracts are also valuable bioactive compounds or chemical intermediates for specific high-value market niches, such as cosmetics, pharmaceuticals and biomedicine. PMID:29763441

Analytical methods for determination of alkaloids and saponins from roots of Caulophyllum thalictroids (L) Michx using UPLC HPLC and HPTLC

USDA-ARS?s Scientific Manuscript database

A comparison study of analytical methods including HPLC, UPLC and HPTLC are presented in this paper for the determination of major alkaloid and triterpene saponins from the roots of Caulophyllum thalictroides (L.) Michx. (blue cohosh) and dietary supplements claiming to contain blue cohosh. The meth...

Major hydrogeochemical processes in an acid mine drainage affected estuary.

PubMed

Asta, Maria P; Calleja, Maria Ll; Pérez-López, Rafael; Auqué, Luis F

2015-02-15

This study provides geochemical data with the aim of identifying and quantifying the main processes occurring in an Acid Mine Drainage (AMD) affected estuary. With that purpose, water samples of the Huelva estuary were collected during a tidal half-cycle and ion-ion plots and geochemical modeling were performed to obtain a general conceptual model. Modeling results indicated that the main processes responsible for the hydrochemical evolution of the waters are: (i) the mixing of acid fluvial water with alkaline ocean water; (ii) precipitation of Fe oxyhydroxysulfates (schwertmannite) and hydroxides (ferrihydrite); (iii) precipitation of Al hydroxysulfates (jurbanite) and hydroxides (amorphous Al(OH)3); (iv) dissolution of calcite; and (v) dissolution of gypsum. All these processes, thermodynamically feasible in the light of their calculated saturation states, were quantified by mass-balance calculations and validated by reaction-path calculations. In addition, sorption processes were deduced by the non-conservative behavior of some elements (e.g., Cu and Zn). Copyright © 2014 Elsevier Ltd. All rights reserved.

ω-3 Fatty acids for major depressive disorder in adults: an abridged Cochrane review

PubMed Central

Appleton, Katherine M; Sallis, Hannah M; Perry, Rachel; Ness, Andrew R; Churchill, Rachel

2016-01-01

Objective To assess the effects of n-3 polyunsaturated fatty acids (n-3PUFAs; also known as ω-3 fatty acids) compared with comparator for major depressive disorder (MDD) in adults. Design Systematic review and meta-analyses. Data sources The Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Registers (CCDANCTR) and International Trial Registries searched to May 2015. CINAHL searched to September 2013. Trial selection Inclusion criteria: a randomised controlled trial (RCT); that provided n-3PUFAs as an intervention; used a comparator; measured depressive symptomology as an outcome; and was conducted in adults with MDD. Outcomes Primary outcomes were depressive symptomology and adverse events. Results 20 trials encompassing 26 relevant studies were found. For n-3PUFAs versus placebo, n-3PUFA supplementation resulted in a small-to-modest benefit for depressive symptomology: SMD=−0.32 (95% CI −0.52 to −0.12; 25 studies, 1373 participants, very low-quality evidence), but this effect is unlikely to be clinically meaningful, is very imprecise and, based on funnel plot inspection, sensitivity analyses and comparison with large well-conducted trials, is likely to be biased. Considerable evidence of heterogeneity between studies was also found, and was not explained by subgroup or sensitivity analyses. Numbers of individuals experiencing adverse events were similar in intervention and placebo groups (OR=1.24, 95% CI 0.95 to 1.62; 19 studies, 1207 participants; very low-quality evidence). For n-3PUFAs versus antidepressants, no differences were found between treatments in depressive symptomology (MD=−0.70 (95% CI −5.88 to 4.48); 1 study, 40 participants, very low-quality evidence). Conclusions At present, we do not have sufficient evidence to determine the effects of n-3PUFAs as a treatment for MDD. Further research in the form of adequately powered RCTs is needed. PMID:26936905

Screening and Analysis of the Marker Components in Ganoderma lucidum by HPLC and HPLC-MSn with the Aid of Chemometrics.

PubMed

Wu, Lingfang; Liang, Wenyi; Chen, Wenjing; Li, Shi; Cui, Yaping; Qi, Qi; Zhang, Lanzhen

2017-04-06

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum , which is a popularly used traditional Chinese medicine for complementary cancer therapy. The present study was to establish a fingerprint evaluation system based on Similarity Analysis (SA), Cluster Analysis (CA) and Principal Component Analysis (PCA) for the identification and quality control of G. lucidum . Fifteen samples from the Chinese provinces of Hainan, Neimeng, Shangdong, Jilin, Anhui, Henan, Yunnan, Guangxi and Fujian were analyzed by HPLC-PAD and HPLC-MS n . Forty-seven compounds were detected by HPLC, of which forty-two compounds were tentatively identified by comparing their retention times and mass spectrometry data with that of reference compounds and reviewing the literature. Ganoderic acid B, 3,7,15-trihydroxy-11,23-dioxolanost-8,16-dien-26-oic acid, lucidenic acid A, ganoderic acid G, and 3,7-oxo-12-acetylganoderic acid DM were deemed to be the marker compounds to distinguish the samples with different quality according to both CA and PCA. This study provides helpful chemical information for further research on the anti-tumor activity and mechanism of action of G. lucidum . The results proved that fingerprints combined with chemometrics are a simple, rapid and effective method for the quality control of G. lucidum .

Phytochemical investigations and antiproliferative secondary metabolites from Thymus alternans growing in Slovakia.

PubMed

Dall'Acqua, Stefano; Peron, Gregorio; Ferrari, Sara; Gandin, Valentina; Bramucci, Massimo; Quassinti, Luana; Mártonfi, Pavol; Maggi, Filippo

2017-12-01

Thymus alternans Klokov (Lamiaceae) is a neglected species of the genus Thymus (Sect. Serpyllum) endemic to Carpathian area, where it is used as a flavouring agent and for medicinal purposes. The aim of the work was to identify antiproliferative constituents from the flowering aerial parts of this plant. Thymus alternans extracts were analyzed by HPLC-MS n and subjected to extensive chromatographic separations. The isolated compounds (phenolics and triterpenes) were structurally elucidated by MS and 1D and 2D NMR experiments. Essential oil (EO) composition was determined by GC-FID and GC-MS. Six purified triterpenes and EO were assayed for in vitro antiproliferative activity against a panel of human cancer cells, namely, breast (MDA-MB 231), colon (HCT-15 and HCT116), lung (U1810), pancreatic (BxPC3), melanoma (A375) and cervical carcinoma (A431) cells. The structures of the isolated compounds were achieved on the basis of H-NMR and MS experiments. Luteolin-4'-O-β-d-glucopyranoside (P1), chrysoeriol-7-O-β-d-glucopyranoside (P2), chrysoeriol-5-O-β-d-glucopyranoside (P3), apigenin-7-O-β-d-glucopyranoside (P4), rosmarinic acid (P5), rosmarinic acid-3'-O-β-d-glucopyranoside (P6), caffeic acid-3-O-β-d-glucopyranoside (P7), 3α-hydroxy-urs-12,15-diene (T1), α-amyrin (T2), β-amyrin (T3), isoursenol (T4), epitaraxerol (T5), and oleanolic acid (T6). GC-MS analysis revealed that the EO of T. alternans was devoid of phenols and belonged to the nerolidol-chemotype, that is typical of the Sect. Serpyllum. The six purified triterpenes (T1-T6) were active with IC 50 ranging from 0.5 to 5 μM being comparable or better than those of reference compounds betulinic acid and cisplatin. The EO exhibited significant effects on A375, MDA-MB 231 and HCT116 cell lines with IC 50 in the range of 5-8 μg/mL. The reported results suggest that T. alternans can be considered as a good source of phytoconstituents with possible importance in the pharmaceutical field.

Hypolipidemic and hypoglycemic activities of a oleanolic acid derivative from Malva parviflora on streptozotocin-induced diabetic mice.

PubMed

Gutiérrez, Rosa Martha Pérez

2017-05-01

One new oleanolic acid derivative, 2α,3β,23α,29α tetrahydroxyolean-12(13)-en-28-oic acid (1) was isolated from the aerial parts of Malva parviflora. Their structure was characterized by spectroscopic methods. The hypolipidemic and hypoglycemic activities of 1 was analyzed in in streptozotocin (STZ)-nicotinamide-induced type 2 diabetes in mice (MD) and type 1 diabetes in streptozotocin-induced diabetic mice (SD). Triterpene was administered orally at doses of 20 mg/kg for 4 weeks. Organ weight, body weight, glucose, fasting insulin, cholesterol-related lipid profile parameters, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP), glucokinase, hexokinase, glucose-6-phosphatase activities and glycogen in liver were measured after 4 weeks of treatment. The results indicated that 1 regulate glucose metabolism, lipid profile, lipid peroxidation, increased body weight, glucokinase and hexokinase activities inhibited triglycerides, total cholesterol, low density lipoproteins level, SGOT, SGPT, SALP, glycogen in liver and glucose-6-phosphatase. In addition, improvement of insulin resistance and protective effect for pancreatic β-cells, also 1 may changes the expression of pro-inflammatory cytokine (IL-6 and TNF-α levels) and enzymes (PAL2, COX-2, and LOX). The results suggest that 1 has hypolipidemic and hypoglycemic, anti-inflammatory, activities, improve insulin resistance and hepatic enzymes in streptozotocin-induced diabetic mice.

Multiple Active Compounds from Viscum album L. Synergistically Converge to Promote Apoptosis in Ewing Sarcoma

PubMed Central

Twardziok, Monika; Kleinsimon, Susann; Rolff, Jana; Jäger, Sebastian; Eggert, Angelika

2016-01-01

Ewing sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10–15% of relapses. Hydrophobic triterpene acids and hydrophilic lectins and viscotoxins from European mistletoe (Viscum album L.) demonstrate anticancer properties, but have not yet been investigated for Ewing sarcoma. Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We recreated a total mistletoe effect by combining an aqueous extract (viscum) and a triterpene extract (TT) solubilized with cyclodextrins. Ewing sarcoma cells were treated with viscum, TT and viscumTT in vitro, ex vivo and in vivo. In vitro and ex vivo treatment of Ewing sarcoma cells with viscum inhibited proliferation and induced apoptosis in a dose-dependent fashion, while viscumTT combination treatment generated a synergistic effect. Apoptosis occurred via intrinsic and extrinsic apoptotic pathways, evidenced by activation of both CASP8 and CASP9. We show that viscumTT treatment shifts the balance of apoptotic regulatory proteins towards apoptosis, mainly via CLSPN, MCL1, BIRC5 and XIAP downregulation. ViscumTT also demonstrated strong antitumor activity in a cell line- and patient-derived mouse model, and may be considered an adjuvant therapy option for pediatric patients with Ewing sarcoma. PMID:27589063

[Simultaneous determination of ten major compounds including iridoid glycosides and phenolic acids in Pterocephalus hookeri by UPLC-PDA].

PubMed

Tang, Ce; Wen, Jian; Wang, Jing; Zhao, Ke-Hui; Fan, Gang; Meng, Xian-Li; Zou, Zhong-Mei; Zhang, Yi

2017-04-01

This study is to develop an UPLC-PDA method for determination of 10 major components in Pterocephalus. The UPLC-PDA assay was performed on a Waters Acquity UPLCR BEH C₁₈（2.1 mm ×100 mm,1.7 μm）, and the column temperature was at 30 ℃. The mobile phase consists of water containing 0.2% phosphoric acid (A) and acetonitrile (B) in gradient elution at a flow rate of 0.4 mL•min⁻¹. The detection wave length was set at 237 and 325 nm, and the injection volume was 1 μL in the UPLC system. The linear range of 10 detected compounds were good (r≥0.999 7), and the overall recoveries ranged from 96.30% to 103.0%, with the RSD ranging from 0.72% to 2.9%. The method was simple, accurate and reproducible, which can be used for the simultaneous determination of the content of ten major components in P. hookeri. Copyright© by the Chinese Pharmaceutical Association.

Isolation and Identification of Intestinal CYP3A Inhibitors from Cranberry (Vaccinium macrocarpon) using Human Intestinal Microsomes

PubMed Central

Kim, Eunkyung; Sy-Cordero, Arlene; Graf, Tyler N.; Brantley, Scott J.; Paine, Mary F.; Oberlies, Nicholas H.

2010-01-01

Cranberry juice is used routinely, especially among women and the elderly, to prevent and treat urinary tract infections. These individuals are likely to be taking medications concomitantly with cranberry juice, leading to concern about potential drug-dietary substance interactions, particularly in the intestine, which, along with the liver, is rich in expression of the prominent drug metabolizing enzyme, cytochrome P450 3A (CYP3A). Using a systematic in vitro-in vivo approach, a cranberry juice product was identified recently that elicited a pharmacokinetic interaction with the CYP3A probe substrate midazolam in 16 healthy volunteers. Relative to water, a cranberry juice inhibited intestinal first-pass midazolam metabolism. In vitro studies were initiated to identify potential enteric CYP3A inhibitors from cranberry via a bioactivity-directed fractionation approach involving dried whole cranberry [Vaccinium macrocarpon Ait. (Ericaceae)], midazolam, and human intestinal microsomes (HIM). Three triterpenes (maslinic acid, corosolic acid, and ursolic acid) were isolated. The inhibitory potency (IC50) of maslinic acid, corosolic acid, and ursolic acid was 7.4, 8.8, and <10 μM, respectively, using HIM as the enzyme source and was 2.8, 4.3, and <10 μM, respectively, using recombinant CYP3A4 as the enzyme source. These in vitro inhibitory potencies, which are within the range of those reported for two CYP3A inhibitory components in grapefruit juice, suggest that these triterpenes may have contributed to the midazolam-cranberry juice interaction observed in the clinical study. PMID:20717876

Isolation and identification of intestinal CYP3A inhibitors from cranberry (Vaccinium macrocarpon) using human intestinal microsomes.

PubMed

Kim, Eunkyung; Sy-Cordero, Arlene; Graf, Tyler N; Brantley, Scott J; Paine, Mary F; Oberlies, Nicholas H

2011-02-01

Cranberry juice is used routinely, especially among women and the elderly, to prevent and treat urinary tract infections. These individuals are likely to be taking medications concomitantly with cranberry juice, leading to concern about potential drug-dietary substance interactions, particularly in the intestine, which, along with the liver, is rich in expression of the prominent drug metabolizing enzyme, cytochrome P450 3A (CYP3A). Using a systematic in vitro-in vivo approach, a cranberry juice product was identified recently that elicited a pharmacokinetic interaction with the CYP3A probe substrate midazolam in 16 healthy volunteers. Relative to water, cranberry juice inhibited intestinal first-pass midazolam metabolism. In vitro studies were initiated to identify potential enteric CYP3A inhibitors from cranberry via a bioactivity-directed fractionation approach involving dried whole cranberry [Vaccinium macrocarpon Ait. (Ericaceae)], midazolam, and human intestinal microsomes (HIM). Three triterpenes (maslinic acid, corosolic acid, and ursolic acid) were isolated. The inhibitory potency (IC(50)) of maslinic acid, corosolic acid, and ursolic acid was 7.4, 8.8, and < 10 µM, respectively, using HIM as the enzyme source and 2.8, 4.3, and < 10 µM, respectively, using recombinant CYP3A4 as the enzyme source. These in vitro inhibitory potencies, which are within the range of those reported for two CYP3A inhibitory components in grapefruit juice, suggest that these triterpenes may have contributed to the midazolam-cranberry juice interaction observed in the clinical study. © Georg Thieme Verlag KG Stuttgart · New York.

Characterization of major ripening events during softening in grape: turgor, sugar accumulation, abscisic acid metabolism, colour development, and their relationship with growth

PubMed Central

Castellarin, Simone D.; Gambetta, Gregory A.; Wada, Hiroshi; Krasnow, Mark N.; Cramer, Grant R.; Peterlunger, Enrico; Shackel, Kenneth A.; Matthews, Mark A.

2016-01-01

Along with sugar accumulation and colour development, softening is an important physiological change during the onset of ripening in fruits. In this work, we investigated the relationships among major events during softening in grape (Vitis vinifera L.) by quantifying elasticity in individual berries. In addition, we delayed softening and inhibited sugar accumulation using a mechanical growth-preventing treatment in order to identify processes that are sugar and/or growth dependent. Ripening processes commenced on various days after anthesis, but always at similarly low elasticity and turgor. Much of the softening occurred in the absence of other changes in berry physiology investigated here. Several genes encoding key cell wall-modifying enzymes were not up-regulated until softening was largely completed, suggesting softening may result primarily from decreases in turgor. Similarly, there was no decrease in solute potential, increase in sugar concentration, or colour development until elasticity and turgor were near minimum values, and these processes were inhibited when berry growth was prevented. Increases in abscisic acid occurred early during softening and in the absence of significant expression of the V. vinifera 9-cis-epoxycarotenoid dioxygenases. However, these increases were coincident with decreases in the abscisic acid catabolite diphasic acid, indicating that initial increases in abscisic acid may result from decreases in catabolism and/or exogenous import. These data suggest that softening, decreases in turgor, and increases in abscisic acid represent some of the earliest events during the onset of ripening. Later, physical growth, further increases in abscisic acid, and the accumulation of sugar are integral for colour development. PMID:26590311

Beneficial Effects of Early Enteral Nutrition After Major Rectal Surgery: A Possible Role for Conditionally Essential Amino Acids? Results of a Randomized Clinical Trial.

