Piperine: researchers discover new flavor in an ancient spice.

PubMed

Szallasi, Arpad

2005-09-01

Studies with animals that are deficient in the vanilloid (capsaicin) receptor TRPV1 have confirmed the pivotal role that TRPV1 has in the development of post-inflammatory hyperalgesia, and enhanced TRPV1 expression has been described in various human disorders. Natural products have provided several lead structures for the development of vanilloid ligands. A recent study shows that piperine, the irritant principle in black pepper, is more efficient than capsaicin in the desensitization of human TRPV1, which suggests that this pharmacological aspect of vanilloids can be dissociated from its potency. This finding raises the intriguing possibility that piperine can be used as a chemical template for the design of improved TRPV1 agonists.

Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers

PubMed Central

Volak, Laurie P; Hanley, Michael J; Masse, Gina; Hazarika, Suwagmani; Harmatz, Jerold S; Badmaev, Vladimir; Majeed, Muhammed; Greenblatt, David J; Court, Michael H

2013-01-01

Aims Turmeric extract derived curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) are currently being evaluated for the treatment of cancer and Alzheimer's dementia. Previous in vitro studies indicate that curcuminoids and piperine (a black pepper derivative that enhances curcuminoid bioavailability) could inhibit human CYP3A, CYP2C9, UGT and SULT dependent drug metabolism. The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers. Methods A randomized placebo-controlled six way crossover study was conducted in eight healthy volunteers. A standardized curcuminoid/piperine preparation (4 g curcuminoids plus 24 mg piperine) or matched placebo was given orally four times over 2 days before oral administration of midazolam (CYP3A probe), flurbiprofen (CYP2C9 probe) or paracetamol (acetaminophen) (dual UGT and SULT probe). Plasma and urine concentrations of drugs, metabolites and herbals were measured by HPLC. Subject sedation and electroencephalograph effects were also measured following midazolam dosing. Results Compared with placebo, the curcuminoid/piperine treatment produced no meaningful changes in plasma Cmax, AUC, clearance, elimination half-life or metabolite levels of midazolam, flurbiprofen or paracetamol (α = 0.05, paired t-tests). There was also no effect of curcuminoid/piperine treatment on the pharmacodynamics of midazolam. Although curcuminoid and piperine concentrations were readily measured in plasma following glucuronidase/sulfatase treatment, unconjugated concentrations were consistently below the assay thresholds (0.05–0.08 μm and 0.6 μm, respectively). Conclusion The results indicate that short term use of this piperine-enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes. PMID:22725836

Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers.

PubMed

Volak, Laurie P; Hanley, Michael J; Masse, Gina; Hazarika, Suwagmani; Harmatz, Jerold S; Badmaev, Vladimir; Majeed, Muhammed; Greenblatt, David J; Court, Michael H

2013-02-01

Turmeric extract derived curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) are currently being evaluated for the treatment of cancer and Alzheimer's dementia. Previous in vitro studies indicate that curcuminoids and piperine (a black pepper derivative that enhances curcuminoid bioavailability) could inhibit human CYP3A, CYP2C9, UGT and SULT dependent drug metabolism. The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers. A randomized placebo-controlled six way crossover study was conducted in eight healthy volunteers. A standardized curcuminoid/piperine preparation (4 g curcuminoids plus 24 mg piperine) or matched placebo was given orally four times over 2 days before oral administration of midazolam (CYP3A probe), flurbiprofen (CYP2C9 probe) or paracetamol (acetaminophen) (dual UGT and SULT probe). Plasma and urine concentrations of drugs, metabolites and herbals were measured by HPLC. Subject sedation and electroencephalograph effects were also measured following midazolam dosing. Compared with placebo, the curcuminoid/piperine treatment produced no meaningful changes in plasma C(max), AUC, clearance, elimination half-life or metabolite levels of midazolam, flurbiprofen or paracetamol (α = 0.05, paired t-tests). There was also no effect of curcuminoid/piperine treatment on the pharmacodynamics of midazolam. Although curcuminoid and piperine concentrations were readily measured in plasma following glucuronidase/sulfatase treatment, unconjugated concentrations were consistently below the assay thresholds (0.05-0.08 μM and 0.6 μM, respectively). The results indicate that short term use of this piperine-enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes. © 2012 The Authors. British Journal of Clinical

[Optimization and characterization of curcumin-piperine dual drug loaded self-microemulsifying drug delivery system by simplex lattice design].

PubMed

Li, Qiu-Ping; Dai, Jun-Dong; Zhai, Wen-Wen; Jiang, Qiao-Li

2014-10-01

The objective of the study was to prepare and evaluate the quality of curcumin-piperinedual drug loaded self-microemulsifying drug delivery system(Cur-PIP-SMEDDS). Simplex lattice design was constructed using optimal oil phase, surfactant and co-surfactant concentration as independent variables, and the curcumin and piperine were used as model drugs to optimize Cur-PIP-SMEDDS formulation. In the present study, the drug loadings of curcumin and piperine, mean particle size of Cur-PIP-SMEDDS were made as indicators, and the experiment design, model building and response surface analysis were established using Design Expert 8. 06 software to optimize and verify the composition of SMEDDS formulation. The quality of Cur-PIP-SMEDDS was evaluated by observing the appearance status, transmission electron microscope micrographs and determining particle diameter, electric potential, drug entrapment efficiency and drug loading of it. As a result, the optimal formulation of SMEDDS was CapryoL 90-Cremophor RH40-TranscutoL HP (10:60:30). The appearance of Cur-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation with uniform particle size distribution. The mean size of microemulsion droplet formed from Cur-PIP-SMEDDS was 15.33 nm, the drug loading of SMEDDS for Cur and PIP were 40.90 mg · g(-1) and 0.97 mg · g(-1), respectively, the drug entrapment efficiency were 94.98% and 90.96%, respectively. The results show that Cur-PIP-SMEDDS can increase the solubility and stability of curcumin significantly, in the expectation of enhancing the bioavailability of it. Taken together, these findings can provide the reference to a preferable choice of the Cur formulation and contribute to therapeutic application in clinical research.

Physiological barriers to the oral delivery of curcumin.

PubMed

Berginc, K; Trontelj, J; Basnet, N Skalko; Kristl, A

2012-06-01

Curcumin, a principal component from Curcuma longa, with antioxidant and anti-inflammatory activities was proposed as a potential candidate for the preventation and/or treatment of cancer and chronic diseases. However, curcumin could not achieve its expected therapeutic outcome in clinical trials due to its low solubility and poor bioavailability. The actual intestinal physiological barriers limiting curcumin absorption after oral administration have not been fully investigated. To identify the main barriers curtailing its absorption, in vitro permeability of curcumin and flux of its glucuronide were monitored in rat jejunum and Transwell grown Caco-2 cells. Curcumin was more permeable under acidic conditions, but the permeability was substantially below the permeability of highly permeable standards. Its efflux could not be inhibited by specific Pgp and MRP inhibitors. BCRP was found to participate in curcumin transport, but the Organic Anion Transporting Polypeptide (OATP) did not. The permeability of curcumin significantly increased when the structure of mucus was compromised. The inhibitor of curcumin metabolism, piperin, failed to act as a permeability enhancer. Piperin inhibited Pgp and MRP transporters and decreased the amount of glucuronide transported back into the intestine. Inclusion of piperin in curcumin-containing formulations is highly recommended as to inhibit curcumin glucuronidation and to increase the transport of formed glucuronides into the plasma, therefore increasing the probability of glucuronide distribution into target tissue and inter-convertion to curcumin. It would also be beneficial, if curcumin delivery systems could reversibly compromise the mucous integrity to minimize the non-specific binding of curcumin to its constituents.

Transcriptomic profiling of curcumin treated human breast stem cells identifies a role for stearoyl coa-desaturase in breast cancer prevention

PubMed Central

Colacino, Justin A.; McDermott, Sean P.; Sartor, Maureen A.; Wicha, Max S.; Rozek, Laura S.

2017-01-01

Curcumin is a potential agent for both the prevention and treatment of cancers. Curcumin treatment alone, or in combination with piperine, limits breast stem cell self-renewal while remaining non-toxic to normal differentiated cells. We paired fluorescence activated cell sorting with RNA sequencing to characterize the genome-wide changes induced specifically in normal breast stem cells following treatment with these compounds. We generated genome-wide maps of the transcriptional changes that occur in epithelial-like (ALDH+) and mesenchymal-like (ALDH−/CD44+/CD24−) normal breast stem/progenitor cells following treatment with curcumin and piperine. We show that curcumin targets both stem cell populations by down-regulating expression of breast stem cell genes including ALDH1A3, CD49f, PROM1, and TP63. We also identified novel genes and pathways targeted by curcumin, including downregulation of SCD. Transient siRNA knockdown of SCD in MCF10A cells significantly inhibited mammosphere formation and the mean proportion of CD44+/CD24− cells, suggesting that SCD is a regulator of breast stemness and a target of curcumin in breast stem cells. These findings extend previous reports of curcumin targeting stem cells, here in two phenotypically distinct stem/progenitor populations isolated from normal human breast tissue. We identified novel mechanisms by which curcumin and piperine target breast stem cell self-renewal, such as by targeting lipid metabolism, providing a mechanistic link between curcumin treatment and stem cell self renewal. These results elucidate the mechanisms by which curcumin may act as a cancer preventive compound and provide novel targets for cancer prevention and treatment. PMID:27306423

Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention.

PubMed

Colacino, Justin A; McDermott, Sean P; Sartor, Maureen A; Wicha, Max S; Rozek, Laura S

2016-07-01

Curcumin is a potential agent for both the prevention and treatment of cancers. Curcumin treatment alone, or in combination with piperine, limits breast stem cell self-renewal, while remaining non-toxic to normal differentiated cells. We paired fluorescence-activated cell sorting with RNA sequencing to characterize the genome-wide changes induced specifically in normal breast stem cells following treatment with these compounds. We generated genome-wide maps of the transcriptional changes that occur in epithelial-like (ALDH+) and mesenchymal-like (ALDH-/CD44+/CD24-) normal breast stem/progenitor cells following treatment with curcumin and piperine. We show that curcumin targets both stem cell populations by down-regulating expression of breast stem cell genes including ALDH1A3, CD49f, PROM1, and TP63. We also identified novel genes and pathways targeted by curcumin, including downregulation of SCD. Transient siRNA knockdown of SCD in MCF10A cells significantly inhibited mammosphere formation and the mean proportion of CD44+/CD24- cells, suggesting that SCD is a regulator of breast stemness and a target of curcumin in breast stem cells. These findings extend previous reports of curcumin targeting stem cells, here in two phenotypically distinct stem/progenitor populations isolated from normal human breast tissue. We identified novel mechanisms by which curcumin and piperine target breast stem cell self-renewal, such as by targeting lipid metabolism, providing a mechanistic link between curcumin treatment and stem cell self-renewal. These results elucidate the mechanisms by which curcumin may act as a cancer-preventive compound and provide novel targets for cancer prevention and treatment.

Bioavailability of curcumin: problems and promises.

PubMed

Anand, Preetha; Kunnumakkara, Ajaikumar B; Newman, Robert A; Aggarwal, Bharat B

2007-01-01

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.

Spice phenolics inhibit human PMNL 5-lipoxygenase.

PubMed

Prasad, N Satya; Raghavendra, R; Lokesh, B R; Naidu, K Akhilender

2004-06-01

A wide variety of phenolic compounds and flavonoids present in spices possess potent antioxidant, antimutagenic and anticarcinogenic activities. We examined whether 5-lipoxygenase (5-LO), the key enzyme involved in biosynthesis of leukotrienes is a possible target for the spices. Effect of aqueous extracts of turmeric, cloves, pepper, chili, cinnamon, onion and also their respective active principles viz., curcumin, eugenol, piperine, capsaicin, cinnamaldehyde, quercetin, and allyl sulfide were tested on human PMNL 5-LO activity by spectrophotomeric and HPLC methods. The formation of 5-LO product 5-HETE was significantly inhibited in a concentration-dependent manner with IC(50) values of 0.122-1.44 mg for aqueous extracts of spices and 25-83 microM for active principles, respectively. The order of inhibitory activity was of quercetin>eugenol>curcumin>cinnamaldehyde>piperine>capsaicin>allyl sulfide. Quercetin, eugenol and curcumin with one or more phenolic ring and methoxy groups in their structure showed high inhibitory effect, while the non-phenolic spice principle allyl sulfide showed least inhibitory effect on 5-LO. The inhibitory effect of quercetin, curcumin and eugenol was similar to that of synthetic 5-LO inhibitors-phenidone and NDGA. Moreover, the inhibitory potency of aqueous extracts of spice correlated with the active principles of their respective spices. The synergistic or antagonistic effect of mixtures of spice active principles and spice extracts were investigated and all the combinations of spice active principles/extracts exerted synergistic effect in inhibiting 5-LO activity. These findings clearly suggest that phenolic compounds present in spices might have physiological role in modulating 5-LO pathway.

Lessons from black pepper: piperine and derivatives thereof.

PubMed

Chavarria, D; Silva, T; Magalhães e Silva, D; Remião, F; Borges, F

2016-01-01

Piperine is a simple and pungent alkaloid found in the seeds of black pepper (Piper nigrum). Following its isolation and full characterization, the biological properties of piperine have been extensively studied, and piperine-like derivatives have shown an interesting range of pharmacological activities. In this context, significant advances have been made in the discovery of new chemical entities based on the piperine scaffold endowed with therapeutic potential. The aim of this review is to provide a thorough inquiry on the therapeutic potential of piperine and related derivatives. It provides an overview of recent developments in patented processes and applications thereof between 2000 and 2015. Cumulative evidence shows that piperine is currently paving its way to become a privileged scaffold for the development of bioactive compounds with therapeutic application in multiple human diseases. In particular, piperine derivatives were shown to modulate the activity of several targets related to neurological disorders, including epilepsy, Parkinson's disease, depression and pain related disorders. Moreover, the efflux pump inhibitory ability of piperine and its analogues tackles important drug resistance mechanisms and may improve the clinical efficacy of antibiotic and anticancer drugs. Although the use of piperine as a scaffold for bioactive compounds is still in its early stages, the continuous exploration of this structure may lead to remarkable advances in drug discovery programs.

Piper nigrum and piperine: an update.

PubMed

Meghwal, Murlidhar; Goswami, T K

2013-08-01

Black pepper (Piper nigrum L.) is a very widely used spice, known for its pungent constituent piperine. However, in addition to its culinary uses, pepper has important medicinal and preservative properties, and, more recently, piperine has been shown to have fundamental effects on p-glycoprotein and many enzyme systems, leading to biotransformative effects including chemoprevention, detoxification, and enhancement of the absorption and bioavailability of herbal and conventional drugs. Based on modern cell, animal, and human studies, piperine has been found to have immunomodulatory, anti-oxidant, anti-asthmatic, anti-carcinogenic, anti-inflammatory, anti-ulcer, and anti-amoebic properties. In this review, the chemical constituents, biological activities, effects of processing, and future potential of black pepper and piperine have been discussed thoroughly. Copyright © 2013 John Wiley & Sons, Ltd.

Mechanisms of curcumin-induced gastroprotection against ethanol-induced gastric mucosal lesions.

PubMed

Czekaj, Renata; Majka, Jolanta; Magierowska, Katarzyna; Sliwowski, Zbigniew; Magierowski, Marcin; Pajdo, Robert; Ptak-Belowska, Agata; Surmiak, Marcin; Kwiecien, Slawomir; Brzozowski, Tomasz

2018-05-01

Curcumin, a pleiotropic substance used for centuries in traditional medicine, exhibits antioxidant, anti-inflammatory and antiproliferative efficacy against various tumours, but the role of curcumin in gastroprotection is little studied. We determined the effect of curcumin against gastric haemorrhagic lesions induced by 75% ethanol and alterations in gastric blood flow (GBF) in rats with cyclooxygenase-1 (COX-1) and COX-2 activity inhibited by indomethacin, SC-560 or rofecoxib, inhibited NO-synthase activity, capsaicin denervation and blockade of TRPV1 receptors by capsazepine. One hour after ethanol administration, the gastric mucosal lesions were assessed by planimetry, the GBF was examined by H 2 gas clearance, plasma gastrin was determined by radioimmunoassay, and the gastric mucosal mRNA expression of Cdx-2, HIF-1α, HO-1 and SOD 2 was analysed by RT-PCR. Curcumin, in a dose-dependent manner, reduced ethanol-induced gastric lesions and significantly increased GBF and plasma gastrin levels. Curcumin-induced protection was completely reversed by indomethacin and SC-560, and significantly attenuated by rofecoxib, L-NNA, capsaicin denervation and capsazepine. Curcumin downregulated Cdx-2 and Hif-1α mRNA expression and upregulated HO-1 and SOD 2, and these effects were reversed by L-NNA and further restored by co-treatment of L-NNA with L-arginine. Curcumin-induced protection against ethanol damage involves endogenous PG, NO, gastrin and CGRP released from sensory nerves due to activation of the vanilloid TRPV1 receptor. This protective effect can be attributed to the inhibition of HIF-1α and Cdx-2 expression and the activation of HO-1 and SOD 2 expression.

Neuroprotective potential of curcumin in combination with piperine against 6-hydroxy dopamine induced motor deficit and neurochemical alterations in rats.

PubMed

Singh, Shamsher; Kumar, Puneet

2017-02-01

6-hydroxy dopamine (6-OHDA) is a neurotoxin which on intranigral administration produces severe nigrostriatal damage with motor and cognitive deficit in animals. Curcumin (CMN) in combination with bioenhancer piperine (PP) in 6-hydroxydopamine-induced Parkinsonian rats was used to investigate the antioxidant, neuromodulatory and neuroprotective mechanisms. Hemi-Parkinson's rat model was developed with intranigral infusion of 6-OHDA (8 μg/2 μl, once, unilaterally), treatment with CMN (25 and 50 mg/kg) and combination of PP (2.5 mg/kg) with CMN (25 mg/kg) was given daily for 21 days starting from the 7th day after 6-OHDA infusion. The behavioral (locomotor, grip strength, and narrow beam walk) parameters were studied on weekly basis. On 22nd day, isolated brain preparations were subjected to biochemical (lipid peroxidation, glutathione, and nitrite), neuroinflammatory (IL-1β, IL-6, and TNF- α), and neurochemical (DA, NE, 5- HT, GABA, Glutamate, DOPAC, HVA, and 5-HIAA) analysis. Oral administration of CMN had significantly prevented behavioral, neuroinflammatory, and neurochemical changes and preserved the antioxidant potential of the nigrostriatum in rats treated with 6-OHDA. In the present study, PP and CMN had afforded a better neuroprotective effect compared to alone treatment on behavior, biochemical, neuroinflammatory, and neurochemical parameters in rats.

Effects of Phytochemical P-Glycoprotein Modulators on the Pharmacokinetics and Tissue Distribution of Doxorubicin in Mice.

PubMed

Kim, Tae Hwan; Shin, Soyoung; Yoo, Sun Dong; Shin, Beom Soo

2018-02-07

Pungent spice constituents such as piperine, capsaicin and [6]-gingerol consumed via daily diet or traditional Chinese medicine, have been reported to possess various pharmacological activities. These dietary phytochemicals have also been reported to inhibit P-glycoprotein (P-gp) in vitro and act as an alternative to synthetic P-gp modulators. However, the in vivo effects on P-gp inhibition are currently unknown. This study aimed to test the hypothesis that phytochemical P-gp inhibitors, i.e., piperine, capsaicin and [6]-gingerol, modulate the in vivo tissue distribution of doxorubicin, a representative P-gp substrate. Mice were divided into four groups and each group was pretreated with intraperitoneal injections of control vehicle, piperine, capsaicin, or [6]-gingerol and doxorubicin (1 mg/kg) was administered via the penile vein. The concentrations of the phytochemicals and doxorubicin in the plasma and tissues were determined by LC-MS/MS. The overall plasma concentration-time profiles of doxorubicin were not significantly affected by piperine, capsaicin, or [6]-gingerol. In contrast, doxorubicin accumulation was observed in tissues pretreated with piperine or capsaicin. The tissue to plasma partition coefficients, K p , for the liver and kidney were higher in the piperine-pretreated group, while the K p for kidney, brain and liver were higher in the capsaicin-pretreated group. [6]-Gingerol did not affect doxorubicin tissue distribution. The data demonstrated that the phytochemicals modulated doxorubicin tissue distribution, which suggested their potential to induce food-drug interactions and act as a strategy for the delivery of P-gp substrate drugs to target tissues and tumors.

Curcumin: A Review of Its' Effects on Human Health.

PubMed

Hewlings, Susan J; Kalman, Douglas S

2017-10-22

Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose of this review is to provide a brief overview of the plethora of research regarding the health benefits of curcumin.

Cancer Chemoprevention and Piperine: Molecular Mechanisms and Therapeutic Opportunities

PubMed Central

Rather, Rafiq A.; Bhagat, Madhulika

2018-01-01

Cancer is a genetic disease characterized by unregulated growth and dissemination of malignantly transformed neoplastic cells. The process of cancer development goes through several stages of biochemical and genetic alterations in a target cell. Several dietary alkaloids have been found to inhibit the molecular events and signaling pathways associated with various stages of cancer development and therefore are useful in cancer chemoprevention. Cancer chemoprevention has long been recognized as an important prophylactic strategy to reduce the burden of cancer on health care system. Cancer chemoprevention assumes the use of one or more pharmacologically active agents to block, suppress, prevent, or reverse the development of invasive cancer. Piperine is an active alkaloid with an excellent spectrum of therapeutic activities such as anti-oxidant, anti-inflammatory, immunomodulatory, anti-asthmatic, anti-convulsant, anti-mutagenic, antimycobacterial, anti-amoebic, and anti-cancer activities. In this article, we made an attempt to sum up the current knowledge on piperine that supports the chemopreventive potential of this dietary phytochemical. Many mechanisms have been purported to understand the chemopreventive action of piperine. Piperine has been reported to inhibit the proliferation and survival of many types of cancer cells through its influence on activation of apoptotic signaling and inhibition of cell cycle progression. Piperine is known to affect cancer cells in variety of other ways such as influencing the redox homeostasis, inhibiting cancer stem cell (CSC) self-renewal and modulation of ER stress and autophagy. Piperine can modify activity of many enzymes and transcription factors to inhibit invasion, metastasis, and angiogenesis. Piperine is a potent inhibitor of p-glycoprotein (P-gp) and has a significant effect on the drug metabolizing enzyme (DME) system. Because of its inhibitory influence on P-gp activity, piperine can reverse multidrug resistance

Enhanced solubility of piperine using hydrophilic carrier-based potent solid dispersion systems.

PubMed

Thenmozhi, Kathavarayan; Yoo, Young Je

2017-09-01

Piperine alkaloid, an important constituent of black pepper, exhibits numerous therapeutic properties, whereas its usage as a drug is limited due to its poor solubility in aqueous medium, which leads to poor bioavailability. Herein, a new method has been developed to improve the solubility of this drug based on the development of solid dispersions with improved dissolution rate using hydrophilic carriers such as sorbitol (Sor), polyethylene glycol (PEG) and polyvinyl pyrrolidone K30 (PVP) by solvent method. Physical mixtures of piperine and carriers were also prepared for comparison. The physicochemical properties of the prepared solid dispersions were examined using SEM, TEM, DSC, XRD and FT-IR. In vitro dissolution profile of the solid dispersions was recorded and compared with that of the pure piperine and physical mixtures. The effect of these carriers on the aqueous solubility of piperine has been investigated. The solid dispersions of piperine with Sor, PEG and PVP exhibited superior performance for the dissolution of piperine with a drug release of 70%, 76% and 89%, respectively after 2 h compared to physical mixtures and pure piperine, which could be due to its transformation from crystalline to amorphous form as well as the attachment of hydrophilic carriers to the surface of poorly water-soluble piperine. Results suggest that the piperine solid dispersions prepared with improved in vitro release exhibit potential advantage in delivering poorly water-soluble piperine as an oral supplement.

Piperine production by endophytic fungus Colletotrichum gloeosporioides isolated from Piper nigrum.

PubMed

Chithra, S; Jasim, B; Sachidanandan, P; Jyothis, M; Radhakrishnan, E K

2014-03-15

Many endophytic fungi have been reported with the biosynthetic potential to produce same or similar metabolites present in host plants. The adaptations that might have acquired by these fungi as a result of the long-term association with their host plants can be the possible basis of their biosynthetic potential. The bioactive compounds originated from endophytes are currently explored for their potential applications in pharmaceutical, agriculture and food industries. Piper nigrum, a plant of the Piperaceae is very remarkable because of the presence of the alkaloid piperine. Piperine has been reported to have broad bioactive properties ranging from antimicrobial, antidepressant, anti-inflammatory, antioxidative to anticancer activities. Interestingly, piperine also plays a vital role in increasing the bioavailability of many drugs which again is a promising property. The current study was carried out to identify piperine producing endophytic fungus from Piper nigrum L. By screening various endophytic fungi, the isolate which was identified as member of Colletotrichum gloeosporioides was found to have the ability to form piperine and was confirmed by HPLC and LCMS. Considering the broad bioactive potential of piperine, the piperine producing fungi identified in the study can expect to have much industrial potential. Copyright © 2013 Elsevier GmbH. All rights reserved.

Enhancing the bioavailability of resveratrol by combining it with piperine

PubMed Central

Johnson, Jeremy J.; Nihal, Minakshi; Siddiqui, Imtiaz A.; Scarlett, Cameron O.; Bailey, Howard H.; Mukhtar, Hasan; Ahmad, Nihal

2012-01-01

Scope Resveratrol (3,5,4′-trihydroxystilbene) is a phytoalexin shown to possess a multitude of health-promoting properties in pre-clinical studies. However, the poor in vivo bioavailability of resveratrol due to its rapid metabolism is being considered as a major obstacle in translating its effects in humans. In this study, we examined the hypothesis that piperine will enhance the pharmacokinetic parameters of resveratrol via inhibiting its glucuronidation, thereby slowing its elimination. Methods and results Employing a standardized LC/MS assay, we determined the effect of piperine co-administration with resveratrol on serum levels resveratrol and resveratrol-3-O-β-d-glucuronide in C57BL mice. Mice were administered resveratrol (100 mg/kg; oral gavage) or resveratrol (100 mg/kg; oral gavage) + piperine (10 mg/kg; oral gavage), and the serum levels of resveratrol and resveratrol-3-O-β-d-glucuronide were analyzed at different times. We found that the degree of exposure (i.e. AUC) to resveratrol was enhanced to 229% and the maximum serum concentration (Cmax) was increased to 1544% with the addition of piperine. Conclusion Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol. However, further detailed research is needed to study the mechanism of improved bioavailability of resveratrol via its combination with piperine as well as its effect on resveratrol metabolism. PMID:21714124

Piperine from black pepper inhibits activation-induced proliferation and effector function of T lymphocytes.

PubMed

Doucette, Carolyn D; Rodgers, Gemma; Liwski, Robert S; Hoskin, David W

2015-11-01

Piperine is a major alkaloid component of black pepper (Piper nigrum Linn), which is a widely consumed spice. Here, we investigated the effect of piperine on mouse T lymphocyte activation. Piperine inhibited polyclonal and antigen-specific T lymphocyte proliferation without affecting cell viability. Piperine also suppressed T lymphocyte entry into the S and G2 /M phases of the cell cycle, and decreased expression of G1 -associated cyclin D3, CDK4, and CDK6. In addition, piperine inhibited CD25 expression, synthesis of interferon-γ, interleukin (IL)-2, IL-4, and IL-17A, and the generation of cytotoxic effector cells. The inhibitory effect of piperine on T lymphocytes was associated with hypophosphorylation of Akt, extracellular signal-regulated kinase, and inhibitor of κBα, but not ZAP-70. The ability of piperine to inhibit several key signaling pathways involved in T lymphocyte activation and the acquisition of effector function suggests that piperine might be useful in the management of T lymphocyte-mediated autoimmune and chronic inflammatory disorders. © 2015 Wiley Periodicals, Inc.

Piperine ameliorates oxidative stress, inflammation and histological outcome in collagen induced arthritis.

PubMed

Umar, Sadiq; Golam Sarwar, Abu Hasnath Md; Umar, Khalid; Ahmad, Niyaz; Sajad, Mir; Ahmad, Sayeed; Katiyar, Chandra Kant; Khan, Haider A

2013-01-01

Piperine, a main component of Piper species, is a plant alkaloid with a long history of medical use in a variety of inflammatory disorders like rheumatoid arthritis. Due to side effects in current treatment modalities of rheumatoid arthritis, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. The aim of this work was to evaluate the anti-inflammatory and antiarthritic effects of piperine. Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. Piperine was administered at a dose of 100mgkg(-1) and indomethacin at 1mgkg(-1) body weight once daily for 21days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO), inflammatory mediators (IL-1β, TNF-α, IL-10 and PGE2) and histological studies in joints. Piperine was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO) studied. Oral administration of piperine resulted in significantly reduced the levels of pro-inflammatory mediators (IL-1β, TNF-α and PGE2) and increased level of IL-10. The protective effects of piperine against RA were also evident from the decrease in arthritis scoring and bone histology. In conclusion, the fact that piperine alter a number of factors known to be involved in RA pathogenesis indicates that piperine can be used similar to indomethacin as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis. Copyright © 2013 Elsevier Inc. All rights reserved.

Antigenotoxic Effect of Piperine in Broiler Chickens Intoxicated with Aflatoxin B1

PubMed Central

da Silva Cardoso, Verônica; Vermelho, Alane Beatriz; Ribeiro de Lima, Cristina Amorim; Mendes de Oliveira, Jéssica; Freire de Lima, Marco Edilson; Pinto da Silva, Lúcia Helena; Direito, Glória Maria; Miranda Danelli, Maria das Graças

2016-01-01

Piperine is an abundant amide extracted from black pepper seeds which has been shown to have protective effects against cytotoxic and genotoxic carcinogenesis induced by certain chemical carcinogens and aflatoxin B1 (AFB1) in vitro. The aim of this work was to study, in vivo, the antigenotoxic potential of feed-added piperine on broiler chickens experimentally intoxicated with AFB1, using micronucleus and comet assays. The antigenotoxicity assessment of 9-day-old chicks was performed on a total of 60 chickens divided into four groups of 15 broilers each: (C) control, (P) 60 mg·piperine kg−1 feed, (A) 0.5 mg·AFB1·kg−1 body weight, (daily by oral route), and (P + A) co-treatment with piperine and AFB1. The experiment was conducted for 26 days. Chicks intoxicated with AFB1 showed significant genotoxic effects in the first 24 h post intoxication, and the effects remained in the other periods analyzed (48, 72, and 96 h and 26 days of treatment). The DNA damage in peripheral blood cells, the number of erythrocytes with micronuclei, and polychromatic-to-normochromatic erythrocyte ratio were significantly reduced or absent in the piperine/AFB1 group. No significant differences were observed between the group piperine/AFB1 and the control and piperine-alone groups. The addition 60 mg·kg−1 of piperine to the diet of the broiler chicks was safe, promoting beneficial effects in poultry health with respect to the toxic effects 0.5 mg·AFB1·kg−1 body weight. PMID:27809242

Antigenotoxic Effect of Piperine in Broiler Chickens Intoxicated with Aflatoxin B1.

PubMed

da Silva Cardoso, Verônica; Vermelho, Alane Beatriz; Ribeiro de Lima, Cristina Amorim; Mendes de Oliveira, Jéssica; Freire de Lima, Marco Edilson; Pinto da Silva, Lúcia Helena; Direito, Glória Maria; Miranda Danelli, Maria das Graças

2016-10-31

Piperine is an abundant amide extracted from black pepper seeds which has been shown to have protective effects against cytotoxic and genotoxic carcinogenesis induced by certain chemical carcinogens and aflatoxin B₁ (AFB₁) in vitro. The aim of this work was to study, in vivo, the antigenotoxic potential of feed-added piperine on broiler chickens experimentally intoxicated with AFB₁, using micronucleus and comet assays. The antigenotoxicity assessment of 9-day-old chicks was performed on a total of 60 chickens divided into four groups of 15 broilers each: (C) control, (P) 60 mg·piperine kg -1 feed, (A) 0.5 mg·AFB₁·kg -1 body weight, (daily by oral route), and (P + A) co-treatment with piperine and AFB₁. The experiment was conducted for 26 days. Chicks intoxicated with AFB₁ showed significant genotoxic effects in the first 24 h post intoxication, and the effects remained in the other periods analyzed (48, 72, and 96 h and 26 days of treatment). The DNA damage in peripheral blood cells, the number of erythrocytes with micronuclei, and polychromatic-to-normochromatic erythrocyte ratio were significantly reduced or absent in the piperine/AFB₁ group. No significant differences were observed between the group piperine/AFB₁ and the control and piperine-alone groups. The addition 60 mg·kg -1 of piperine to the diet of the broiler chicks was safe, promoting beneficial effects in poultry health with respect to the toxic effects 0.5 mg·AFB₁·kg -1 body weight.

Black pepper constituent piperine: genotoxicity studies in vitro and in vivo.

PubMed

Thiel, Anette; Buskens, Carin; Woehrle, Tina; Etheve, Stéphane; Schoenmakers, Ankie; Fehr, Markus; Beilstein, Paul

2014-04-01

Piperine is responsible for the hot taste of black pepper. Publications on genotoxicity of piperine are reported: negative Ames Tests and one in vitro micronucleus test (MNT). In vivo tests were mainly negative. In the majority of the data the administered dose levels did not follow the dose selection requirements of regulatory guidelines of having dose levels up to the maximum tolerated dose (MTD). The only oral high dose studies were a positive in vivo MNT in mice in contrast to a negative in vivo chromosome aberration test in rats. Thus, conflicting results in genotoxicity testing are published. To investigate this further, we administered piperine to mice up to the MTD and determined micronuclei-frequency. Piperine reduces core body temperature and interferes with blood cells both being known to result in irrelevant positive in vivo MNTs. Therefore we added mechanistic endpoints: core body temperature, haematology, erythropoietin level, and organ weights. Additionally an in vitro MNT in Chinese hamster ovary cells was performed. Piperine was negative in the in vitro MNT. It caused significant reduction of core body temperature, decrease of white blood cells and spleen weights but no increase in the micronucleus-frequency. Thus, in our studies piperine was not genotoxic. Copyright © 2014 Elsevier Ltd. All rights reserved.

Piperine metabolically regulates peritoneal resident macrophages to potentiate their functions against bacterial infection

PubMed Central

Huang, Mei-Yun; Zha, Qing-Bing; Zhao, Gao-Xiang; Hou, Xiao-Feng; Shi, Zi-Jian; Lin, Qiu-Ru; Ouyang, Dong-Yun; He, Xian-Hui

2015-01-01

Pepper, a daily-used seasoning for promoting appetite, is widely used in folk medicine for treating gastrointestinal diseases. Piperine is the major alkaloid in pepper and possesses a wide range of pharmacological activities. However, the mechanism for linking metabolic and medicinal activities of piperine remains unknown. Here we report that piperine robustly boosts mTORC1 activity by recruiting more system L1 amino acid transporter (SLC7A5/SLC3A2) to the cell membrane, thus promoting amino acid metabolism. Piperine-induced increase of mTORC1 activity in resident peritoneal macrophages (pMΦs) is correlated with enhanced production of IL-6 and TNF-α upon LPS stimulation. Such an enhancement of cytokine production could be abrogated by inhibitors of the mTOR signaling pathway, indicating mTOR's action in this process. Moreover, piperine treatment protected resident pMΦs from bacterium-induced apoptosis and disappearance, and increased their bacterial phagocytic ability. Consequently, piperine administration conferred mice resistance against bacterial infection and even sepsis. Our data highlight that piperine has the capacity to metabolically reprogram peritoneal resident macrophages to fortify their innate functions against bacterial infection. PMID:26439699

Effect of piperine on the bioavailability and pharmacokinetics of emodin in rats.

PubMed

Di, Xin; Wang, Xin; Di, Xin; Liu, Youping

2015-11-10

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) has been widely used as a traditional medicine and was shown to possess a multitude of health-promoting properties in pre-clinical studies, but its bioavailability was low due to the extensive glucuronidation in liver and intestine, hindering the development of emodin as a feasible chemopreventive agent. In this study, piperine, as a bioenhancer, was used to enhance the bioavailability of emodin by inhibiting its glucuronidation. The pharmacokinetic profiles of emodin after oral administration of emodin (20mg/kg) alone and in combination with piperine (20mg/kg) to rats were investigated via a validated LC/MS/MS method. As the in vivo pharmacokinetic studies had indicated, the AUC and Cmax of emodin were increased significantly after piperine treatment, and the glucuronidation of emodin was markedly inhibited. Our study demonstrated that piperine significantly improved the in vivo bioavailability of emodin and the influence of piperine on the pharmacokinetics of emodin may be attributed to the inhibition of glucuronidation of emodin. Further research is needed to investigate the detailed mechanism of improved bioavailability of emodin via its combination with piperine. Copyright © 2015 Elsevier B.V. All rights reserved.

Vasculoprotective and vasodilatation effects of herbal formula (Sahatsatara) and piperine in spontaneously hypertensive rats.

PubMed

Booranasubkajorn, Suksalin; Huabprasert, Sukit; Wattanarangsan, Jantanee; Chotitham, Pruksa; Jutasompakorn, Pinpilai; Laohapand, Tawee; Akarasereenont, Pravit; Tripatara, Pinpat

2017-01-15

The herbal formula (Sahatsatara, STF), the Thai traditional poly-herbal recipe, has been used for treatment of muscle pain, anti-flatulence and numbness on hands and feet, with the caution when used in hypertensive patients. However, there is no scientific evidence to prove its effects on cardiovascular system. Piperine is the proposed major active compound in STF. It is shown to have antihypertensive effect in the L-NAME-induced endothelial dysfunction rats. This study investigated the pharmacokinetics, mechanism of action, as well as the hemodynamic and vasoactive effect and toxicity of STF and piperine using spontaneously hypertensive rats (SHR) and normal Wistar rats (NWR). The amount of piperine in STF was measured by ultra performance liquid chromatography (UPLC). SHR and NWR were gavaged with piperine (50mg/kg/day) or STF (100, 300, or 1000mg/kg/day) alone or together with L-NAME (in drinking water) for 28 days. Hemodynamic effects were monitored by noninvasive tail cuff every 7 days. Vasorelaxation effect on the thoracic aorta in organ chamber was observed through force transducer at the end of the experiment. Biochemical parameters for kidney and liver toxicity were measured. In addition, pharmacokinetic study was performed using non-compartment analysis. The amount of piperine in STF was 1.29%w/w. Both STF and piperine did not affect blood pressure and heart rate in both SHR and NWR. Interestingly, STF and piperine increased acetylcholine-induced vasorelaxation of isolated thoracic aorta and have vascoluprotective effect in nitric oxide (NO) impaired rats. No liver or kidney toxicity was found in this study. Non-compartment pharmacokinetic analysis showed that the time to reach maximum concentration (T max ) of plasma piperine after administration of piperine and STF were 3.9 and 1.7h, respectively. This result suggested that piperine in the recipe had better absorption than the pure standard piperine. STF had no effect on blood pressure in both SHR and

Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases.

PubMed

Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Padmavathi, Ganesan; Monisha, Javadi; Roy, Nand Kishor; Prasad, Sahdeo; Aggarwal, Bharat B

2017-06-01

Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti-inflammatory activity through the suppression of numerous cell signalling pathways including NF-κB, STAT3, Nrf2, ROS and COX-2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases

PubMed Central

Bordoloi, Devivasha; Padmavathi, Ganesan; Monisha, Javadi; Roy, Nand Kishor; Prasad, Sahdeo

2016-01-01

Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti‐inflammatory activity through the suppression of numerous cell signalling pathways including NF‐κB, STAT3, Nrf2, ROS and COX‐2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc PMID:27638428

Piperine impairs cell cycle progression and causes reactive oxygen species-dependent apoptosis in rectal cancer cells.

PubMed

Yaffe, Paul B; Doucette, Carolyn D; Walsh, Mark; Hoskin, David W

2013-02-01

Piperine, an alkaloid phytochemical found in the fruit of black and long pepper plants, is reported to inhibit the growth of cancer cells; however, the mechanism of action in human cancer cells is not clear. In this study we investigated the effect of piperine on the growth of HRT-18 human rectal adenocarcinoma cells. MTT assays showed that piperine inhibited the metabolic activity of HRT-18 cells in a dose- and time-dependent fashion, suggesting a cytostatic and/or cytotoxic effect. Flow cytometric analysis of Oregon Green 488-stained and propidium iodide-stained HRT-18 cells showed that piperine inhibited cell cycle progression. Piperine also caused HRT-18 cells to die by apoptosis, as determined by Annexin-V-FLUOS staining and characteristic changes in cell morphology. Flow cytometric analysis of dihydroethidium- and 2',7'-dichlorofluorescein diacetate-stained HRT-18 cells showed increased production of reactive oxygen species in piperine-treated cells. Furthermore, the antioxidant N-acetylcysteine reduced apoptosis in cultures of piperine-treated HRT-18 cells, indicating that piperine-induced cytotoxicity was mediated at least in part by reactive oxygen species. The cytostatic and cytotoxic effects of piperine on rectal cancer cells suggest that this dietary phytochemical may be useful in cancer treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Hot Melt Extrusion as an Approach to Improve Solubility, Permeability, and Oral Absorption of a Psychoactive Natural Product, Piperine

PubMed Central

Ashour, Eman A.; Majumdar, Soumyajit; Alsheteli, Abdulla; Alshehri, Sultan; Alsulays, Bader; Feng, Xin; Gryczke, Andreas; Kolter, Karl; Langley, Nigel; Repka, Michael A.

2016-01-01

Objective The aims of the current research project were to investigate the efficiency of various polymers to enhance the solubility and increase the systemic absorption of piperine using hot melt extrusion technology. Methods Piperine 10–40% w/w and Eudragit® EPO/ Kollidon® VA 64 or Soluplus® were mixed and the resulting blends were extruded using a twin-screw extruder (Process 11, Thermo Fisher Scientific). Drug release profiles and piperine solubility studies of the extrudates were evaluated. A non-everted intestinal sac was employed for the most promising formulation, 10% w/w piperine/Soluplus®, and pure piperine to study the permeability characteristics. Key Findings Dissolution studies demonstrated enhancement in piperine percent release of 10% and 20% w/w piperine/Soluplus® extrudates up to 95% and 74%, respectively. The solubility of 10% and 20% piperine/Soluplus® increased more than 160- and 45-fold in water, respectively. Furthermore, permeability studies demonstrated the enhancement in piperine absorption of 10% w/w piperine/Soluplus® extrudates up to 158.9 μg/5mL compared to pure piperine at 1.3 μg/5mL within 20 minutes. Conclusion These results demonstrated that increasing the bioavailability of piperine may be achieved as demonstrated by findings in this study. PMID:27283755

Fat digestion and absorption in spice-pretreated rats.

PubMed

Prakash, Usha N S; Srinivasan, Krishnapura

2012-02-01

A few common spices are known to stimulate secretion of bile with higher amount of bile acids which play a major role in digestion and absorption of dietary lipids. It would be appropriate to verify if these spices enable efficient digestion and absorption during high-fat intake. In this context, dietary ginger (0.05%), piperine (0.02%), capsaicin (0.015%), and curcumin (0.5%) were examined for their influence on bile secretion, digestive enzymes of pancreas and absorption of dietary fat in high-fat (30%) fed Wistar rats for 8 weeks. These spices enhanced the activity of pancreatic lipase, amylase, trypsin and chymotrypsin by 22-57%, 32-51%, 63-81% and 12-38%, respectively. Dietary intake of spices along with high-fat enhanced fat absorption. These dietary spices increased bile secretion with higher bile acid content. Stimulation of lipid mobilisation from adipose tissue was suggested by the decrease in perirenal adipose tissue weight by dietary capsaicin and piperine. This was also accompanied by prevention of the accumulation of triglyceride in liver and serum in high-fat fed rats. Activities of key lipogenic enzymes in liver were reduced which was accompanied by an increased activity of hormone-sensitive lipase. Thus, dietary ginger and other spice compounds enhance fat digestion and absorption in high-fat fed situation through enhanced secretion of bile salts and a stimulation of the activity pancreatic lipase. At the same time, the energy expenditure is facilitated by these spices to prevent the accumulation of absorbed fat. Copyright © 2011 Society of Chemical Industry.

Protective effects of piperine on lead acetate induced-nephrotoxicity in rats.

PubMed

Sudjarwo, Sri Agus; Eraiko, Koerniasari; Sudjarwo, Giftania Wardani; Koerniasari

2017-11-01

In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue. Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5 th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies. The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats. From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats.

In vitro cytotoxic and in silico activity of piperine isolated from Piper nigrum fruits Linn.

PubMed

Paarakh, Padmaa M; Sreeram, Dileep Chandra; D, Shruthi S; Ganapathy, Sujan P S

2015-12-01

Piper nigrum [Piperaceae], commonly known as black pepper is used as medicine fairly throughout the greater part of India and as a spice globally. To isolate piperine and evaluate in vitro cytotoxic [antiproliferative] activity and in silico method. Piperine was isolated from the fruits of P.nigrum. Piperine was characterized by UV,IR, (1)H-NMR, (13)C-NMR and Mass spectrum. Standardization of piperine was done also by HPTLC fingerprinting. In vitro cytotoxic activity was done using HeLa cell lines by MTT assay at different concentrations ranging from 20 to 100 μg/ml in triplicate and in silico docking studies using enzyme EGFR tyrosine kinase. Fingerprinting of isolated piperine were done by HPTLC method. The IC50 value was found to be 61.94 ± 0.054 μg/ml in in vitro cytotoxic activity in HeLa Cell lines. Piperine was subjected to molecular docking studies for the inhibition of the enzyme EGFR tyrosine kinase, which is one of the targets for inhibition of cancer cells. It has shown -7.6 kJ mol(-1) binding and 7.06 kJ mol(-1) docking energy with two hydrogen bonds. piperine has shown to possess in vitro cytotoxic activity and in silico studies.

Bio-enhancing Effect of Piperine with Metformin on Lowering Blood Glucose Level in Alloxan Induced Diabetic Mice.

PubMed

Atal, Shubham; Atal, Sarjana; Vyas, Savita; Phadnis, Pradeep

2016-01-01

Diabetes mellitus is the most rampant metabolic pandemic of the 21(st) century. Piperine, the chief alkaloid of Piper nigrum (black pepper) is widely used in alternative and complementary therapies has been extensively studied for its bio-enhancing property. To evaluate the bio-enhancing effect of piperine with metformin in lowering blood glucose levels in alloxan-induced diabetic mice. Piperine was isolated from an extract of fruits of P. nigrum. Alloxan-induced (150 mg/kg intraperitoneal) diabetic mice were divided into four groups. Group I (control 2% gum acacia 2 g/100 mL), Group II (metformin 250 mg/kg), Group III (metformin and piperine 250 mg/kg + 10 mg/kg), and Group IV (metformin and piperine 125 mg/kg + 10 mg/kg). All the drugs were administered orally once daily for 28 days. Blood glucose levels were estimated at day 0, day 14, and end of the study (day 28). The combination of piperine with therapeutic dose of metformin (10 mg/kg + 250 mg/kg) showed significantly more lowering of blood glucose level as compared to metformin alone on both 14(th) and 28(th) day (P < 0.05). Piperine in combination with sub-therapeutic dose of metformin (10 mg/kg + 125 mg/kg) showed significantly more lowering of blood glucose as compared to control group and also showed greater lowering of blood glucose as compared to metformin (250 mg/kg) alone. Piperine has the potential to be used as a bio-enhancing agent in combination with metformin which can help reduce the dose of metformin and its adverse effects. Piperine is known for its bioenhancing property. This study evaluates the effect of piperine in combination with oral antidiabetic drug metformin. Drugs were administered for 28 days in alloxan induced diabetic mice and blood glucose lowering effect was seen. Results showed significantly better effect of combination of piperine with therapeutic dose of metformin in comparison to metformin alone. Piperine in combination with subtherapeutic dose of metformin also showed

Bio-enhancing Effect of Piperine with Metformin on Lowering Blood Glucose Level in Alloxan Induced Diabetic Mice

PubMed Central

Atal, Shubham; Atal, Sarjana; Vyas, Savita; Phadnis, Pradeep

2016-01-01

Background: Diabetes mellitus is the most rampant metabolic pandemic of the 21st century. Piperine, the chief alkaloid of Piper nigrum (black pepper) is widely used in alternative and complementary therapies has been extensively studied for its bio-enhancing property. Objective: To evaluate the bio-enhancing effect of piperine with metformin in lowering blood glucose levels in alloxan-induced diabetic mice. Materials and Methods: Piperine was isolated from an extract of fruits of P. nigrum. Alloxan-induced (150 mg/kg intraperitoneal) diabetic mice were divided into four groups. Group I (control 2% gum acacia 2 g/100 mL), Group II (metformin 250 mg/kg), Group III (metformin and piperine 250 mg/kg + 10 mg/kg), and Group IV (metformin and piperine 125 mg/kg + 10 mg/kg). All the drugs were administered orally once daily for 28 days. Blood glucose levels were estimated at day 0, day 14, and end of the study (day 28). Results: The combination of piperine with therapeutic dose of metformin (10 mg/kg + 250 mg/kg) showed significantly more lowering of blood glucose level as compared to metformin alone on both 14th and 28th day (P < 0.05). Piperine in combination with sub-therapeutic dose of metformin (10 mg/kg + 125 mg/kg) showed significantly more lowering of blood glucose as compared to control group and also showed greater lowering of blood glucose as compared to metformin (250 mg/kg) alone. Conclusion: Piperine has the potential to be used as a bio-enhancing agent in combination with metformin which can help reduce the dose of metformin and its adverse effects. SUMMARY Piperine is known for its bioenhancing property. This study evaluates the effect of piperine in combination with oral antidiabetic drug metformin. Drugs were administered for 28 days in alloxan induced diabetic mice and blood glucose lowering effect was seen. Results showed significantly better effect of combination of piperine with therapeutic dose of metformin in comparison to metformin alone. Piperine

Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins.

PubMed

Duangjai, Acharaporn; Ingkaninan, Kornkanok; Praputbut, Sakonwun; Limpeanchob, Nanteetip

2013-04-01

Black pepper (Piper nigrum L.) lowers blood lipids in vivo and inhibits cholesterol uptake in vitro, and piperine may mediate these effects. To test this, the present study aimed to compare actions of black pepper extract and piperine on (1) cholesterol uptake and efflux in Caco-2 cells, (2) the membrane/cytosol distribution of cholesterol transport proteins in these cells, and (3) the physicochemical properties of cholesterol micelles. Piperine or black pepper extract (containing the same amount of piperine) dose-dependently reduced cholesterol uptake into Caco-2 cells in a similar manner. Both preparations reduced the membrane levels of NPC1L1 and SR-BI proteins but not their overall cellular expression. Micellar cholesterol solubility of lipid micelles was unaffected except by 1 mg/mL concentration of black pepper extract. These data suggest that piperine is the active compound in black pepper and reduces cholesterol uptake by internalizing the cholesterol transporter proteins.

Protective effects of piperine on lead acetate induced-nephrotoxicity in rats

PubMed Central

Sudjarwo, Sri Agus; Eraiko, Koerniasari; Sudjarwo, Giftania Wardani; Koerniasari

2017-01-01

Objective(s): In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue. Materials and Methods: Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies. Results: The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats. Conclusion: From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats. PMID:29299200

Monitoring human melanocytic cell responses to piperine using multispectral imaging

NASA Astrophysics Data System (ADS)

Samatham, Ravikant; Phillips, Kevin G.; Sonka, Julia; Yelma, Aznegashe; Reddy, Neha; Vanka, Meenakshi; Thuillier, Philippe; Soumyanath, Amala; Jacques, Steven

2011-03-01

Vitiligo is a depigmentary disease characterized by melanocyte loss attributed most commonly to autoimmune mechanisms. Currently vitiligo has a high incidence (1% worldwide) but a poor set of treatment options. Piperine, a compound found in black pepper, is a potential treatment for the depigmentary skin disease vitiligo, due to its ability to stimulate mouse epidermal melanocyte proliferation in vitro and in vivo. The present study investigates the use of multispectral imaging and an image processing technique based on local contrast to quantify the stimulatory effects of piperine on human melanocyte proliferation in reconstructed epidermis. We demonstrate the ability of the imaging method to quantify increased pigmentation in response to piperine treatment. The quantization of melanocyte stimulation by the proposed imaging technique illustrates the potential use of this technology to quickly assess therapeutic responses of vitiligo tissue culture models to treatment non-invasively.

Development and evaluation of a novel drug delivery: Soluplus®/TPGS mixed micelles loaded with piperine in vitro and in vivo.

PubMed

Ding, Yingying; Wang, Changyuan; Wang, Yutong; Xu, Youwei; Zhao, Jing; Gao, Meng; Ding, Yanfang; Peng, Jinyong; Li, Lei

2018-05-27

Although piperine can inhibit cells of tumors, the poor water solubility restricted its clinical application. This paper aimed to develop mixed micelles based on Soluplus ® and D-α-tocopherol polyethylene glycol succinate (TPGS) to improve the aqueous solubility and anti-cancer effect. Piperine-loaded mixed micelles were prepared using a thin-film hydration method, and their physicochemical properties were characterized. The cellular uptake of the micelles was confirmed by confocal laser scanning microscopy in A549 lung cancer cells and HepG 2 liver cancer cells. In addition, cytotoxicity of the piperine mixed micelles was studied in A549 lung cancer cells and HepG 2 liver cancer cells. Free piperine or piperine-loaded Soluplus ® /TPGS mixed micelles were administered at an equivalent dose of piperine at 3.2 mg/kg via a single intravenous injection in the tail vain for the pharmacokinetic study in vivo. The diameter of piperine-loaded Soluplus ® /TPGS (4:1) mixed micelles was about 61.9 nm and the zeta potential -1.16 ± 1.06 mV with 90.9% of drug encapsulation efficiency and 4.67% of drug-loading efficiency. Differential scanning calorimetry (DSC) studies confirmed that piperine is encapsulated by the Soluplus ® /TPGS. The release results in vitro showed that the piperine-loaded Soluplus ® /TPGS mixed micelles presented sustained release behavior compared to the free piperine. The mixed micelles exhibited better antitumor efficacy compared to free piperine and physical mixture against in A549 and HepG 2 cells by MTT assay. The pharmacokinetic study revealed that the AUC of piperine-loaded mixed micelles was 2.56 times higher than that of piperine and the MRT for piperine-loaded mixed micelles was 1.2-fold higher than piperine (p < .05). The results of the study suggested that the piperine-loaded mixed micelles developed might be a potential nano-drug delivery system for cancer chemotherapy. These results demonstrated that piperine

LC-MS/MS based identification of piperine production by endophytic Mycosphaerella sp. PF13 from Piper nigrum.