PubMed

van Barneveld, Kevin W Y; Smeets, Boudewijn J J; Heesakkers, Fanny F B M; Bosmans, Joanna W A M; Luyer, Misha D; Wasowicz, Dareczka; Bakker, Jaap A; Roos, Arnout N; Rutten, Harm J T; Bouvy, Nicole D; Boelens, Petra G

2016-06-01

To investigate direct postoperative outcome and plasma amino acid concentrations in a study comparing early enteral nutrition versus early parenteral nutrition after major rectal surgery. Previously, it was shown that a low plasma glutamine concentration represents poor prognosis in ICU patients. A preplanned substudy of a previous prospective, randomized, open-label, single-centre study, comparing early enteral nutrition versus early parenteral nutrition in patients at high risk of postoperative ileus after surgery for locally advanced or locally recurrent rectal cancer. Early enteral nutrition reduced postoperative ileus, anastomotic leakage, and hospital stay. Tertiary referral centre for locally advanced and recurrent rectal cancer. A total of 123 patients with locally advanced or recurrent rectal carcinoma requiring major rectal surgery. Patients were randomized (ALEA web-based external randomization) preoperatively into two groups: early enteral nutrition (early enteral nutrition, intervention) by nasojejunal tube (n = 61) or early parenteral nutrition (early parenteral nutrition, control) by jugular vein catheter (n = 62). Eight hours after the surgical procedure artificial nutrition was started in hemodynamically stable patients, stimulating oral intake in both groups. Blood samples were collected to measure plasma glutamine, citrulline, and arginine concentrations using a validated ultra performance liquid chromatography-tandem mass spectrometric method. Baseline concentrations were comparable for both groups. Directly after rectal surgery, a decrease in plasma amino acids was observed. Plasma glutamine concentrations were higher in the parenteral group than in the enteral group on postoperative day 1 (p = 0.027) and day 5 (p = 0.008). Arginine concentrations were also significantly increased in the parenteral group at day 1 (p < 0.001) and day 5 (p = 0.001). Lower plasma glutamine and arginine concentrations were measured in the enteral group, whereas a

Study on impact of habitat degradation on proximate composition and amino acid profile of Indian major carps from different habitats.

PubMed

Hussain, Bilal; Sultana, Tayyaba; Sultana, Salma; Ahmed, Z; Mahboob, Shahid

2018-05-01

This investigation is aimed to study an impact of habitat degradation on proximate composition and amino acid (AAs) profile of Catla catla, Labeo rohita and Cirrhinus mrigala collected from polluted, non-polluted area (upstream) and a commercial fish farm. The amino acid profile was estimated by the amino acid analyzer. C. catla collected from the polluted environment had highest lipid, protein and ash contents (12.04 ± 0.01, 13.45 ± 0.01 and 0.93 ± 0.03%, respectively). The high protein content (14.73 ± 0.01 and 14.12 ± 0. 01%) was recorded in C. catla procured from non-polluted (upstream) wild habitat of River Chenab and controlled commercial fish farm. Farmed fish species showed comparatively higher moisture contents followed by upstream and polluted area fishes. C. mrigala showed significant differences in amino acid and proximate composition collected from a polluted site of the river Chenab. C. catla collected from non-polluted site of the river showed an excellent nutrient profile, followed by L. rohita (wild and farmed) and C. mrigala (polluted area), respectively. All fishes from the polluted areas of the River Chenab indicated a significant decrease in the concentration of some AAs when compared to farmed and wild (upstream) major carps. Omitting of some important AAs was also observed in the meat of fish harvested from polluted habitat of this river. C. mrigala and L. rohita exhibited a significant increase in the concentration of some of non-essential amino acids such as cysteine in their meat. The results indicated that wild fish (upstream) and farmed fish species had highest protein contents and amino acid profile and hence appeared to be the best for human consumption. The proximate composition and AAs profiles of fish harvested from the polluted area of the river clearly indicated that efforts shall be made for the restoration of habitat to continue the requirement of high quality fish meat at a low cost to the human

Cycloartenol triterpenoid saponins from Cimicifuga simplex (Ranunculaceae) and their biological effects.

PubMed

Wu, Lun; Chen, Zhi-Li; Su, Yang; Wang, Qiu-Hong; Kuang, Hai-Xue

2015-02-01

The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9,19-cyclolanostane triterpenoid glycosides, which are distributed widely in Cimicifuga plants, but not in other members of the Ranunculaceae family, and are considered to be characteristics of the Cimicifuga genus. This type of triterpenoid glycoside possesses several important biological activities. More than 120 cycloartane triterpene glycosides have been isolated from Cimicifuga simplex Wormsk. The aim of this review article is to summarize all the major findings based on the available scientific literatures on C. simplex, with a focus on the identified 9,19-cyclolanostane triterpenoid glycosides. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Sea Cucumber Glycosides: Chemical Structures, Producing Species and Important Biological Properties.

PubMed

Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Rahman, M Aminur; Islam, Mohamad Tofazzal

2017-10-17

Sea cucumbers belonging to echinoderm are traditionally used as tonic food in China and other Asian countries. They produce abundant biologically active triterpene glycosides. More than 300 triterpene glycosides have been isolated and characterized from various species of sea cucumbers, which are classified as holostane and nonholostane depending on the presence or absence of a specific structural unit γ(18,20)-lactone in the aglycone. Triterpene glycosides contain a carbohydrate chain up to six monosaccharide units mainly consisting of d-xylose, 3-O-methy-d-xylose, d-glucose, 3-O-methyl-d-glucose, and d-quinovose. Cytotoxicity is the common biological property of triterpene glycosides isolated from sea cucumbers. Besides cytotoxicity, triterpene glycosides also exhibit antifungal, antiviral and hemolytic activities. This review updates and summarizes our understanding on diverse chemical structures of triterpene glycosides from various species of sea cucumbers and their important biological activities. Mechanisms of action and structural-activity relationships (SARs) of sea cucumber glycosides are also discussed briefly.

Sea Cucumber Glycosides: Chemical Structures, Producing Species and Important Biological Properties

PubMed Central

Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Rahman, M. Aminur; Islam, Mohamad Tofazzal

2017-01-01

Sea cucumbers belonging to echinoderm are traditionally used as tonic food in China and other Asian countries. They produce abundant biologically active triterpene glycosides. More than 300 triterpene glycosides have been isolated and characterized from various species of sea cucumbers, which are classified as holostane and nonholostane depending on the presence or absence of a specific structural unit γ(18,20)-lactone in the aglycone. Triterpene glycosides contain a carbohydrate chain up to six monosaccharide units mainly consisting of d-xylose, 3-O-methy-d-xylose, d-glucose, 3-O-methyl-d-glucose, and d-quinovose. Cytotoxicity is the common biological property of triterpene glycosides isolated from sea cucumbers. Besides cytotoxicity, triterpene glycosides also exhibit antifungal, antiviral and hemolytic activities. This review updates and summarizes our understanding on diverse chemical structures of triterpene glycosides from various species of sea cucumbers and their important biological activities. Mechanisms of action and structural–activity relationships (SARs) of sea cucumber glycosides are also discussed briefly. PMID:29039760

[Chemical constituents from Imperata cylindrica].

PubMed

Liu, Xuan; Zhang, Binfeng; Chou, Guixin; Yang, Li; Wang, Zhengtao

2012-08-01

Chemical investigation of Imperata cylindrica led to the isolation of thirteen compounds using various chromatographic techniques. The structure of these compounds were identified as: three phenylpropanoids, 1-(3,4,5-trimethoxyphenyl)-1,2,3-propanetriol ( 1 ), 1-O-p-coumaroylglycerol (2), 4-methoxy-5-methyl coumarin-7-O-beta-D-glucopyranoside (3); four organic acids, 4-hydroxybenzene carboxylic acid(4), 3,4-dihydroxybenzoic acid (5), vanillic acid (6), 3, 4-dihydroxybutyric acid (7); one phenolic compound, salicin (8); and five triterpenes, namely, arundoin (9), cylindrin (10), fernenol (11), simiarenol (12), glutinone (13) by their physicochemical properties and spectral data analysis. Among them, compounds 1-8 were isolated from the genus Imperata for the first time.

Anti-emetic principles of Poria cocos.

PubMed

Tai, T; Akita, Y; Kinoshita, K; Koyama, K; Takahashi, K; Watanabe, K

1995-12-01

The triterpenes isolated from P. cocos and their derivatives were examined for anti-emetic activity. Some of these triterpenes inhibited emetic action induced by oral administration of copper sulfate pentahydrate to leopard frog. The triterpenes having an exomethylene group at C-24 showed anti-emetic activity to frogs.

Characterization of major ripening events during softening in grape: turgor, sugar accumulation, abscisic acid metabolism, colour development, and their relationship with growth.

PubMed

Castellarin, Simone D; Gambetta, Gregory A; Wada, Hiroshi; Krasnow, Mark N; Cramer, Grant R; Peterlunger, Enrico; Shackel, Kenneth A; Matthews, Mark A

2016-02-01

Along with sugar accumulation and colour development, softening is an important physiological change during the onset of ripening in fruits. In this work, we investigated the relationships among major events during softening in grape (Vitis vinifera L.) by quantifying elasticity in individual berries. In addition, we delayed softening and inhibited sugar accumulation using a mechanical growth-preventing treatment in order to identify processes that are sugar and/or growth dependent. Ripening processes commenced on various days after anthesis, but always at similarly low elasticity and turgor. Much of the softening occurred in the absence of other changes in berry physiology investigated here. Several genes encoding key cell wall-modifying enzymes were not up-regulated until softening was largely completed, suggesting softening may result primarily from decreases in turgor. Similarly, there was no decrease in solute potential, increase in sugar concentration, or colour development until elasticity and turgor were near minimum values, and these processes were inhibited when berry growth was prevented. Increases in abscisic acid occurred early during softening and in the absence of significant expression of the V. vinifera 9-cis-epoxycarotenoid dioxygenases. However, these increases were coincident with decreases in the abscisic acid catabolite diphasic acid, indicating that initial increases in abscisic acid may result from decreases in catabolism and/or exogenous import. These data suggest that softening, decreases in turgor, and increases in abscisic acid represent some of the earliest events during the onset of ripening. Later, physical growth, further increases in abscisic acid, and the accumulation of sugar are integral for colour development. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Simultaneous quantification of the major bile acids in artificial Calculus bovis by high-performance liquid chromatography with precolumn derivatization and its application in quality control.

PubMed

Shi, Yan; Xiong, Jing; Sun, Dongmei; Liu, Wei; Wei, Feng; Ma, Shuangcheng; Lin, Ruichao

2015-08-01

An accurate and sensitive high-performance liquid chromatography method coupled with ultralviolet detection and precolumn derivatization was developed for the simultaneous quantification of the major bile acids in Artificial Calculus bovis, including cholic acid, hyodeoxycholic acid, chenodeoxycholic acid, and deoxycholic acid. The extraction, derivatization, chromatographic separation, and detection parameters were fully optimized. The samples were extracted with methanol by ultrasonic extraction. Then, 2-bromine-4'-nitroacetophenone and 18-crown ether-6 were used for derivatization. The chromatographic separation was performed on an Agilent SB-C18 column (250 × 4.6 mm id, 5 μm) at a column temperature of 30°C and liquid flow rate of 1.0 mL/min using water and methanol as the mobile phase with a gradient elution. The detection wavelength was 263 nm. The method was extensively validated by evaluating the linearity (r(2) ≥ 0.9980), recovery (94.24-98.91%), limits of detection (0.25-0.31 ng) and limits of quantification (0.83-1.02 ng). Seventeen samples were analyzed using the developed and validated method. Then, the amounts of bile acids were analyzed by hierarchical agglomerative clustering analysis and principal component analysis. The results of the chemometric analysis showed that the contents of these compounds reflect the intrinsic quality of artificial Calculus bovis, and two compounds (hyodeoxycholic acid and chenodeoxycholic acid) were the most important markers for quality evaluating. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Epsilon Aminocaproic Acid on Red-Cell Transfusion Requirements in Major Spinal Surgery

PubMed Central

Berenholtz, Sean M.; Pham, Julius Cuong; Garrett-Mayer, Elizabeth; Atchison, Christine W; Kostuik, John P.; Cohen, David B.; Nundy, Shantanu; Dorman, Todd; Ness, Paul M.; Klag, Michael J.; Pronovost, Peter J.; Kebaish, Khaled M.

2009-01-01

Study Design Randomized, placebo-controlled trial Objective To evaluate the efficacy of epsilon aminocaproic acid (EACA) to reduce the number of red-cell (RBC) transfusions in adult patients undergoing major spinal surgery. Summary of Background Data Reconstructive spinal surgery is associated with significant blood loss. The number of studies evaluating the efficacy of EACA in adult patients undergoing spinal surgery remains scarce and limited. Methods EACA (100 mg/kg) or placebo was administered to 182 adult patients after the induction of anesthesia followed by an infusion that was continued for 8 hours postoperatively. Primary end-points included total allogeneic RBC transfusions through postoperative day (POD) 8 and postoperative allogeneic plus autologus RBC transfusions through POD 8. Results Mean total allogeneic RBC transfusions were not statistically different between the groups (5.9 units EACA versus 6.9 units placebo; P=0.17). Mean postoperative RBC transfusions in the EACA group was less (2.0 units versus 2.8 units placebo; P=0.03). There was no significant difference in mean estimated intraoperative EBL (2938 cc EACA vs. 3273 cc placebo; P=0.32). Mean intensive care unit length of stay was decreased (EACA 1.8 days versus 2.8 days placebo; P=0.04). The incidence of thromboembolic complications was similar (2.2% EACA vs 6.6% placebo; P=0.15). Conclusions The difference in total allogeneic RBC transfusions between the groups was not statistically significant. EACA was associated with a 30% (0.8 units) reduction in postoperative RBC transfusions and a one-day reduction in ICU LOS, without an increased incidence of thromboembolic events. EACA may be considered for patients undergoing major spinal surgery. Larger studies are needed to evaluate the relationship between EACA and total RBC requirements. PMID:19730217

Effect of epsilon aminocaproic acid on red-cell transfusion requirements in major spinal surgery.

PubMed

Berenholtz, Sean M; Pham, Julius Cuong; Garrett-Mayer, Elizabeth; Atchison, Christine W; Kostuik, John P; Cohen, David B; Nundy, Shantanu; Dorman, Todd; Ness, Paul M; Klag, Michael J; Pronovost, Peter J; Kebaish, Khaled M

2009-09-01

: Randomized, placebo-controlled trial. : To evaluate the efficacy of epsilon aminocaproic acid (EACA) to reduce the number of red-cell (RBC) transfusions in adult patients undergoing major spinal surgery. : Reconstructive spinal surgery is associated with significant blood loss. The number of studies evaluating the efficacy of EACA in adult patients undergoing spinal surgery remains scarce and limited. : EACA (100 mg/kg) or placebo was administered to 182 adult patients after the induction of anesthesia followed by an infusion that was continued for 8 hours after surgery. Primary end points included total allogeneic RBC transfusions through postoperative day 8 and postoperative allogeneic plus autologus RBC transfusions through postoperative day 8. : Mean total allogeneic RBC transfusions were not statistically different between the groups (5.9 units EACA vs. 6.9 units placebo; P = 0.17). Mean postoperative RBC transfusions in the EACA group was less (2.0 units vs. 2.8 units placebo; P = 0.03). There was no significantdifference in mean estimated intraoperative estimated-blood loss (2938 cc EACA vs. 3273 cc placebo; P = 0.32). Mean intensive care unit length of stay was decreased (EACA: 1.8 days vs. 2.8 days placebo; P = 0.04). The incidence of thromboembolic complications was similar (2.2% EACA vs. 6.6% placebo; P = 0.15). : The difference in total allogeneic RBC transfusions between the groups was not statistically significant. EACA was associated with a 30% (0.8 units) reduction in postoperative RBC transfusions and a 1-day reduction in ICU LOS, without an increased incidence of thromboembolic events. EACA may be considered for patients undergoing major spinal surgery. Larger studies are needed to evaluate the relationship between EACA and total RBC requirements.

Effect of pretreatment severity on accumulation of major degradation products from dilute acid pretreated corn stover and subsequent inhibition of enzymatic hydrolysis of cellulose.