PubMed

Chithra, S; Jasim, B; Anisha, C; Mathew, Jyothis; Radhakrishnan, E K

2014-05-01

Piper nigrum is very remarkable for its medicinal properties due to the presence of metabolites like piperine. Emerging understanding on the biosynthetic potential of endophytic fungi suggests the possibility to have piperine producing fungi in P. nigrum. In the current study, endophytic fungi isolated from P. nigrum were screened for the presence of piperine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This resulted in the identification of a Mycosphaerella sp. with the ability to produce piperine extracellularly. The biosynthesis of piperine (C17H19NO3) by the endophytic fungal isolate was confirmed by the presence of m/z 286.1 (M + H(+)) in the LC-MS/MS analysis using positive mode ionization. This was further supported by the presence of specific fragment ions with masses 135, 143, 171 and 201 formed due to the fragmentation of piperine present in the fungal extract.

Capsaicin in Metabolic Syndrome

PubMed Central

Bliss, Edward

2018-01-01

Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders. These responses of capsaicin are mediated through activation of TRPV1, which can then modulate processes such as browning of adipocytes, and activation of metabolic modulators including AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 1 (UCP1), and glucagon-like peptide 1 (GLP-1). Modulation of these pathways by capsaicin can increase fat oxidation, improve insulin sensitivity, decrease body fat, and improve heart and liver function. Identifying suitable ways of administering capsaicin at an effective dose would warrant its clinical use through the activation of TRPV1. This review highlights the mechanistic options to improve metabolic syndrome with capsaicin. PMID:29772784

Capsaicin in Metabolic Syndrome.

PubMed

Panchal, Sunil K; Bliss, Edward; Brown, Lindsay

2018-05-17

Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders. These responses of capsaicin are mediated through activation of TRPV1, which can then modulate processes such as browning of adipocytes, and activation of metabolic modulators including AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 1 (UCP1), and glucagon-like peptide 1 (GLP-1). Modulation of these pathways by capsaicin can increase fat oxidation, improve insulin sensitivity, decrease body fat, and improve heart and liver function. Identifying suitable ways of administering capsaicin at an effective dose would warrant its clinical use through the activation of TRPV1. This review highlights the mechanistic options to improve metabolic syndrome with capsaicin.

Bioconversion of Capsaicin by Aspergillus oryzae.

PubMed

Lee, Minji; Cho, Jeong-Yong; Lee, Yu Geon; Lee, Hyoung Jae; Lim, Seong-Il; Park, So-Lim; Moon, Jae-Hak

2015-07-08

This study identified metabolites of capsaicin bioconverted by Aspergillus oryzae, which is generally used for mass production of gochujang prepared by fermenting red pepper powder in Korea. A. oryzae was incubated with capsaicin in potato dextrose broth. Capsaicin decreased depending on the incubation period, but new metabolites increased. Five capsaicin metabolites purified from the ethyl acetate fraction of the capsaicin culture were identified as N-vanillylcarbamoylbutyric acid, N-vanillyl-9-hydroxy-8-methyloctanamide, ω-hydroxycapsaicin, 8-methyl-N-vanillylcarbamoyl-6(E)-octenoic acid, and 2-methyl-N-vanillylcarbamoyl-6(Z)-octenoic acid by nuclear magnetic resonance (NMR) and mass spectrometry (MS). The capsaicin metabolites in gochujang were confirmed and quantitated by selective multiple reaction monitoring detection after liquid chromatography electrospray ionization MS using the isolated compounds as external standards. On the basis of the structures of the capsaicin metabolites, it is proposed that capsaicin metabolites were converted by A. oryzae by ω-hydroxylation, alcohol oxidation, hydrogenation, isomerization, and α- and/or β-oxidation.

Piperine inhibits ABCA1 degradation and promotes cholesterol efflux from THP‐1‐derived macrophages

PubMed Central

Wang, Limei; Palme, Veronika; Rotter, Susanne; Schilcher, Nicole; Cukaj, Malsor; Wang, Dongdong; Ladurner, Angela; Heiss, Elke H.; Stangl, Herbert; Dirsch, Verena M.

2016-01-01

1 Scope Increased macrophage cholesterol efflux (ChE) is considered to have anti‐atherosclerotic effect counteracting cardiovascular disease. The principle pungent ingredient of the fruits of Piper nigrum, piperine, is identified in this study as a ChE inducer in THP‐1‐derived macrophages, and mechanisms underlying this effect are explored. 2 Methods and results Without affecting cell viability, piperine concentration‐dependently enhances ChE in THP‐1‐derived macrophages from 25 to 100 μM. The expression level of the key cholesterol transporter protein ATP‐binding cassette transporter A1 (ABCA1) is significantly upregulated by piperine, as revealed by western blot analyses. However, two other ChE‐mediating transporter proteins, ATP‐binding cassette transporter G1 (ABCG1) and scavenger receptor class B member 1 (SR‐B1), remain unaffected. Piperine exerts no influence on ABCA1 mRNA levels, but significantly inhibits the degradation of ABCA1, as evident by an increased half‐life of the protein in the presence of cycloheximide. Furthermore, it is found that piperine likely interferes with the calpain‐mediated ABCA1 degradation pathway and exhibits significant inhibition of calpain activity. 3 Conclusion Our findings suggest that piperine promotes ChE in THP‐1‐derived macrophages by upregulation of ABCA1, which might be mediated by inhibition of calpain activity. This novel bioactivity makes the dietary constituent piperine a good candidate to be further explored for therapeutic or preventive applications in the context of atherosclerosis. PMID:27862930

Pharmacological basis for the medicinal use of black pepper and piperine in gastrointestinal disorders.

PubMed

Mehmood, Malik Hassan; Gilani, Anwarul Hassan

2010-10-01

Dried fruits of Piper nigrum (black pepper) are commonly used in gastrointestinal disorders. The aim of this study was to rationalize the medicinal use of pepper and its principal alkaloid, piperine, in constipation and diarrhea using in vitro and in vivo assays. When tested in isolated guinea pig ileum, the crude extract of pepper (Pn.Cr) (1–10 mg/mL) and piperine (3–300 μM) caused a concentration-dependent and atropine-sensitive stimulant effect. In rabbit jejunum, Pn.Cr (0.01–3.0 mg/mL) and piperine (30–1,000 μM) relaxed spontaneous contractions, similar to loperamide and nifedipine. The relaxant effect of Pn.Cr and piperine was partially inhibited in the presence of naloxone (1 μM) similar to that of loperamide, suggesting the naloxone-sensitive effect in addition to the Ca(2+) channel blocking (CCB)-like activity, which was evident by its relaxant effect on K+ (80 mM)-induced contractions. The CCB activity was confirmed when pretreatment of the tissue with Pn.Cr (0.03–0.3 mg/mL) or piperine (10–100 μM) caused a rightward shift in the concentration–response curves of Ca(2+), similar to loperamide and nifedipine. In mice, Pn.Cr and piperine exhibited a partially atropine-sensitive laxative effect at lower doses, whereas at higher doses it caused antisecretory and antidiarrheal activities that were partially inhibited in mice pretreated with naloxone (1.5 mg/kg), similar to loperamide. This study illustrates the presence of spasmodic (cholinergic) and antispasmodic (opioid agonist and Ca(2+) antagonist) effects, thus providing the possible explanation for the medicinal use of pepper and piperine in gastrointestinal motility disorders.

Optimisation of a Naviglio-assisted extraction followed by determination of piperine content in Piper longum extracts.

PubMed

Gigliarelli, Giulia; Pagiotti, Rita; Persia, Diana; Marcotullio, Maria Carla

2017-01-01

Studies were made to increase the yield of piperine extraction using Naviglio Extractor® solid-liquid dynamic extractor (SLDE) from fruits of Piper longum. The effects of ratio w/v were investigated and optimised for the best method. The maximum yield of piperine (317.7 mg/g) from P. longum fruits was obtained in SLDE 1:50 ethanol extract. Extraction yields of piperine obtained from Soxhlet extraction, decotion (International Organization for Standardization) and conventional maceration extraction methods were found to be 233.7, 231.8 and 143.6 mg/g, respectively. The results of the present study indicated that Naviglio Extractor® is an effective technique for the extraction of piperine from long pepper.

In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression

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

Han Yi; Chin Tan, Theresa May; Lim, Lee-Yong

2008-08-01

Piperine, a major component of black pepper, is used as spice and nutrient enhancer. The purpose of the present study was to evaluate the effects of acute and prolonged piperine exposure on cellular P-gp expression and function in vitro and in vivo. Piperine at concentrations ranging from 10 to 100 {mu}M, determined by MTT assay to be non-cytotoxic, was observed to inhibit P-gp mediated efflux transport of [{sup 3}H]-digoxin across L-MDR1 and Caco-2 cell monolayers. The acute inhibitory effect was dependent on piperine concentration, with abolishment of [{sup 3}H]-digoxin polarized transport attained at 50 {mu}M of piperine. In contrast, prolongedmore » (48 and 72 h) co-incubation of Caco-2 cell monolayers with piperine (50 and 100 {mu}M) increased P-gp activity through an up-regulation of cellular P-gp protein and MDR1 mRNA levels. The up-regulated protein was functionally active, as demonstrated by a higher degree of [{sup 3}H]-digoxin efflux across the cell monolayers, but the induction was readily reversed by the removal of the spice from the culture medium. Peroral administration of piperine at the dose of 112 {mu}g/kg body weight/day to male Wistar rats for 14 consecutive days also led to increased intestinal P-gp levels. However, there was a concomitant reduction in the rodent liver P-gp although the kidney P-gp level was unaffected. Our data suggest that caution should be exercised when piperine is to be co-administered with drugs that are P-gp substrates, particularly for patients whose diet relies heavily on pepper.« less

Compound Specific Extraction of Camptothecin from Nothapodytes nimmoniana and Piperine from Piper nigrum Using Accelerated Solvent Extractor

PubMed Central

Upadhya, Vinayak; Pai, Sandeep R.; Sharma, Ajay K.; Hegde, Harsha V.; Kholkute, Sanjiva D.; Joshi, Rajesh K.

2014-01-01

Effects of varying temperatures with constant pressure of solvent on extraction efficiency of two chemically different alkaloids were studied. Camptothecin (CPT) from stem of Nothapodytes nimmoniana (Grah.) Mabb. and piperine from the fruits of Piper nigrum L. were extracted using Accelerated Solvent Extractor (ASE). Three cycles of extraction for a particular sample cell at a given temperature assured complete extraction. CPT and piperine were determined and quantified by using a simple and efficient UFLC-PDA (245 and 343 nm) method. Temperature increased efficiency of extraction to yield higher amount of CPT, whereas temperature had diminutive effect on yield of piperine. Maximum yield for CPT was achieved at 80°C and for piperine at 40°C. Thus, the study determines compound specific extraction of CPT from N. nimmoniana and piperine from P. nigrum using ASE method. The present study indicates the use of this method for simple, fast, and accurate extraction of the compound of interest. PMID:24527258

Spices for Prevention and Treatment of Cancers

PubMed Central

Zheng, Jie; Zhou, Yue; Li, Ya; Xu, Dong-Ping; Li, Sha; Li, Hua-Bin

2016-01-01

Spices have been widely used as food flavorings and folk medicines for thousands of years. Numerous studies have documented the antioxidant, anti-inflammatory and immunomodulatory effects of spices, which might be related to prevention and treatment of several cancers, including lung, liver, breast, stomach, colorectum, cervix, and prostate cancers. Several spices are potential sources for prevention and treatment of cancers, such as Curcuma longa (tumeric), Nigella sativa (black cumin), Zingiber officinale (ginger), Allium sativum (garlic), Crocus sativus (saffron), Piper nigrum (black pepper) and Capsicum annum (chili pepper), which contained several important bioactive compounds, such as curcumin, thymoquinone, piperine and capsaicin. The main mechanisms of action include inducing apoptosis, inhibiting proliferation, migration and invasion of tumors, and sensitizing tumors to radiotherapy and chemotherapy. This review summarized recent studies on some spices for prevention and treatment of cancers, and special attention was paid to bioactive components and mechanisms of action. PMID:27529277

Spices for Prevention and Treatment of Cancers.

PubMed

Zheng, Jie; Zhou, Yue; Li, Ya; Xu, Dong-Ping; Li, Sha; Li, Hua-Bin

2016-08-12

Spices have been widely used as food flavorings and folk medicines for thousands of years. Numerous studies have documented the antioxidant, anti-inflammatory and immunomodulatory effects of spices, which might be related to prevention and treatment of several cancers, including lung, liver, breast, stomach, colorectum, cervix, and prostate cancers. Several spices are potential sources for prevention and treatment of cancers, such as Curcuma longa (tumeric), Nigella sativa (black cumin), Zingiber officinale (ginger), Allium sativum (garlic), Crocus sativus (saffron), Piper nigrum (black pepper) and Capsicum annum (chili pepper), which contained several important bioactive compounds, such as curcumin, thymoquinone, piperine and capsaicin. The main mechanisms of action include inducing apoptosis, inhibiting proliferation, migration and invasion of tumors, and sensitizing tumors to radiotherapy and chemotherapy. This review summarized recent studies on some spices for prevention and treatment of cancers, and special attention was paid to bioactive components and mechanisms of action.

Characterization of capsaicin synthase and identification of its gene (csy1) for pungency factor capsaicin in pepper (Capsicum sp.)

PubMed Central

Prasad, B. C. Narasimha; Kumar, Vinod; Gururaj, H. B.; Parimalan, R.; Giridhar, P.; Ravishankar, G. A.

2006-01-01

Capsaicin is a unique alkaloid of the plant kingdom restricted to the genus Capsicum. Capsaicin is the pungency factor, a bioactive molecule of food and of medicinal importance. Capsaicin is useful as a counterirritant, antiarthritic, analgesic, antioxidant, and anticancer agent. Capsaicin biosynthesis involves condensation of vanillylamine and 8-methyl nonenoic acid, brought about by capsaicin synthase (CS). We found that CS activity correlated with genotype-specific capsaicin levels. We purified and characterized CS (≈35 kDa). Immunolocalization studies confirmed that CS is specifically localized to the placental tissues of Capsicum fruits. Western blot analysis revealed concomitant enhancement of CS levels and capsaicin accumulation during fruit development. We determined the N-terminal amino acid sequence of purified CS, cloned the CS gene (csy1) and sequenced full-length cDNA (981 bp). The deduced amino acid sequence of CS from full-length cDNA was 38 kDa. Functionality of csy1 through heterologous expression in recombinant Escherichia coli was also demonstrated. Here we report the gene responsible for capsaicin biosynthesis, which is unique to Capsicum spp. With this information on the CS gene, speculation on the gene for pungency is unequivocally resolved. Our findings have implications in the regulation of capsaicin levels in Capsicum genotypes. PMID:16938870

Anticancer Properties of Capsaicin Against Human Cancer.

PubMed

Clark, Ruth; Lee, Seong-Ho

2016-03-01

There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity. Capsaicin is a bioactive phytochemical abundant in red and chili peppers. While the preponderance of the data strongly indicates significant anticancer benefits of capsaicin, more information to highlight molecular mechanisms of its action is required to improve our knowledge to be able to propose a potential therapeutic strategy for use of capsaicin against cancer. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. In this review article, we highlight multiple molecular targets responsible for the anticancer mechanism of capsaicin. In addition, we deal with the benefits of combinational use of capsaicin with other dietary or chemotherapeutic compounds, focusing on synergistic anticancer activities. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Capsaicin and arterial hypertensive crisis.

PubMed

Patanè, Salvatore; Marte, Filippo; La Rosa, Felice Carmelo; La Rocca, Roberto

2010-10-08

Chili peppers are rich in capsaicin. The potent vasodilator calcitonin gene-related peptide (CGRP) is stored in a population of C-fiber afferents that are sensitive to capsaicin. CGRP and peptides released from cardiac C fibers have a beneficial effect in myocardial ischemia and reperfusion. It has been reported that capsaicin pretreatment can deplete cardiac C-fiber peptide stores. Furthermore, it has also been reported that capsaicin-treated pigs have significantly increased mean arterial blood pressure compared with controls, and that the decrease in CGRP synthesis and release contributes to the elevated blood pressure. A case has also been reported of an arterial hypertensive crisis in a patient with a large ingestion of peppers and chili peppers the day before. We present a case of an arterial hypertensive crisis in a 19-year-old Italian man with an abundant ingestion of peppers and of chili peppers the preceding day. This case describes an unusual pattern of arterial hypertensive crisis due to capsaicin. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.

Efficient modulation of γ-aminobutyric acid type A receptors by piperine derivatives.

PubMed

Schöffmann, Angela; Wimmer, Laurin; Goldmann, Daria; Khom, Sophia; Hintersteiner, Juliane; Baburin, Igor; Schwarz, Thomas; Hintersteininger, Michael; Pakfeifer, Peter; Oufir, Mouhssin; Hamburger, Matthias; Erker, Thomas; Ecker, Gerhard F; Mihovilovic, Marko D; Hering, Steffen

2014-07-10

Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates γ-aminobutyric acid type A receptors (GABAAR). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced chloride current modulation (IGABA-max = 1673% ± 146%, EC50 = 51.7 ± 9.5 μM), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 ± 1.8 μM, IGABA-max = 760% ± 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABAAR modulators.

Antifungal and Antiaflatoxigenic Methylenedioxy-Containing Compounds and Piperine-Like Synthetic Compounds

PubMed Central

Moon, Young-Sun; Choi, Won-Sik; Park, Eun-Sil; Bae, In Kyung; Choi, Sung-Deuk; Paek, Ockjin; Kim, Sheen-Hee; Chun, Hyang Sook; Lee, Sung-Eun

2016-01-01

Twelve methylenedioxy-containing compounds including piperine and 10 piperine-like synthetic compounds were assessed to determine their antifungal and antiaflatoxigenic activities against Aspergillus flavus ATCC 22546 in terms of their structure–activity relationships. Piperonal and 1,3-benzodioxole had inhibitory effects against A. flavus mycelial growth and aflatoxin B1 production up to a concentration of 1000 μg/mL. Ten piperine-like synthetic compounds were synthesized that differed in terms of the carbon length in the hydrocarbon backbone and the presence of the methylenedioxy moiety. In particular, 1-(2-methylpiperidin-1-yl)-3-phenylprop-2-en-1-one had potent antifungal and antiaflatoxigenic effects against A. flavus up to a concentration of 1 μg/mL. This synthetic compound was remarkable because the positive control thiabendazole had no inhibitory effect at this concentration. Reverse transcription-PCR analysis showed that five genes involved in aflatoxin biosynthesis pathways were down-regulated in A. flavus, i.e., aflD, aflK, aflQ, aflR, and aflS; therefore, the synthetic compound inhibited aflatoxin production by down-regulating these genes. PMID:27537912

Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch

PubMed Central

Anand, P.; Bley, K.

2011-01-01

Summary Topical capsaicin formulations are used for pain management. Safety and modest efficacy of low-concentration capsaicin formulations, which require repeated daily self-administration, are supported by meta-analyses of numerous studies. A high-concentration capsaicin 8% patch (Qutenza™) was recently approved in the EU and USA. A single 60-min application in patients with neuropathic pain produced effective pain relief for up to 12 weeks. Advantages of the high-concentration capsaicin patch include longer duration of effect, patient compliance, and low risk for systemic effects or drug–drug interactions. The mechanism of action of topical capsaicin has been ascribed to depletion of substance P. However, experimental and clinical studies show that depletion of substance P from nociceptors is only a correlate of capsaicin treatment and has little, if any, causative role in pain relief. Rather, topical capsaicin acts in the skin to attenuate cutaneous hypersensitivity and reduce pain by a process best described as ‘defunctionalization’ of nociceptor fibres. Defunctionalization is due to a number of effects that include temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fibre terminals. Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms, including altered expression of the capsaicin receptor TRPV1 or other key ion channels in affected or intact adjacent peripheral nociceptive nerve fibres, aberrant re-innervation, and collateral sprouting, all of which are defunctionalized by topical capsaicin. Evidence suggests that the utility of topical capsaicin may extend beyond painful peripheral neuropathies. PMID:21852280

In vitro blood-brain barrier permeability predictions for GABAA receptor modulating piperine analogs.

PubMed

Eigenmann, Daniela Elisabeth; Dürig, Carmen; Jähne, Evelyn Andrea; Smieško, Martin; Culot, Maxime; Gosselet, Fabien; Cecchelli, Romeo; Helms, Hans Christian Cederberg; Brodin, Birger; Wimmer, Laurin; Mihovilovic, Marko D; Hamburger, Matthias; Oufir, Mouhssin

2016-06-01

The alkaloid piperine from black pepper (Piper nigrum L.) and several synthetic piperine analogs were recently identified as positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors. In order to reach their target sites of action, these compounds need to enter the brain by crossing the blood-brain barrier (BBB). We here evaluated piperine and five selected analogs (SCT-66, SCT-64, SCT-29, LAU397, and LAU399) regarding their BBB permeability. Data were obtained in three in vitro BBB models, namely a recently established human model with immortalized hBMEC cells, a human brain-like endothelial cells (BLEC) model, and a primary animal (bovine endothelial/rat astrocytes co-culture) model. For each compound, quantitative UHPLC-MS/MS methods in the range of 5.00-500ng/mL in the corresponding matrix were developed, and permeability coefficients in the three BBB models were determined. In vitro predictions from the two human BBB models were in good agreement, while permeability data from the animal model differed to some extent, possibly due to protein binding of the screened compounds. In all three BBB models, piperine and SCT-64 displayed the highest BBB permeation potential. This was corroborated by data from in silico prediction. For the other piperine analogs (SCT-66, SCT-29, LAU397, and LAU399), BBB permeability was low to moderate in the two human BBB models, and moderate to high in the animal BBB model. Efflux ratios (ER) calculated from bidirectional permeability experiments indicated that the compounds were likely not substrates of active efflux transporters. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus.

PubMed

Kumar, Ashwani; Khan, Inshad Ali; Koul, Surrinder; Koul, Jawahir Lal; Taneja, Subhash Chandra; Ali, Intzar; Ali, Furqan; Sharma, Sandeep; Mirza, Zahid Mehmood; Kumar, Manoj; Sangwan, Pyare Lal; Gupta, Pankaj; Thota, Niranjan; Qazi, Ghulam Nabi

2008-06-01

Evaluation of novel synthetic analogues of piperine as inhibitors of multidrug efflux pump NorA of Staphylococcus aureus. A library of piperine-derived compounds was evaluated for their potential to inhibit ethidium bromide efflux in NorA-overexpressing S. aureus SA 1199B. The active compounds were then individually combined with ciprofloxacin to study the potentiation of ciprofloxacin's activity. Based on the efflux inhibition assay, a library of 200 compounds was screened. Three piperine analogues, namely SK-20, SK-56 and SK-29, were found to be the most potent inhibitors of the NorA efflux pump. These inhibitors acted in a synergistic manner with ciprofloxacin, by substantially increasing its activity against both NorA-overexpressing and wild-type S. aureus isolates. These analogues were 2- to 4-fold more potent than piperine at a significantly lower minimal effective concentration. Furthermore, these inhibitors also significantly suppressed the in vitro emergence of ciprofloxacin-resistant S. aureus. A newly identified class of compounds derived from a natural amide, piperine, is more potent than the parent molecule in potentiating the activity of ciprofloxacin through the inhibition of the NorA efflux pump. These molecules may prove useful in augmenting the antibacterial activities of fluoroquinolones in a clinical setting.

Piperine treatment suppresses Helicobacter pylori toxin entry in to gastric epithelium and minimizes β-catenin mediated oncogenesis and IL-8 secretion in vitro

PubMed Central

Tharmalingam, Nagendran; Park, Min; Lee, Min Ho; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong-Bae

2016-01-01

Helicobacter pylori related gastric cancer initiation has been studied widely. The objective of our present study was to evaluate the effect of a single compound piperine on H. pylori infection and its anti-inflammatory and anti-cancer effects in vitro. Cytotoxicity was tested by Ez-cytox cell viability assay kit. Effects of piperine on H. pylori toxin gene expression and IL-8 expression in mammalian cells during infection were assessed by RT-PCR. Effects of piperine on toxin entry into host cells, E-cadherin cleavage by H. pylori, and the changes in H. pylori mediated β-catenin expression and IL-8 secretion were determined by immunoblotting. Piperine treatment restrained the entry of CagA and VacA into AGS cells. Piperine administration in H. pylori infection reduced E-cadherin cleavage in stomach epithelium. In addition, H. pylori induced β-catenin up-regulation was reduced. Piperine administration impaired IL-8 secretion in H. pylori-infected gastric epithelial cells. As we reported previously piperine restrained H. pylori motility. The possible reason behind the H. pylori inhibition mechanism of piperine could be the dwindled motility, which weakened H. pylori adhesion to gastric epithelial cells. The reduced adhesion decreased the toxin entry thereby secreting less amount of IL-8. In addition, piperine treatment suppressed H. pylori protease led to reduction of E-cadherin cleavage and β-catenin expression resulting in diminished β-catenin translocation into the nucleus thus decreasing the risk of oncogenesis. To our knowledge, this is the preliminary report of piperine mediated H. pylori infection control on gastric epithelial cells in-vitro. PMID:27158376

Efficient Modulation of γ-Aminobutyric Acid Type A Receptors by Piperine Derivatives

PubMed Central

2014-01-01

Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates γ-aminobutyric acid type A receptors (GABAAR). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were expressed in Xenopus laevis oocytes. Structure–activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced chloride current modulation (IGABA-max = 1673% ± 146%, EC50 = 51.7 ± 9.5 μM), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 ± 1.8 μM, IGABA-max = 760% ± 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABAAR modulators. PMID:24905252

GABAA receptor activity modulating piperine analogs: In vitro metabolic stability, metabolite identification, CYP450 reaction phenotyping, and protein binding.

PubMed

Zabela, Volha; Hettich, Timm; Schlotterbeck, Götz; Wimmer, Laurin; Mihovilovic, Marko D; Guillet, Fabrice; Bouaita, Belkacem; Shevchenko, Bénédicte; Hamburger, Matthias; Oufir, Mouhssin

2018-01-01

In a screening of natural products for allosteric modulators of GABA A receptors (γ-aminobutyric acid type A receptor), piperine was identified as a compound targeting a benzodiazepine-independent binding site. Given that piperine is also an activator of TRPV1 (transient receptor potential vanilloid type 1) receptors involved in pain signaling and thermoregulation, a series of piperine analogs were prepared in several cycles of structural optimization, with the aim of separating GABA A and TRPV1 activating properties. We here investigated the metabolism of piperine and selected analogs in view of further cycles of lead optimization. Metabolic stability of the compounds was evaluated by incubation with pooled human liver microsomes, and metabolites were analyzed by UHPLC-Q-TOF-MS. CYP450 isoenzymes involved in metabolism of compounds were identified by reaction phenotyping with Silensomes™. Unbound fraction in whole blood was determined by rapid equilibrium dialysis. Piperine was the metabolically most stable compound. Aliphatic hydroxylation, and N- and O-dealkylation were the major routes of oxidative metabolism. Piperine was exclusively metabolized by CYP1A2, whereas CYP2C9 contributed significantly in the oxidative metabolism of all analogs. Extensive binding to blood constituents was observed for all compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation.

PubMed

Hu, Donghua; Wang, Yuguang; Chen, Zhiwu; Ma, Zengchun; You, Qing; Zhang, Xianxie; Liang, Qiande; Tan, Hongling; Xiao, Chengrong; Tang, Xianglin; Gao, Yue

2015-07-01

Inflammatory bowel disease (IBD) is associated with chronic inflammation of the intestinal tract. Piperine (1-peperoylpiperidine), the primary lipophilic component in black pepper (Piper nigrum) and long pepper (Piper longum), has been reported to be effective for anti-inflammatory. Rencently, several ethnopharmacological purity compounds, such as baicalin and artemisinin, are reported to have potentially therapeutic role in treating IBD. In the present study, the effects of piperine on pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in IBD were investigated. LS174T cells and C57BL/6J mice were treated by the piperine. Gene expressions were analyzed by real-time PCR, Western blot analysis, transient transfections assay and histological analysis. Data indicated that treatment of LS174T cells with piperine markedly increased both CYP3A4 and PXR mRNA and protein. Transient transfection experiments indicated that transcriptional activation of the CYP3A4 gene via piperine was PXR-dependent. Data show that pre-administration of piperine decreased clinical hallmarks of colitis in DSS-treated PXR mice as measured by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. Inflammatory mediators (CCR2, ICAM-1, IL-1β, IL-6, IL-10, iNOS, MCP-1, and TNFα) after DSS treatment were significantly decreased in mice pretreated with piperine but corresponding conditions did not occur in mice with down-regulation of PXR by small interfering RNA (siRNA). Piperine is a potential agonist of PXR and an inducer of PXR, which may induce CYP3A4 gene expression at the mRNA and protein levels. These results establish that piperine may contribute to prevention or reduction of colonic inflammation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The effect of topical piperine combined with narrowband UVB on vitiligo treatment: A clinical trial study.

PubMed

Shafiee, Anoosh; Hoormand, Mahmood; Shahidi-Dadras, Mohammad; Abadi, Alireza

2018-05-21

Vitiligo is the most common acquired hypopigmentary disease in the community. Piperine as an herbal extract derived from black pepper has strong impact on the melanocyte proliferation and adverse side effects less than synthetic drugs such as corticosteroids. For the first time, this study was aimed to evaluate the effect of topical piperine combined with narrowband ultraviolet B (NB-UVB) on vitiligo treatment. In this double-blind clinical trial, 63 patients with facial vitiligo were randomly divided into 2 groups: treated with piperine (case) and placebo (control). Also, both groups received NB-UVB phototherapy every other day for 3 months. In the case group, 10 patients have burning sensation on their skin areas (p value = .002). Also, redness of the treated areas was observed in 6 patients (p value = .028). Both side effects were temporary. Regarding repigmentation at time intervals of 1, 2, and 3 months after treatment, its level in the case group was significantly higher than the control group (p value < .001). Based on our findings, the combination therapy with NB-UVB/topical piperine has more influence on facial vitiligo than that of NB-UVB alone. It could be concluded that the simultaneous use of NB-UVB and topical piperine has a remarkable effect on treatment of vitiligo. Copyright © 2018 John Wiley & Sons, Ltd.

Proposed structural basis of interaction of piperine and related compounds with monoamine oxidases.

PubMed

Rahman, Taufiq; Rahmatullah, Mohammed

2010-01-15

Several studies have revealed piperine and a few related compounds as potent inhibitors of monoamine oxidases without delineating the underlying mechanism. Using in silico modelling, we propose a structural basis of such activity by showing that these compounds can successfully dock into the inhibitor binding pockets of human monoamine oxidase isoforms with predicted affinities comparable to some known inhibitors. The results therefore suggest that piperine can be a promising lead for developing novel monoamine oxidase inhibitors. Copyright 2009 Elsevier Ltd. All rights reserved.

Current Understanding of Antiobesity Property of Capsaicin

PubMed Central

Narang, Nithida; Jiraungkoorskul, Wannee; Jamrus, Parinda

2017-01-01

The capsaicin is an ingredient that we normally mix in food in many cultural cuisines even in fresh and dried production. Because of its anticancer, anticholesterolemic, antidiabetic, antihypertensive, anti-inflammatory, antimicrobial, and antioxidant properties, capsaicin is used worldwide. Moreover, capsaicin is also used for the protection of cardiovascular and hepatic diseases. The electronic databases PubMed, Scopus, Web of Science, Google Scholar, and ScienceDirect were searched since 2000 to present for antiobesity term. This review article is provided the update information about the antiobesity property and mechanism of capsaicin for further researches. PMID:28503049

The larvicidal effects of black pepper (Piper nigrum L.) and piperine against insecticide resistant and susceptible strains of Anopheles malaria vector mosquitoes.

PubMed

Samuel, Michael; Oliver, Shüné V; Coetzee, Maureen; Brooke, Basil D

2016-04-26

Insecticide resistance carries the potential to undermine the efficacy of insecticide based malaria vector control strategies. Therefore, there is an urgent need for new insecticidal compounds. Black pepper (dried fruit from the vine, Piper nigrum), used as a food additive and spice, and its principal alkaloid piperine, have previously been shown to have larvicidal properties. The aim of this study was to investigate the larvicidal effects of ground black pepper and piperine against third and fourth instar Anopheles larvae drawn from several laboratory-reared insecticide resistant and susceptible strains of Anopheles arabiensis, An. coluzzii, An. gambiae, An. quadriannulatus and An. funestus. Larvae were fed with mixtures of standard larval food and either ground black pepper or piperine in different proportions. Mortality was recorded 24 h after black pepper and 48 h after piperine were applied to the larval bowls. Black pepper and piperine mixtures caused high mortality in the An. gambiae complex strains, with black pepper proving significantly more toxic than piperine. The An. funestus strains were substantially less sensitive to black pepper and piperine which may reflect a marked difference in the feeding habits of this species compared to that of the Gambiae complex or a difference in food metabolism as a consequence of differences in breeding habitat between species. Insecticide resistant and susceptible strains by species proved equally susceptible to black pepper and piperine. It is concluded that black pepper shows potential as a larvicide for the control of certain malaria vector species.

CAPSAICIN: ITS BIOLOGICAL ACTIVITIES AND IN SILICO TARGET FISHING.

PubMed

Akhtar, Fahad; Muhammad Sharif, Hajra; Arshad Mallick, Muhammad; Zahoor, Fareeha; Abdulmalik, Attiya; Baig, Warda; Shujaat, Nodia; Gul, Sundas; Bibi, Gulfam; Ramzan, Rahdia; Murtaza, Ghulam

2017-03-01

Capsicum annuum L. is a rich source of capsaicin, an alkaloid, which is a very pungent compound. Due to ever growing need of capsaicin, an extensive research on its efficient cultivation as well as chemical synthesis is underway. Owing to the pungent nature of capsaicin, its analogous molecules without pungent effect are being explored. The objective of this descriptive review is to comprehensively present the updates on the bioactivities of capsaicin. Additionally, the in silico target fishing approach has been used to identify the possible protein targets of capsaicin. This article will definitely provide future perspectives of research on capsaicin.

Mediation of cholino-piperine like receptors by extracts of Piper nigrum induces melanin dispersion in Rana tigerina tadpole melanophores.

PubMed

Sajid, Mohammed; Ali, Sharique A

2011-08-01

The present study was carried out to determine the effects of lyophilized dried fruit extracts of Piper nigrum and pure piperine on the tadpole melanophores of frog Rana tigerina which offer excellent in vitro opportunities for studying the effects of pharmacological and pharmaceutical agents. The nature of specific cellular receptors present on the neuro-melanophore junction and their involvement in pigmentary responses has been explored. Effects of lyophilized extracts of P. nigrum and pure piperine were studied on the isolated tail melanophores of tadpoles of the frog R. tigerina as per the modified method. The extract of P. nigrum and its active ingredient piperine caused significant melanin dispersal responses leading to darkening of the tail melanophores, which were completely antagonized by atropine and hyoscine. These per se melanin dispersal effects were also found to be markedly potentiated by neostigmine an anticholinesterase agent. It appears that the melanin dispersal effects of the extracts of P. nigrum and pure piperine leading to skin darkening are mediated by cholinergic muscarinic or piperine-like receptors having similar properties.

Integrating TRPV1 Receptor Function with Capsaicin Psychophysics

PubMed Central

Smutzer, Gregory; Devassy, Roni K.

2016-01-01

Capsaicin is a naturally occurring vanilloid that causes a hot, pungent sensation in the human oral cavity. This trigeminal stimulus activates TRPV1 receptors and stimulates an influx of cations into sensory cells. TRPV1 receptors function as homotetramers that also respond to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Kinase-mediated phosphorylation of TRPV1 leads to increased sensitivity to both chemical and thermal stimuli. In contrast, desensitization occurs via a calcium-dependent mechanism that results in receptor dephosphorylation. Human psychophysical studies have shown that capsaicin is detected at nanomole amounts and causes desensitization in the oral cavity. Psychophysical studies further indicate that desensitization can be temporarily reversed in the oral cavity if stimulation with capsaicin is resumed at short interstimulus intervals. Pretreatment of lingual epithelium with capsaicin modulates the perception of several primary taste qualities. Also, sweet taste stimuli may decrease the intensity of capsaicin perception in the oral cavity. In addition, capsaicin perception and hedonic responses may be modified by diet. Psychophysical studies with capsaicin are consistent with recent findings that have identified TRPV1 channel modulation by phosphorylation and interactions with membrane inositol phospholipids. Future studies will further clarify the importance of capsaicin and its receptor in human health and nutrition. PMID:26884754

In Silico and In Vitro Investigation of the Piperine's Male Contraceptive Effect: Docking and Molecular Dynamics Simulation Studies in Androgen-Binding Protein and Androgen Receptor.

PubMed

Chinta, Gopichand; Ramya Chandar Charles, Mariasoosai; Klopčič, Ivana; Sollner Dolenc, Marija; Periyasamy, Latha; Selvaraj Coumar, Mohane

2015-07-01

Understanding the molecular mechanism of action of traditional medicines is an important step towards developing marketable drugs from them. Piperine, an active constituent present in the Piper species, is used extensively in Ayurvedic medicines (practiced on the Indian subcontinent). Among others, piperine is known to possess a male contraceptive effect; however, the molecular mechanism of action for this effect is not very clear. In this regard, detailed docking and molecular dynamics simulation studies of piperine with the androgen-binding protein and androgen receptors were carried out. Androgen receptors control male sexual behavior and fertility, while the androgen-binding protein binds testosterone and maintains its concentration at optimal levels to stimulate spermatogenesis in the testis. It was found that piperine docks to the androgen-binding protein, similar to dihydrotestosterone, and to androgen receptors, similar to cyproterone acetate (antagonist). Also, the piperine-androgen-binding protein and piperine-androgen receptors interactions were found to be stable throughout 30 ns of molecular dynamics simulation. Further, two independent simulations for 10 ns each also confirmed the stability of these interactions. Detailed analysis of the piperine-androgen-binding protein interactions shows that piperine interacts with Ser42 of the androgen-binding protein and could block the binding with its natural ligands dihydrotestosterone/testosterone. Moreover, piperine interacts with Thr577 of the androgen receptors in a manner similar to the antagonist cyproterone acetate. Based on the in silico results, piperine was tested in the MDA-kb2 cell line using the luciferase reporter gene assay and was found to antagonize the effect of dihydrotestosterone at nanomolar concentrations. Further detailed biochemical experiments could help to develop piperine as an effective male contraceptive agent in the future. Georg Thieme Verlag KG Stuttgart · New York.

Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies

PubMed Central

Jin, Xin; Zhang, Zhen-hai; Sun, E; Tan, Xiao-bin; Li, Song-lin; Cheng, Xu-dong; You, Ming; Jia, Xiao-bin

2013-01-01

Background 20(S)-protopanaxadiol (PPD), similar to several other anticancer agents, has low oral absorption and is extensively metabolized. These factors limit the use of PPD for treatment of human diseases. Methods In this study, we used cubic nanoparticles containing piperine to improve the oral bioavailability of PPD and to enhance its absorption and inhibit its metabolism. Cubic nanoparticles loaded with PPD and piperine were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel and verified using transmission electron microscopy and differential scanning calorimetry. We evaluated the in vitro release of PPD from these nanoparticles and its absorption across the Caco-2 cell monolayer model, and subsequently, we examined the bioavailability and metabolism of PPD and its nanoparticles in vivo. Results The in vitro release of PPD from these nanoparticles was less than 5% at 12 hours. PPD-cubosome and PPD-cubosome loaded with piperine (molar ratio PPD/piperine, 1:3) increased the apical to basolateral permeability values of PPD across the Caco-2 cell monolayer from 53% to 64%, respectively. In addition, the results of a pharmacokinetic study in rats showed that the relative bioavailabilities of PPD-cubosome [area under concentration–time curve (AUC)0–∞] and PPD-cubosome containing piperine (AUC0–∞) compared to that of raw PPD (AUC0–∞) were 166% and 248%, respectively. Conclusion The increased bioavailability of PPD-cubosome loaded with piperine is due to an increase in absorption and inhibition of metabolism of PPD by cubic nanoparticles containing piperine rather than because of improved release of PPD. The cubic nanoparticles containing piperine may be a promising oral carrier for anticancer drugs with poor oral absorption and that undergo extensive metabolism by cytochrome P450. PMID:23426652

Enhanced Oral Bioavailability of Domperidone with Piperine in Male Wistar Rats: Involvement of CYP3A1 and P-gp Inhibition.

PubMed

Athukuri, Bhargavi Latha; Neerati, Prasad

2017-01-01

Domperidone is a commonly used antiemetic drug. The oral bioavailability of domperidone is very low due to its rapid first pass metabolism in the intestine and liver. Piperine, the main alkaloid present in black pepper has been reported to show inhibitory effects on Cytochrome P-450 (CYP-450) enzymes and P-glycoprotein (P-gp). In the present study we investigated the effect of piperine pretreatment on the intestinal transport and oral bioavailability of domperidone in male Wistar rats. The intestinal transport of domperidone was evaluated by an in-vitro non-everted sac method and in-situ single pass intestinal perfusion (SPIP) study. The oral pharmacokinetics of domperidone was evaluated by conducting oral bioavailability study in rats. A statistically significant improvement in apparent permeability (Papp) was observed in rats pretreated with piperine compared to the respective control group. The effective permeability (Peff) of domperidone was increased in the ileum of the piperine treated group. Following pretreatment with piperine, the peak plasma concentration (Cmax) and area under the concentration- time curve (AUC) were significantly increased. A significant decrease in time to reach maximum plasma concentration (Tmax), clearance and elimination rate constant (Kel) was observed in rats pretreated with piperine. Piperine enhanced the oral bioavailability of domperidone by inhibiting CYP3A1 and P-gp in rats. This observation suggests the possibility that the combination of piperine with other CYP3A4 and P-gp dual substrates may also improve bioavailability. Further clinical studies are recommended to verify this drug interaction in human volunteers and patients. 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.

Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

PubMed

Leung, Felix W

2008-07-04

This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral

Piperine Promotes Glucose Uptake through ROS-Dependent Activation of the CAMKK/AMPK Signaling Pathway in Skeletal Muscle.

PubMed

Maeda, Ayumi; Shirao, Takeshi; Shirasaya, Daishi; Yoshioka, Yasukiyo; Yamashita, Yoko; Akagawa, Mitsugu; Ashida, Hitoshi

2018-06-01

The prevalence of type 2 diabetes mellitus (T2DM) is increasing yearly worldwide. Glycemic control is the basis for the treatment of T2DM, as it can prevent the progress of associated complications. Spices possess various health beneficial effects on humans. The aim of this study is to search for spices that can promote glucose uptake and to elucidate the underlying molecular mechanism(s). Among 24 spice extracts, the extracts from black pepper and white pepper significantly increase glucose uptake in L6 myotubes. Piperine is found to be the active compound in these extracts. Treatment of myotubes with piperine induces the translocation of glucose transporter 4 (GLUT4) to the plasma membrane by phosphorylation of AMP-activated protein kinase (AMPK). Piperine increases the intracellular Ca 2+ level and reactive oxygen species (ROS) generation through transient receptor potential vanilloid channel 1 (TRPV1), followed by activation of Ca 2+ /calmodulin-dependent protein kinase kinase-beta (CaMKKβ) as the upstream events for AMPK phosphorylation. Furthermore, oral administration of piperine to Wistar rats at 0.01 and 0.1 mg kg -1 body weight decreases postprandial hyperglycemia accompanied by GLUT4 translocation and AMPK phosphorylation. Piperine in pepper prevents hyperglycemia by GLUT4 translocation through CaMKKβ/AMPK signaling via TRPV1-dependent increase in the intracellular Ca 2+ level and ROS generation. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Capsaicin-enriched diet ameliorates autoimmune neuritis in rats.

PubMed

Motte, Jeremias; Ambrosius, Björn; Grüter, Thomas; Bachir, Hussein; Sgodzai, Melissa; Pedreiturria, Xiomara; Pitarokoili, Kalliopi; Gold, Ralf

2018-04-24

Autoimmune neuropathies are common PNS disorders and effective treatment is challenging. Environmental influence and dietary components are known to affect the course of autoimmune diseases. Capsaicin as pungent component of chili-peppers is common in human nutrition. An influence of capsaicin on autoimmune diseases has been postulated. We tested capsaicin in the animal model of experimental autoimmune neuritis (EAN) in Lewis rat. Rats were immunized with P2-peptide and were treated with capsaicin in different preventive settings. Electrophysiological, histological, and molecular biological analyses of the sciatic nerve were performed to analyze T-cell and macrophage cell count, TRPV1, and cytokine expression. Moreover, FACS analyses including the intestinal immune system were executed. We observed an immunomodulatory effect of an early preventive diet-concept, where a physiological dosage of oral capsaicin was given 10 days before immunization in EAN. A reduced inflammation of the sciatic nerve was significant detectable clinically, electrophysiologically (CMAPs reduced in control group p < 0.01; increase of nerve conduction blocks in control group p < 0.05), histologically (significant reduction of T-cells, macrophages and demyelination), and at cytokine level. In contrast, this therapeutic effect was missing with capsaicin given from the day of immunization onwards. As possible underlying mechanism, we were able to show changes in the expression of the capsaicin receptor in the sciatic nerve and the small intestine, as well as altered immune cell populations in the small intestine. This is the first report about the immunomodulatory effect of the common nutrient, capsaicin, in an experimental model for autoimmune neuropathies.

Piperine, a piperidine alkaloid from Piper nigrum re-sensitizes P-gp, MRP1 and BCRP dependent multidrug resistant cancer cells.

PubMed

Li, Sen; Lei, Yu; Jia, Yingjie; Li, Na; Wink, Michael; Ma, Yonggang

2011-12-15

Over-expression of P-gp, MRP1 and BCRP in tumor cells is one of the important mechanisms leading to multidrug resistance (MDR), which impairs the efficacy of chemotherapy. P-gp, MRP1 and BCRP are ABC (ATP-Binding Cassette) transporters, which can expel a variety of lipophilic anti-cancer drugs and protect tumor cells. During a screening of MDR reversal agents among alkaloids of various structural types, a piperidine alkaloid, piperine (a main piperidine alkaloid in Piper nigurm) was identified as an inhibitor. Piperine can potentiate the cytotoxicity of anti-cancer drugs in resistant sublines, such as MCF-7/DOX and A-549/DDP, which were derived from MCF-7 and A-549 cell lines. At a concentration of 50 μM piperine could reverse the resistance to doxorubicin 32.16 and 14.14 folds, respectively. It also re-sensitized cells to mitoxantrone 6.98 folds. In addition, long-term treatment of cells by piperine inhibits transcription of the corresponding ABC transporter genes. These results suggest that piperine can reverse MDR by multiple mechanisms and it may be a promising lead compound for future studies. Copyright © 2011 Elsevier GmbH. All rights reserved.

Electrostimulated Release of Neutral Drugs from Polythiophene Nanoparticles: Smart Regulation of Drug-Polymer Interactions.

PubMed

Puiggalí-Jou, Anna; Micheletti, Paolo; Estrany, Francesc; Del Valle, Luis J; Alemán, Carlos

2017-09-01

Poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles are loaded with curcumin and piperine by in situ emulsion polymerization using dodecyl benzene sulfonic acid both as a stabilizer and a doping agent. The loaded drugs affect the morphology, size, and colloidal stability of the nanoparticles. Furthermore, kinetics studies of nonstimulated drug release have evidenced that polymer···drug interactions are stronger for curcumin than for piperine. This observation suggests that drug delivery systems based on combination of the former drug with PEDOT are much appropriated to show an externally tailored release profile. This is demonstrated by comparing the release profiles obtained in presence and absence of electrical stimulus. Results indicate that controlled and time-programmed release of curcumin is achieved in a physiological medium by applying a negative voltage of -1.25 V to loaded PEDOT nanoparticles. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Incorporation of capsaicin in silicone coatings for enhanced antifouling performance

NASA Astrophysics Data System (ADS)

Reddy Jaggari, Karunakar; Zhang Newby, Bi-Min

2002-03-01

Successful use of capsaicin as insect and animal repellant propelled us to use it as a possible antifouling agent. Its non-toxic, non-biocidal, non-leaching properties make it a viable alternative to organotin compounds. In order to optimize the anti-fouling performance of the coating, silicone, the most effective foul-release marine coating, was chosen as the carrier. We have incorporated capsaicin into silicone coating, by both bulk entrapment and surface immobilization. Contact angle measurements on capsaicin-incorporated silicone exhibited an increase in wettability, owing to the presence of capsaicin. FTIR study further confirmed the incorporation of capsaicin in silicone. Bacterial attachment studies were conducted using lake Erie water. While bacteria liberally inhabited the control coating, their presence on the capsaicin-incorporated coating was found to be minimal. These preliminary studies indicate that capsaicin incorporated silicone could be a viable environment friendly alternative to currently used antifouling coatings.

Piperine, a component of black pepper, decreases eugenol-induced cAMP and calcium levels in non-chemosensory 3T3-L1 cells.

PubMed

Yoon, Yeo Cho; Kim, Sung-Hee; Kim, Min Jung; Yang, Hye Jeong; Rhyu, Mee-Ra; Park, Jae-Ho

2015-01-01

This study investigated the effects of an ethanol extract of black pepper and its constituent, piperine, on odorant-induced signal transduction in non-chemosensory cells. An ethanol extract of black pepper decreased eugenol-induced cAMP and calcium levels in preadipocyte 3T3-L1 cells with no toxicity. Phosphorylation of CREB (cAMP response element-binding protein) was down-regulated by the black pepper extract. The concentration (133.8 mg/g) and retention time (5.5 min) of piperine in the ethanol extract were quantified using UPLC-MS/MS. Pretreatment with piperine decreased eugenol-induced cAMP and calcium levels in 3T3-L1 cells. Piperine also decreased the phosphorylation of CREB, which is up-regulated by eugenol. These results suggest that piperine inhibits the eugenol-induced signal transduction pathway through modulation of cAMP and calcium levels and phosphorylation of CREB in non-chemosensory cells.

Capsaicin pre- and post-treatment on rat monocrotaline pneumotoxicity.

PubMed

Katzman, N J; Lai, Y L

2000-12-31

Monocrotaline (MCT) produces respiratory dysfunction, pulmonary hypertension (PH), and right ventricular hypertrophy (RVH) in rats. Tachykinins, such as substance P (SP) and neurokinin A (NKA), may mediate these effects. The purpose of this study was to investigate the length of tachykinin depletion (via capsaicin treatment) is needed to prevent (or attenuate) PH and/or RVH. Six groups of rats were injected subcutaneously with saline (3 ml/kg); capsaicin followed by saline or MCT (60 mg/kg); or MCT followed 7, 11, or 14 days later by capsaicin. Capsaicin (cumulative dose, 500 mg/kg) was given over a period of 4-5 days. Respiratory function, pulmonary vascular parameters, lung tachykinin levels, and tracheal neutral endopeptidase (NEP) activity were measured 21 days after MCT or saline injection. Capsaicin significantly decreased lung levels of SP but not NKA. Both capsaicin pretreatment and posttreatment blocked the following MCT-induced alterations: increases in lung SP and airway constriction; decreases in tracheal NEP activity and dynamic respiratory compliance. Administration of capsaicin before or 7 days after MCT blocked MCT-induced PH and RVH. The above data suggest that the early tachykinin-mediated airway dysfunction requires only transient elevated tachykinins, while progression of late tachykinin-mediated effects (PH and RVH) requires elevated tachykinins for more than one week.

Detection and modulation of capsaicin perception in the human oral cavity.

PubMed

Smutzer, Gregory; Jacob, Jeswin C; Tran, Joseph T; Shah, Darshan I; Gambhir, Shilpa; Devassy, Roni K; Tran, Eric B; Hoang, Brian T; McCune, Joseph F

2018-05-09

Capsaicin causes a burning or spicy sensation when this vanilloid compound comes in contact with trigeminal neurons of the tongue. This compound has low solubility in water, which presents difficulties in examining the psychophysical properties of capsaicin by standard aqueous chemosensory tests. This report describes a new approach that utilizes edible strips for delivering precise amounts of capsaicin to the human oral cavity for examining threshold and suprathreshold amounts of this irritant. When incorporated into pullulan-based edible strips, recognition thresholds for capsaicin occurred over a narrow range, with a mean value near 1 nmol. When incorporated into edible strips at suprathreshold amounts, capsaicin yielded robust intensity values that were readily measured in our subject population. Maximal capsaicin intensity was observed 20 s after strips dissolved on the tongue surface, and then decreased in intensity. Suprathreshold studies showed that complete blockage of nasal airflow diminished capsaicin perception in the oral cavity. Oral rinses with vanillin-linoleic acid emulsions decreased mean intensity values for capsaicin by approximately 75%, but only modestly affected recognition threshold values. Also, oral rinses with isointense amounts of aqueous sucrose and sucralose solutions decreased mean intensity values for capsaicin by approximately 50%. In addition, this decrease in capsaicin intensity following an oral rinse with sucrose was partially reversed by the sweet taste inhibitor lactisole. These results suggest that blockage of nasal airflow, vanillin, sucrose, and sucralose modulate capsaicin perception in the human oral cavity. The results further suggest a chemosensory link between receptor cells that detect sweet taste stimuli and trigeminal neurons that detect capsaicin. Copyright © 2018 Elsevier Inc. All rights reserved.

Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction

PubMed Central

Sun, Fang; Xiong, Shiqiang; Zhu, Zhiming

2016-01-01

Chili peppers have a long history of use for flavoring, coloring, and preserving food, as well as for medical purposes. The increased use of chili peppers in food is very popular worldwide. Capsaicin is the major pungent bioactivator in chili peppers. The beneficial effects of capsaicin on cardiovascular function and metabolic regulation have been validated in experimental and population studies. The receptor for capsaicin is called the transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is ubiquitously distributed in the brain, sensory nerves, dorsal root ganglia, bladder, gut, and blood vessels. Activation of TRPV1 leads to increased intracellular calcium signaling and, subsequently, various physiological effects. TRPV1 is well known for its prominent roles in inflammation, oxidation stress, and pain sensation. Recently, TRPV1 was found to play critical roles in cardiovascular function and metabolic homeostasis. Experimental studies demonstrated that activation of TRPV1 by capsaicin could ameliorate obesity, diabetes, and hypertension. Additionally, TRPV1 activation preserved the function of cardiometabolic organs. Furthermore, population studies also confirmed the beneficial effects of capsaicin on human health. The habitual consumption of spicy foods was inversely associated with both total and certain causes of specific mortality after adjustment for other known or potential risk factors. The enjoyment of spicy flavors in food was associated with a lower prevalence of obesity, type 2 diabetes, and cardiovascular diseases. These results suggest that capsaicin and TRPV1 may be potential targets for the management of cardiometabolic vascular diseases and their related target organs dysfunction. PMID:27120617

Intracolonic capsaicin stimulates colonic motility and defecation in conscious dogs.

PubMed

Hayashi, Keiichi; Shibata, Chikashi; Nagao, Munenori; Sato, Manabu; Kakyo, Masayuki; Kinouchi, Makoto; Saijo, Fumito; Miura, Koh; Ogawa, Hitoshi; Sasaki, Iwao

2010-06-01

The aim of this study was to investigate the effects of intracolonic capsaicin on colonic motility and defecation. The effects of capsaicin (1, 2, 5, and 10 mg) administrated into the proximal colon on ileocolonic motility and defecation were studied in neurally intact dogs with or without various antagonists (atropine, hexamethonium, ondansetron, propranolol, and FK224), dogs with extrinsic denervation of an ileocolonic segment, and dogs with enterically isolated ileocolonic loops equipped with strain gauge force transducers. Capsaicin at 5 and 10 mg evoked giant migrating contractions in a dose-independent manner, and it induced defecations with more than 90% probability in neurally intact dogs. These effects of capsaicin were abolished by atropine and hexamethonium. Ondansetron inhibited the capsaicin-induced increase in colonic motility but did not affect the induction of defecation. The other antagonists had no effect. In dogs with extrinsic denervation, capsaicin did not evoke giant migrating contractions in the colon but still induced defecation in 30-40% of experiments. In dogs with ileocolonic loops, capsaicin did not stimulate colonic motility nor induce defecation. These results indicate that intracolonic capsaicin causes giant migrating contractions and defecation. Intact extrinsic innervation, continuity of the colon, and intraluminal contents were considered necessary for this effect. Copyright 2010 Mosby, Inc. All rights reserved.

Tachykinin-independent activity of capsaicin on in-vitro lamb detrusor.

PubMed

Tucci, Paolo; Evandri, Maria Grazia; Bolle, Paola

2002-08-01

The capsicum alkaloid capsaicin is an afferent fibre exciter. In the vesical bladder, capsaicin acts by releasing peptides stored in afferent fibres. The aim of this work was to verify the activity of capsaicin on in-vitro lamb urinary bladder and to ascertain whether this alkaloid evokes peptide release. Capsaicin relaxed about 80% of the lamb detrusor muscle preparations tested and contracted about 20%. Whereas neurokinin A and substance P antagonists, administered alone or together, left the contractile responses to capsaicin unchanged, atropine and tetrodotoxin totally inhibited contraction. Ruthenium red and indometacin abolished contractions and relaxation. The substance P and neurokinin A antagonists and the NO-synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) left relaxation unchanged; conversely, the calcitonin gene-related peptide antagonist alpha h-CGRP (8-37) abolished this response. These results suggest that capsaicin relaxes lamb detrusor muscle not through tachykinins but by releasing CGRP from afferent fibres. Our observation that indometacin blocks the capsaicin response in in-vitro lamb urinary bladder also suggests a role of prostanoids.

Effects of capsaicin in the motor nerve.

PubMed

Pettorossi, V E; Bortolami, R; Della Torre, G; Brunetti, O

1994-08-01

The injection of capsaicin into the lateral gastrocnemius (LG) muscle of the rat induced an immediate and sustained reduction in the A delta and C components of the compound action potential (CAP) of the LG motor nerve. Conversely, the drug did not immediately affect the CAP wave belonging to fast-conducting fibers or the motor responses to LG nerve stimulation. It seems that capsaicin only affects the group III and IV afferents of LG nerve. However, a week after the injection the capsaicin also altered the motor responses, as shown by the threshold enhancement and amplitude reduction of the muscle twitch and by the decrease of the A alpha-beta CAP components. This late motor impairment was attributed to a central depression following a reduction of capsaicin-sensitive neuron input into the CNS. However, this motor effect was transient since the LG nerve regained the preinjection excitability level in a week and the muscle twitch amplitude reached the control value in a month.

Pharmacokinetics of Curcumin Diethyl Disuccinate, a Prodrug of Curcumin, in Wistar Rats.

PubMed

Bangphumi, Kunan; Kittiviriyakul, Chuleeporn; Towiwat, Pasarapa; Rojsitthisak, Pornchai; Khemawoot, Phisit

2016-12-01

Curcumin is the major bioactive component of turmeric, but has poor oral bioavailability that limits its clinical applications. To improve the in vitro solubility and alkaline stability, we developed a prodrug of curcumin by succinylation to obtain curcumin diethyl disuccinate, with the goal of improving the oral bioavailability of curcumin. The in vivo pharmacokinetic profile of curcumin diethyl disuccinate was compared with that of curcumin in male Wistar rats. Doses of curcumin 20 mg/kg intravenous or 40 mg/kg oral were used as standard regimens for comparison with the prodrug at equivalent doses in healthy adult rats. Blood, tissues, urine, and faeces were collected from time zero to 48 h after dosing to determine the prodrug level, curcumin level and a major metabolite by liquid chromatography-tandem spectrometry. The absolute oral bioavailability of curcumin diethyl disuccinate was not significantly improved compared with curcumin, with both compounds having oral bioavailability of curcumin less than 1 %. The major metabolic pathway of the prodrug was rapid hydrolysis to obtain curcumin, followed by glucuronidation. Interestingly, curcumin diethyl disuccinate gave superior tissue distribution with higher tissue to plasma ratio of curcumin and curcumin glucuronide in several organs after intravenous dosing at 1 and 4 h. The primary elimination route of curcumin glucuronide occurred via biliary and faecal excretion, with evidence of an entry into the enterohepatic circulation. Curcumin diethyl disuccinate did not significantly improve the oral bioavailability of curcumin due to first pass metabolism in the gastrointestinal tract. Further studies on reduction of first pass metabolism are required to optimise delivery of curcumin using a prodrug approach.

Bioavailability of curcumin and curcumin glucuronide in the central nervous system of mice after oral delivery of nano-curcumin.

PubMed

Szymusiak, Magdalena; Hu, Xiaoyu; Leon Plata, Paola A; Ciupinski, Paulina; Wang, Zaijie Jim; Liu, Ying

2016-09-10

Curcumin is a bioactive molecule extracted from Turmeric roots that has been recognized to possess a wide variety of important biological activities. Despite its great pharmacological activities, curcumin is highly hydrophobic, which results in poor bioavailability. We have formulated this hydrophobic compound into stable polymeric nanoparticles (nano-curcumin) to enhance its oral absorption. Pharmacokinetic analysis after oral delivery of nano-curcumin in mice demonstrated approximately 20-fold reduction in dose requirement when compared to unformulated curcumin to achieve comparable plasma and central nervous system (CNS) tissue concentrations. This investigation corroborated our previous study of curcumin functionality of attenuating opioid tolerance and dependence, which shows equivalent efficacy of low-dose (20mg/kg) nano-curcumin and high-dose (400mg/kg) pure curcumin in mice. Furthermore, the highly selective and validated liquid chromatography-mass spectrometry (LC-MS) method was developed to quantify curcumin glucuronide, the major metabolite of curcumin. The results suggest that the presence of curcumin in the CNS is essential for prevention and reversal of opioid tolerance and dependence. Copyright © 2016 Elsevier B.V. All rights reserved.

Hard cap espresso extraction and liquid chromatography determination of bioactive compounds in vegetables and spices.

PubMed

Martinez-Sena, María Teresa; de la Guardia, Miguel; Esteve-Turrillas, Francesc A; Armenta, Sergio

2017-12-15

A new analytical procedure, based on liquid chromatography with diode array and fluorescence detection, has been proposed for the determination of bioactive compounds in vegetables and spices after hard cap espresso extraction. This novel extraction system has been tested for the determination of capsaicin and dihydrocapsaicin from fresh chilli and sweet pepper, piperine from ground pepper, curcumin from turmeric and curry, and myristicin from nutmeg. Extraction efficiency was evaluated by using acetonitrile:water and ethanol:water mixtures. The proposed method allows the extraction of samples with 100mL of 60% (v/v) ethanol in water. The obtained limits of quantification for the proposed procedure ranged from 0.07 to 0.30mgg -1 and results were statistically comparable with those obtained by ultrasound assisted extraction. Hard cap espresso machines offer a fast, effective and quantitative tool for the extraction of bioactive compounds from food samples with an extraction time lower than 30s, using a global available and low cost equipment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synergistic antidepressant-like effect of ferulic acid in combination with piperine: involvement of monoaminergic system

PubMed Central

Li, Gaowen; Ruan, Lina; Chen, Ruijie; Wang, Renye; Xie, Xupei; Zhang, Meixi; Chen, Lichao; Yan, Qizhi; Reed, Miranda; Chen, Jiechun; Xu, Ying; Pan, Jianchun; Huang, Wu

2016-01-01

The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects. PMID:26220010

Diversity effect of capsaicin on different types of skeletal muscle.

PubMed

Zhou, Gan; Wang, Lina; Xu, Yaqiong; Yang, Kelin; Luo, Lv; Wang, Leshan; Li, Yongxiang; Wang, Jiawen; Shu, Gang; Wang, Songbo; Gao, Ping; Zhu, Xiaotong; Xi, Qianyun; Sun, Jiajie; Zhang, Yongliang; Jiang, Qingyan

2018-06-01

Capsaicin is a major pungent content in green and red peppers which are widely used as spice, and capsaicin may activate different receptors. To determine whether capsaicin has different effects on different types of skeletal muscle, we applied different concentrations (0, 0.01, and 0.02%) of capsaicin in the normal diet and conducted a four-week experiment on Sprague-Dawley rats. The fiber type composition, glucose metabolism enzyme activity, and different signaling molecules' expressions of receptors were detected. Our results suggested that capsaicin reduced the body fat deposition, while promoting the slow muscle-related gene expression and increasing the enzyme activity in the gastrocnemius and soleus muscles. However, fatty acid metabolism was significantly increased only in the soleus muscle. The study of intracellular signaling suggested that the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid receptors in the soleus muscle were more sensitive to capsaicin. In conclusion, the distribution of TRPV1 and cannabinoid receptors differs in different types of muscle, and the different roles of capsaicin in different types of muscle may be related to the different degrees of activation of receptors.

Capsaicin cough sensitivity in bronchiectasis.

PubMed

Torrego, A; Haque, R A; Nguyen, L T; Hew, M; Carr, D H; Wilson, R; Chung, K F

2006-08-01

Bronchiectasis is a suppurative airway disease characterised by persistent cough and sputum production associated with bronchial dilatation. A study was undertaken to determine whether cough sensitivity is increased in bronchiectatic patients. Twenty two patients with bronchiectasis and 20 healthy non-smoking controls matched for age and sex were recruited into the study. Quality of life (Leicester Cough Questionnaire score), total cough symptom score, and extent of bronchiectasis on HRCT scans were recorded. Cough sensitivity was assessed using incremental inhalation of capsaicin concentrations; the concentration at which 5 or more coughs occurred (C5) was recorded. Patients with bronchiectasis had increased sensitivity to capsaicin compared with controls (mean (SE) log10 C5 1.22 (0.20) v 1.89 (0.21); p<0.03). Capsaicin sensitivity correlated positively with the Leicester Cough Questionnaire score (r = 0.64; p = 0.005) and inversely with the total cough symptom score (r = -0.58; p = 0.004), but not with the extent of the disease. It also correlated with forced expiratory volume in 1 second (FEV1) in litres (r = 0.58; p = 0.005) but not with FEV1 % predicted. Capsaicin sensitivity was not related to the presence of infected sputum or to corticosteroid or bronchodilator use. : Patients with bronchiectasis have a sensitive cough reflex which reflects the severity of cough symptoms. A measure of cough severity could be part of health assessment for patients with bronchiectasis.

Production of high titre antibody response against Russell's viper venom in mice immunized with ethanolic extract of fruits of Piper longum L. (Piperaceae) and piperine.

PubMed

Shenoy, P A; Nipate, S S; Sonpetkar, J M; Salvi, N C; Waghmare, A B; Chaudhari, P D

2014-01-15

Piper longum L. fruits have been traditionally used against snakebites in north-eastern and southern region of India. The aim of the study was to assess the production of antibody response against Russell's viper venom in mice after prophylactic immunization with ethanolic extract of fruits of Piper longum L. and piperine. The mice sera were tested for the presence of antibodies against Russell's viper venom by in vitro lethality neutralization assay and in vivo lethality neutralization assay. Polyvalent anti-snake venom serum (antivenom) manufactured by Haffkine Bio-Pharmaceutical Corporation Ltd. was used as standard. Further confirmation of presence of antibodies against the venom in sera of mice immunized with PLE and piperine was done using indirect enzyme-linked immunosorbent assay (ELISA) and double immunodiffusion test. Treatment with PLE-treated mice serum and piperine-treated mice serum was found to inhibit the lethal action of venom both in the in vitro lethality neutralization assay and in vivo lethality neutralization assay. ELISA testing indicated that there were significantly high (p<0.01) levels of cross reactions between the PLE and piperine treated mice serum and the venom antigens. In double immunodiffusion test, a white band was observed between the two wells of antigen and antibodies for both the PLE-treated and piperine-treated mice serum. Thus it can be concluded that immunization with ethanolic extract of fruits of Piper longum and piperine produced a high titre antibody response against Russell's viper venom in mice. The antibodies against PLE and piperine could be useful in antivenom therapy of Russell's viper bites. PLE and piperine may also have a potential interest in view of the development of antivenom formulations used as antidote against snake bites. Copyright © 2013 Elsevier GmbH. All rights reserved.

Mitigating efficacy of piperine in the physiological derangements of high fat diet induced obesity in Sprague Dawley rats.

PubMed

BrahmaNaidu, Parim; Nemani, Harishankar; Meriga, Balaji; Mehar, Santosh Kumar; Potana, Sailaja; Ramgopalrao, Sajjalaguddam

2014-09-25

An increased risk of obesity has become a common public health concern as it is associated with hypertension, diabetes, osteoarthritis, heart diseases, liver steatosis etc. Pharmacological intervention with natural product-based drugs is considered a healthier alternative to treat obesity. This study was aimed to evaluate anti-obesity effects of piperine on high fat diet (HFD) induced obesity in rats. Piperine was isolated from methanolic extract of Piper nigrum by using column chromatography and confirmed by LC-MS analysis. Male SD rats were fed HFD initially for 15weeks to induce obesity. After induction of obesity, piperine was supplemented in different doses (20, 30 and 40mg/kgb.wt) through HFD for 42days to experimental rats. HFD induced changes in body weight, body composition, fat percentage, adiposity index, blood pressure, plasma levels of glucose, insulin resistance, leptin, adiponectin, plasma and tissue lipid profiles, liver antioxidants were explained. The activities of lipase, amylase and lipid metabolic marker enzymes such as HMG-CoA reductase, carnitine palmitoyl transferase (CPT), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), lecithin-cholesterol acyl transferase (LCAT) and lipoprotein lipase (LPL) were assessed in experimental rats. Supplementation of piperine at a dose of 40mg/kgb.wt has significantly (p<0.05) reversed the HFD-induced alterations in experimental rats in a dose dependant manner, the maximum therapeutic effect being noted at a dose of 40mg/kgb.wt. Our study concludes that piperine can be well considered as an effective bioactive molecule to suppress of body weight, improve insulin and leptin sensitivity, ultimately leading to regulate obesity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Capsaicin represses transcriptional activity of β-catenin in human colorectal cancer cells

PubMed Central

Lee, Seong-Ho; Richardson, Raphael L.; Dashwood, Roderick H.; Baek, Seung Joon

2011-01-01

Capsaicin is a pungent ingredient in chili red peppers and has been linked to suppression of growth in various cancer cells. However, the underlying mechanism(s) by which capsaicin induces growth arrest and apoptosis of cancer cells is not completely understood. In the present study, we investigated whether capsaicin alters β-catenin-dependent signaling in human colorectal cancer cells in vitro. Exposure of SW480, LoVo, and HCT-116 cells to capsaicin suppressed cell proliferation. Transient transfection with a β-catenin/T-cell factor (TCF)-responsive reporter indicated that capsaicin suppressed the transcriptional activity of β-catenin/TCF. Capsaicin treatment resulted in a decrease of intracellular β-catenin levels and a reduction of transcripts from the β-catenin gene (CTNNB1). These results were confirmed by a reduced luciferase reporter activity driven by promoter-reporter construct containing the promoter region of the Catnb gene. In addition, capsaicin destabilized β-catenin through enhancement of proteosomal-dependent degradation. Western blot and immunoprecipitation studies indicated that capsaicin treatment suppressed TCF-4 expression and disrupted the interaction of TCF-4 and β-catenin. This study identifies a role for the β-catenin/TCF-dependent pathway that potentially contributes to the anti-cancer activity of capsaicin in human colorectal cancer cells. PMID:21764279

[In vitro and in vivo recoveries of cutaneous micro-dialysis probe of paeonol, eugenol and piperine].

PubMed

Yang, Chang; Bai, Jie; Du, Shou-Ying; Cui, Ya-Hua; Zhang, Qin-Shuai; Ma, Jun-Ming

2016-11-01

To establish a method for detecting micro-dialysis recovery of paeonol, eugenol and piperine in Huoxue Zhitong patch, in order to provide the basis for further percutaneous pharmacokinetics studies. The concentrations of paeonol, eugenol and piperine in dialysates were determined by HPLC, and probe deliveries were calculated respectively. The effects of concentration and calibration approaches on the micro-dialysis probe deliveries of the three components were investigated, and their probe absorbability, in vitro and in vivo probe stability and repeatability were also studied.The results indicated that little paeonol, eugenol and piperine were observed in probes with 30% alcohol as the perfusate, and could be cleaned from probe in a short time. And the in vivo and in vitro probe deliveries of three components were stable within 8 h, drug-containing solution and blank perfusate were alternatively used for three times, and the in vivo and in vitro probe deliveries of three components were basically unchanged. The in vitro recoveries of paeonol, eugenol and piperine with a range of concentration were respectively (45.7±4.66)%, (27.82±2.95)%, (41.3±3.96)%, which indicated no concentration independent. Under the same conditions, the similar delivery was observed by dialysis, retrodialysis and no-net flux. Therefore, the concentrations of analyses of the collected fraction could be calibrated by in vitro or in vivo recoveries. Meanwhile, this also proved that the micro-dialysis method built by this study is applicable to the study on percutaneous pharmacokinetics of Huoxue Zhitong patch. Copyright© by the Chinese Pharmaceutical Association.

The pepper's natural ingredient capsaicin induces autophagy blockage in prostate cancer cells

PubMed Central

Ramos-Torres, Ágata; Bort, Alicia; Morell, Cecilia; Rodríguez-Henche, Nieves; Díaz-Laviada, Inés

2016-01-01

Capsaicin, the pungent ingredient of red hot chili peepers, has been shown to have anti-cancer activities in several cancer cells, including prostate cancer. Several molecular mechanisms have been proposed on its chemopreventive action, including ceramide accumulation, endoplasmic reticulum stress induction and NFκB inhibition. However, the precise mechanisms by which capsaicin exerts its anti-proliferative effect in prostate cancer cells remain questionable. Herein, we have tested the involvement of autophagy on the capsaicin mechanism of action on prostate cancer LNCaP and PC-3 cells. The results showed that capsaicin induced prostate cancer cell death in a time- and concentration-dependent manner, increased the levels of microtubule-associated protein light chain 3-II (LC3-II, a marker of autophagy) and the accumulation of the cargo protein p62 suggesting an autophagy blockage. Moreover, confocal microscopy revealed that capsaicin treatment increased lysosomes which co-localized with LC3 positive vesicles in a similar extent to that produced by the lysosomal protease inhibitors E64 and pepstatin pointing to an autophagolysosomes breakdown inhibition. Furthermore, we found that capsaicin triggered ROS generation in cells, while the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Co-treatment of cells with NAC and capsaicin abrogated the effects of capsaicin on autophagy and cell death. Normal prostate PNT2 and RWPE-1 cells were more resistant to capsaicin-induced cytotoxicity and did not accumulate p62 protein. Taken together, these results suggest that ROS-mediated capsaicin-induced autophagy blockage contributes to antiproliferation in prostate cancer cells, which provides new insights into the anticancer molecular mechanism of capsaicin. PMID:26625315

Cooking enhances curcumin anti-cancerogenic activity through pyrolytic formation of "deketene curcumin".

PubMed

Dahmke, Indra N; Boettcher, Stefan P; Groh, Matthias; Mahlknecht, Ulrich

2014-05-15

Curcumin is widely used in traditional Asian kitchen as a cooking ingredient. Despite its low bioavailability, epidemiological data, on low cancer incidence in Asia, suggest beneficial health effects of this compound. Therefore, the question arose whether cooking modifies the anti-cancerogenic effects of curcumin. To evaluate this, we pyrolysed curcumin with and without coconut fat or olive oil, and analysed the products by high-performance liquid chromatography (HPLC). A number of more hydrophilic curcumin isoforms and decomposition products, including a compound later identified by nuclear magnetic resonance spectroscopy (NMR) as "deketene curcumin" (1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one), formerly described as a synthetic curcumin derivative, were detected. Additionally, we proved that deketene curcumin, compared to curcumin, exhibits higher toxicity on B78H1 melanoma cells resulting in G2 arrest. In conclusion, deketene curcumin is formed as a consequence of pyrolysis during common household cooking, showing stronger anti-cancer effects than curcumin. Moreover, we propose a chemical reaction-pathway for this process. Copyright © 2013 Elsevier Ltd. All rights reserved.

Supercritical CO2 as a reaction medium for synthesis of capsaicin analogues by lipase-catalyzed transacylation of capsaicin.

PubMed

Kobata, Kenji; Kobayashi, Mamiko; Kinpara, Sachiyo; Watanabe, Tatsuo

2003-09-01

Capsaicin analogues having different acyl moiety were synthesized by lipase-catalyzed transacylation of capsaicin with a corresponding acyl donor in supercritical CO2 as a reaction medium. Transacylation with methyl tetradecanoate using Novozym 435 as a catalyst gave vanillyl tetradecanamide in a 54% yield at 80 degrees C and 19 MPa over 72 h. Vanillyl (Z)-9-octadecenamide, olvanil, was synthesized from triolein in a 21% yield over 7 d.

Capsaicin Interaction with TRPV1 Channels in a Lipid Bilayer: Molecular Dynamics Simulation

PubMed Central

Hanson, Sonya M.; Newstead, Simon; Swartz, Kenton J.; Sansom, Mark S.P.

2015-01-01

Transient receptor potential vanilloid subtype 1 (TRPV1) is a heat-sensitive ion channel also involved in pain sensation, and is the receptor for capsaicin, the active ingredient of hot chili peppers. The recent structures of TRPV1 revealed putative ligand density within the S1 to S4 voltage-sensor-like domain of the protein. However, questions remain regarding the dynamic role of the lipid bilayer in ligand binding to TRPV1. Molecular dynamics simulations were used to explore behavior of capsaicin in a 1-palmitoyl-2-oleoyl phosphatidylcholine bilayer and with the target S1–S4 transmembrane helices of TRPV1. Equilibrium simulations reveal a preferred interfacial localization for capsaicin. We also observed a capsaicin molecule flipping from the extracellular to the intracellular leaflet, and subsequently able to access the intracellular TRPV1 binding site. Calculation of the potential of mean force (i.e., free energy profile) of capsaicin along the bilayer normal confirms that it prefers an interfacial localization. The free energy profile indicates that there is a nontrivial but surmountable barrier to the flipping of capsaicin between opposing leaflets of the bilayer. Molecular dynamics of the S1–S4 transmembrane helices of the TRPV1 in a lipid bilayer confirm that Y511, known to be crucial to capsaicin binding, has a distribution along the bilayer normal similar to that of the aromatic group of capsaicin. Simulations were conducted of the TRPV1 S1–S4 transmembrane helices in the presence of capsaicin placed in the aqueous phase, in the lipid, or docked to the protein. No stable interaction between ligand and protein was seen for simulations initiated with capsaicin in the bilayer. However, interactions were seen between TRPV1 and capsaicin starting from the cytosolic aqueous phase, and capsaicin remained stable in the majority of simulations from the docked pose. We discuss the significance of capsaicin flipping from the extracellular to the intracellular

In vitro and in vivo evaluation of capsaicin-loaded microemulsion for enhanced oral bioavailability.

PubMed

Zhu, Yuan; Zhang, Jiajia; Zheng, Qianfeng; Wang, Miaomiao; Deng, Wenwen; Li, Qiang; Firempong, Caleb Kesse; Wang, Shengli; Tong, Shanshan; Xu, Ximing; Yu, Jiangnan

2015-10-01

Capsaicin, as a food additive, has attracted worldwide concern owing to its pungency and multiple pharmacological effects. However, poor water solubility and low bioavailability have limited its application. This study aims to develop a capsaicin-loaded microemulsion to enhance the oral bioavailability of the anti-neuropathic-pain component, capsaicin, which is poorly water soluble. In this study, the microemulsion consisting of Cremophor EL, ethanol, medium-chain triglycerides (oil phase) and water (external phase) was prepared and characterized (particle size, morphology, stability and encapsulation efficiency). The gastric mucosa irritation test of formulated capsaicin was performed in rats to evaluate its oral feasibility, followed by the pharmacokinetic study in vivo. Under these conditions, the encapsulated capsaicin revealed a faster capsaicin release in vitro coupled with a greater absorption in vivo when compared to the free capsaicin. The oral bioavailability of the formulated capsaicin-loaded microemulsions was 2.64-fold faster than that of free capsaicin. No significant irritation was observed on the mucosa from the pathological section of capsaicin-loaded microemulsion treated stomach. These results indicate that the developed microemulsion represents a safe and orally effective carrier for poorly soluble substances. The formulation could be used for clinical trials and expand the application of capsaicin. © 2014 Society of Chemical Industry.

Inhibition of monoamine oxidase by derivatives of piperine, an alkaloid from the pepper plant Piper nigrum, for possible use in Parkinson's disease.