PubMed

Um, Byung-Hwan; van Walsum, G Peter

2012-09-01

The concept of reaction severity, which combines residence time and temperature, is often used in the pulp and paper and biorefining industries. The influence of corn stover pretreatment severity on yield of sugar and major degradation products and subsequent effects on enzymatic cellulose hydrolysis was investigated. The pretreatment residence time and temperature, combined into the severity factor (Log R(o)), were varied with constant acid concentration. With increasing severity, increasing concentrations of furfural and 5-hydroxymethylfurfural (5-HMF) coincided with decreasing yields of oligosaccharides. With further increase in severity factor, the concentrations of furans decreased, while the formation of formic acid and lactic acid increased. For example, from severity 3.87 to 4.32, xylose decreased from 6.39 to 5.26 mg/mL, while furfural increased from 1.04 to 1.33 mg/mL; as the severity was further increased to 4.42, furfural diminished to 1.23 mg/mL as formate rose from 0.62 to 1.83 mg/mL. The effects of dilute acid hydrolyzate, acetic acid, and lignin, in particular, on enzymatic hydrolysis were investigated with a rapid microassay method. The microplate method gave considerable time and cost savings compared to the traditional assay protocol, and it is applicable to a broad range of lignocellulosic substrates.

Phytochemical Comparison of the Water and Ethanol Leaf Extracts of the Cree medicinal plant, Sarracenia purpurea L. (Sarraceniaceae).

PubMed

Cieniak, Carolina; Walshe-Roussel, Brendan; Liu, Rui; Muhammad, Asim; Saleem, Ammar; Haddad, Pierre S; Cuerrier, Alain; Foster, Brian C; Arnason, John T

2015-01-01

The Cree of Eeyou Istchee in Northern Quebec identified Sarracenia purpurea L. as an important plant for the treatment of Type 2 diabetes. Traditionally the plant is used as a decoction (boiling water extract) of the leaf, however, in order to study the extract in a laboratory setting, an 80% ethanol extract was used. In this study, the phytochemistry of both extracts of the leaves was compared and quantified. Two S. purpurea leaf extracts were prepared, one a traditional hot water extract and the other an 80% ethanol extract. Using UPLC-ESI-MS, the extracts were phytochemically compared for 2 triterpenes, betulinic acid and ursolic acid, using one gradient method and for 10 additional substances, including the actives quercetin-3-O-galactoside and morroniside, using a different method. The concentrations of the nine phenolic substances present, as well as an active principle, the iridoid glycoside morroniside, were very similar between the two extracts, with generally slightly higher concentrations of phenolics in the ethanol extract as expected. However, two triterpenes, betulinic acid and ursolic acid, were 107 and 93 times more concentrated, respectively, in the ethanol extract compared to the water extract. The main phytochemical markers and most importantly the antidiabetic active principles, quercetin-3-O-galactoside and morroniside, were present in similar amounts in the two extracts, which predicts similar bioactivity.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Anti-glioma activity and the mechanism of cellular uptake of asiatic acid-loaded solid lipid nanoparticles.

PubMed

Garanti, Tanem; Stasik, Aneta; Burrow, Andrea Julie; Alhnan, Mohamed A; Wan, Ka-Wai

2016-03-16

Asiatic acid (AA), a pentacyclic triterpene found in Centella Asiatica, has shown neuroprotective and anti-cancer activity against glioma. However, owing to its poor aqueous solubility, effective delivery and absorption across biological barriers, in particular the blood brain barrier (BBB), are challenging. Solid lipid nanoparticles (SLNs) have shown a promising potential as a drug delivery system to carry lipophilic drugs across the BBB, a major obstacle in brain cancer therapy. Nevertheless, limited information is available about the cytotoxic mechanisms of nano-lipidic carriers with AA on normal and glioma cells. This study assessed the anti-cancer efficacy of AA-loaded SLNs against glioblastoma and their cellular uptake mechanism in comparison with SVG P12 (human foetal glial) cells. SLNs were systematically investigated for three different solid lipids; glyceryl monostearate (MS), glyceryl distearate (DS) and glyceryl tristearate (TS). The non-drug containing MS-SLNs (E-MS-SLNs) did not show any apparent toxicity towards normal SVG P12 cells, whilst the AA-loaded MS-SLNs (AA-MS-SLNs) displayed a more favourable drug release profile and higher cytotoxicity towards U87 MG cells. Therefore, MS-SLNs were chosen for further in vitro studies. Cytotoxicity studies of SLNs (± AA) were performed using MTT assay where AA-SLNs showed significantly higher cytotoxicity towards U87 MG cells than SVG P12 normal cells, as confirmed by flow cell cytometry. Cellular uptake of SLNs also appeared to be preferentially facilitated by energy-dependent endocytosis as evidenced by fluorescence imaging and flow cell cytometry. Using the Annexin V-PI double staining technique, it was found that these AA-MS-SLNs displayed concentration-dependent apoptotic activity on glioma cells, which further confirms the potential of exploiting these AA-loaded MS-SLNs for brain cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Docosahexaenoic acid affects arachidonic acid uptake in megakaryocytes

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

Schick, P.K.; Webster, P.

1987-05-01

Dietary omega 3 fatty acids are thought to prevent atherosclerosis, possibly by modifying platelet (PT) function and arachidonic acid (20:4) metabolism. The study was designed to determine whether omega 3 fatty acids primarily affect 20:4 metabolism in megakaryocytes (MK), bone marrow precursors of PT, rather than in circulating PT. MK and PT were isolated from guinea pigs and incubated with (/sup 14/C)-20:4 (0.13uM). Docosahexaenoic acid (22:6) is a major omega 3 fatty acid in marine oils. The incubation of MK with 22:6 (0.1, 1.0 uM) resulted in the decrease of incorporation of (/sup 14/C)-20:4 into total MK phospholipids, 16% andmore » 41% respectively. Alpha-linolenic acid (18:3), a major omega 3 fatty acid present in American diets, had no effect on 20:4 uptake in MK. 22:6 primarily affected the uptake of (/sup 14/C)-20:4 into phosphatidylethanolamine (PE) and phosphatidylserine (PS) in MK. In MK, 22:6 (0.1, 1.0 uM) caused a decrease of incorporation of (/sup 14/C)-20:4 into PE, 21% and 55% respectively; a decrease into PS, 16% and 48% respectively; but only a decrease of 4% and 18%, respectively, into phosphatidylcholine; and a decrease of 3% and 21% into phosphatidylinositol 22:6 (3.0 uM) had no effect on the uptake of AA into PT phospholipids. The study shows that 22:6 has a selective effect on AA uptake in MK and that the acylation or transacylation of PE and PS are primarily affected. 22:6 and other marine omega 3 fatty acids appear to primarily affect megakaryocytes which may result in the production of platelets with abnormal content and compartmentalization of AA.« less

Chemical composition and anti-inflammatory and antioxidant activities of eight pear cultivars.

PubMed

Li, Xia; Zhang, Jun-Ying; Gao, Wen-Yuan; Wang, Ying; Wang, Hai-Yang; Cao, Jing-Guo; Huang, Lu-Qi

2012-09-05

The contents of total phenolics, total flavonoids, total anthocyanins, and total triterpenes of eight pear samples were determined, and the monomeric compounds were identified and quantitated using high-performance liquid chromatography. The in vitro antioxidant and in vivo anti-inflammatory activities of the different pear cultivars were compared. Arbutin and catechin were the dominant polyphenol compounds in the eight pear varieties, followed by chlorogenic acid, quercetin, and rutin. In addition, Xuehua pear and Nanguo pear had significantly higher total phenolics and flavonoids contents, while Dangshansu pear had the largest total triterpenes value (209.2 mg/100 g). Xuehua pear and Nanguo pear also were the highest in total anthocyanins. The pears with high total phenolics and total flavonoids contents had significantly higher antioxidant and anti-inflammatory abilities than those of other species. Anthocyanins were correlated to antioxidant capacity in pears, whereas total triterpenoids were strongly correlated to anti-inflammatory activity.

Mass spectrometric dereplication of nitrogen-containing constituents of black cohosh (Cimicifuga racemosa L.)

PubMed Central

Nikolić, Dejan; Gödecke, Tanja; Chen, Shao-Nong; White, Jerry; Lankin, David C.; Pauli, Guido F.; van Breemen, Richard B.

2011-01-01

Black cohosh preparations are popular dietary supplements among women seeking alternative treatments for menopausal complaints. For decades, triterpene glycosides and phenolic acids have dominated the phytochemical and biomedical research on this plant. In this study, we provide evidence that black cohosh contains an unexpected and highly diverse group of secondary nitrogenous metabolites previously unknown to exist in this plant. Using a dereplication approach that combines accurate mass measurements, database searches and general knowledge of biosynthetic pathways of natural products, we identified or tentatively identified 73 nitrogen-containing metabolites, many of which are new natural products. The identified compounds belong to several structural groups including alkaloids, amides or esters of hydroxycinnamic acids and betains. Among the alkaloids, several classes such as guanidino alkaloids, isoquinolines and β-carbolines were identified. Fragmentation patterns for major compound classes are discussed, which provides a framework for the discovery of these compounds from other sources. Identification of alkaloids as a well-known group of bioactive natural products represents an important advance in better understanding of the pharmacological profile of black cohosh. PMID:22178683

A Demonstration of Acid Rain

ERIC Educational Resources Information Center

Fong, Man Wai

2004-01-01

A demonstration showing acid rain formation is described. Oxides of sulfur and nitrogen that result from the burning of fossil fuels are the major pollutants of acid rain. In this demonstration, SO[subscript 2] gas is produced by the burning of matches. An acid-base indicator will show that the dissolved gas turns an aqueous solution acidic.

Bioactive constituents of Chinese natural medicines. I. New sesquiterpene ketones with vasorelaxant effect from Chinese moxa, the processed leaves of Artemisia argyi Levl. et Vant.: moxartenone and moxartenolide.

PubMed

Yoshikawa, M; Shimada, H; Matsuda, H; Yamahara, J; Murakami, N

1996-09-01

Two new sesquiterpene ketones, moxartenone and moxartenolide, and three octadecadienoic acids were isolated from Chinese moxa, the processed leaves of Artemisia argyi LEVL. et VANT., together with two sesquiterpenes, five triterpenes, two phenyl propanoids and three polyoxyflavones. The chemical structures of new sesquiterpenes, moxartenone, moxartenolide, and octadecadienoic acids were determined on the basis of chemical and physiochemical evidence. Moxartenolide was found to inhibit the contractions induced by a high concentration of K+, by norepinephrine, and by serotonin in isolated aortic strips of rat, while moxartenone showed little activity.

Anti-inflammatory activity and chemical profile of Galphimia glauca.

PubMed

González-Cortazar, Manasés; Herrera-Ruiz, Maribel; Zamilpa, Alejandro; Jiménez-Ferrer, Enrique; Marquina, Silvia; Alvarez, Laura; Tortoriello, Jaime

2014-01-01

Galphimia glauca, commonly known as "flor de estrella", is a plant species used in Mexican traditional medicine for the treatment of different diseases that have an acute or chronic inflammatory process in common. Aerial parts of this plant contain nor-seco-triterpenoids with anxiolytic properties, which have been denominated galphimines. Other compounds identified in the plant are tetragalloyl-quinic acid, gallic acid, and quercetin, which are able to inhibit the bronchial obstruction induced by platelet-activating factor. The objective of this work was to evaluate the anti-inflammatory effect of crude extracts from G. glauca and, by means of bioguided chemical separation, to identify the compounds responsible for this pharmacological activity. n-Hexane, ethyl acetate, dichloromethane, and methanol extracts showed an important anti-inflammatory effect. Chemical separation of the active methanol extract allowed us to identify the nor-seco-triterpenes galphimine-A (1) and galphimine-E (3) as the anti-inflammatory principles. Analysis of structure-activity relationships evidenced that the presence of an oxygenated function in C6 is absolutely necessary to show activity. In this work, the isolation and structural elucidation of two new nor-seco-triterpenes denominated as galphimine-K (4) and galphimine-L (5), together with different alkanes, fatty acids, as well as three flavonoids (17-19), are described, to our knowledge for the first time, from Galphimia glauca. Georg Thieme Verlag KG Stuttgart · New York.

Age-related changes of n-3 and n-6 polyunsaturated fatty acids in the anterior cingulate cortex of individuals with major depressive disorder.

PubMed

Conklin, Sarah M; Runyan, Caroline A; Leonard, Sherry; Reddy, Ravinder D; Muldoon, Matthew F; Yao, Jeffrey K

2010-01-01

Accumulating evidence finds a relative deficiency of peripheral membrane fatty acids in persons with affective disorders such as unipolar and bipolar depression. Here we sought to investigate whether postmortem brain fatty acids within the anterior cingulate cortex (BA-24) varied according to the presence of major depression at the time of death. Using capillary gas chromatography we measured fatty acids in a depressed group (n=12), and in a control group without lifetime history of psychiatric diagnosis (n=14). Compared to the control group, the depressed group showed significantly lower concentrations of numerous saturated and polyunsaturated fatty acids including both the n-3 and n-6 fatty acids. Additionally, significant correlations between age at death and precursor (or metabolites) in the n-3 fatty acid pathway were demonstrated in the depressed group but not in control subjects. In the n-6 fatty acid family, the ratio of 20:3(n-6)/18:2(n-6) was higher in patients than in control groups, whereas the ratio of 20:4(n-6)/20:3(n-6) was relatively decreased in patients. Lastly, a significant negative correlation between age and the ratio of 20:4(n-6) to 22:6(n-3) was found in patients, but not in controls. Taken together, decreases in 22:6(n-3) may be caused, at least in part, by the diminished formation of 20:5(n-3), which is derived from 20:4(n-3) through a Delta5 desaturase reaction. The present findings from postmortem brain tissue raise the possibility that an increased ratio of 20:4(n-6) to 22:6(n-3) may provide us with a biomarker for depression. Future research should further investigate these relationships. Published by Elsevier Ltd.

Purity-activity relationships of natural products: the case of anti-TB active ursolic acid.

PubMed

Jaki, Birgit U; Franzblau, Scott G; Chadwick, Lucas R; Lankin, David C; Zhang, Fangqiu; Wang, Yuehong; Pauli, Guido F

2008-10-01

The present study explores the variability of biological responses from the perspective of sample purity and introduces the concept of purity-activity relationships (PARs) in natural product research. The abundant plant triterpene ursolic acid (1) was selected as an exemplary natural product due to the overwhelming number yet inconsistent nature of its approximate 120 reported biological activities, which include anti-TB potential. Nine different samples of ursolic acid with purity certifications were obtained, and their purity was independently assessed by means of quantitative 1H NMR (qHNMR). Biological evaluation consisted of determining MICs against two strains of virulent Mycobacterium tuberculosis and IC50 values in Vero cells. Ab initio structure elucidation provided unequivocal structural confirmation and included an extensive 1H NMR spin system analysis, determination of nearly all J couplings and the complete NOE pattern, and led to the revision of earlier reports. As a net result, a sigmoid PAR profile of 1 was obtained, demonstrating the inverse correlation of purity and anti-TB bioactivity. The results imply that synergistic effects of 1 and its varying impurities are the likely cause of previously reported antimycobacterial potential. Generating PARs is a powerful extension of the routinely performed quantitative correlation of structure and activity ([Q]SAR). Advanced by the use of primary analytical methods such as qHNMR, PARs enable the elucidation of cases like 1 when increasing purity voids biological activity. This underlines the potential of PARs as a tool in drug discovery and synergy research and accentuates the need to routinely combine biological testing with purity assessment.

Production of the quinone-methide triterpene maytenin by in vitro adventitious roots of Peritassa campestris (Cambess.) A.C.Sm. (Celastraceae) and rapid detection and identification by APCI-IT-MS/MS.

PubMed

Paz, Tiago Antunes; dos Santos, Vânia A F F M; Inácio, Marielle Cascaes; Pina, Edieidia Souza; Pereira, Ana Maria Soares; Furlan, Maysa

2013-01-01

Establishment of adventitious root cultures of Peritassa campestris (Celastraceae) was achieved from seed cotyledons cultured in semisolid Woody Plant Medium (WPM) supplemented with 2% sucrose, 0.01% PVP, and 4.0 mg L⁻¹ IBA. Culture period on accumulation of biomass and quinone-methide triterpene maytenin in adventitious root were investigated. The accumulation of maytenin in these roots was compared with its accumulation in the roots of seedlings grown in a greenhouse (one year old). A rapid detection and identification of maytenin by direct injection into an atmospheric-pressure chemical ionization ion trap tandem mass spectrometer (APCI-IT-MS/MS) were performed without prior chromatographic separation. In vitro, the greatest accumulation of biomass occurred within 60 days of culture. The highest level of maytenin--972.11  μ g·g⁻¹ dry weight--was detected at seven days of cultivation; this value was 5.55-fold higher than that found in the roots of seedlings grown in a greenhouse.