PubMed

Al-Baghdadi, Osamah B; Prater, Natalie I; Van der Schyf, Cornelis J; Geldenhuys, Werner J

2012-12-01

A series of compounds related to piperine and antiepilepsirine was screened in a monoamine oxidase A and B assay. Piperine is an alkaloid from the source plant of both black and white pepper grains, Piper nigrum. Piperine has been shown to have a wide range of activity, including MAO inhibitory activity. The z-factor for the screening assay was found to be greater than 0.8 for both assays. Notably, the compounds tested were selective towards MAO-B, with the most potent compound having an IC(50) of 498 nM. To estimate blood-brain barrier (BBB) permeability, we used a PAMPA assay, which suggested that the compounds are likely to penetrate the BBB. A fluorescent bovine serum albumin (BSA) high-throughput screening (HTS) binding assay showed an affinity of 8 μM for piperine, with more modest binding for other test compounds. Taken together, the data described here may be useful in gaining insight towards the design of selective MAO-B inhibitory compounds devoid of MAO-A activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Altered respiratory response to substance P in capsaicin-treated rats.

PubMed

Towle, A C; Mueller, R A; Breese, G R; Lauder, J

1985-01-01

The present investigation sought to examine the importance of substance P in the altered respiratory activity after neonatal capsaicin administration. Halothane-anesthetized adult rats given capsaicin neonatally exhibit a decreased basal minute ventilation with PaCO2 equal to and PaO2 greater than vehicle injected controls. In addition, the minute ventilation-PaCO2 curve was displaced to the right. Acute bilateral cervical vagotomy severely blunted the minute ventilation response to PaCO2 and abolished the differences in ventilation between capsaicin treated and control rats. Neonatal capsaicin significantly reduced pons-medulla substance P content but not TRH, serotonin or 5-hydroxyindole acetic acid. Immunohistochemical studies revealed that substance P fibers of the trigeminal spinal nucleus were the most severely affected in the brain stem and that substance P fibers in the lung were totally absent. The intracerebroventricular administration of substance P increased minute ventilation similarly in both control and capsaicin treated rats, largely as a result of increases in tidal volume. The minute ventilation-PaCO2 curve was similar in both groups after substance P administration. Simultaneous administration of the peptidase inhibitor captopril with substance P increased the respiratory response to substance P in normal rats. Administration of captopril to capsaicin treated rats restored the ventilation-PaCO2 curve to the position observed in normal rats. The hypotensive response to intracerebroventricular captopril alone in control rats was less profound in rats given neonatal capsaicin. These results are consistent with the thesis that respiratory depression after capsaicin treatment is at least in part due to the loss of substance P primary afferent nerve terminals in the brain stem, suggesting that substance P fibers in the brain stem may participate in the normal modulation of respiratory activity.

Inhibition of HIV-1 by curcumin A, a novel curcumin analog

PubMed Central

Kumari, Namita; Kulkarni, Amol A; Lin, Xionghao; McLean, Charlee; Ammosova, Tatiana; Ivanov, Andrey; Hipolito, Maria; Nekhai, Sergei; Nwulia, Evaristus

2015-01-01

Despite the remarkable success of combination antiretroviral therapy at curtailing HIV progression, emergence of drug-resistant viruses, chronic low-grade inflammation, and adverse effects of combination antiretroviral therapy treatments, including metabolic disorders collectively present the impetus for development of newer and safer antiretroviral drugs. Curcumin, a phytochemical compound, was previously reported to have some in vitro anti-HIV and anti-inflammatory activities, but poor bioavailability has limited its clinical utility. To circumvent the bioavailability problem, we derivatized curcumin to sustain retro-aldol decomposition at physiological pH. The lead compound derived, curcumin A, showed increased stability, especially in murine serum where it was stable for up to 25 hours, as compared to curcumin that only had a half-life of 10 hours. Both curcumin and curcumin A showed similar inhibition of one round of HIV-1 infection in cultured lymphoblastoid (also called CEM) T cells (IC50=0.7 μM). But in primary peripheral blood mononuclear cells, curcumin A inhibited HIV-1 more potently (IC50=2 μM) compared to curcumin (IC50=12 μM). Analysis of specific steps of HIV-1 replication showed that curcumin A inhibited HIV-1 reverse transcription, but had no effect on HIV-1 long terminal repeat basal or Tat-induced transcription, or NF-κB-driven transcription at low concentrations that affected reverse transcription. Finally, we showed curcumin A induced expression of HO-1 and decreased cell cycle progression of T cells. Our findings thus indicate that altering the core structure of curcumin could yield more stable compounds with potent antiretroviral and anti-inflammatory activities. PMID:26366056

Capsaicin-loaded nanolipoidal carriers for topical application: design, characterization, and in vitro/in vivo evaluation.

PubMed

Wang, Xia-Rong; Gao, Si-Qian; Niu, Xiao-Qian; Li, Long-Jian; Ying, Xiao-Ying; Hu, Zhong-Jie; Gao, Jian-Qing

2017-01-01

Capsaicin has been used in clinical applications for the treatment of pain disorders and inflammatory diseases. Given the strong pungency and high oil/water partition coefficient of capsaicin, capsaicin-loaded nanolipoidal carriers (NLCs) were designed to increase permeation and achieve the analgesic, anti-inflammatory effect with lower skin irritation. Capsaicin-loaded NLCs were prepared and later optimized by the Box-Behnken design. The physicochemical characterizations, morphology, and encapsulation of the capsaicin-loaded NLCs were subsequently confirmed. Capsaicin-loaded NLCs and capsaicin-loaded NLCs gel exhibited sustained release and no cytotoxicity properties. Also, they could significantly enhance the penetration amount, permeation flux, and skin retention amounts of capsaicin due to the application of NLCs. To study the topical permeation mechanism of capsaicin, 3,3'-dioctadecyloxacarbocyanine perchlorate (Dio) was used as a fluorescent dye. Dio-loaded NLCs and Dio-loaded NLCs gel could effectively deliver Dio up to a skin depth of 260 and 210 μm, respectively, primarily through the appendage route on the basis of version skin sections compared with Dio solution, which only delivered Dio up to 150 μm. In vivo therapeutic experiments demonstrated that capsaicin-loaded NLCs and capsaicin-loaded NLCs gel could improve the pain threshold in a dose-dependent manner and inhibit inflammation, primarily by reducing the prostaglandin E2 levels in the tissue compared with capsaicin cream and capsaicin solution. Meanwhile, skin irritation was reduced, indicating that application of NLCs could decrease the irritation caused by capsaicin. Overall, NLCs may be a potential carrier for topical delivery of capsaicin for useful pain and inflammation therapy.

Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis.

PubMed

Jain, S K; Gill, M S; Pawar, H S; Suresh, Sarasija

2014-09-01

Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (P<0.01) alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.

Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration.

PubMed

Cherniakov, Irina; Izgelov, Dvora; Barasch, Dinorah; Davidson, Elyad; Domb, Abraham J; Hoffman, Amnon

2017-11-28

Nowadays, therapeutic indications for cannabinoids, specifically Δ 9 -tetrahydrocannabinol (THC) and Cannabidiol (CBD) are widening. However, the oral consumption of the molecules is very limited due to their highly lipophilic nature that leads to poor solubility at the aqueous environment. Additionally, THC and CBD are prone to extensive first pass mechanisms. These absorption obstacles render the molecules with low and variable oral bioavailability. To overcome these limitations we designed and developed the advanced pro-nanolipospheres (PNL) formulation. The PNL delivery system is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer: piperine. Piperine was selected due to its distinctive inhibitory properties affecting both Phase I and Phase II metabolism. This constellation self emulsifies into nano particles that entrap the cannabinoids and the piperine in their core and thus improve their solubility while piperine and the other PNL excipients inhibit their intestinal metabolism. Another clear advantage of the formulation is that its composition of materials is approved for human consumption. The safe nature of the excipients enabled their direct evaluation in humans. In order to evaluate the pharmacokinetic profile of the THC-CBD-piperine-PNL formulation, a two-way crossover, single administration clinical study was conducted. The trial comprised of 9 healthy volunteers under fasted conditions. Each subject received a THC-CBD (10.8mg, 10mg respectively) piperine (20mg)-PNL filled capsule and an equivalent dose of the oromucosal spray Sativex® with a washout period in between treatments. Single oral administration of the piperine-PNL formulation resulted in a 3-fold increase in Cmax and a 1.5-fold increase in AUC for THC when compared to Sativex®. For CBD, a 4-fold increase in Cmax and a 2.2-fold increase in AUC was observed. These findings demonstrate the potential this formulation has

[Piperine regulates glucose metabolism disorder in HepG2 cells of insulin resistance models via targeting upstream target of AMPK signaling pathway].

PubMed

Wan, Chun-Ping; Wei, Ya-Gai; Li, Xiao-Xue; Zhang, Li-Jun; Yang, Rui; Bao, Zhao-Ri-Ge-Tu

2017-02-01

To investigate the effect of piperine on the disorder of glucose metabolism in the cell model with insulin resistance (IR) and explore the molecules mechanism on intervening the upstream target of AMPK signaling pathway. The insulin resistance models in HepG2 cells were established by fat emulsion stimulation. Then glucose consumption in culture supernatant was detected by GOD-POD method. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of leptin(LEP) and adiponectin(APN) in culture supernatant; Real-time quantitative PCR was used to assess the mRNA expression of APN and LEP; and the protein expression levels of LepR, AdipoR1, AdipoR2 and the activation of AMPK signaling pathway were detected by Western blot analysis. The results showed that piperine, rosiglitazone and AMPK agonist AICAR could significantly elevate the glucose consumption in insulin resistance cell models, enhance the level of APN, promote APN mRNA transcripts and increase the protein expression of Adipo receptor. Meanwhile,AMPKα mRNA and р-AMPKα protein expressions were also increased in piperine treated cells, but both LEP mRNA expression and LepR protein expressions were decreased in piperine treated group. The results indicated that piperine could significantly ameliorate the glucose metabolism disorder in insulin resistance cell models through regulating upstream molecules (APN and LEP) of AMPK signaling pathway, and thus activate the AMPK signaling pathway. Copyright© by the Chinese Pharmaceutical Association.

Modulation of the Proteasome Pathway by Nano-Curcumin and Curcumin in Retinal Pigment Epithelial Cells.

PubMed

Ramos de Carvalho, J Emanuel; Verwoert, Milan T; Vogels, Ilse M C; Schipper-Krom, Sabine; Van Noorden, Cornelis J F; Reits, Eric A; Klaassen, Ingeborg; Schlingemann, Reinier O

2018-01-01

Curcumin has multiple biological effects including the modulation of protein homeostasis by the ubiquitin-proteasome system. The purpose of this study was to assess the in vitro cytotoxic and oxidative effects of nano-curcumin and standard curcumin and characterize their effects on proteasome regulation in retinal pigment epithelial (RPE) cells. Viability, cell cycle progression, and reactive oxygen species (ROS) production were determined after treatment with nano-curcumin or curcumin. Subsequently, the effects of nano-curcumin and curcumin on proteasome activity and the gene and protein expression of proteasome subunits PA28α, α7, β5, and β5i were assessed. Nano-curcumin (5-100 μM) did not show significant cytotoxicity or anti-oxidative effects against H2O2-induced oxidative stress, whereas curcumin (≥10 μM) was cytotoxic and a potent inducer of ROS production. Both nano-curcumin and curcumin induced changes in proteasome-mediated proteolytic activity characterized by increased activity of the proteasome subunits β2 and β5i/β1 and reduced activity of β5/β1i. Likewise, nano-curcumin and curcumin affected mRNA and protein levels of household and immunoproteasome subunits. Nano-curcumin is less toxic to RPE cells and less prone to induce ROS production than curcumin. Both nano-curcumin and curcumin increase proteasome-mediated proteolytic activity. These results suggest that nano-curcumin may be regarded as a proteasome-modulating agent of limited cytotoxicity for RPE cells. The Author(s). Published by S. Karger AG, Basel.

Structure-activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro.

PubMed

Hammad, Ayat S; Ravindran, Sreenithya; Khalil, Ashraf; Munusamy, Shankar

2017-05-01

Endoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD. Piperine and its analogs have been reported to exhibit multiple pharmacological activities; however, their efficacy against ER stress in kidney cells has not been studied yet. Hence, the goal of this study was to synthesize amide-substituted piperine analogs and screen them for pharmacological activity to relieve ER stress using an in vitro model of tunicamycin-induced ER stress using normal rat kidney (NRK-52E) cells. Five amide-substituted piperine analogs were synthesized and their chemical structures were elucidated by pertinent spectroscopic techniques. An in vitro model of ER stress was developed using tunicamycin, and the compounds of interest were screened for their effect on cell viability, and the expression of ER chaperone GRP78, the pro-apoptotic ER stress marker CHOP, and apoptotic caspases 3 and 12 (via western blotting). Our findings indicate that exposure to tunicamycin (0.5 μg/mL) for 2 h induces the expression of GRP78 and CHOP, and apoptotic markers (caspase-3 and caspase-12) and causes a significant reduction in renal cell viability. Pre-treatment of cells with piperine and its cyclohexylamino analog decreased the tunicamycin-induced upregulation of GRP78 and CHOP and cell death. Taken together, our findings demonstrate that piperine and its analogs differentially regulate ER stress, and thus represent potential therapeutic agents to treat ER stress-related renal disorders. Graphical Abstract Piperine (PIP) reduces the expression of ER stress markers (GRP78 and CHOP) induced by pathologic stimuli and consequently decreases the activation of apoptotic caspase-12 and caspase-3; all of which contributes to its chemical chaperone and cytoprotective properties to protect

Mechanisms underlying capsaicin effects in canine coronary artery: implications for coronary spasm

PubMed Central

Hiett, S. Christopher; Owen, Meredith K.; Li, Wennan; Chen, Xingjuan; Riley, Ashley; Noblet, Jillian; Flores, Sarah; Sturek, Michael; Tune, Johnathan D.; Obukhov, Alexander G.

2014-01-01

Aims The TRPV1, transient receptor potential vanilloid type 1, agonist capsaicin is considered to be beneficial for cardiovascular health because it dilates coronary arteries through an endothelial-dependent mechanism and may slow atheroma progression. However, recent reports indicate that high doses of capsaicin may constrict coronary arterioles and even provoke myocardial infarction. Thus far, the mechanisms by which TRPV1 activation modulates coronary vascular tone remain poorly understood. This investigation examined whether there is a synergistic interplay between locally acting vasoconstrictive pro-inflammatory hormones (autacoids) and capsaicin effects in the coronary circulation. Methods and results Experiments were performed in canine conduit coronary artery rings and isolated smooth muscle cells (CASMCs). Isometric tension measurements revealed that 1–10 μM capsaicin alone did not affect resting tension of coronary artery rings. In contrast, in endothelium-intact rings pre-contracted with a Gq/11-coupled FP/TP (prostaglandin F/thromboxane) receptor agonist, prostaglandin F2α (PGF2α; 10 μM), capsaicin first induced transient dilation that was followed by sustained contraction. In endothelium-denuded rings pre-contracted with PGF2α or thromboxane analogue U46619 (1 μM, a TP receptor agonist), capsaicin induced only sustained contraction. Blockers of the TP receptor or TRPV1 significantly inhibited capsaicin effects, but these were still observed in the presence of 50 μM nifedipine and 70 mM KCl. Capsaicin also potentiated 20 mM KCl-induced contractions. Fluorescence imaging experiments in CASMCs revealed that the Gq/11-phospholipase C (PLC)-protein kinase C (PKC) and Ca2+-PLC-PKC pathways are likely involved in sensitizing CASMC TRPV1 channels. Conclusion Capsaicin alone does not cause contractions in conduit canine coronary artery; however, pre-treatment with pro-inflammatory prostaglandin–thromboxane agonists may unmask capsaicin

Effect of capsaicin on thermoregulation: an update with new aspects

PubMed Central

Szolcsányi, János

2015-01-01

Capsaicin, a selective activator of the chemo- and heat-sensitive transient receptor potential (TRP) V1 cation channel, has characteristic feature of causing long-term functional and structural impairment of neural elements supplied by TRPV1/capsaicin receptor. In mammals, systemic application of capsaicin induces complex heat-loss response characteristic for each species and avoidance of warm environment. Capsaicin activates cutaneous warm receptors and polymodal nociceptors but has no effect on cold receptors or mechanoreceptors. In this review, thermoregulatory features of capsaicin-pretreated rodents and TRPV1-mediated neural elements with innocuous heat sensitivity are summarized. Recent data support a novel hypothesis for the role of visceral warmth sensors in monitoring core body temperature. Furthermore, strong evidence suggests that central presynaptic nerve terminals of TRPV1-expressing cutaneous, thoracic and abdominal visceral receptors are activated by innocuous warmth stimuli and capsaicin. These responses are absent in TRPV1 knockout mice. Thermoregulatory disturbance induced by systemic capsaicin pretreatment lasts for months and is characterized by a normal body temperature at cool environment up to a total dose of 150 mg/kg s.c. Upward differential shift of set points for activation vasodilation, other heat-loss effectors and thermopreference develops. Avoidance of warm ambient temperature (35°C, 40°C) is severely impaired but thermopreference at cool ambient temperatures (Tas) are not altered. TRPV1 knockout or knockdown and genetically altered TRPV1, TRPV2 and TRPM8 knockout mice have normal core temperature in thermoneutral or cool environments, but the combined mutant mice have impaired regulation in warm or cold (4°C) environments. Several lines of evidence support that in the preoptic area warmth sensitive neurons are activated and desensitized by capsaicin, but morphological evidence for it is controversial. It is suggested that these

Anti-snake venom activities of ethanolic extract of fruits of Piper longum L. (Piperaceae) against Russell's viper venom: characterization of piperine as active principle.

PubMed

Shenoy, P A; Nipate, S S; Sonpetkar, J M; Salvi, N C; Waghmare, A B; Chaudhari, P D

2013-05-20

Piper longum L. fruits have been traditionally used against snakebites in north-eastern and southern region of India. To examine the ability of ethanolic extract of fruits of Piper longum L., Piperaceae (PLE) and piperine, one of the main active principles of Piper longum, to inhibit the Russell's viper (Doboia russelii, Viperidae) snake venom activities. Anti-snake venom activities of ethanolic extract of fruits of Piper longum L. (Piperaceae) and piperine against Russell's viper venom was studied in embryonated fertile chicken eggs, mice and rats by using various models as follows: inhibition of venom lethal action, inhibition of venom haemorrhagic action (in vitro), inhibition of venom haemorrhagic action (in vivo), inhibition of venom necrotizing action, inhibition of venom defibrinogenating action, inhibition of venom induced paw edema, inhibition of venom induced mast cell degranulation, creatine kinase assay and assay for catalase activity. PLE was found to inhibit the venom induced haemorrhage in embryonated fertile chicken eggs. Administration of PLE and piperine significantly (p<0.01) inhibited venom induced lethality, haemorrhage, necrosis, defibrinogenation and inflammatory paw edema in mice in a dose dependent manner. PLE and piperine also significantly (p<0.01) reduced venom induced mast cell degranulation in rats. Venom induced decrease in catalase enzyme levels in mice kidney tissue and increase in creatine kinase enzyme levels in mice serum were significantly (p<0.01) reversed by administration of both PLE and piperine. PLE possesses good anti-snake venom properties and piperine is one of the compounds responsible for the effective venom neutralizing ability of the plant. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Topical capsaicin (high concentration) for chronic neuropathic pain in adults.

PubMed

Derry, Sheena; Rice, Andrew Sc; Cole, Peter; Tan, Toni; Moore, R Andrew

2017-01-13

This review is an update of 'Topical capsaicin (high concentration) for chronic neuropathic pain in adults' last updated in Issue 2, 2013. Topical creams with capsaicin are used to treat peripheral neuropathic pain. Following application to the skin, capsaicin causes enhanced sensitivity, followed by a period with reduced sensitivity and, after repeated applications, persistent desensitisation. High-concentration (8%) capsaicin patches were developed to increase the amount of capsaicin delivered; rapid delivery was thought to improve tolerability because cutaneous nociceptors are 'defunctionalised' quickly. The single application avoids noncompliance. Only the 8% patch formulation of capsaicin is available, with a capsaicin concentration about 100 times greater than conventional creams. High-concentration topical capsaicin is given as a single patch application to the affected part. It must be applied under highly controlled conditions, often following local anaesthetic, due to the initial intense burning sensation it causes. The benefits are expected to last for about 12 weeks, when another application might be made. To review the evidence from controlled trials on the efficacy and tolerability of topically applied, high-concentration (8%) capsaicin in chronic neuropathic pain in adults. For this update, we searched CENTRAL, MEDLINE, Embase, two clinical trials registries, and a pharmaceutical company's website to 10 June 2016. Randomised, double-blind, placebo-controlled studies of at least 6 weeks' duration, using high-concentration (5% or more) topical capsaicin to treat neuropathic pain. Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods.Efficacy outcomes reflecting long-duration pain relief after a

Comparison of the effects of curcumin and curcumin glucuronide in human hepatocellular carcinoma HepG2 cells.

PubMed

Shoji, Motomu; Nakagawa, Kiyotaka; Watanabe, Akio; Tsuduki, Tsuyoshi; Yamada, Teiko; Kuwahara, Shigefumi; Kimura, Fumiko; Miyazawa, Teruo

2014-05-15

Curcumin is a yellow pigment found in turmeric (Curcuma Longa L.), and is reported, in recent studies, to have several pharmacological effects, including anti-oxidant, anti-inflammatory, anti-tumour and lipid-lowering properties. However, as most curcumin is conjugated when absorbed through the intestine, free curcumin is present at extremely low levels inside the body. Therefore, curcumin metabolites have been presumed to be responsible for the curcumin bioactivity. In this study, we first confirmed that curcumin glucuronide is the major metabolite of curcumin found in the plasma after oral administration of curcumin in rats. Next, we synthesised curcumin glucuronide and compared the effects of curcumin and curcumin glucuronide on gene expression in a human hepatoma cell line (HepG2). We found that the effects of curcumin glucuronide are weaker than those of curcumin and that this difference is related to relative absorption rates of curcumin and curcumin glucuronide into HepG2 cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

Unravelling the Mystery of Capsaicin: A Tool to Understand and Treat Pain

PubMed Central

Brock, Christina; Olesen, Anne Estrup; Andresen, Trine; Nilsson, Matias; Dickenson, Anthony H.

2012-01-01

A large number of pharmacological studies have used capsaicin as a tool to activate many physiological systems, with an emphasis on pain research but also including functions such as the cardiovascular system, the respiratory system, and the urinary tract. Understanding the actions of capsaicin led to the discovery its receptor, transient receptor potential (TRP) vanilloid subfamily member 1 (TRPV1), part of the superfamily of TRP receptors, sensing external events. This receptor is found on key fine sensory afferents, and so the use of capsaicin to selectively activate pain afferents has been exploited in animal studies, human psychophysics, and imaging studies. Its effects depend on the dose and route of administration and may include sensitization, desensitization, withdrawal of afferent nerve terminals, or even overt death of afferent fibers. The ability of capsaicin to generate central hypersensitivity has been valuable in understanding the consequences and mechanisms behind enhanced central processing of pain. In addition, capsaicin has been used as a therapeutic agent when applied topically, and antagonists of the TRPV1 receptor have been developed. Overall, the numerous uses for capsaicin are clear; hence, the rationale of this review is to bring together and discuss the different types of studies that exploit these actions to shed light upon capsaicin working both as a tool to understand pain but also as a treatment for chronic pain. This review will discuss the various actions of capsaicin and how it lends itself to these different purposes. PMID:23023032

Enzyme-assisted supercritical carbon dioxide extraction of black pepper oleoresin for enhanced yield of piperine-rich extract.

PubMed

Dutta, Sayantani; Bhattacharjee, Paramita

2015-07-01

Black pepper (Piper nigrum L.), the King of Spices is the most popular spice globally and its active ingredient, piperine, is reportedly known for its therapeutic potency. In this work, enzyme-assisted supercritical carbon dioxide (SC-CO2) extraction of black pepper oleoresin was investigated using α-amylase (from Bacillus licheniformis) for enhanced yield of piperine-rich extract possessing good combination of phytochemical properties. Optimization of the extraction parameters (without enzyme), mainly temperature and pressure, was conducted in both batch and continuous modes and the optimized conditions that provided the maximum yield of piperine was in the batch mode, with a sample size of 20 g of black pepper powder (particle diameter 0.42 ± 0.02 mm) at 60 °C and 300 bar at 2 L/min of CO2 flow. Studies on activity of α-amylase were conducted under these optimized conditions in both batch and continuous modes, with varying amounts of lyophilized enzyme (2 mg, 5 mg and 10 mg) and time of exposure of the enzyme to SC-CO2 (2.25 h and 4.25 h). The specific activity of the enzyme increased by 2.13 times when treated in the continuous mode than in the batch mode (1.25 times increase). The structural changes of the treated enzymes were studied by (1)H NMR analyses. In case of α-amylase assisted extractions of black pepper, both batch and continuous modes significantly increased the yields and phytochemical properties of piperine-rich extracts; with higher increase in batch mode than in continuous. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Influence of capsaicin infusion on secondary peristalsis in patients with gastroesophageal reflux disease

PubMed Central

Yi, Chih-Hsun; Lei, Wei-Yi; Hung, Jui-Sheng; Liu, Tso-Tsai; Chen, Chien-Lin; Pace, Fabio

2016-01-01

AIM To determine whether capsaicin infusion could influence heartburn perception and secondary peristalsis in patients with gastroesophageal reflux disease (GERD). METHODS Secondary peristalsis was performed with slow and rapid mid-esophageal injections of air in 10 patients with GERD. In a first protocol, saline and capsaicin-containing red pepper sauce infusions were randomly performed, whereas 2 consecutive sessions of capsaicin-containing red pepper sauce infusions were performed in a second protocol. Tested solutions including 5 mL of red pepper sauce diluted with 15 mL of saline and 20 mL of 0.9% saline were infused into the mid-esophagus via the manometric catheter at a rate of 10 mL/min with a randomized and double-blind fashion. During each study protocol, perception of heartburn, threshold volumes and peristaltic parameters for secondary peristalsis were analyzed and compared between different stimuli. RESULTS Infusion of capsaicin significantly increased heartburn perception in patients with GERD (P < 0.001), whereas repeated capsaicin infusion significantly reduced heartburn perception (P = 0.003). Acute capsaicin infusion decreased threshold volume of secondary peristalsis (P = 0.001) and increased its frequency (P = 0.01) during rapid air injection. The prevalence of GERD patients with successive secondary peristalsis during slow air injection significantly increased after capsaicin infusion (P = 0.001). Repeated capsaicin infusion increased threshold volume of secondary peristalsis (P = 0.002) and reduced the frequency of secondary peristalsis (P = 0.02) during rapid air injection. CONCLUSION Acute esophageal exposure to capsaicin enhances heartburn sensation and promotes secondary peristalsis in gastroesophageal reflux disease, but repetitive capsaicin infusion reverses these effects. PMID:28018112

Curcumin and aging

USDA-ARS?s Scientific Manuscript database

Curcumin has been used commonly as a spice, food additive, and an herbal medicine worldwide. Known as a bioactive polyphenolic, curcumin has a broad range of beneficial properties to human health. Recently, active research on curcumin with respect to aging and related traits in model organisms has d...

Early experience of intra-ureteric capsaicin infusion in loin pain haematuria syndrome.

PubMed

Armstrong, T; McLean, A D; Hayes, M; Morgans, B T; Tulloch, D N

2000-02-01

To evaluate early results of the intra-ureteric instillation of capsaicin for the treatment of loin pain haematuria syndrome (LPHS). Ten patients with LPHS were treated using intra-ureteric capsaicin instillation. A solution of capsaicin was infused into the affected ureter through an embolectomy catheter, under anaesthesia. The success of the treatment was assessed using patient questionnaires and the quantitative reduction in the patients' analgesic requirements measured. During a mean follow-up of 6 months, six of the 10 patients had short- to medium-term symptomatic relief after one or more treatments; four had no relief from their symptoms. One patient had a mucosal ulceration in the bladder after extravasation of the capsaicin solution. Two patients subsequently underwent simple nephrectomy for symptomatic nonfunctioning kidneys. These results are consistent with other preliminary reports of the efficacy of capsaicin treatment in LPHS and such treatment therefore has a definite therapeutic role in this difficult condition. We are uncertain if the treatment contributed to the deterioration of the excised kidneys. This early experience suggests a need for careful consideration when contemplating this treatment, with attention directed to both the initial diagnosis and possibly the technique of capsaicin/instillation. We include a protocol to follow when preparing patients for capsaicin treatment.

Environmental risk assessment on capsaicin used as active substance for antifouling system on ships.

PubMed

Wang, Jianbing; Shi, Ting; Yang, Xiaoling; Han, Wenya; Zhou, Yunrui

2014-06-01

Biodegradation experiments were carried out with capsaicin to evaluate its degradability. The results show that capsaicin was readily biodegradable under aerobic conditions. The values of Kow and the calculated bioconcentration factor indicate that capsaicin have a low potential for bioconcentration. The fish acute toxicity tests conducted with Brachydanio rerio show LC50 for capsaicin was 5.98 mg L(-1). The tests of alga growth inhibition conducted with Selenastrum capricornutum suggest EC50 for capsaicin was 114 mg L(-1). The calculated PNEC (Predicted No Effect Concentration) was 4.9×10(-4) mg L(-1). The average PEC (Predicted Environmental Concentration) for OECD-EU commercial harbor and marina were 3.99×10(-6) and 2.49×10(-5) mg L(-1), respectively. These indicate that the PEC was much less than the PNEC for capsaicin. The low Kp value of capsaicin suggests the data about the risk of capsaicin to sediment organisms can be waived. According to the results from the analysis of the degradation, bioaccumulation, toxicity and accumulation in sediment, it can be concluded that capsaicin used as active substance for antifouling system on ships poses relatively low risk to marine environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Capsaicin: Friend or Foe in Skin Cancer and Other Related Malignancies?

PubMed

Georgescu, Simona-Roxana; Sârbu, Maria-Isabela; Matei, Clara; Ilie, Mihaela Adriana; Caruntu, Constantin; Constantin, Carolina; Neagu, Monica; Tampa, Mircea

2017-12-16

Capsaicin is the main pungent in chili peppers, one of the most commonly used spices in the world; its analgesic and anti-inflammatory properties have been proven in various cultures for centuries. It is a lipophilic substance belonging to the class of vanilloids and an agonist of the transient receptor potential vanilloid 1 receptor. Taking into consideration the complex neuro-immune impact of capsaicin and the potential link between inflammation and carcinogenesis, the effect of capsaicin on muco-cutaneous cancer has aroused a growing interest. The aim of this review is to look over the most recent data regarding the connection between capsaicin and muco-cutaneous cancers, with emphasis on melanoma and muco-cutaneous squamous cell carcinoma.

Capsaicin-capped silver nanoparticles: its kinetics, characterization and biocompatibility assay

NASA Astrophysics Data System (ADS)

Amruthraj, Nagoth Joseph; Preetam Raj, John Poonga; Lebel, Antoine

2015-04-01

Capsaicin was used as a bio-reductant for the reduction of silver nitrate to form silver nanoparticles. The formation of the silver nanoparticles was initially confirmed by color change and Tyndall effect of light scattering. It was characterized with UV-visible spectroscopy, FTIR and TEM. Hemagglutination (H) test and H-inhibition assay were performed in the presence of AgNPs-capsaicin conjugates. The silver colloid solution after complete reduction turned into pale gray color. The characteristic surface plasmon resonance of silver nanoparticles (SNPs) was observed at 450 nm. Time taken for complete bio-reduction of silver nitrate and capping was found to be 16 hours. The amount of capsaicin required to reduce 20 ml of 1 mM silver nitrate solution was found to be 40 μg approximately. The FTIR results confirmed the capping of capsaicin on the silver metal. The particle size was within the range of 20-30 nm. The hemagglutination and H-inhibition test was negative for all the blood groups. The capsaicin-capped silver nanoparticles were compatible with blood cells in hemagglutination test implying biocompatibility as future therapeutic drug.

Structural mechanism underlying capsaicin binding and activation of TRPV1 ion channel

PubMed Central

Cheng, Wei; Yang, Wei; Yu, Peilin; Song, Zhenzhen; Yarov-Yarovoy, Vladimir; Zheng, Jie

2015-01-01

Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Capsaicin-bound channel structure was previously resolved by cryo-EM at 4.2-to-4.5 Å resolution, however important details required for mechanistic understandings are unavailable: capsaicin was registered as a small electron density, reflecting neither its chemical structure nor specific ligand-channel interactions. We obtained the missing atomic-level details by iterative computation, which were confirmed by systematic site-specific functional tests. We observed that the bound capsaicin takes “tail-up, head-down” configurations. The vanillyl and amide groups form specific interactions to anchor its bound position, while the aliphatic tail may sample a range of conformations, making it invisible in cryo-EM images. Capsaicin stabilizes the open state by “pull-and-contact” interactions between the vanillyl group and the S4-S5 linker. Our study provided a structural mechanism for the agonistic function of capsaicin and its analogs, and demonstrated an effective approach to obtain atomic level information from cryo-EM structures. PMID:26053297

Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review.

PubMed

Srinivasan, Krishnapura

2016-07-03

Capsaicin, the pungent alkaloid of red pepper (Capsicum annuum) has been extensively studied for its biological effects which are of pharmacological relevance. These include: cardio protective influence, antilithogenic effect, antiinflammatory, and analgesia, thermogenic influence, and beneficial effects on gastrointestinal system. Therefore, capsaicinoids may have the potential clinical value for pain relief, cancer prevention and weight loss. It has been shown that capsaicinoids are potential agonists of capsaicin receptor (TRPV1). They could exert the effects not only through the receptor-dependent pathway but also through the receptor-independent one. The involvement of neuropeptide Substance P, serotonin, and somatostatin in the pharmacological actions of capsaicin has been extensively investigated. Topical application of capsaicin is proved to alleviate pain in arthritis, postoperative neuralgia, diabetic neuropathy, psoriasis, etc. Toxicological studies on capsaicin administered by different routes are documented. Capsaicin inhibits acid secretion, stimulates alkali and mucus secretion and particularly gastric mucosal blood flow which helps in prevention and healing of gastric ulcers. Antioxidant and antiinflammatory properties of capsaicin are established in a number of studies. Chemopreventive potential of capsaicin is evidenced in cell line studies. The health beneficial hypocholesterolemic influence of capsaicin besides being cardio protective has other implications, viz., prevention of cholesterol gallstones and protection of the structural integrity of erythrocytes under conditions of hypercholesterolemia. Beneficial influences of capsaicin on gastrointestinal system include digestive stimulant action and modulation of intestinal ultrastructure so as to enhance permeability to micronutrients.

Treatment of Neuropathic Pain with the Capsaicin 8% Patch: Is Pretreatment with Lidocaine Necessary?

PubMed Central

Kern, Kai-Uwe; Nowack, Walburga; Poole, Chris

2014-01-01

The capsaicin 8% patch can effectively treat neuropathic pain, but application can cause discomfort or a burning sensation. Until March 2013, it was recommended that patients be pretreated with a topical anesthetic, for example lidocaine, before capsaicin patch application. However, speculation existed over the need for pretreatment and its effectiveness in alleviating treatment-associated discomfort. This article compares tolerability to and efficacy of the capsaicin patch in pretreated and non-pretreated patients. All patients received a single capsaicin patch application. Pretreated patients received a lidocaine plaster before and intravenous lidocaine and metamizole infusions during capsaicin patch application. Pain levels, assessed using a Numeric Rating Scale (NRS), were used to determine tolerability and efficacy. All patients (pretreated n = 32; non-pretreated n = 26) completed 100% of the intended capsaicin patch application duration. At the time of capsaicin patch removal, 69% of pretreated and 88% of non-pretreated patients reported an NRS score increase, which returned to baseline by 6 hours post-treatment. There was no significant difference in mean NRS score between patient groups at any time during or after capsaicin patch treatment. Response was similar between patient groups; capsaicin patch treatment provided rapid and significant pain reductions that were sustained over 12 weeks. The same proportion of pretreated and non-pretreated patients reported willingness to receive retreatment with the capsaicin patch. This analysis shows that the capsaicin 8% patch is generally tolerable, and the small discomfort associated with patch application is short-lived. Lidocaine pretreatment does not have a significant effect on tolerability, efficacy, or patient willingness to receive retreatment. PMID:24289500

Behavioral characteristics of capsaicin mediated cutaneous, myogenic, and arthrogenic orofacial nociception in rats.

PubMed

Rohrs, Eric L; Neubert, John K; Caudle, Robert M; Allen, Kyle D

2018-04-30

To assess changes in orofacial tactile sensitivity and gnawing related to capsaicin-mediated cutaneous, myogenic, and arthrogenic nociception in the rat. After recovery from anesthesia, orofacial tactile sensitivity and gnawing were assessed using operant testing methods following capsaicin application. Twenty female CD-Hairless rats were tested with bilateral capsaicin cream application to the cheek or with isoflurane anesthesia alone. Following several weeks of recovery, animals (n = 20) received either 10 μL unilateral masseter injections of vehicle, or phosphate buffered saline (PBS) to assess injection sensitization. After several weeks, masseter capsaicin (1.0%) injections (10 μL) were assessed compared to vehicle and PBS (n = 13). Weeks later capsaicin TMJ injections were evaluated. Animals (n = 11) received either 10 μL unilateral TMJ injections of capsaicin solution (1%) or vehicle. Capsaicin cream to the skin significantly altered gnawing activity (increased puncture time by 248 s (p = 0.0002)) and tactile sensitivity (decreased tolerated bottle distance by 0.980 cm compared to isoflurane only (p = 0.0001)). Similarly, capsaicin masseter injection increased puncture time (339.6 s, p = 0.07) and decreased tolerated bottle distance (1.04 cm, p = 0.005) compared to vehicle. However, intra-articular capsaicin in the TMJ only modified gnawing (increased puncture time by 133 s), with no changes found in tactile sensitivity compared to vehicle. Application of capsaicin to the skin and masseter had similar behavioral effects; however, intra-articular injections to the TMJ only affected gnawing. These data indicate the behavioral changes in rodent models of myogenic and cutaneous pain may be markedly different than models of arthrogenic pain originating from the TMJ. Copyright © 2018. Published by Elsevier Ltd.

Vascular and Psychophysical Effects of Topical Capsaicin Application to Orofacial Tissues

PubMed Central

Boudreau, Shellie A.; Wang, Kelun; Svensson, Peter; Sessle, Barry J.; Arendt-Nielsen, Lars

2011-01-01

Aims To characterize and contrast human sensory and vascular changes produced by topical application of the algesic chemical capsaicin to the glabrous lips and tongue. Methods Applications of 1% capsaicin or vehicle cream to the glabrous lips and tongue were randomized between two two-trial sessions. The capsaicin trial followed the vehicle trial for each session. Before and 5, 15, and 30 minutes after capsaicin or vehicle cream application, six parameters were recorded from the glabrous lips or the tongue dorsum: (1) burning pain intensity, as measured on a visual analog scale; (2) burning pain area, as indicated by subjects on an orofacial drawing; (3) mechanical sensitivity, as measured by a von Frey filament; (4) visual flare; (5) blood flow and temperature, as measured by laser-Doppler imaging and thermography, respectively; and (6) areas of increased temperature (hot spots), as calculated by a digital tracer from the thermographs. Data were analyzed by ANOVAs and Pearson’s correlations. Results Compared to vehicle application, capsaicin elicited burning pain, increases in blood flow and temperature, but no change in mechanical sensitivity in the glabrous lips or tongue. Greater increases in blood flow and temperature paralleled more intense burning pain and larger areas of perceived pain for the lips compared to the tongue. The location of distinct areas of increased temperature within the orofacial area differed between the capsaicin-lip and capsaicin-tongue trials. Conclusion The several differences between these responses to noxious stimulation of the glabrous lips and tongue may have implications for examinations of orofacial somatosensory functions. PMID:19639105

Distinct Modulations of Human Capsaicin Receptor by Protons and Magnesium through Different Domains*

PubMed Central

Wang, Shu; Poon, Kinning; Oswald, Robert E.; Chuang, Huai-hu

2010-01-01

The capsaicin receptor (TRPV1) is a nonselective cation channel that integrates multiple painful stimuli, including capsaicin, protons, and heat. Protons facilitate the capsaicin- and heat-induced currents by decreasing thermal threshold or increasing agonist potency for TRPV1 activation (Tominaga, M., Caterina, M. J., Malmberg, A. B., Rosen, T. A., Gilbert, H., Skinner, K., Raumann, B. E., Basbaum, A. I., and Julius, D. (1998) Neuron 21, 531–543). In the presence of saturating capsaicin, rat TRPV1 (rTRPV1) reaches full activation, with no further stimulation by protons. Human TRPV1 (hTRPV1), a species ortholog with high homology to rTRPV1, is potentiated by extracellular protons and magnesium, even at saturating capsaicin. We investigated the structural basis for protons and magnesium modulation of fully capsaicin-bound human receptors. By analysis of chimeric channels between hTRPV1 and rTRPV1, we found that transmembrane domain 1–4 (TM1–4) of TRPV1 determines whether protons can further open the fully capsaicin-bound receptors. Mutational analysis identified a titratable glutamate residue (Glu-536) in the linker between TM3 and TM4 critical for further stimulation of fully liganded hTRPV1. In contrast, hTRPV1 TM5–6 is required for magnesium augmentation of capsaicin efficacy. Our results demonstrate that capsaicin efficacy of hTRPV1 correlates with the extracellular ion milieu and unravel the relevant structural basis of modulation by protons and magnesium. PMID:20145248

Topical capsaicin for pain in osteoarthritis: A literature review.

PubMed

Guedes, Vânia; Castro, João Paulo; Brito, Iva

Osteoarthritis is the most common joint disorder worldwide. The predominant symptom, pain, is usually treated with acetaminophen or oral non-steroidal anti-inflammatory drugs, although they are associated with a significant risk of side effects. Topical capsaicin may represent an effective and safe alternative. The aim of this review is to examine the evidence for the efficacy and safety profile of topical capsaicin in the management of pain caused by osteoarthritis. Databases were searched for articles published between 2004 and 2016, in Portuguese, English or Spanish, using the search terms "capsaicin" and "osteoarthritis". When compared to placebo, it was found that topical capsaicin has a good safety profile and efficacy in reducing osteoarthritis pain of the hand, knee, hip or shoulder. However, the studies have significant limitations, the most important the difficulty of blinding. It is attributed to this review the strength of recommendation B. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Curcumin Nanotechnologies and Its Anticancer Activity.

PubMed

Subramani, Parasuraman Aiya; Panati, Kalpana; Narala, Venkata Ramireddy

2017-04-01

Cancer is one of the leading causes of death worldwide. Curcumin is a well-established anticancer agent in vitro but its efficacy is yet to be proven in clinical trials. Poor bioavailability of curcumin is the principal reason behind the lack of efficiency of curcumin in clinical trials. Many studies prove that the bioavailability of curcumin can be improved by administering it through nanoparticle drug carriers. This review focuses on the efforts made in the field of nanotechnology to improve the bioavailability of curcumin. Nanotechnologies of curcumin come in various shapes and sizes. The simplest curcumin nanoparticle that increased the bioavailability of curcumin is the curcumin-metal complex. On the other hand, we have intricate thermoresponsive nanoparticles that can release curcumin upon stimulation (analogous to a remote control). Future research required for developing potent curcumin nanoparticles is also discussed.

Piperine activates human pregnane X receptor to induce the expression of cytochrome P450 3A4 and multidrug resistance protein 1

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

Wang, Yue-Ming; Lin, Wenwei; Chai, Sergio C.

2013-10-01

Activation of the pregnane X receptor (PXR) and subsequently its target genes, including those encoding drug transporters and metabolizing enzymes, while playing substantial roles in xenobiotic detoxification, might cause undesired drug-drug interactions. Recently, an increased awareness has been given to dietary components for potential induction of diet–drug interactions through activation of PXR. Here, we studied, whether piperine (PIP), a major component extracted from the widely-used daily spice black pepper, could induce PXR-mediated expression of cytochrome P450 3A4 (CYP3A4) and multidrug resistance protein 1 (MDR1). Our results showed that PIP activated human PXR (hPXR)-mediated CYP3A4 and MDR1 expression in human hepatocytes,more » intestine cells, and a mouse model; PIP activated hPXR by recruiting its coactivator SRC-1 in both cellular and cell-free systems; PIP bound to the hPXR ligand binding domain in a competitive ligand binding assay in vitro. The dichotomous effects of PIP on induction of CYP3A4 and MDR1 expression observed here and inhibition of their activity reported elsewhere challenges the potential use of PIP as a bioavailability enhancer and suggests that caution should be taken in PIP consumption during drug treatment in patients, particularly those who favor daily pepper spice or rely on certain pepper remedies. - Highlights: • Piperine induces PXR-mediated CYP3A4 and MDR1 expression. • Piperine activates PXR by binding to PXR and recruiting coactivator SRC-1. • Piperine induces PXR activation in vivo. • Caution should be taken in piperine consumption during drug treatment.« less

Caloric Restriction reduces inflammation and improves T cell-mediated immune response in obese mice but concomitant consumption of curcumin/piperine adds no further benefit

USDA-ARS?s Scientific Manuscript database

Obesity is associated with low-grade inflammation and impaired immune response. Caloric restriction (CR) has been shown to inhibit inflammatory response and enhance cell-mediated immune function. Curcumin, the bioactive phenolic component of turmeric spice, is proposed to have anti-obesity and anti-...

The effects of juvenile capsaicin desensitization in rats: behavioral impairments.

PubMed

Petrovszki, Zita; Adam, Gábor; Kekesi, Gabriella; Tuboly, Gábor; Morvay, Zita; Nagy, Endre; Benedek, György; Horvath, Gyöngyi

2014-02-10

Capsaicin desensitization leads to behavioral changes, some of which are related to schizophrenia, but investigations into these effects have been scarce. The goal of this study was to characterize the consequences of juvenile capsaicin desensitization on different functions: acute and inflammation-induced thermal and mechanical sensitivity, urinary bladder capacity and thermoregulation, and also on the potentially schizophrenia-related impairments in sensory-motor gating, motor activity and cognitive functioning. Male Wistar rats desensitized with increasing doses of subcutaneous capsaicin after weaning were investigated. Heat and mechanical pain sensitivity did not change significantly; however, morphine produced a prolonged decrease in the nociceptive response to inflammation in desensitized animals. Ultrasound examination of the bladder revealed enhanced bladder volume in treated animals. Capsaicin-treated animals had higher body temperature at 22 °C in both dark and light periods, and they also showed prolonged hyperthermia in new environmental circumstances. Warm environment induced a profound impairment of thermoregulation in desensitized animals. The treated animals also showed higher levels of activity during the active phase and at both cool and warm temperatures. The amplitude of the responses to auditory stimuli and prepulse inhibition did not differ between the two groups, but the desensitized animals showed learning impairments in the novel object recognition test. These results suggest that juvenile capsaicin desensitization leads to sustained changes in several functions that may be related to schizophrenia. We propose that capsaicin desensitization, together with other interventions, may lead to an improved chronic animal model of schizophrenia. Copyright © 2013 Elsevier Inc. All rights reserved.

The effect of capsaicin application on mast cells in normal human skin.

PubMed

Bunker, C B; Cerio, R; Bull, H A; Evans, J; Dowd, P M; Foreman, J C

1991-05-01

Peptides released from sensory nerves during an axon reflex are thought to cause mast cell degranulation, histamine (Hi) release and Hi-induced vasodilatation leading to the flare of the triple response. Capsaicin stimulates peptide release from sensory neurones and causes flare in vivo but does not cause Hi release from mast cells in vitro. The effects of capsaicin on mast cell degranulation in human skin in vivo has been studied by histological examination of skin biopsies after topical capsicin (1%) treatment of stratum corneum-denuded forearm in four volunteers. The results show a significant reduction in the visible numbers of mast cells and the appearance of degranulated mast cells ghosts in the skin six hours after capsaicin application. Since capsaicin itself does not release Hi from mast cells, these data suggest that capsaicin-induced release of peptides from neurones could cause mast cell degranulation.

Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer's disease.

PubMed

Chonpathompikunlert, Pennapa; Wattanathorn, Jintanaporn; Muchimapura, Supaporn

2010-03-01

Recently, numerous medicinal plants possessing profound central nervous system effects and antioxidant activity have received much attention as food supplement to improve cognitive function against cognitive deficit condition including in Alzheimer's disease condition. Based on this information, the effect of piperine, a main active alkaloid in fruit of Piper nigrum, on memory performance and neurodegeneration in animal model of Alzheimer's disease have been investigated. Adult male Wistar rats (180-220 g) were orally given piperine at various doses ranging from 5, 10 and 20mg/kg BW at a period of 2 weeks before and 1 week after the intracerebroventricular administration of ethylcholine aziridinium ion (AF64A) bilaterally. The results showed that piperine at all dosage range used in this study significantly improved memory impairment and neurodegeneration in hippocampus. The possible underlying mechanisms might be partly associated with the decrease lipid peroxidation and acetylcholinesterase enzyme. Moreover, piperine also demonstrated the neurotrophic effect in hippocampus. However, further researches about the precise underlying mechanism are still required. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and curcumin metabolites in mice

PubMed Central

Zhongfa, Liu; Chiu, Ming; Wang, Jiang; Chen, Wei; Yen, Winston; Fan-Havard, Patty; Yee, Lisa D.; Chan, Kenneth K.

2012-01-01

Purpose Curcumin has shown a variety of biological activity for various human diseases including cancer in preclinical setting. Its poor oral bioavailability poses significant pharmacological barriers to its clinical application. Here, we established a practical nano-emulsion curcumin (NEC) containing up to 20% curcumin (w/w) and conducted the pharmacokinetics of curcuminoids and curcumin metabolites in mice. Methods This high loading NEC was formulated based on the high solubility of curcumin in polyethylene glycols (PEGs) and the synergistic enhancement of curcumin absorption by PEGs and Cremophor EL. The pharmacokinetics of curcuminoids and curcumin metabolites was characterized in mice using a LC–MS/MS method, and the pharmacokinetic parameters were determined using WinNonlin computer software. Results A tenfold increase in the AUC0→24h and more than 40-fold increase in the Cmax in mice were observed after an oral dose of NEC compared with suspension curcumin in 1% methylcellulose. The plasma pharmacokinetics of its two natural congeners, demethoxycurcumin and bisdemethoxycurcumin, and three metabolites, tetrahydrocurcumin (THC), curcumin-O-glucuronide, and curcumin-O-sulfate, was characterized for the first time in mice after an oral dose of NEC. Conclusion This oral absorption enhanced NEC may provide a practical formulation to conduct the correlative study of the PK of curcuminoids and their pharmacodynamics, e.g., hypomethylation activity in vivo. PMID:21968952

Role of intrinsic nitrergic neurones on vagally mediated striated muscle contractions in the hamster oesophagus

PubMed Central

Izumi, Noriaki; Matsuyama, Hayato; Ko, Mifa; Shimizu, Yasutake; Takewaki, Tadashi

2003-01-01

Oesophageal peristalsis is controlled by vagal motor neurones, and intrinsic neurones have been identified in the striated muscle oesophagus. However, the effect(s) of intrinsic neurones on vagally mediated contractions of oesophageal striated muscles has not been defined. The present study was designed to investigate the role of intrinsic neurones on vagally evoked contractions of oesophageal striated muscles, using hamster oesophageal strips maintained in an organ bath. Stimulation (30 μs, 20 V) of the vagus nerve trunk produced twitch contractions. Piperine inhibited vagally evoked contractions, while capsaicin and NG-nitro-L-arginine methyl ester (L-NAME) abolished the inhibitory effect of piperine. The effect of L-NAME was reversed by subsequent addition of L-arginine, but not by D-arginine. L-NAME did not have any effect on the vagally mediated contractions and presumed 3H-ACh release. NONOate, a nitric oxide donor, and dibutyryl cyclic GMP inhibited twitch contractions. Inhibition of vagally evoked contractions by piperine and NONOate was fully reversed by ODQ, an inhibitor of guanylate cyclase. Immunohistochemical staining showed immunoreactivity for nitric oxide synthase (NOS) in nerve cell bodies and fibres in the myenteric plexus and the presence of choline acetyltransferase and NOS in the motor endplates. Only a few NOS-immunoreactive portions in the myenteric plexus showed vanilloid receptor 1 (VR1) immunoreactivity. Our results suggest that there is a local neural reflex that involves capsaicin-sensitive neurones, nitrergic myenteric neurones and vagal motor neurones. PMID:12813149

Bronchodilatation by tachykinins and capsaicin in the mouse main bronchus.

PubMed

Manzini, S

1992-04-01

1. The effect of sensory neuropeptides and capsaicin on basal and stimulated tone of mouse bronchial smooth muscle has been evaluated. 2. In basal conditions neither sensory neuropeptides (substance P, neurokinin A or calcitonin gene-related peptide (CGRP) nor capsaicin exerted any contractile effects. However, when a tonic contraction was induced with carbachol (1 microM) a prompt relaxation was induced by substance P (1- 100 nM) and by neurokinin A (1- 100 nM), with substance P being more potent. A second application of substance P was without effect. CGRP (10 nM) produced only a very small and erratic relaxation. Relaxation was also induced by capsaicin (1 microM), and this response could be evoked only once in each preparation. In 4 out of 6 preparations a cross-desensitization between substance P and capsaicin was observed. 3. The selective NK1 tachykinin agonist, [Pro9]-SP sulphone (1 microM), exerted potent bronchodilator actions on carbachol-contracted mouse bronchial preparations. In contrast, neither [beta Ala8]-NKA (4-10) nor [MePhe7]-NKB (both at a concentration of 1 microM), selective synthetic agonists for NK2 and NK3 receptors, exerted significant relaxant effects. Furthermore, the selective NK1 tachykinin antagonist, (+/-)-CP 96,345 (1 microM), abolished substance P (1 nM)- but not isoprenaline (0.1 microM)-induced relaxations. 4. Application of electrical field stimulation (EFS) (20 Hz, supramaximal voltage, 0.5 ms for 10 s) to carbachol-contracted preparations evoked a transient contraction followed by a relaxation. The tetrodotoxin-sensitive slow component of this relaxation was reduced following capsaicin desensitization. 5. In the presence of indomethacin (5 microM) the relaxation induced by substance P, capsaicin or EFS was suppressed.6. In conclusion, the mouse main bronchus appears to be a monoreceptorial tissue containing only NK, receptors which subserve bronchodilator functions. Such receptors could be activated by exogenous or

Cytometric analysis on cytotoxicity of curcumin on rat thymocytes: Proapoptotic and antiapoptotic actions of curcumin.