Production of the Quinone-Methide Triterpene Maytenin by In Vitro Adventitious Roots of Peritassa campestris (Cambess.) A.C.Sm. (Celastraceae) and Rapid Detection and Identification by APCI-IT-MS/MS

PubMed Central

Paz, Tiago Antunes; dos Santos, Vânia A. F. F. M.; Inácio, Marielle Cascaes; Pina, Edieidia Souza; Pereira, Ana Maria Soares; Furlan, Maysa

2013-01-01

Establishment of adventitious root cultures of Peritassa campestris (Celastraceae) was achieved from seed cotyledons cultured in semisolid Woody Plant Medium (WPM) supplemented with 2% sucrose, 0.01% PVP, and 4.0 mg L−1 IBA. Culture period on accumulation of biomass and quinone-methide triterpene maytenin in adventitious root were investigated. The accumulation of maytenin in these roots was compared with its accumulation in the roots of seedlings grown in a greenhouse (one year old). A rapid detection and identification of maytenin by direct injection into an atmospheric-pressure chemical ionization ion trap tandem mass spectrometer (APCI-IT-MS/MS) were performed without prior chromatographic separation. In vitro, the greatest accumulation of biomass occurred within 60 days of culture. The highest level of maytenin—972.11 μg·g−1 dry weight—was detected at seven days of cultivation; this value was 5.55-fold higher than that found in the roots of seedlings grown in a greenhouse. PMID:24205504

A review on phytochemistry and ethnopharmacological aspects of genus Calendula

PubMed Central

Arora, Disha; Rani, Anita; Sharma, Anupam

2013-01-01

This review includes 84 references on the genus Calendula (Asteraceae) and comprises ethnopharmacology, morphology and microscopy, phytoconstituents, pharmacological reports, clinical studies and toxicology of the prominent species of Calendula. Triterpene alcohols, triterpene saponins, flavonoids, carotenoids and polysaccharides constitute major classes of phytoconstituents of the genus. A few species of this genus have medicinal value, among these Calendula officinalis Linn., has been traditionally used in the treatment of various skin tumors, dermatological lesions, ulcers, swellings and nervous disorders as well as almost 200 cosmetic formulations, i.e., creams, lotions, shampoos. Despite a long tradition of use of some species, the genus has not been explored properly. In the concluding part, the future scope of Calendula species has been emphasized with a view to establish their multifarious biological activities and mode of action. PMID:24347926

Alternative splicing of SMPD1 coding for acid sphingomyelinase in major depression.

PubMed

Rhein, Cosima; Reichel, Martin; Kramer, Marcel; Rotter, Andrea; Lenz, Bernd; Mühle, Christiane; Gulbins, Erich; Kornhuber, Johannes

2017-02-01

Major depressive disorder (MDD) is a psychiatric disorder characterized by key symptoms that include depressed mood and a loss of interest and pleasure. A recently developed pathogenic model of MDD involves disturbed neurogenesis in the hippocampus, where the acid sphingomyelinase (ASM)/ceramide system plays an important role and is proposed as a molecular target for antidepressant action. Because alternative splicing of SMPD1 mRNA, coding for ASM, is relevant for the regulation of ASM enzymatic activity, we investigated the frequency of alternatively spliced ASM isoforms in peripheral blood cells of MDD patients versus healthy controls. Because the full-length transcript variant 1 of SMPD1 (termed ASM-1) is the only known form within the splicing pattern that encodes an enzymatically fully active ASM, we determined a fraction of splice isoforms deviating from ASM-1 using PCR amplification and capillary electrophoresis with laser-induced fluorescence analysis. ASM alternative splicing events occurred significantly less frequently in MDD patients compared to healthy subjects. After 5 days of antidepressant treatment, the frequency of alternatively spliced ASM isoforms decreased in those patients who were treated with a functional inhibitor of ASM activity (FIASMA) but remained constant in MDD patients treated with other antidepressant drugs. This effect was more pronounced when healthy male volunteers were treated with the FIASMAs fluoxetine or paroxetine, in contrast to a placebo group. Patients were treated with different antidepressant drugs, depending on individual parameters and disease courses. This study shows that the ASM alternative splicing pattern could be a biological target with diagnostic relevance and could serve as a novel biomarker for MDD. Copyright © 2016 Elsevier B.V. All rights reserved.

Lipid and fatty acid analysis of the Plodia interpunctella granulosis virus (PiGV) envelope

NASA Technical Reports Server (NTRS)

Shastri-Bhalla, K.; Funk, C. J.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

1993-01-01

Virus envelope was isolated from Plodia interpunctella granulosis virus, produced in early fourth-instar larvae. Both polar and neutral lipids were analyzed by two-dimensional thin-layer chromatography. Fatty acid composition of various individual neutral and polar lipids was determined by gas-liquid chromatography. The major components of envelope neutral lipid were diacylglycerols. Palmitic acid and stearic acid were the major saturated fatty acids in both polar and neutral lipids. Whereas palmitoleic acid was the major unsaturated fatty acids in neutral lipids, oleic acid was the major unsaturated fatty acid in the polar lipids.

Perfluoroalkylated acids in the eggs of great tits (Parus major) near a fluorochemical plant in Flanders, Belgium.

PubMed

Groffen, Thimo; Lopez-Antia, Ana; D'Hollander, Wendy; Prinsen, Els; Eens, Marcel; Bervoets, Lieven

2017-09-01

Perfluoroalkyl acids (PFAAs) are highly persistent substances which have been detected in wildlife around the world, including birds. Although bird eggs have often been used to determine and monitor PFAAs levels in the marine environment, this has rarely been done in the terrestrial environment. In the present study we examined the concentrations and composition profile of 12 PFAAs (4 perfluoroalkyl sulfonic acids (PFSAs) and 8 perfluoroalkyl carboxylic acids (PFCAs) in the eggs of great tits (Parus major) collected at a fluorochemical plant and in three other areas, representing a gradient in distance from the pollution source (from 1 to 70 km), in Antwerp, Belgium. The PFSA concentrations measured at the site of the fluorochemical plant were among the highest ever reported in eggs with median concentrations of 10380 ng/g (extrapolated), 99.3 ng/g and 47.7 ng/g for PFOS, PFHxS and PFDS respectively. Furthermore, the median concentration of 19.8 ng/g for PFOA was also among the highest ever reported in bird eggs. Although these concentrations decreased sharply with distance from the fluorochemical plant, levels found in the adjacent sites were still high compared to what has been reported in literature. Moreover, based on what is known in literature, it is likely that these concentrations may cause toxicological effects. PFOS was the dominant contributor to the PFSA and PFAAs (63.4-97.6%) profile at each site, whereas for PFCAs this was PFOA at the plant site and the nearest locations (41.0-52.8%) but PFDoA (37.7%) at the farthest location. Although there is some evidence that PFAAs concentrations close to the plant site are decreasing in comparison with earlier measurements, which may be due to the phase out of PFOS, more research is necessary to understand the extent of the toxicological effects in the vicinity of this PFAAs hotspot. Copyright © 2017 Elsevier Ltd. All rights reserved.

Retigeric acid B exerts antifungal effect through enhanced reactive oxygen species and decreased cAMP.

PubMed

Chang, Wen-Qiang; Wu, Xiu-Zhen; Cheng, Ai-Xia; Zhang, Li; Ji, Mei; Lou, Hong-Xiang

2011-05-01

Retigeric acid B (RAB), a triterpene acid isolated from Lobaria kurokawae exerts antifungal effect. The present study was designed to elucidate the underlying mechanisms by which RAB regulates the proliferation and cell death of Candida albicans. We measured the metabolic activity of C. albicans with WST1 Cell Proliferation and Cytotoxicity Assay Kit, analyzed the cell cycle by flow cytometry, visualized the ultrastructure by transmission electron microscopy (TEM) and investigated the apoptosis and necrosis induced by RAB using confocal microscopy. The reactive oxygen species (ROS) accumulation was determined by spectrophotometry, flow cytometry and fluorescent microscopy. The mtΔψ was detected using flow cytometry. And the levels of intracellular cAMP and ATP were measured with cAMP ELISA and ATP Assay Kits, respectively. The proliferation of the yeasts was blocked in G(2)/M phase by a low dose of RAB treatment and in G(1) phase at high concentration. When cultured in phosphate buffered saline (PBS) deprived of energy source, yeasts displayed the phenotype of death caused by accumulated ROS, mtΔψ hyperpolarization and dramatic decrease in ATP level in the presence of high dose of RAB. RAB inhibits the growth of C. albicans by stimulating ROS production and reducing intracellular cAMP. The ROS accumulation, mtΔψ hyperpolarization, ATP depletion and damaged plasma membrane integrity together mediate cell death of C. albicans induced by RAB. Our findings provide a novel molecular mechanism for exploring possible applications of lichen derived metabolites in fighting fungal infection in humans. Copyright © 2011 Elsevier B.V. All rights reserved.

Protective effect of boswellic acids versus pioglitazone in a rat model of diet-induced non-alcoholic fatty liver disease: influence on insulin resistance and energy expenditure.

PubMed

Zaitone, Sawsan A; Barakat, Bassant M; Bilasy, Shymaa E; Fawzy, Manal S; Abdelaziz, Eman Z; Farag, Noha E

2015-06-01

Non-alcoholic fatty liver disease (NAFLD) is closely linked to insulin resistance, oxidative stress, and cytokine imbalance. Boswellic acids, a series of pentacyclic triterpene molecules that are produced by plants in the genus Boswellia, has been traditionally used for the treatment of a variety of diseases. This study aimed at evaluating the protective effect of boswellic acids in a model of diet-induced NAFLD in rats in comparison to the standard insulin sensitizer, pioglitazone. Rats were fed with a high-fat diet (HFD) for 12 weeks to induce NAFLD. Starting from week 5, rats received boswellic acids (125 or 250 mg/kg) or pioglitazone parallel to the HFD. Feeding with HFD induced hepatic steatosis and inflammation in rats. In addition, liver index, insulin resistance index, activities of liver enzymes, and serum lipids deviated from normal. Further, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cyclooxygenase 2 were elevated; this was associated with an increase in hepatic expression of inducible nitric oxide synthase (iNOS) and formation of 4-hydroxy-2-nonenal (HNE). Rats treated with boswellic acids (125 or 250 mg/kg) or pioglitazone showed improved insulin sensitivity and a reduction in liver index, activities of liver enzymes, serum TNF-α and IL-6 as well as hepatic iNOS expression and HNE formation compared to HFD group. Furthermore, at the cellular level, boswellic acids (250 mg/kg) ameliorated the expression of thermogenesis-related mitochondrial uncoupling protein-1 and carnitine palmitoyl transferase-1 in white adipose tissues. Data from this study indicated that boswellic acids might be a promising therapy in the clinical management of NAFLD if appropriate safety and efficacy data are available.

Release of Polyphenols Is the Major Factor Influencing the Bioconversion of Rice Straw to Lactic Acid.

PubMed

Chen, Xingxuan; Xue, Yiyun; Hu, Jiajun; Tsang, Yiu Fai; Gao, Min-Tian

2017-11-01

In this study, we found that p-coumaric acid (p-CA), ferulic acid (FA), and condensed tannins were released from rice straw during saccharification. The presence of polyphenols prolonged the lag phase and lowered the productivity of lactic acid. p-CA was identified as a key inhibitor. Tannins had a lower inhibitory effect than p-CA; FA had little inhibitory effect. Acid, alkaline, and ball milling pretreatments elicited different levels of polyphenol release from rice straw. Due to the different levels of polyphenol release in the pretreatment step, the enzymatic hydrolysates contained different concentrations of polyphenols. Compared with fermentation with a synthetic medium, fermentation with the hydrolysates of ball-milled rice straw provided much lower productivity and yield of lactic acid due to the presence of polyphenols. Removal of these compounds played an important role in lactic acid fermentation. When rice straw was alkaline pretreated, the hydrolysates contained few phenolic compounds, resulting in high productivity and yield of lactic acid (1.8 g/L/h and 26.7 g/100 g straw), which were comparable to those in a synthetic medium. This indicates that there is a correlation between removal of phenolic compounds and efficiency in lactic acid fermentation.

Evaluation of glutamic acid and glycine as sources of nonessential amino acids for lake trout (Salvelinus namaycush) and rainbow trout (Salmo gairdnerii)

USGS Publications Warehouse

Hughes, S.G.

1985-01-01

1. A semi-purified test diet which contained either glutamic acid or glycine as the major source of nonessential amino acids (NEAA) was fed to lake and rainbow trout.2. Trout fed the diet containing glutamic acid consistently showed better growth and feed conversion efficiencies than those fed the diets containing glycine.3. The data indicate that these trout utilize glutamic acid more efficiently than glycine when no other major sources of NEAA are present.

Two Major Bile Acids in the Hornbills, (24R,25S)-3α,7α,24-Trihydroxy-5β-cholestan-27-oyl Taurine and Its 12α-Hydroxy Derivative.

PubMed

Satoh, Rika; Ogata, Hiroaki; Saito, Tetsuya; Zhou, Biao; Omura, Kaoru; Kurabuchi, Satoshi; Mitamura, Kuniko; Ikegawa, Shigeo; Hagey, Lee R; Hofmann, Alan F; Iida, Takashi

2016-06-01

Two major bile acids were isolated from the gallbladder bile of two hornbill species from the Bucerotidae family of the avian order Bucerotiformes Buceros bicornis (great hornbill) and Penelopides panini (Visayan tarictic hornbill). Their structures were determined to be 3α,7α,24-dihydroxy-5β-cholestan-27-oic acid and its 12α-hydroxy derivative, 3α,7α,12α,24-tetrahydroxy-5β-cholestan-27-oic acid (varanic acid, VA), both present in bile as their corresponding taurine amidates. The four diastereomers of varanic acid were synthesized and their assigned structures were confirmed by X-ray crystallographic analysis. VA and its 12-deoxy derivative were found to have a (24R,25S)-configuration. 13 additional hornbill species were also analyzed by HPLC and showed similar bile acid patterns to B. bicornis and P. panini. The previous stereochemical assignment for (24R,25S)-VA isolated from the bile of varanid lizards and the Gila monster should now be revised to the (24S,25S)-configuration.

Unusual binding of ursodeoxycholic acid to ileal bile acid binding protein: role in activation of FXRα.

PubMed

Fang, Changming; Filipp, Fabian V; Smith, Jeffrey W

2012-04-01

Ursodeoxycholic acid (UDCA, ursodiol) is used to prevent damage to the liver in patients with primary biliary cirrhosis. The drug also prevents the progression of colorectal cancer and the recurrence of high-grade colonic dysplasia. However, the molecular mechanism by which UDCA elicits its beneficial effects is not entirely understood. The aim of this study was to determine whether ileal bile acid binding protein (IBABP) has a role in mediating the effects of UDCA. We find that UDCA binds to a single site on IBABP and increases the affinity for major human bile acids at a second binding site. As UDCA occupies one of the bile acid binding sites on IBABP, it reduces the cooperative binding that is often observed for the major human bile acids. Furthermore, IBABP is necessary for the full activation of farnesoid X receptor α (FXRα) by bile acids, including UDCA. These observations suggest that IBABP may have a role in mediating some of the intestinal effects of UDCA.

Factors Associated With Major Bleeding Events

PubMed Central

Goodman, Shaun G.; Wojdyla, Daniel M.; Piccini, Jonathan P.; White, Harvey D.; Paolini, John F.; Nessel, Christopher C.; Berkowitz, Scott D.; Mahaffey, Kenneth W.; Patel, Manesh R.; Sherwood, Matthew W.; Becker, Richard C.; Halperin, Jonathan L.; Hacke, Werner; Singer, Daniel E.; Hankey, Graeme J.; Breithardt, Gunter; Fox, Keith A. A.; Califf, Robert M.

2014-01-01

Objectives This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). Background The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin. Methods The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model. Results The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk. Conclusions Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non

Toward an Increased Functionality in Oyster ( Pleurotus) Mushrooms Produced on Grape Marc or Olive Mill Wastes Serving as Sources of Bioactive Compounds.

PubMed

Koutrotsios, Georgios; Kalogeropoulos, Nick; Kaliora, Andriana C; Zervakis, Georgios I

2018-06-20

Pleurotus ostreatus, P. eryngii, and P. nebrodensis were cultivated on nonconventional substrates containing grape marc (GMC) or olive mill byproducts (OMB); wheat straw (WHS) served as control. GMC-based media demonstrated equal/better mushroom productivity than WHS for P. eryngii and P. nebrodensis, while the cultivation performance of P. eryngii was improved in OMB-based media. Both GMC and OMB substrates led to large increase of fruit-bodies content in phenolic acids, resveratrol, triterpenic compounds, and ergosterol; in particular, P. eryngii mushrooms presented significantly more total phenolics and exhibited much higher antioxidant activity (2- to 8-fold increase). Furthermore, substrates containing GMC or OMB presented up to 27% increase in mushroom β-glucans. Overall, Pleurotus species responded in a different and mostly substrate-specific manner by selectively absorbing organic compounds. Phenolics and squalene content of substrates correlated very well with mushrooms antioxidant activity and ergosterol, respectively; the same was observed for triterpenics' content of substrates and mushrooms.

Characterization and quantification of γ-oryzanol in grains of 16 Korean rice varieties.

PubMed

Kim, Heon Woong; Kim, Jung Bong; Cho, Soo-Muk; Cho, Il Kyu; Li, Qing X; Jang, Hwan-Hee; Lee, Sung-Hyeon; Lee, Young-Min; Hwang, Kyung-A

2015-03-01

γ-Oryzanol, a mixture of ferulic acid esters of triterpene alcohols and sterols, is a nutritionally important group of rice secondary metabolites. A library of 27 γ-oryzanol was assembled from existing data and used to assist identification and quantification of γ-oryzanol isolated from 16 Korean rice varieties (11 white and 5 pigmented). γ-Oryzanol was analyzed with liquid chromatography with diode array detection and electrospray ionization mass spectrometry. Nineteen different γ-oryzanol were observed and identified as stigmasterol, campesterol and sitosterol or common and hydroxylated triterpene alcohols. In the 16 varieties, the total γ-oryzanol content averaged 43.8 mg/100 g (range, 26.7-61.6 mg/100 g), which Josaengheugchal exhibited the highest level (61.6 mg/100 g). The Korean rice varieties were classified based on qualitative and quantitative γ-oryzanol data by multivariate statistical analysis. Clusters of specialty rice varieties exhibited higher γ-oryzanol levels than those of common rice varieties.

Excretion of Avenanthramides, Phenolic Acids and their Major Metabolites Following Intake of Oat Bran

PubMed Central

Schär, Manuel Y.; Corona, Giulia; Soycan, Gulten; Dine, Clemence; Kristek, Angelika; Alsharif, Sarah N. S.; Behrends, Volker; Lovegrove, Alison; Shewry, Peter R.

2017-01-01

Scope Wholegrain has been associated with reduced chronic disease mortality, with oat intake particularly notable for lowering blood cholesterol and glycemia. To better understand the complex nutrient profile of oats, we studied urinary excretion of phenolic acids and avenanthramides after ingestion of oat bran in humans. Methods and results After a 2‐d (poly)phenol‐low diet, seven healthy men provided urine 12 h before and 48 h after consuming 60 g oat bran (7.8 μmol avenanthramides, 139.2 μmol phenolic acids) or a phenolic‐low (traces of phenolics) control in a crossover design. Analysis by ultra‐high performance liquid chromatography (UPLC)–MS/MS showed that oat bran intake resulted in an elevation in urinary excretion of 30 phenolics relative to the control, suggesting that they are oat bran‐derived. Mean excretion levels were elevated between 0–2 and 4–8 h, following oat bran intake, and amounted to a total of 33.7 ± 7.3 μmol total excretion (mean recovery: 22.9 ± 5.0%), relative to control. The predominant metabolites included: vanillic acid, 4‐ and 3‐hydroxyhippuric acids, and sulfate‐conjugates of benzoic and ferulic acids, which accounted collectively for two thirds of total excretion. Conclusion Oat bran phenolics follow a relatively rapid urinary excretion, with 30 metabolites excreted within 8 h of intake. These levels of excretion suggest that bound phenolics are, in part, rapidly released by the microbiota. PMID:29024323

Dysregulation of major functional genes in frontal cortex by maternal exposure to carbon black nanoparticle is not ameliorated by ascorbic acid pretreatment.

PubMed

Onoda, Atsuto; Takeda, Ken; Umezawa, Masakazu

2018-09-01

Recent cohort studies have revealed that perinatal exposure to particulate air pollution, including carbon-based nanoparticles, increases the risk of brain disorders. Although developmental neurotoxicity is currently a major issue in the toxicology of nanoparticles, critical information for understanding the mechanisms underlying the developmental neurotoxicity of airway exposure to carbon black nanoparticle (CB-NP) is still lacking. In order to investigate these mechanisms, we comprehensively analyzed fluctuations in the gene expression profile of the frontal cortex of offspring mice exposed maternally to CB-NP, using microarray analysis combined with Gene Ontology information. We also analyzed differences in the enriched function of genes dysregulated by maternal CB-NP exposure with and without ascorbic acid pretreatment to refine specific alterations in gene expression induced by CB-NP. Total of 652 and 775 genes were dysregulated by CB-NP in the frontal cortex of 6- and 12-week-old offspring mice, respectively. Among the genes dysregulated by CB-NP, those related to extracellular matrix structural constituent, cellular response to interferon-beta, muscle organ development, and cysteine-type endopeptidase inhibitor activity were ameliorated by ascorbic acid pretreatment. A large proportion of the dysregulated genes, categorized in hemostasis, growth factor, chemotaxis, cell proliferation, blood vessel, and dopaminergic neurotransmission, were, however, not ameliorated by ascorbic acid pretreatment. The lack of effects of ascorbic acid on the dysregulation of genes following maternal CB-NP exposure suggests that the contribution of oxidative stress to the effects of CB-NP on these biological functions, i.e., cell migration and proliferation, blood vessel maintenance, and dopaminergic neuron system, may be limited. At least, ascorbic acid pretreatment is hardly likely to be able to protect the brain of offspring from developmental neurotoxicity of CB-NP. The

C. elegans Major Fats Are Stored in Vesicles Distinct from Lysosome-Related Organelles

PubMed Central

O’Rourke, Eyleen J.; Soukas, Alexander A.; Carr, Christopher E.; Ruvkun, Gary

2010-01-01

SUMMARY Genetic conservation allows ancient features of fat storage endocrine pathways to be explored in C. elegans. Multiple studies have used Nile red or BODIPY-labeled fatty acids to identify regulators of fat mass. When mixed with their food, E. coli bacteria, Nile red, and BODIPY-labeled fatty acids stain multiple spherical cellular structures in the C. elegans major fat storage organ, the intestine. However, here we demonstrate that, in the conditions previously reported, the lysosome-related organelles stained by Nile red and BODIPY-labeled fatty acids are not the C. elegans major fat storage compartment. We show that the major fat stores are contained in a distinct cellular compartment that is not stained by Nile red. Using biochemical assays, we validate oil red O staining as a method to assess major fat stores in C. elegans, allowing for efficient and accurate genetic and functional genomic screens for genes that control fat accumulation at the organismal level. PMID:19883620

New compounds from acid hydrolyzed products of the fruits of Momordica charantia L. and their inhibitory activity against protein tyrosine phosphatas 1B.

PubMed

Zeng, Ke; He, Yan-Ni; Yang, Di; Cao, Jia-Qing; Xia, Xi-Chun; Zhang, Shi-Jun; Bi, Xiu-Li; Zhao, Yu-Qing

2014-06-23

Four new cucurbitane-type triterpene sapogenins, compounds 1-4, together with other eight known compounds were isolated from the acid-hydrolyzed fruits extract of Momordica charantia L. Their chemical structures were established by NMR, mass spectrometry and X-ray crystallography. Compounds 1-7 and 9-12 were evaluated for their inhibitory activities toward protein tyrosine phosphatase 1B (PTP1B), a tyrosine phosphatase that has been implicated as a key target for therapy against type II diabetes. Compounds 1, 2, 4, 7 and 9 were shown inhibitory activities of 77%, 62%, 62% 60% and 68% against PTP1B, respectively. All of these tested compounds were exhibited higher PTP1B inhibition activities than that of the Na3VO4, a known PTP1B inhibitor used as positive control in present study. Structure activity relationship (SAR) analysis indicated that the inhibition activity of PTP1B was associated with the presence and number of -OH groups. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The potent insulin secretagogue effect of betulinic acid is mediated by potassium and chloride channels.

PubMed

Gomes Castro, Allisson Jhonatan; Cazarolli, Luisa Helena; Bretanha, Lizandra C; Sulis, Paola Miranda; Rey Padilla, Diana Patricia; Aragón Novoa, Diana Marcela; Dambrós, Betina Fernanda; Pizzolatti, Moacir G; Mena Barreto Silva, Fátima Regina

2018-06-15

Betulinic acid (BA) has been described as an insulin secretagogue which may explain its potent antihyperglycemic effect; however, the exact role of BA as an insulinogenic agent is not clear. The aim of this study was to investigate the mechanism of BA on calcium influx and static insulin secretion in pancreatic islets isolated from euglycemic rats. We found that BA triggers calcium influx by a mechanism dependent on ATP-dependent potassium channels and L-type voltage-dependent calcium channels. Additionally, the voltage-dependent and calcium-dependent chloride channels are also involved in the mechanism of BA, probably due to an indirect stimulation of calcium entry and increased intracellular calcium. Additionally, the downstream activation of PKC, which is necessary for the effect of BA on calcium influx, is involved in the full stimulatory response of the triterpene. BA stimulated the static secretion of insulin in pancreatic islets, indicating that the abrupt calcium influx may be a key step in its secretagogue effect. As such, BA stimulates insulin secretion through the activation of electrophysiological mechanisms, such as the closure of potassium channels and opening of calcium and chloride channels, inducing cellular depolarization associated with metabolic-biochemical effects, in turn activating PKC and ensuring the secretion of insulin. Copyright © 2018 Elsevier Inc. All rights reserved.

Delayed ripening of banana fruit by salicylic acid.

PubMed

Srivastava; Dwivedi

2000-09-08

Salicylic acid treatment has been found to delay the ripening of banana fruits (Musa acuminata). Fruit softening, pulp:peel ratio, reducing sugar content, invertase and respiration rate have been found to decrease in salicylic acid treated fruits as compared with control ones. The activities of major cell wall degrading enzymes, viz. cellulase, polygalacturonase and xylanase were found to be decreased in presence of salicylic acid. The major enzymatic antioxidants namely, catalase and peroxidase, were also found to be decreased in presence of salicylic acid during banana fruit ripening.

Acid Rain

USGS Publications Warehouse

Bricker, Owen P.; Rice, Karen C.

1995-01-01

Although acid rain is fading as a political issue in the United States and funds for research in this area have largely disappeared, the acidity of rain in the Eastern United States has not changed significantly over the last decade, and it continues to be a serious environmental problem. Acid deposition (commonly called acid rain) is a term applied to all forms of atmospheric deposition of acidic substances - rain, snow, fog, acidic dry particulates, aerosols, and acid-forming gases. Water in the atmosphere reacts with certain atmospheric gases to become acidic. For example, water reacts with carbon dioxide in the atmosphere to produce a solution with a pH of about 5.6. Gases that produce acids in the presence of water in the atmosphere include carbon dioxide (which converts to carbonic acid), oxides of sulfur and nitrogen (which convert to sulfuric and nitric acids}, and hydrogen chloride (which converts to hydrochloric acid). These acid-producing gases are released to the atmosphere through natural processes, such as volcanic emissions, lightning, forest fires, and decay of organic matter. Accordingly, precipitation is slightly acidic, with a pH of 5.0 to 5.7 even in undeveloped areas. In industrialized areas, most of the acid-producing gases are released to the atmosphere from burning fossil fuels. Major emitters of acid-producing gases include power plants, industrial operations, and motor vehicles. Acid-producing gases can be transported through the atmosphere for hundreds of miles before being converted to acids and deposited as acid rain. Because acids tend to build up in the atmosphere between storms, the most acidic rain falls at the beginning of a storm, and as the rain continues, the acids "wash out" of the atmosphere.

Unusual binding of ursodeoxycholic acid to ileal bile acid binding protein: role in activation of FXRα[S

PubMed Central

Fang, Changming; Filipp, Fabian V.; Smith, Jeffrey W.

2012-01-01

Ursodeoxycholic acid (UDCA, ursodiol) is used to prevent damage to the liver in patients with primary biliary cirrhosis. The drug also prevents the progression of colorectal cancer and the recurrence of high-grade colonic dysplasia. However, the molecular mechanism by which UDCA elicits its beneficial effects is not entirely understood. The aim of this study was to determine whether ileal bile acid binding protein (IBABP) has a role in mediating the effects of UDCA. We find that UDCA binds to a single site on IBABP and increases the affinity for major human bile acids at a second binding site. As UDCA occupies one of the bile acid binding sites on IBABP, it reduces the cooperative binding that is often observed for the major human bile acids. Furthermore, IBABP is necessary for the full activation of farnesoid X receptor α (FXRα) by bile acids, including UDCA. These observations suggest that IBABP may have a role in mediating some of the intestinal effects of UDCA. PMID:22223860

Muscle antioxidant (vitamin E) and major fatty acid groups, lipid oxidation and retail colour of meat from lambs fed a roughage based diet with flaxseed or algae.

PubMed

Ponnampalam, Eric N; Burnett, Viv F; Norng, Sorn; Hopkins, David L; Plozza, Tim; Jacobs, Joe L

2016-01-01

The effect of feeding flaxseed or algae supplements to lambs on muscle antioxidant potential (vitamin E), major fatty acid groups, lipid oxidation and retail colour was investigated. Lambs (n=120) were randomly allocated to one of 4 dietary treatments according to liveweight and fed the following diets for eight weeks: Annual ryegrass hay [60%]+subterranean clover hay [40%] pellets=Basal diet; Basal diet with flaxseed (10.7%)=Flax; Basal diet with algae (1.8%)=Algae; Basal diet with flaxseed (10.7%) and algae (1.8%)=FlaxAlgae. Flaxseed or algae supplementation significantly affected major fatty acid groups in muscle. The addition of algae (average of Algae and FlaxAlgae) resulted in lower vitamin E concentration in muscle (P<0.003; 1.0 vs 1.3mg/kg of muscle) compared with lambs fed a diet without algae (average of Basal and Flax). Increasing muscle EPA+DHA by algae supplementation significantly increased lipid oxidation, but retail display colour of fresh meat was not affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical constituents and biological activities from branches of Colubrina asiatica.

PubMed

Sangsopha, Watchara; Kanokmedhakul, Kwanjai; Lekphrom, Ratsami; Kanokmedhakul, Somdej

2018-05-01

Sixteen compounds were isolated from a Thai medicinal plant, Colubrina asiatica. The isolated compounds were elucidated on the basis of spectroscopic methods (IR, 1D and 2D NMR) as six triterpene acids (1-6), five steroids (7-11), one benzoic acid derivative (12), two peptides (13 and 14), one sesquiterpenoid (15) and one jujubogenin (16). Compounds 3 and 10 showed antimalarial activity against Plasmodium falciparum. Compound 5 showed antimycobacterial activity. Moreover, compounds 3, 5, 6, 10 and 14 exhibited weak cytotoxicity against cancer cell lines. Compounds 1-15 have been isolated for the first time from this plant.

Production of polymalic acid and malic acid by Aureobasidium pullulans fermentation and acid hydrolysis.

PubMed

Zou, Xiang; Zhou, Yipin; Yang, Shang-Tian

2013-08-01

Malic acid is a dicarboxylic acid widely used in the food industry and also a potential C4 platform chemical that can be produced from biomass. However, microbial fermentation for direct malic acid production is limited by low product yield, titer, and productivity due to end-product inhibition. In this work, a novel process for malic acid production from polymalic acid (PMA) fermentation followed by acid hydrolysis was developed. First, a PMA-producing Aureobasidium pullulans strain ZX-10 was screened and isolated. This microbe produced PMA as the major fermentation product at a high-titer equivalent to 87.6 g/L of malic acid and high-productivity of 0.61 g/L h in free-cell fermentation in a stirred-tank bioreactor. Fed-batch fermentations with cells immobilized in a fibrous-bed bioreactor (FBB) achieved the highest product titer of 144.2 g/L and productivity of 0.74 g/L h. The fermentation produced PMA was purified by adsorption with IRA-900 anion-exchange resins, achieving a ∼100% purity and a high recovery rate of 84%. Pure malic acid was then produced from PMA by hydrolysis with 2 M sulfuric acid at 85°C, which followed the first-order reaction kinetics. This process provides an efficient and economical way for PMA and malic acid production, and is promising for industrial application. Copyright © 2013 Wiley Periodicals, Inc.

Unsaturated fatty acids protect trophoblast cells from saturated fatty acid-induced autophagy defects.

PubMed

Hong, Ye-Ji; Ahn, Hyo-Ju; Shin, Jongdae; Lee, Joon H; Kim, Jin-Hoi; Park, Hwan-Woo; Lee, Sung Ki

2018-02-01

Dysregulated serum fatty acids are associated with a lipotoxic placental environment, which contributes to increased pregnancy complications via altered trophoblast invasion. However, the role of saturated and unsaturated fatty acids in trophoblastic autophagy has yet to be explored. Here, we demonstrated that prolonged exposure of saturated fatty acids interferes with the invasiveness of human extravillous trophoblasts. Saturated fatty acids (but not unsaturated fatty acids) inhibited the fusion of autophagosomes and lysosomes, resulting in the formation of intracellular protein aggregates. Furthermore, when the trophoblast cells were exposed to saturated fatty acids, unsaturated fatty acids counteracted the effects of saturated fatty acids by increasing degradation of autophagic vacuoles. Saturated fatty acids reduced the levels of the matrix metalloproteinases (MMP)-2 and MMP-9, while unsaturated fatty acids maintained their levels. In conclusion, saturated fatty acids induced decreased trophoblast invasion, of which autophagy dysfunction plays a major role. Copyright © 2017 Elsevier B.V. All rights reserved.

Spectra-structure correlations of saturated and unsaturated medium-chain fatty acids. Near-infrared and anharmonic DFT study of hexanoic acid and sorbic acid

NASA Astrophysics Data System (ADS)

Grabska, Justyna; Beć, Krzysztof B.; Ishigaki, Mika; Wójcik, Marek J.; Ozaki, Yukihiro

2017-10-01

Quantum chemical reproduction of entire NIR spectra is a new trend, enabled by contemporary advances in the anharmonic approaches. At the same time, recent increase of the importance of NIR spectroscopy of biological samples raises high demand for gaining deeper understanding of NIR spectra of biomolecules, i.e. fatty acids. In this work we investigate saturated and unsaturated medium-chain fatty acids, hexanoic acid and sorbic acid, in the near-infrared region. By employing fully anharmonic density functional theory (DFT) calculations we reproduce the experimental NIR spectra of these systems, including the highly specific spectral features corresponding to the dimerization of fatty acids. Broad range of concentration levels from 5 · 10- 4 M in CCl4 to pure samples are investigated. The major role of cyclic dimers can be evidenced for the vast majority of these samples. A highly specific NIR feature of fatty acids, the elevation of spectral baseline around 6500-4000 cm- 1, is being explained by the contributions of combination bands resulting from the vibrations of hydrogen-bonded OH groups in the cyclic dimers. Based on the high agreement between the calculated and experimental NIR spectra, a detailed NIR band assignments are proposed for hexanoic acid and sorbic acid. Subsequently, the correlations between the structure and NIR spectra are elucidated, emphasizing the regions in which clear and universal traces of specific bands corresponding to saturated and unsaturated alkyl chains can be established, thus demonstrating the wavenumber regions highly valuable for structural identifications.

Itaconic acid production in microorganisms.

PubMed

Zhao, Meilin; Lu, Xinyao; Zong, Hong; Li, Jinyang; Zhuge, Bin

2018-03-01

Itaconic acid, 2-methylidenebutanedioic acid, is a precursor of polymers, chemicals, and fuels. Many fungi can synthesize itaconic acid; Aspergillus terreus and Ustilago maydis produce up to 85 and 53 g l -1 , respectively. Other organisms, including Aspergillus niger and yeasts, have been engineered to produce itaconic acid. However, the titer of itaconic acid is low compared with the analogous major fermentation product, citric acid, for which the yield is > 200 g l -1 . Here, we review two types of pathway for itaconic acid biosynthesis as well as recent advances by metabolic engineering strategies and process optimization to enhance itaconic acid productivity in native producers and heterologous hosts. We also propose further improvements to overcome existing problems.

Chlorogenic acids and the acyl-quinic acids: discovery, biosynthesis, bioavailability and bioactivity.

PubMed

Clifford, Michael N; Jaganath, Indu B; Ludwig, Iziar A; Crozier, Alan

2017-12-13

Covering: 2000 up to late 2017This review is focussed upon the acyl-quinic acids, the most studied group within the ca. 400 chlorogenic acids so far reported. The acyl-quinic acids, the first of which was characterised in 1846, are a diverse group of plant-derived compounds produced principally through esterification of an hydroxycinnamic acid and 1l-(-)-quinic acid. Topics addressed in this review include the confusing nomenclature, quantification and characterisation by NMR and MS, biosynthesis and role in planta, and the occurrence of acyl-quinic acids in coffee, their transformation during roasting and delivery to the beverage. Coffee is the major human dietary source world-wide of acyl-quinic acids and consideration is given to their absorption and metabolism in the upper gastrointestinal tract, and the colon where the microbiota play a key role in the formation of catabolites. Evidence on the potential of the in vivo metabolites and catabolites of acyl-quinic acids to promote the consumer's health is evaluated.

Stearic Acid

ERIC Educational Resources Information Center

Young, Jay A.

2004-01-01

A chemical laboratory information profile (CLIP) is presented for the chemical, stearic acid. The profile lists the chemical's physical and harmful characteristics, exposure limits, and symptoms of major exposure, for the benefit of teachers and students, who use the chemical in the laboratory.

Mammalian Cell Cytotoxicity and Genotoxicity of the Haloacetic Acids, A Major Class of Drinking Water Disinfection By-Products

EPA Science Inventory

The haloacetic acids (HAAs) are disinfection by-products (DBPs) that are formed during the disinfection of drinking water, wastewaters and recreational pool waters. Currently, five HAAs [bromoacetic acid (BAA), dibromoacetic acid (DBAA), chloroacetic acid (CAA), dichloroacetic ac...

Probing fatty acid metabolism in bacteria, cyanobacteria, green microalgae and diatoms with natural and unnatural fatty acids.

PubMed

Beld, Joris; Abbriano, Raffaela; Finzel, Kara; Hildebrand, Mark; Burkart, Michael D

2016-04-01

In both eukaryotes and prokaryotes, fatty acid synthases are responsible for the biosynthesis of fatty acids in an iterative process, extending the fatty acid by two carbon units every cycle. Thus, odd numbered fatty acids are rarely found in nature. We tested whether representatives of diverse microbial phyla have the ability to incorporate odd-chain fatty acids as substrates for their fatty acid synthases and their downstream enzymes. We fed various odd and short chain fatty acids to the bacterium Escherichia coli, cyanobacterium Synechocystis sp. PCC 6803, green microalga Chlamydomonas reinhardtii and diatom Thalassiosira pseudonana. Major differences were observed, specifically in the ability among species to incorporate and elongate short chain fatty acids. We demonstrate that E. coli, C. reinhardtii, and T. pseudonana can produce longer fatty acid products from short chain precursors (C3 and C5), while Synechocystis sp. PCC 6803 lacks this ability. However, Synechocystis can incorporate and elongate longer chain fatty acids due to acyl-acyl carrier protein synthetase (AasS) activity, and knockout of this protein eliminates the ability to incorporate these fatty acids. In addition, expression of a characterized AasS from Vibrio harveyii confers a similar capability to E. coli. The ability to desaturate exogenously added fatty acids was only observed in Synechocystis and C. reinhardtii. We further probed fatty acid metabolism of these organisms by feeding desaturase inhibitors to test the specificity of long-chain fatty acid desaturases. In particular, supplementation with thia fatty acids can alter fatty acid profiles based on the location of the sulfur in the chain. We show that coupling sensitive gas chromatography mass spectrometry to supplementation of unnatural fatty acids can reveal major differences between fatty acid metabolism in various organisms. Often unnatural fatty acids have antibacterial or even therapeutic properties. Feeding of short

Alkane, terpene and polycyclic aromatic hydrocarbon geochemistry of the Mackenzie River and Mackenzie shelf: Riverine contributions to Beaufort Sea coastal sediment

NASA Astrophysics Data System (ADS)

Yunker, Mark B.; Macdonald, Robie W.; Cretney, Walter J.; Fowler, Brian R.; McLaughlin, Fiona A.

1993-07-01

To study the largest source of river sediment to the Arctic Ocean, we have collected suspended particulates from the Mackenzie River in all seasons and sediments from the Mackenzie shelf between the river mouth and the shelf edge. These samples have been analyzed for alkanes, triterpenes and polycyclic aromatic hydrocarbons (PAHs). We found that naturally occurring hydrocarbons predominate in the river and on the shelf. These hydrocarbons include biogenic alkanes and triterpenes with a higher plant/peat origin, diagenetic PAHs from peat and plant detritus, petrogenic alkanes, triterpenes and PAHs from oil seeps and/or bitumens and combustion PAHs that are likely relict in peat deposits. Because these components vary independently, the season is found to strongly influence the concentration and composition of hydrocarbons in the Mackenzie River. While essentially the same pattern of alkanes, diagenetic hopanes and alkyl PAHs is observed in all river and most shelf sediment samples, alkane and triterpene concentration variations are strongly linked to the relative amount of higher plant/peat material. Polycyclic aromatic hydrocarbon molecular-mass profiles also appear to be tied primarily to varying proportions of peat, with an additional petrogenic component which is most likely associated with lithic material mobilized by the Mackenzie River at freshet. Consistent with the general lack of alkyl PAHs in peat, the higher PAHs found in the river are probably derived from forest and tundra fires. A few anthropogenic/pyrogenic compounds are manifest only at the shelf edge, probably due to a weakening of the river influence. We take this observation of pyrogenic PAHs and the pronounced source differences between two sediment samples collected at the shelf edge as evidence of a transition from dominance by the Mackenzie River to the geochemistry prevalent in Arctic regions far removed from major rivers.

Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells.

PubMed

Uchida, Yasuo; Ito, Katsuaki; Ohtsuki, Sumio; Kubo, Yoshiyuki; Suzuki, Takashi; Terasaki, Tetsuya

2015-07-01

The purpose of this study was to clarify the expression of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597 fmol/μg protein, respectively, as determined by a quantitative targeted absolute proteomics technique. Using an antibody-free method established by Kubo et al. (2015), we found that SLC5A6 was preferentially localized at the luminal membrane of brain capillary endothelium. Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [(3) H]biotin and [(3) H]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line hCMEC/D3. SLC5A6-mediated transport in hCMEC/D3 was markedly inhibited not only by biotin and pantothenic acid, but also by prostaglandin E2, lipoic acid, docosahexaenoic acid, indomethacin, ketoprofen, diclofenac, ibuprofen, phenylbutazone, and flurbiprofen. This study is the first to confirm expression of SLC5A6 in human brain microvessels and to provide evidence that SLC5A6 is a major contributor to luminal uptake of biotin and pantothenic acid at the human blood-brain barrier. In humans, it was unclear (not concluded) about what transport system at the blood-brain barrier (BBB) is responsible for the brain uptakes of two vitamins, biotin and pantothenic acid, which are necessary for brain proper function. This study clarified for the first time that the solute carrier 5A6/Na(+) -dependent multivitamin transporter SLC5A6/SMVT is responsible for the supplies of biotin and pantothenic acid into brain across the BBB in humans. DHA, docosahexaenoic acid; NSAID, non-steroidal anti-inflammatory drug; PGE2, prostaglandin E2. © 2015

Aortic relaxant activity of Crataegus gracilior Phipps and identification of some of its chemical constituents.

PubMed

Hernández-Pérez, Abigail; Bah, Moustapha; Ibarra-Alvarado, César; Rivero-Cruz, José Fausto; Rojas-Molina, Alejandra; Rojas-Molina, Juana Isela; Cabrera-Luna, José Alejandro

2014-12-15

This study focused on the assessment of the vasorelaxant activity of the organic and aqueous extracts obtained from leaves and fruits of a Mexican hawthorn (Crataegus gracilior) on isolated rat aorta, and on the purification and identification of some of their secondary metabolites by the use of chromatographic and spectroscopic techniques. The results obtained showed that the methanol extract has a significantly more potent and effective vasorelaxant effect than the other tested extracts, with an EC50 = 8.69 ± 4.34 µg/mL and an Emax = 94.6% ± 11.30%, values that are close to that of acetylcholine, the positive control. From the same extract, two major triterpenes were isolated and identified as ursolic and corosolic acids by comparison of their experimental NMR spectroscopic data with those reported in the literature. Chlorogenic acid, rutin, quercetin, kaempferol and (+)-catechin were also identified using HPLC coupled with PDAD. All these compounds have already been proven to possess on their own antihypertensive effect and other benefits on cardiovascular diseases and they can support, at least in part, the traditional use of this plant species.

Distribution and expression characteristics of triterpenoids and OSC genes in white birch (Betula platyphylla suk.).

PubMed

Yin, Jing; Ren, Chun-Lin; Zhan, Ya-Guang; Li, Chun-Xiao; Xiao, Jia-Lei; Qiu, Wei; Li, Xin-Yu; Peng, Hong-Mei

2012-03-01

Betulin and oleanolic acids (pentacyclic triterpenoid secondary metabolites) have broad pharmacological activities and can be potentially used for the development of anti-cancer and anti-AIDS drugs. In this study, we detected the accumulation and the distribution characteristics of betulin and oleanolic acid in various organs of white birch at different ages. We also determined the expression of 4 OSC genes (LUS, β-AS, CAS1 and CAS2) involved in the triterpenoid synthesis pathways by real time RT-PCR. The result showed that the 1-year old birch can synthesize betulin and oleanolic acid. In addition, betulin and oleanolic acids were mainly distributed in the bark, while the content in the root skin and leaf was very low. The content of betulin and oleanolic acid in birch varied in different seasons. The content of betulin and oleanolic acid and their corresponding LUS and β-AS gene expression were very low in 1-year old birch. With increasing age of birch, betulin content was increased, while oleanolic acid was decreased. Similar changes were also observed for their corresponding synthesis genes LUS and β-AS. In the leaf of 1-year old plant, the highest expression of CAS1 and CAS2 occurred at end of September, while expression of LUS and the β-AS was low from June to October. In the stem skin,high expression of β-AS and the LUS genes occurred from the end of July to September. In the root, high expression of the β-AS gene was observed at the end of October. These results indicated that triterpenoid gene expression was similar to the triterpene accumulation. Expression of LUS gene and β-AS gene in birch with different ages were corresponding to the betulinic and oleanolic acid accumulation. Expression of CAS1 and CAS2 genes were elevated with increasing age of birch. This study provides molecular mechanisms of triterpenes synthesis in birch plants.

Spectra-structure correlations of saturated and unsaturated medium-chain fatty acids. Near-infrared and anharmonic DFT study of hexanoic acid and sorbic acid.

PubMed

Grabska, Justyna; Beć, Krzysztof B; Ishigaki, Mika; Wójcik, Marek J; Ozaki, Yukihiro

2017-10-05

Quantum chemical reproduction of entire NIR spectra is a new trend, enabled by contemporary advances in the anharmonic approaches. At the same time, recent increase of the importance of NIR spectroscopy of biological samples raises high demand for gaining deeper understanding of NIR spectra of biomolecules, i.e. fatty acids. In this work we investigate saturated and unsaturated medium-chain fatty acids, hexanoic acid and sorbic acid, in the near-infrared region. By employing fully anharmonic density functional theory (DFT) calculations we reproduce the experimental NIR spectra of these systems, including the highly specific spectral features corresponding to the dimerization of fatty acids. Broad range of concentration levels from 5·10 -4 M in CCl 4 to pure samples are investigated. The major role of cyclic dimers can be evidenced for the vast majority of these samples. A highly specific NIR feature of fatty acids, the elevation of spectral baseline around 6500-4000cm -1 , is being explained by the contributions of combination bands resulting from the vibrations of hydrogen-bonded OH groups in the cyclic dimers. Based on the high agreement between the calculated and experimental NIR spectra, a detailed NIR band assignments are proposed for hexanoic acid and sorbic acid. Subsequently, the correlations between the structure and NIR spectra are elucidated, emphasizing the regions in which clear and universal traces of specific bands corresponding to saturated and unsaturated alkyl chains can be established, thus demonstrating the wavenumber regions highly valuable for structural identifications. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical profile and anti-leishmanial activity of three Ecuadorian propolis samples from Quito, Guayaquil and Cotacachi regions.

PubMed

Cuesta-Rubio, Osmany; Campo Fernández, Mercedes; Márquez Hernández, Ingrid; Jaramillo, Carmita Gladys Jaramillo; González, Victor Hugo; Montes De Oca Porto, Rodny; Marrero Delange, David; Monzote Fidalgo, Lianet; Piccinelli, Anna Lisa; Campone, Luca; Rastrelli, Luca

2017-07-01

Three propolis samples were collected from different regions of Ecuador (Quito, Guayaquil and Cotacachi) and their methanolic extracts were prepared. Preliminary information supplied by TLC and NMR data, allowed us to define two main types of propolis: Cotacachi propoli sample (CPS), rich in flavonoids and Quito and Guayaquil samples (QPS and GPS) containing triterpenic alcohols and acetyl triterpenes as the main constituents. Two different approaches based on RP-HPLC preparative procedure and NMR structural determination (CPS) and GC-MS analysis (QPS and GPS) were successfully used for the chemical characterization of their major compounds. All three propolis extracts were able to inhibit Leishmania amazonensis growth but propolis sample rich in flavonoids was the most active (IC 50 =17.1±1.7μg/mL). In the literature this is the first study on propolis from Ecuador. Copyright © 2017. Published by Elsevier B.V.

Effects of Virgin Olive Oils Differing in Their Bioactive Compound Contents on Metabolic Syndrome and Endothelial Functional Risk Biomarkers in Healthy Adults: A Randomized Double-Blind Controlled Trial

PubMed Central

Sanchez-Rodriguez, Estefania; Lima-Cabello, Elena; Biel-Glesson, Sara; Fernandez-Navarro, Jose R.; Calleja, Miguel A.; Roca, Maria; Espejo-Calvo, Juan A.; Gil-Extremera, Blas; de la Torre, Rafael; Fito, Montserrat; Covas, Maria-Isabel; Alche, Juan de Dios; Martinez de Victoria, Emilio; Mesa, Maria D.

2018-01-01

The aim of this study was to evaluate the effect of virgin olive oils (VOOs) enriched with phenolic compounds and triterpenes on metabolic syndrome and endothelial function biomarkers in healthy adults. The trial was a three-week randomized, crossover, controlled, double-blind, intervention study involving 58 subjects supplemented with a daily dose (30 mL) of three oils: (1) a VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes); (2) an optimized VOO (OVOO) (490 ppm of phenolic compounds and 86 ppm of triterpenes); and (3) a functional olive oil (FOO) high in phenolic compounds (487 ppm) and enriched with triterpenes (389 ppm). Metabolic syndrome and endothelial function biomarkers were determined in vivo and ex vivo. Plasma high density lipoprotein cholesterol (HDLc) increased after the OVOO intake. Plasma endothelin-1 levels decreased after the intake of the three olive oils, and in blood cell cultures challenged. Daily intake of VOO enriched in phenolic compounds improved plasma HDLc, although no differences were found at the end of the three interventions, while VOO with at least 124 ppm of phenolic compounds, regardless of the triterpenes content improved the systemic endothelin-1 levels in vivo and ex vivo. No effect of triterpenes was observed after three weeks of interventions. Results need to be confirmed in subjects with metabolic syndrome and impaired endothelial function (Clinical Trials number NCT02520739). PMID:29772657

Effects of Virgin Olive Oils Differing in Their Bioactive Compound Contents on Metabolic Syndrome and Endothelial Functional Risk Biomarkers in Healthy Adults: A Randomized Double-Blind Controlled Trial.

PubMed

Sanchez-Rodriguez, Estefania; Lima-Cabello, Elena; Biel-Glesson, Sara; Fernandez-Navarro, Jose R; Calleja, Miguel A; Roca, Maria; Espejo-Calvo, Juan A; Gil-Extremera, Blas; Soria-Florido, Maria; de la Torre, Rafael; Fito, Montserrat; Covas, Maria-Isabel; Alche, Juan de Dios; Martinez de Victoria, Emilio; Gil, Angel; Mesa, Maria D

2018-05-16

The aim of this study was to evaluate the effect of virgin olive oils (VOOs) enriched with phenolic compounds and triterpenes on metabolic syndrome and endothelial function biomarkers in healthy adults. The trial was a three-week randomized, crossover, controlled, double-blind, intervention study involving 58 subjects supplemented with a daily dose (30 mL) of three oils: (1) a VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes); (2) an optimized VOO (OVOO) (490 ppm of phenolic compounds and 86 ppm of triterpenes); and (3) a functional olive oil (FOO) high in phenolic compounds (487 ppm) and enriched with triterpenes (389 ppm). Metabolic syndrome and endothelial function biomarkers were determined in vivo and ex vivo. Plasma high density lipoprotein cholesterol (HDLc) increased after the OVOO intake. Plasma endothelin-1 levels decreased after the intake of the three olive oils, and in blood cell cultures challenged. Daily intake of VOO enriched in phenolic compounds improved plasma HDLc, although no differences were found at the end of the three interventions, while VOO with at least 124 ppm of phenolic compounds, regardless of the triterpenes content improved the systemic endothelin-1 levels in vivo and ex vivo. No effect of triterpenes was observed after three weeks of interventions. Results need to be confirmed in subjects with metabolic syndrome and impaired endothelial function (Clinical Trials number NCT02520739).

Oleic acid and linoleic acid from Tenebrio molitor larvae inhibit BACE1 activity in vitro: molecular docking studies.

PubMed

Youn, Kumju; Yun, Eun-Young; Lee, Jinhyuk; Kim, Ji-Young; Hwang, Jae-Sam; Jeong, Woo-Sik; Jun, Mira

2014-02-01

In our ongoing research to find therapeutic compounds for Alzheimer's disease (AD) from natural resources, the inhibitory activity of the BACE1 enzyme by Tenebrio molitor larvae and its major compounds were evaluated. The T. molitor larvae extract and its fractions exhibited strong BACE1 suppression. The major components of hexane fraction possessing both high yield and strong BACE1 inhibition were determined by thin layer chromatography, gas chromatography, and nuclear magnetic resonance analysis. A remarkable composition of unsaturated long chain fatty acids, including oleic acid and linoleic acid, were identified. Oleic acid, in particular, noncompetitively attenuated BACE1 activity with a half-maximal inhibitory concentration (IC₅₀) value of 61.31 μM and Ki value of 34.3 μM. Furthermore, the fatty acids were stably interacted with BACE1 at different allosteric sites of the enzyme bound with the OH of CYS319 and the NH₃ of TYR320 for oleic acid and with the C=O group of GLN304 for linoleic acid. Here, we first revealed novel pharmacophore features of oleic acids and linoleic acid to BACE1 by in silico docking studies. The present findings would clearly suggest potential guidelines for designing novel BACE1 selective inhibitors.

Acid Rain: Activities for Science Teachers.

ERIC Educational Resources Information Center

Johnson, Eric; And Others

1983-01-01

Seven complete secondary/college level acid rain activities are provided. Activities include overview; background information and societal implications; major concepts; student objectives; vocabulary/material lists; procedures; instructional strategies; and questions/discussion and extension suggestions. Activities consider effects of acid rain on…

A novel approach in acidic disinfection through inhibition of acid resistance mechanisms; Maleic acid-mediated inhibition of glutamate decarboxylase activity enhances acid sensitivity of Listeria monocytogenes.

PubMed

Paudyal, Ranju; Barnes, Ruth H; Karatzas, Kimon Andreas G

2018-02-01

Here it is demonstrated a novel approach in disinfection regimes where specific molecular acid resistance systems are inhibited aiming to eliminate microorganisms under acidic conditions. Despite the importance of the Glutamate Decarboxylase (GAD) system for survival of Listeria monocytogenes and other pathogens under acidic conditions, its potential inhibition by specific compounds that could lead to its elimination from foods or food preparation premises has not been studied. The effects of maleic acid on the acid resistance of L. monocytogenes were investigated and found that it has a higher antimicrobial activity under acidic conditions than other organic acids, while this could not be explained by its pKa or Ka values. The effects were found to be more pronounced on strains with higher GAD activity. Maleic acid affected the extracellular GABA levels while it did not affect the intracellular ones. Maleic acid had a major impact mainly on GadD2 activity as also shown in cell lysates. Furthermore, it was demonstrated that maleic acid is able to partly remove biofilms of L. monocytogenes. Maleic acid is able to inhibit the GAD of L. monocytogenes significantly enhancing its sensitivity to acidic conditions and together with its ability to remove biofilms, make a good candidate for disinfection regimes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Major-ion chemistry of the Rocky Mountain snowpack, USA

USGS Publications Warehouse

Turk, J.T.; Taylor, Howard E.; Ingersoll, G.P.; Tonnessen, K.A.; Clow, D.W.; Mast, M.A.; Campbell, D.H.; Melack, J.M.

2001-01-01

During 1993-97, samples of the full depth of the Rocky Mountain snowpack were collected at 52 sites from northern New Mexico to Montana and analyzed for major-ion concentrations. Concentrations of acidity, sulfate, nitrate, and calcium increased from north to south along the mountain range. In the northern part of the study area, acidity was most correlated (negatively) with calcium. Acidity was strongly correlated (positively) with nitrate and sulfate in the southern part and for the entire network. Acidity in the south exceeded the maximum acidity measured in snowpack of the Sierra Nevada and Cascade Mountains. Principal component analysis indicates three solute associations we characterize as: (1) acid (acidity, sulfate, and nitrate), (2) soil (calcium, magnesium, and potassium), and (3) salt (sodium, chloride, and ammonium). Concentrations of acid solutes in the snowpack are similar to concentrations in nearby wetfall collectors, whereas, concentrations of soil solutes are much higher in the snowpack than in wetfall. Thus, dryfall of acid solutes during the snow season is negligible, as is gypsum from soils. Snowpack sampling offers a cost-effective complement to sampling of wetfall in areas where wetfall is difficult to sample and where the snowpack accumulates throughout the winter. Copyright ?? 2001 .

Selective Serotonergic (SSRI) Versus Noradrenergic (SNRI) Reuptake Inhibitors with and without Acetylsalicylic Acid in Major Depressive Disorder.

PubMed

Zdanowicz, Nicolas; Reynaert, Christine; Jacques, Denis; Lepiece, Brice; Dubois, Thomas

2017-09-01

Antidepressant medication efficacy remains a major research challenge. Here, we explored four questions: whether noradrenergic antidepressants are more effective than serotonergic antidepressants; whether the addition of 100 mg acetylsalicylic acid (ASA) changes antidepressant efficacy; whether the long-term efficacy differs depending on the antidepressant and the addition of ASA; and whether serum levels of brain-derived neurotrophic factor (BDNF) are clinically informative. In a two-year study, forty people with major depressive disorder were randomly assigned to groups that received an SSRI (escitalopram) or an SNRI (duloxetine), each group received concomitant ASA (100 mg) or a placebo. Sociodemographic data were recorded and patients under went regular assessments with the Hamilton depression scale (HDS) and clinical global impression (CGI) scale. Serum levels of BDNF were measured four times per year. There was no significant difference in efficacy between the two antidepressants or between antidepressant treatment with and without ASA. However, subgroup comparisons revealed that the duloxetine + ASA (DASA) subgroup showed a more rapid improvement in HDS score as early as 2 months (t=-3.114, p=0.01), in CGI score at 5 months (t=-2.119, p=0.05), and a better remission rate (χ 2 =6.296, p 0.012) than the escitalopram + placebo (EP) subgroup. Serum BDNF before treatment was also higher in the DASA subgroup than in the EP subgroup (t=3.713; p=0.002). This suggest two hypotheses: either a noradrenergic agent combined with ASA is more effective in treating depression than a serotonergic agent alone, or the level of serum BDNF before treatment is a precursor marker of the response to antidepressants. Further research is needed to test these hypotheses.

Epicuticular Wax in Developing Olives (Olea europaea) Is Highly Dependent upon Cultivar and Fruit Ripeness.

PubMed

Vichi, Stefania; Cortés-Francisco, Nuria; Caixach, Josep; Barrios, Gonçal; Mateu, Jordi; Ninot, Antonia; Romero, Agustí

2016-08-03

The epicuticular wax (EW) layer is located on the surface of most plant organs. It provides the cuticle with most of its properties and is the primary barrier against biotic and abiotic stress. Despite the importance of Olea europaea cultivation, few studies have characterized the EW covering leaves and olives, which could be involved in resistance to both infection and environmental conditions. In the present study, wide-ranging screening was carried out using direct-injection electrospray ionization coupled to high-resolution mass spectrometry to analyze EW in developing olives of nine varieties. The proportions of EW fractions [wax esters (WEs), diacylglycerols, triacylglycerols (TAGs), triterpenic acids, and aldehydes] strongly depended upon the olive cultivar and, in only a few cases, were influenced by the sampling date. The specific compositions of the major fractions, WEs and TAGs, were strictly related to the cultivar, while the degree of unsaturation and chain length of the WEs evolved throughout the 4 weeks prior to the olive turning color.

Genetic mapping of QTLs controlling fatty acids provided insights into the genetic control of fatty acid synthesis pathway in peanut (Arachis hypogaea L.).

PubMed

Wang, Ming Li; Khera, Pawan; Pandey, Manish K; Wang, Hui; Qiao, Lixian; Feng, Suping; Tonnis, Brandon; Barkley, Noelle A; Pinnow, David; Holbrook, Corley C; Culbreath, Albert K; Varshney, Rajeev K; Guo, Baozhu

2015-01-01

Peanut, a high-oil crop with about 50% oil content, is either crushed for oil or used as edible products. Fatty acid composition determines the oil quality which has high relevance to consumer health, flavor, and shelf life of commercial products. In addition to the major fatty acids, oleic acid (C18:1) and linoleic acid (C18:2) accounting for about 80% of peanut oil, the six other fatty acids namely palmitic acid (C16:0), stearic acid (C18:0), arachidic acid (C20:0), gadoleic acid (C20:1), behenic acid (C22:0), and lignoceric acid (C24:0) are accounted for the rest 20%. To determine the genetic basis and to improve further understanding on effect of FAD2 genes on these fatty acids, two recombinant inbred line (RIL) populations namely S-population (high oleic line 'SunOleic 97R' × low oleic line 'NC94022') and T-population (normal oleic line 'Tifrunner' × low oleic line 'GT-C20') were developed. Genetic maps with 206 and 378 marker loci for the S- and the T-population, respectively were used for quantitative trait locus (QTL) analysis. As a result, a total of 164 main-effect (M-QTLs) and 27 epistatic (E-QTLs) QTLs associated with the minor fatty acids were identified with 0.16% to 40.56% phenotypic variation explained (PVE). Thirty four major QTLs (>10% of PVE) mapped on five linkage groups and 28 clusters containing more than three QTLs were also identified. These results suggest that the major QTLs with large additive effects would play an important role in controlling composition of these minor fatty acids in addition to the oleic and linoleic acids in peanut oil. The interrelationship among these fatty acids should be considered while breeding for improved peanut genotypes with good oil quality and desired fatty acid composition.

Neuroprotective effect of asiatic acid on rotenone-induced mitochondrial dysfunction and oxidative stress-mediated apoptosis in differentiated SH-SYS5Y cells.

PubMed

Nataraj, Jagatheesan; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed

2017-07-01

Parkinson's disease (PD) is a chronic neurodegenerative disease, manifested due to the loss of dopaminergic neurons, which ultimately leads to impaired movement in elderly populations. The pathogenesis of PD is associated with numerous factors including oxidative stress, mitochondrial dysfunction and apoptosis. There is no effective therapy available to cure or halt the progression of this disease still now. Asiatic acid (AA) is a triterpene extracted from Centella asiatica has been reported as an antioxidant and anti-inflammatory agent, that offers neuroprotection against glutamate toxicity. Therefore, in this study, we have investigated the effect of AA in a rotenone (an inhibitor of mitochondrial complex I) induced in vitro model of PD. Following the exposure of SH-SY5Y cells to rotenone, there was a marked overproduction of ROS, mitochondrial dysfunction (as indexed by the decrease in mitochondrial membrane potential) and apoptosis (Hoechst and dual staining, comet assay; expressions of pro-apoptotic and anti-apoptotic indices). Pre-treatment with AA reversed these changes might be due to its antioxidant, mitoprotective and anti-apoptotic properties. However further extensive studies on in vivo models of PD are warranted to prove AA neuroprotective effect before entering into the clinical trial.

Identification of major allergens in watermelon.

PubMed

Pastor, Carlos; Cuesta-Herranz, Javier; Cases, Barbara; Pérez-Gordo, Marina; Figueredo, Elena; de las Heras, Manuel; Vivanco, Fernando

2009-01-01

Watermelon is a worldwide consumed Cucurbitaceae fruit that can elicit allergic reactions. However, the major allergens of watermelon are not known. The aim of this study is to identify and characterize major allergens in watermelon. Twenty-three patients allergic to watermelon took part in the study. The diagnosis was based on a history of symptoms and positive skin prick-prick tests to watermelon, confirmed by positive open oral challenge testing to watermelon pulp. Allergenic components were detected by SDS-PAGE and immunoblotting. Molecular characterization of IgE-binding bands was performed by N-terminal amino acid sequencing and mass spectrometry. Allergens were purified combining several chromatographic steps. Several IgE binding bands (8-120 kDa) were detected in watermelon extract. Three major allergens were identified as malate dehydrogenase (36 kDa), triose phosphate isomerase (28 kDa) and profilin (13 kDa). Purified allergens individually inhibited IgE binding to the whole watermelon extract. All in all these results indicate that malate dehydrogenase, triose phosphate isomerase and profilin are major allergens involved in watermelon allergy. Copyright (C) 2009 S. Karger AG, Basel.

Major proteins of yam bean tubers.

PubMed

Gomes, A V; Sirju-Charran, G; Barnes, J A

1997-09-01

The tuberous roots of the Mexican yam bean, jicama, (Pachyrhizus erosus L. Urban) contained large quantities of two acidic glycoproteins which accounted for more than 70% of the total soluble proteins (about 3 g per 100 g of tuber on a dry weight basis). The two major proteins, tentatively named YBG1 and YBG2, had apparent M(r)s of 28,000 and 26,000, respectively, by SDS-PAGE. A third protein named YBP22 which accounted for 2-5% of the total soluble proteins had an M(r) of 22,000. YBG1 and YBG2 exhibited great similarity on the basis of their amino acid composition and had identical N-terminal amino acid sequences. The first 23 amino acids in the N-terminal region of YBG2 were DDLPDYVDWRDYGAVTRIKNQGQ which showed strong homology with the papain class of cysteine proteases. YBG1 and YBG2 were found to bind to a Concanavalin A-Sepharose column and were also stained positively by a sensitive glycoprotein stain. Both glycoproteins exhibited cysteine proteolytic activity. In contrast, YBP22 showed sequence homology with several known protease inhibitors, and a polyclonal antibody raised against this protein cross reacted with soybean trypsin inhibitor.

The Genus Luehea (Malvaceae-Tiliaceae): Review about Chemical and Pharmacological Aspects

PubMed Central

de Morais, Selene Maia; Colares, Aracélio Viana

2016-01-01

Popularly known as “açoita-cavalo” (whips-horse), Luehea species (Malvaceae-Tilioideae) are native to America and are used in folk medicine as anti-inflammatory, antidiarrheal, antiseptic, expectorant, and depurative and against skin infections. Although there are studies showing the chemical constituents of some species, the active substances have not been properly identified. A systematic study was carried out through a computer search of data on CAPES journals, SciELO, ISI Bireme, PubMed, ScienceDirect, ScienceDomain Medline, and Google Scholar from published articles using key words: Luehea, açoita-cavalo, and Malvaceae. Luehea divaricata was the species with the highest number of studies observed. Triterpenes (9), flavonoids (6), and steroids (4), including saponins, organic acids (4), and one lignan, are the main types of secondary metabolites registered and the most cited flavonoids were rutin and quercetin and among triterpenes there was maslinic acid, which might be associated with the popular indication of its anti-inflammatory action. The vitexin, a C-glycosylated flavone, isolated from three different species, is cited as a possible taxonomic marker of the genus. Studies confirm in part the medicinal uses of plants named as “açoita-cavalo” species. Some pharmacological activities, not assigned to the species of the genus Luehea by populations, were observed in laboratory experiments. PMID:27818835

Cytotoxic Triterpenoids from the Stalks of Microtropis triflora.

PubMed

Zhang, Xiao-Wei; Wang, Kui-Wu; Zhou, Man-Qing

2017-07-01

Bioassay-guided phytochemical investigation of the stalks of Microtropis triflora Merr. & F.L. Freeman led to the isolation of ten triterpenes 1 - 10, including one novel compound 3,24-epoxy-2α,24-dihydroxyfriedelan-29-oic acid (1). Their chemical structures were identified on the basis of spectroscopic analysis, including HR-ESI mass spectrometry, 1D- and 2D-NMR ( 1 H, 13 C, 1 H, 1 H-COSY, HSQC, HMBC, and NOESY), and by comparison with the data reported. The cytotoxicities of compounds 1 - 10 against a panel of cultured human tumor cell lines (Bcap37, SMMC7721, HeLa, CNE) were evaluated. The new compound 1 showed moderate anti-tumor activities with IC 50 values of 39.22, 29.24, 23.28, and 68.81 μm/ml, respectively. These results might be helpful for explaining the use of M. triflora in traditional medicine. Triterpenes are characteristic of Microtropis genus and could be useful as potential chemotaxonomic markers. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Systematic chemical profiling of a multicomponent Chinese herbal formula Huo Luo Xiao Ling Dan by ultra high performance liquid chromatography coupled with electrospray ionization quadrupoletime-of-flight mass spectrometry.

PubMed

Wang, Fenrong; Ai, Yu; Wu, Yun; Ma, Wen; Bian, Qiaoxia; Lee, David Y-W; Dai, Ronghua

2015-03-01

Huo Luo Xiao Ling Dan, a Chinese herbal formula consisting of 11 different herbs, has been used in folk medicine for the treatment of arthritis and other chronic inflammatory diseases. However, the chemical compositions of Huo Luo Xiao Ling Dan are not completely characterized. In the present study, an ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry method in positive and negative ion modes was employed to identify biochemical constitutes in Huo Luo Xiao Ling Dan. As a result, a total of 76 compounds including alkaloids, monoterpene glycosides, iridoids, phenolic acids, and tanshinones, coumarins, lactones, flavones, and their glycosides, triterpenes, and triterpene saponins were characterized by comparing the retention time and mass spectrometry data with reference standards within 5 ppm error or by reference to the reference literature. These results would provide the basis for a further in vivo study of Huo Luo Xiao Ling Dan and information for potential new drug candidates for treating arthritis and other chronic inflammatory diseases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative fatty acid composition of four Sargassum species (Fucales, Phaeophyta)

NASA Astrophysics Data System (ADS)

Wu, Xiang-Chun; Lu, Bao-Ren; Tseng, C. K.

1995-12-01

Fatty acid composition of four Sargassum species from Qingdao and Shidao, Shandong Province was investigated. 16:0 (palmitic acid) was the major saturated fatty acid. C18 and C20 were the main polyunsaturated fatty acids (PUFAs). Arachidonic acid and eicosapentaenoic acid predominated among polyenoic acids in all the algal species examined, except for Sargassum sp. which had low concentration of eicosapentaenoic acid.

Echinocystic acid inhibits RANKL-induced osteoclastogenesis by regulating NF-κB and ERK signaling pathways

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

Yang, Jian-hui, E-mail: jianhui_yangxa@163.com; Li, Bing; Wu, Qiong

Receptor activator of nuclear factor-κB ligand (RANKL) is a key factor in the differentiation and activation of osteoclasts. Echinocystic acid (EA), a pentacyclic triterpene isolated from the fruits of Gleditsia sinensis Lam, was reported to prevent reduction of bone mass and strength and improve the cancellous bone structure and biochemical properties in ovariectomy rats. However, the molecular mechanism of EA on the osteoclast formation has not been reported. The purpose of this study was to investigate the effects and mechanism of EA on RANKL-induced osteoclastogenesis. Our results showed that EA inhibited the formation of osteoclast, as well as the expressionmore » of osteoclastogenesis-related marker proteins in bone marrow macrophages (BMMs). At molecular levels, EA inhibited RANKL-induced NF-κB activation and ERK phosphorylation in BMMs. In conclusion, the present study demonstrated that EA can suppress osteoclastogenesis in vitro. Moreover, we clarified that these inhibitory effects of EA occur through suppression of NF-κB and ERK activation. Therefore, EA may be a potential agent in the treatment of osteoclast-related diseases such as osteoporosis. - Highlights: • EA inhibited the formation of osteoclast in BMMs. • EA inhibits the expression of osteoclastogenesis-related marker proteins in BMMs. • EA inhibits RANKL-induced NF-κB activation in BMMs. • EA inhibits RANKL-induced ERK phosphorylation in BMMs.« less

Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine.

PubMed

Westrop, Gareth D; Wang, Lijie; Blackburn, Gavin J; Zhang, Tong; Zheng, Liang; Watson, David G; Coombs, Graham H

2017-01-01

Trichomonas vaginalis and Tritrichomonas foetus are pathogens that parasitise, respectively, human and bovine urogenital tracts causing disease. Using LC-MS, reference metabolomic profiles were obtained for both species and stable isotope labelling with D-[U-13C6] glucose was used to analyse central carbon metabolism. This facilitated a comparison of the metabolic pathways of T. vaginalis and T. foetus, extending earlier targeted biochemical studies. 43 metabolites, whose identities were confirmed by comparison of their retention times with authentic standards, occurred at more than 3-fold difference in peak intensity between T. vaginalis and T. foetus. 18 metabolites that were removed from or released into the medium during growth also showed more than 3-fold difference between the species. Major differences were observed in cysteine and methionine metabolism in which homocysteine, produced as a bi-product of trans-methylation, is catabolised by methionine γ-lyase in T. vaginalis but converted to cystathionine in T. foetus. Both species synthesise methylthioadenosine by an unusual mechanism, but it is not used as a substrate for methionine recycling. T. vaginalis also produces and exports high levels of S-methylcysteine, whereas only negligible levels were found in T. foetus which maintains significantly higher intracellular levels of cysteine. 13C-labeling confirmed that both cysteine and S-methylcysteine are synthesised by T. vaginalis; S-methylcysteine can be generated by recombinant T. vaginalis cysteine synthase using phosphoserine and methanethiol. T. foetus contained higher levels of ornithine and citrulline than T. vaginalis and exported increased levels of putrescine, suggesting greater flux through the arginine dihydrolase pathway. T. vaginalis produced and exported hydroxy acid derivatives of certain amino acids, particularly 2-hydroxyisocaproic acid derived from leucine, whereas negligible levels of these metabolites occurred in T. foetus.

Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine

PubMed Central

Wang, Lijie; Blackburn, Gavin J.; Zhang, Tong; Zheng, Liang; Watson, David G.; Coombs, Graham H.

2017-01-01

Trichomonas vaginalis and Tritrichomonas foetus are pathogens that parasitise, respectively, human and bovine urogenital tracts causing disease. Using LC-MS, reference metabolomic profiles were obtained for both species and stable isotope labelling with D-[U-13C6] glucose was used to analyse central carbon metabolism. This facilitated a comparison of the metabolic pathways of T. vaginalis and T. foetus, extending earlier targeted biochemical studies. 43 metabolites, whose identities were confirmed by comparison of their retention times with authentic standards, occurred at more than 3-fold difference in peak intensity between T. vaginalis and T. foetus. 18 metabolites that were removed from or released into the medium during growth also showed more than 3-fold difference between the species. Major differences were observed in cysteine and methionine metabolism in which homocysteine, produced as a bi-product of trans-methylation, is catabolised by methionine γ-lyase in T. vaginalis but converted to cystathionine in T. foetus. Both species synthesise methylthioadenosine by an unusual mechanism, but it is not used as a substrate for methionine recycling. T. vaginalis also produces and exports high levels of S-methylcysteine, whereas only negligible levels were found in T. foetus which maintains significantly higher intracellular levels of cysteine. 13C-labeling confirmed that both cysteine and S-methylcysteine are synthesised by T. vaginalis; S-methylcysteine can be generated by recombinant T. vaginalis cysteine synthase using phosphoserine and methanethiol. T. foetus contained higher levels of ornithine and citrulline than T. vaginalis and exported increased levels of putrescine, suggesting greater flux through the arginine dihydrolase pathway. T. vaginalis produced and exported hydroxy acid derivatives of certain amino acids, particularly 2-hydroxyisocaproic acid derived from leucine, whereas negligible levels of these metabolites occurred in T. foetus. PMID

Psychotria viridis: Chemical constituents from leaves and biological properties.

PubMed

Soares, Débora B S; Duarte, Lucienir P; Cavalcanti, André D; Silva, Fernando C; Braga, Ariadne D; Lopes, Miriam T P; Takahashi, Jacqueline A; Vieira-Filho, Sidney A

2017-01-01

The phytochemical study of hexane, chloroform and methanol extracts from leaves of Psychotria viridis resulted in the identification of: the pentacyclic triterpenes, ursolic and oleanolic acid; the steroids, 24-methylene-cycloartanol, stigmasterol and β-sitosterol; the glycosylated steroids 3-O-β-D-glucosyl-β-sitosterol and 3-O-β-D-glucosyl-stigmasterol; a polyunsaturated triterpene, squalene; the esters of glycerol, 1-palmitoylglycerol and triacylglycerol; a mixture of long chain hydrocarbons; the aldehyde nonacosanal; the long chain fat acids hentriacontanoic, hexadecanoic and heptadenoic acid; the ester methyl heptadecanoate; the 4-methyl-epi-quinate and two indole alkaloids, N,N-dimethyltryptamine (DMT) and N-methyltryptamine. The chemical structures were determined by means of spectroscopic (IR, 1H and 13C NMR, HSQC, HMBC and NOESY) and spectrometric (CG-MS and LCMS-ESI-ITTOF) methods. The study of biologic properties of P. viridis consisted in the evaluation of the acetylcholinesterase inhibition and cytotoxic activities. The hexane, chloroform, ethyl acetate and methanol extracts, the substances 24-methylene-cycloartanol, DMT and a mixture of 3-O-β-D-glucosyl-β-sitosterol and 3-O-β-D-glucosyl-stigmasterol showed cholinesterase inhibiting activity. This activity induced by chloroform and ethyl acetate extracts was higher than 90%. The methanol and ethyl acetate extracts inhibit the growth and/or induce the death of the tumor cells strains B16F10 and 4T1, without damaging the integrity of the normal cells BHK and CHO. DMT also demonstrated a marked activity against tumor cell strains B16F10 and 4T1.

Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.

PubMed

Priyandoko, Didik; Ishii, Tetsuro; Kaul, Sunil C; Wadhwa, Renu

2011-05-04

The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera) leaf extract on methoxyacetic acid (MAA) induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.

Ashwagandha Leaf Derived Withanone Protects Normal Human Cells Against the Toxicity of Methoxyacetic Acid, a Major Industrial Metabolite

PubMed Central

Priyandoko, Didik; Ishii, Tetsuro; Kaul, Sunil C.; Wadhwa, Renu

2011-01-01

The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera) leaf extract on methoxyacetic acid (MAA) induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates. PMID:21573189

Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses

PubMed Central

Hammer, Christian; Begemann, Martin; McLaren, Paul J.; Bartha, István; Michel, Angelika; Klose, Beate; Schmitt, Corinna; Waterboer, Tim; Pawlita, Michael; Schulz, Thomas F.; Ehrenreich, Hannelore; Fellay, Jacques

2015-01-01

The magnitude of the human antibody response to viral antigens is highly variable. To explore the human genetic contribution to this variability, we performed genome-wide association studies of the immunoglobulin G response to 14 pathogenic viruses in 2,363 immunocompetent adults. Significant associations were observed in the major histocompatibility complex region on chromosome 6 for influenza A virus, Epstein-Barr virus, JC polyomavirus, and Merkel cell polyomavirus. Using local imputation and fine mapping, we identified specific amino acid residues in human leucocyte antigen (HLA) class II proteins as the most probable causal variants underlying these association signals. Common HLA-DRβ1 haplotypes showed virus-specific patterns of humoral-response regulation. We observed an overlap between variants affecting the humoral response to influenza A and EBV and variants previously associated with autoimmune diseases related to these viruses. The results of this study emphasize the central and pathogen-specific role of HLA class II variation in the modulation of humoral immune response to viral antigens in humans. PMID:26456283

A novel β-lactam derivative, albactam from the flowers of Albizia lebbeck with platelets anti-aggregatory activity in vitro.

PubMed

El-Gamal, Ali Ali; Abd-El-Halim, Mohamed Farag; Kalil, Ashraf Taha; Basudan, Omer Ahmed; Al-Rehaily, Adnan Jathlan; Ahmad, Mohamed Shamim; El-Tahir, Kamal Hussin; Al-Massarani, Shaza Mohamed; Abdel-Mageed, Wael Moustafa

2015-03-01

A novel β-lactam derivative, albactam, was isolated from the alcoholic extract of the flowers of Albizia lebbeck. It showed a significant anti-aggregatory activity against adenosine diphosphate and arachidonic acid induced guinea-pigs' platelets aggregation in vitro. Six more known compounds were also isolated and fully characterized by measuring 1D and 2D NMR, two of them are the triterpenes β-amyrin and 11α, 12α-oxidotaraxerol, two ceramide derivatives and two flavonoids, kampferol 3-O-rutinoside and rutin.

Relative stability of major types of beta-turns as a function of amino acid composition: a study based on Ab initio energetic and natural abundance data.

PubMed

Perczel, András; Jákli, Imre; McAllister, Michael A; Csizmadia, Imre G

2003-06-06

Folding properties of small globular proteins are determined by their amino acid sequence (primary structure). This holds both for local (secondary structure) and for global conformational features of linear polypeptides and proteins composed from natural amino acid derivatives. It thus provides the rational basis of structure prediction algorithms. The shortest secondary structure element, the beta-turn, most typically adopts either a type I or a type II form, depending on the amino acid composition. Herein we investigate the sequence-dependent folding stability of both major types of beta-turns using simple dipeptide models (-Xxx-Yyy-). Gas-phase ab initio properties of 16 carefully selected and suitably protected dipeptide models (for example Val-Ser, Ala-Gly, Ser-Ser) were studied. For each backbone fold most probable side-chain conformers were considered. Fully optimized 321G RHF molecular structures were employed in medium level [B3LYP/6-311++G(d,p)//RHF/3-21G] energy calculations to estimate relative populations of the different backbone conformers. Our results show that the preference for beta-turn forms as calculated by quantum mechanics and observed in Xray determined proteins correlates significantly.

Effects of brown seaweed polyphenols, α-tocopherol, and ascorbic acid on protein oxidation and textural properties of fish mince (Pagrosomus major) during frozen storage.

PubMed