PubMed

Koizumi, Kazuki; Kawanai, Takuya; Hashimoto, Erika; Kanbara, Yasuhiro; Masuda, Toshiya; Kanemaru, Kaori; Okano, Yoshiro; Oyama, Yasuo

2011-06-01

Curcumin exhibits various pharmacological actions including anti-inflammatory, anti-infectious, and anticancer actions. Furthermore, the supplements containing curcumin are supplied for persons consuming alcoholic beverage. A primary criterion for an ingredient ingested by general population is that it exerts no harmful effect. In this study, we examined the effect of curcumin on rat thymocytes to see if curcumin exerts cytotoxicity on normal cells. The incubation with 10 μM curcumin for 24h increased the population of dead cells while it was not the case for 5 μM or less. Curcumin at 5-10 μM increased the populations of shrunken cells and the cells positive to annexin V, phenomena for early stage of apoptosis. However, the incubation with 10 μM curcumin suppressed the increase in population of cells with hypodiploid DNA, a phenomenon for late stage of apoptosis. Thus, curcumin at 10 μM may show both proapoptotic and antiapoptotic actions. The simultaneous incubation with 5 μM, but not 3 μM, curcumin and 0.5% ethanol increased the population of shrunken cells. It is likely that curcumin at 5 μM or more exerts cytotoxic action on normal cells although many studies show some anticancer actions of curcumin at 10 μM or more on cancer cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bronchodilatation by tachykinins and capsaicin in the mouse main bronchus.

PubMed Central

Manzini, S.

1992-01-01

1. The effect of sensory neuropeptides and capsaicin on basal and stimulated tone of mouse bronchial smooth muscle has been evaluated. 2. In basal conditions neither sensory neuropeptides (substance P, neurokinin A or calcitonin gene-related peptide (CGRP) nor capsaicin exerted any contractile effects. However, when a tonic contraction was induced with carbachol (1 microM) a prompt relaxation was induced by substance P (1- 100 nM) and by neurokinin A (1- 100 nM), with substance P being more potent. A second application of substance P was without effect. CGRP (10 nM) produced only a very small and erratic relaxation. Relaxation was also induced by capsaicin (1 microM), and this response could be evoked only once in each preparation. In 4 out of 6 preparations a cross-desensitization between substance P and capsaicin was observed. 3. The selective NK1 tachykinin agonist, [Pro9]-SP sulphone (1 microM), exerted potent bronchodilator actions on carbachol-contracted mouse bronchial preparations. In contrast, neither [beta Ala8]-NKA (4-10) nor [MePhe7]-NKB (both at a concentration of 1 microM), selective synthetic agonists for NK2 and NK3 receptors, exerted significant relaxant effects. Furthermore, the selective NK1 tachykinin antagonist, (+/-)-CP 96,345 (1 microM), abolished substance P (1 nM)- but not isoprenaline (0.1 microM)-induced relaxations. 4. Application of electrical field stimulation (EFS) (20 Hz, supramaximal voltage, 0.5 ms for 10 s) to carbachol-contracted preparations evoked a transient contraction followed by a relaxation. The tetrodotoxin-sensitive slow component of this relaxation was reduced following capsaicin desensitization. 5. In the presence of indomethacin (5 microM) the relaxation induced by substance P, capsaicin or EFS was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1380376

Neonatal capsaicin treatment impairs vasopressin-mediated blood pressure recovery following acute hypotension.

PubMed Central

Bennett, T.; Gardiner, S. M.

1984-01-01

Rats were treated with a single injection of either capsaicin (50 mg kg-1 s.c.) or vehicle on day 2 after birth. When the animals were adult, they were challenged with osmotic (water deprivation) and haemodynamic (acute hypotension) stimuli that normally evoke vasopressin release. Capsaicin-treated and vehicle-injected rats showed similar body weight losses and plasma osmolalities following 48 h of water deprivation. Thus it appears that neonatal treatment with capsaicin does not impair the antidiuretic response to plasma hyperosmolality. Following acute ganglion blockade in the presence of angiotensin converting enzyme inhibition, there was some recovery of blood pressure in the vehicle-injected rats, but recovery was significantly (P less than 0.001) less in the capsaicin-treated animals. The recovery may be attributed to vasopressin since it was abolished by an antagonist selective for the pressor action of the peptide (d(CH2)5DAVP). These results suggest that neonatal treatment with capsaicin impairs vasopressin-mediated recovery of blood pressure following acute hypotension. The possible involvement of baro- or chemoreceptor afferents is discussed. PMID:6704593

The capsaicin cough reflex in eczema patients with respiratory symptoms elicited by perfume.

PubMed

Elberling, Jesper; Dirksen, Asger; Johansen, Jeanne Duus; Mosbech, Holger

2006-03-01

Respiratory symptoms elicited by perfume are common in the population but have unclear pathophysiology. Increased capsaicin cough responsiveness has been associated with the symptoms, but it is unknown whether the site of the symptoms in the airways influences this association. The aim of this study was to investigate the association between the site of airway symptoms elicited by perfume and cough responsiveness to bronchial challenge with capsaicin. 21 eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case control study. The participants completed a symptom questionnaire and underwent a bronchial challenge with capsaicin. Lower, but not upper, respiratory symptoms elicited by perfume were associated with increased capsaicin cough responsiveness. Having severe symptoms to perfume (n=11) did not relate to the site of the symptoms in the airways and was not associated with increased capsaicin cough responsiveness. In conclusion, respiratory symptoms elicited by perfume may reflect local hyperreactivity related to defensive reflexes in the airways, and measurements of the capsaicin cough reflex are relevant when patients with lower respiratory symptoms related to environmental perfume exposures are investigated.

A curcumin activated carboxymethyl cellulose-montmorillonite clay nanocomposite having enhanced curcumin release in aqueous media.

PubMed

Madusanka, Nadeesh; de Silva, K M Nalin; Amaratunga, Gehan

2015-12-10

A novel curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is reported. A superabsorbent biopolymer; carboxymethyl cellulose (CMC) was used as an emulsifier for curcumin which is a turmeric derived water insoluble polyphenolic compound with antibacterial/anti-cancer properties. Montmorillonite (MMT) nanoclay was incorporated in the formulation as a matrix material which also plays a role in release kinetics. It was observed that water solubility of curcumin in the nanocomposite has significantly increased (60% release within 2h and 30 min in distilled water at pH 5.4) compared to pure curcumin. The prepared curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is suitable as a curcumin carrier having enhanced release and structural properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

Curcumin and neurodegenerative diseases

PubMed Central

Monroy, Adriana; Lithgow, Gordon J.; Alavez, Silvestre

2013-01-01

Over the last ten years curcumin has been reported to be effective against a wide variety of diseases and is characterized as having anti-carcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, and anti-infectious properties. Recent studies performed in both vertebrate and invertebrate models have been conducted to determine whether curcumin was also neuroprotective. The efficacy of curcumin in several pre-clinical trials for neurodegenerative diseases has created considerable excitement mainly due to its lack of toxicity and low cost. This suggests that curcumin could be a worthy candidate for nutraceutical intervention. Since aging is a common risk factor for neurodegenerative diseases, it is possible that some compounds that target aging mechanisms could also prevent these kinds of diseases. One potential mechanism to explain several of the general health benefits associated with curcumin is that it may prevent aging-associated changes in cellular proteins that lead to protein insolubility and aggregation. This loss in protein homeostasis is associated with several age-related diseases. Recently, curcumin has been found to help maintain protein homeostasis and extend lifespan in the model invertebrate Caenorhabditis elegans. Here, we review the evidence from several animal models that curcumin improves healthspan by preventing or delaying the onset of various neurodegenerative diseases. PMID:23303664

Curcumin-cyclodextrin complexes enhanced the anti-cancer effects of curcumin.

PubMed

Zhang, Lili; Man, Shuli; Qiu, Huanna; Liu, Zhen; Zhang, Mi; Ma, Long; Gao, Wenyuan

2016-12-01

Curcumin (CUR), as a yellow pigment in the spice turmeric (Curcuma longa), possessed a pleiotropic application containing cancer therapy. Due to its poor oral bioavailability, the objective of this study was to investigate the use of curcumin-cyclodextrin complexes (CD15) as an approach to cancer chemoprevention. In this study, CUR encapsulation into the β-cyclodextrin (CD) cavity was achieved by the saturated aqueous solution method. CD15 was characterized by Fourier transform infrared (FTIR) and UV spectra analyses. An optimized CD15 was evaluated by cellular uptake and anti-cancer activity. As a result, CD15 enhanced curcumin delivery and improved its therapeutic efficacy compared with free curcumin in vivo and in vitro. Therefore, through regulation of MAPK/NF-κB pathway, CD15 up-regulated p53/p21 pathway, down-regulated CyclinE-CDK2 combination and increased Bax/caspase 3 expression to induce cellar apoptosis and G1-phase arrest. In conclusion, these results suggested that CD15 formulation should be used as a system for improving curcumin delivery and its therapeutic efficacy in lung cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Targets of curcumin

PubMed Central

Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

2010-01-01

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

Hot Chili Peppers: Extraction, Cleanup, and Measurement of Capsaicin

NASA Astrophysics Data System (ADS)

Huang, Jiping; Mabury, Scott A.; Sagebiel, John C.

2000-12-01

Capsaicin, the pungent ingredient of the red pepper or Capsicum annuum, is widely used in food preparation. The purpose of this experiment was to acquaint students with the active ingredients of hot chili pepper (capsaicin and dihydrocapsaicin), the extraction, cleanup, and analysis of these chemicals, as a fun and informative analytical exercise. Fresh peppers were prepared and extracted with acetonitrile, removing plant co-extractives by addition to a C-18 solid-phase extraction cartridge. Elution of the capsaicinoids was accomplished with a methanol-acetic acid solution. Analysis was completed by reverse-phase HPLC with diode-array or variable wavelength detection and calibration with external standards. Levels of capsaicin and dihydrocapsaicin were typically found to correlate with literature values for a specific hot pepper variety. Students particularly enjoyed relating concentrations of capsaicinoids to their perceived valuation of "hotness".

Reproductive effects of a pegylated curcumin.

PubMed

Murphy, Caitlin J; Tang, Huadong; Van Kirk, Edward A; Shen, Youqing; Murdoch, William J

2012-08-01

Curcumin, a polyphenol derived from the rhizome turmeric, has potential as an anticancer agent. We synthesized an amphipathic/surfactant pegylated curcumin (curcumin-PEG) designed for parenteral administration. Objectives of these investigations were to assess side-effects of a therapeutic regimen of curcumin-PEG in a preclinical model. Intraperitoneal (ip) tumor burdens were reduced in athymic female mice grafted with human SKOV-3 ovarian adenocarcinoma cells and injected intravenously (iv) with curcumin-PEG. There were no gross anatomical or histopathological effects detected in non-reproductive organs. Uteri (luminal fluid imbibition) and ovaries (decreased folliculogenesis) were affected by treatment. Curcumin-PEG ip hastened the onset of puberty in immature female mice. Live births were reduced in mature females housed with males and treated iv with curcumin-PEG; mating (vaginal plugs) was not affected. Accessory gland weights, testicular testosterone concentrations, and spermatogenesis were diminished in mature male mice following iv curcumin-PEG. Estrogenic/antiandrogenic and pregnancy-disrupting effects of a water soluble/bioavailable curcumin were demonstrated. Copyright © 2012 Elsevier Inc. All rights reserved.

Curcumin in inflammatory diseases.

PubMed

Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup

2013-01-01

Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Comparative analysis of protective effects of curcumin, curcumin-β-cyclodextrin nanoparticle and nanoliposomal curcumin on unsymmetrical dimethyl hydrazine poisoning in mice

PubMed Central

Li, Wei; Zhou, Mengzhou; Xu, Ning; Hu, Yong; Wang, Chao; Li, Deyuan; Liu, Liegang; Li, Dongsheng

2016-01-01

ABSTRACT The aim of this study was to compare the protective effects of curcumin, curcumin-β-cyclodextrin nanoparticle curcumin (BCD-CUR) and nanoliposomal curcumin (NLC) on unsymmetrical dimethylhydrazine (UDMH) induced poison in mice. Curcumin, BCD-CUR, and NLC were prepared and their properties of zeta potential, particle size, encapsulation efficiency, and loading capacity were characterized. Eighty-eight male ICR mice on normal chow diet were randomly divided into 11 groups, and intraperitoneally injected with UDMH alone, or together with different doses of curcumin, BCD-CUR or NLC daily for up to 10 d. Enzyme activities of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were analyzed by fully-automatic analyzer and neurotransmitter levels were determined with high performance liquid chromatography (HPLC). 150 mg/kg curcumin treatment alone significantly reduced levels of serum ALT and LDH that were induced by UDMH and markedly increased level of γ-amino butyric acid (GABA) that were reduced by UDMH in the hippocampus. 150 mg/kg BCD-CUR not only decreased significantly the increase of ALT, LDH and glutamate (Glu) but also recovered levels of AST and GABA. 150 mg/kg NLC recovered profoundly levels of AST and GABA while decreased remarkably the UDMH induced increase of ALT, LDH, Glu and 5-hydroxytryptamine (5-HT). In addition, treatments with all tested doses of NLC significantly reduced the UMDH induced dopamine (DA), the monoamine neurotransmitter. NLC had more profound protective effects against liver and central nervous system injury induced by UDMH than a suspension of BCD-CUR or curcumin did in mice. PMID:27710431

Conjugation of curcumin onto alginate enhances aqueous solubility and stability of curcumin.

PubMed

Dey, Soma; Sreenivasan, K

2014-01-01

Curcumin is a potential drug for various diseases including cancer. Prime limitations associated with curcumin are low water solubility, rapid hydrolytic degradation and poor bioavailability. In order to redress these issues we developed Alginate-Curcumin (Alg-Ccm) conjugate which was characterized by FTIR and (1)H NMR spectroscopy. The conjugate self-assembled in aqueous solution forming micelles with an average hydrodynamic diameter of 459 ± 0.32 nm and negative zeta potential. The spherical micelles were visualized by TEM. The critical micelle concentration (CMC) of Alg-Ccm conjugate was determined. A significant enhancement in the aqueous solubility of curcumin was observed upon conjugation with alginate. Formation of micelles improved the stability of curcumin in water at physiological pH. The cytotoxic activity of Alg-Ccm was quantified by MTT assay using L-929 fibroblast cells and it was found to be potentially cytotoxic. Hence, Alg-Ccm could be a promising drug conjugate as well as a nanosized delivery vehicle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multifunctional Curcumin Mediate Multitherapeutic Effects.

PubMed

Shehzad, Adeeb; Qureshi, Munibah; Anwar, Muhammad Nabeel; Lee, Young Sup

2017-09-01

Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases. Numerous studies have shown that curcumin modulate multiple molecular targets and can be translated to the clinics for multiple therapeutic processes. There is compelling evidence that curcumin can block cell proliferation, invasion, and angiogenesis as well as reduced the prolonged survival of cancer cells. Curcumin mediates anti-inflammatory effect through downregulation of inflammatory cytokines, transcription factors, protein kinases, and enzymes that promote inflammation and development of chronic diseases. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways by activating caspase cascades. Curcumin is a safe and nontoxic drug that has been reported to be well tolerated. Available clinical trials support the potential role of curcumin for treatment of various inflammatory disorders. However, curcumin's efficacy is hindered by poor absorption and low bioavailability, which limit its translation into clinics. This review outlines the potential pharmacological and clinical role of curcumin, which provide a gateway for the beneficial role of plant isolated compounds in treatment of various inflammatory diseases and cancer. © 2017 Institute of Food Technologists®.

PKC regulates capsaicin-induced currents of dorsal root ganglion neurons in rats.

PubMed

Zhou, Y; Zhou, Z S; Zhao, Z Q

2001-10-01

Capsaicin activates a non-specific cation conductance in a subset of dorsal root ganglion (DRG) neurons. The inward current and membrane potential of acutely isolated DRG neurons were examined using whole-cell patch recording methods. We report here that the current and voltage responses activated by capsaicin were markedly increased by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC). The mean current, after application of 0.3 microM PMA, was 153.5+/-5.7% of control (n=32) in Ca(2+)-free external solution and 181.6+/-6.8% of control (n=15) in standard external solution. Under current-clamp conditions, 0.3 microM PMA facilitated capsaicin-induced depolarization and action potential generation. Bindolylmaleimide I (BIM), a specific inhibitor of PKC activity, abolished the effect of PMA. In addition, capsaicin-evoked current was attenuated to 68.3+/-5.0% of control (n=13) by individual administration of 1 microM BIM in standard external solution, while 0.3 microM BIM did not have this effect. These data suggest that PKC can directly regulate the capsaicin response in DRG neurons, which could increase nociceptive sensory transmission and contribute to hyperalgesia.

Orally given gastroprotective capsaicin does not modify aspirin-induced platelet aggregation in healthy male volunteers (human phase I examination).

PubMed

Sandor, B; Papp, J; Mozsik, Gy; Szolcsanyi, J; Keszthelyi, Zs; Juricskay, I; Toth, K; Habon, Tamas

2014-12-01

Capsaicin is a well-known component of red pepper. Recent studies have shown that capsaicin could prevent gastric ulcer provoked by various NSAID-s like acetylsalicylic acid (ASA). Primary objective of this human clinical phase I trial was to investigate whether two different doses of capsaicin co-administered with ASA could alter the inhibitory effect of ASA on platelet aggregation. 15 healthy male subjects were involved in the study and treated orally with 400 μg capsaicin, 800 μg capsaicin, 500 mg ASA, 400 μg capsaicin+500 mg ASA and 800 μg capsaicin+500 mg ASA. Blood was drawn before and 1, 2, 6 and 24 hours after the drug administration. After that epinephrine induced platelet aggregation was measured by optical aggregometry. Between treatments, volunteers had a 6-day wash-out period. Our results showed that capsaicin had no effect on platelet aggregation, while as expected, ASA monotherapy resulted in a significant and clinically effective platelet aggregation inhibition (p ≤ 0.001). The combined ASA-capsaicin therapies reached equivalent effectiveness in platelet aggregation inhibition as ASA monotherapy. Our investigation proved that capsaicin did not influence the inhibitory effect of ASA on platelet aggregation, thus the capsaicin-ASA treatment would combine the antiplatelet effect of ASA with the possible gastroprotection of capsaicin.

Thermal conditions influence changes in body temperature induced by intragastric administration of capsaicin in mice.

PubMed

Mori, Noriyuki; Urata, Tomomi; Fukuwatari, Tsutomu

2016-08-01

Capsaicin has been reported to have unique thermoregulatory actions. However, changes in core temperature after the administration of capsaicin are a controversial point. Therefore, we investigated the effects of environmental thermal conditions on changes in body temperature caused by capsaicin in mice. We showed that intragastric administration of 10 and 15 mg/kg capsaicin increased tail temperature and decreased colonic temperatures in the core temperature (CT)-constant and CT-decreasing conditions. In the CT-increasing condition, 15 mg/kg capsaicin increased tail temperature and decreased colonic temperature. However, 10 mg/kg capsaicin increased colonic temperature. Furthermore, the amount of increase in tail temperature was greater in the CT-decreasing condition and lower in the CT-increasing condition, compared with that of the CT-constant condition. These findings suggest that the changes in core temperature were affected by the environmental thermal conditions and that preliminary thermoregulation state might be more important than the constancy of temperature to evaluate the effects of heat diffusion and thermogensis.

Carboplatin resistant human laryngeal carcinoma cells are cross resistant to curcumin due to reduced curcumin accumulation.

PubMed

Rak, Sanjica; Cimbora-Zovko, Tamara; Gajski, Goran; Dubravčić, Klara; Domijan, Ana-Marija; Delaš, Ivančica; Garaj-Vrhovac, Verica; Batinić, Drago; Sorić, Jasna; Osmak, Maja

2013-03-01

Curcumin is a natural compound that exhibits a wide range of beneficial effects, among them the anti-tumor activity. Recently it was shown that curcumin may be efficient against drug resistant tumor cells. The goal of our investigation was to examine if human laryngeal carcinoma cells resistant to carboplatin display sensitivity to curcumin, as compared to parental cells, and if this sensitivity is altered, to determine the molecular mechanisms that are responsible for it. We found that carboplatin resistant 7T cells were also cross resistant to curcumin. After the treatment with equimolar concentration of curcumin, 7T cells exhibited lower intracellular accumulation of curcumin which coincided with reduced formation of reactive oxygen species (ROS), diminished lipid and DNA damage followed by reduced induction of apoptosis and expression of heat shock protein 70 (Hsp70), as compared to parental HEp-2 cells. However, after the treatment with equitoxic concentration of curcumin, intracellular accumulation and all the explored downstream effects were similar in both cell lines suggesting that resistance of 7T cells to curcumin was based on its reduced intracellular accumulation. Since curcumin accumulates mostly in the membranes, we explored the fatty acid composition of both cell lines, but we did not find any difference between them. Copyright © 2012 Elsevier Ltd. All rights reserved.

Delivery of Dual Drug Loaded Lipid Based Nanoparticles across the Blood-Brain Barrier Impart Enhanced Neuroprotection in a Rotenone Induced Mouse Model of Parkinson's Disease.

PubMed

Kundu, Paromita; Das, Manasi; Tripathy, Kalpalata; Sahoo, Sanjeeb K

2016-12-21

Parkinson's disease (PD) is the most widespread form of dementia where there is an age related degeneration of dopaminergic neurons in the substantia nigra region of the brain. Accumulation of α-synuclein (αS) protein aggregate, mitochondrial dysfunction, oxidative stress, and neuronal cell death are the pathological hallmarks of PD. In this context, amalgamation of curcumin and piperine having profound cognitive properties, and antioxidant activity seems beneficial. However, the blood-brain barrier (BBB) is the major impediment for delivery of neurotherapeutics to the brain. The present study involves formulation of curcumin and piperine coloaded glyceryl monooleate (GMO) nanoparticles coated with various surfactants with a view to enhance the bioavailability of curcumin and penetration of both drugs to the brain tissue crossing the BBB and to enhance the anti-parkinsonism effect of both drugs in a single platform. In vitro results demonstrated augmented inhibition of αS protein into oligomers and fibrils, reduced rotenone induced toxicity, oxidative stress, and apoptosis, and activation of autophagic pathway by dual drug loaded NPs compared to native counterpart. Further, in vivo studies revealed that our formulated dual drug loaded NPs were able to cross BBB, rescued the rotenone induced motor coordination impairment, and restrained dopaminergic neuronal degeneration in a PD mouse model.

Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress.

PubMed

Vijayakumar, R S; Surya, D; Nalini, N

2004-01-01

The present study was aimed to explore the effect of black pepper (Piper nigrum L.) on tissue lipid peroxidation, enzymic and non-enzymic antioxidants in rats fed a high-fat diet. Thirty male Wistar rats (95-115 g) were divided into 5 groups. They were fed standard pellet diet, high-fat diet (20% coconut oil, 2% cholesterol and 0.125% bile salts), high-fat diet plus black pepper (0.25 g or 0.5 g/kg body weight), high-fat diet plus piperine (0.02 g/kg body weight) for a period of 10 weeks. Significantly elevated levels of thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and significantly lowered activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) in the liver, heart, kidney, intestine and aorta were observed in rats fed the high fat diet as compared to the control rats. Simultaneous supplementation with black pepper or piperine lowered TBARS and CD levels and maintained SOD, CAT, GPx, GST, and GSH levels to near those of control rats. The data indicate that supplementation with black pepper or the active principle of black pepper, piperine, can reduce high-fat diet induced oxidative stress to the cells.

Curcumin affects development of zebrafish embryo.

PubMed

Wu, Jheng-Yu; Lin, Chin-Yi; Lin, Tien-Wei; Ken, Chuian-Fu; Wen, Yu-Der

2007-07-01

Embryotoxic and teratogenic effects of curcumin on the development of zebrafish embryo were investi-gated in this study. The LD(50) values of curcumin (24-h incubation) were estimated at 7.5 microM and 5 microM for embryos and larvae, respectively. The developmental defects caused by curcumin treatments include bent or hook-like tails, spinal column curving, edema in pericardial sac, retarded yolk sac resorption, and shorter body length. In curcumin-treated larvae, fluorescence signals of curcumin were found in edamae sac and some skin cells. Together, these results indicate that zebrafish are suitable model organisms to study the toxic effects of curcumin.

Curcumin-Eudragit® E PO solid dispersion: A simple and potent method to solve the problems of curcumin.

PubMed

Li, Jinglei; Lee, Il Woo; Shin, Gye Hwa; Chen, Xiguang; Park, Hyun Jin

2015-08-01

Using a simple solution mixing method, curcumin was dispersed in the matrix of Eudragit® E PO polymer. Water solubility of curcumin in curcumin-Eudragit® E PO solid dispersion (Cur@EPO) was greatly increased. Based on the results of several tests, curcumin was demonstrated to exist in the polymer matrix in amorphous state. The interaction between curcumin and the polymer was investigated through Fourier transform infrared spectroscopy and (1)H NMR which implied that OH group of curcumin and carbonyl group of the polymer involved in the H bonding formation. Cur@EPO also provided protection function for curcumin as verified by the pH challenge and UV irradiation test. The pH value influenced curcumin release profile in which sustained release pattern was revealed. Additionally, in vitro transdermal test was conducted to assess the potential of Cur@EPO as a vehicle to deliver curcumin through this alternative administration route. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of repeated infusion of capsaicin-contained red pepper sauce on esophageal secondary peristalsis in humans.

PubMed

Liu, T T; Yi, C H; Lei, W Y; Hung, X S; Yu, H C; Chen, C L

2014-10-01

The transient receptor potential vanilloid 1 has been implicated as a target mediator for heartburn perception and modulation of esophageal secondary peristalsis. Our aim was to determine the effect of repeated esophageal infusion of capsaicin-contained red pepper sauce on heartburn perception and secondary peristalsis in healthy adults. Secondary peristalsis was performed with mid-esophageal injections of air in 15 healthy adults. Two separate protocols including esophageal infusion with saline and capsaicin-contained red pepper sauce and 2 consecutive sessions of capsaicin-contained red pepper sauce were randomly performed. After repeated infusion of capsaicin-contained red pepper sauce, the threshold volume to activate secondary peristalsis was significantly increased during slow (p < 0.001) and rapid air injections (p = 0.004). Acute infusion of capsaicin-contained red pepper sauce enhanced heartburn perception (p < 0.001), but the intensity of heartburn perception was significantly reduced after repeated capsaicin-contained red pepper sauce infusion (p = 0.007). Acute infusion of capsaicin-contained red pepper sauce significantly increased pressure wave amplitudes of distal esophagus during slow (p = 0.003) and rapid air injections (p = 0.01), but repeated infusion of capsaicin-contained red pepper sauce significantly decreased pressure wave amplitude of distal esophagus during slow (p = 0.0005) and rapid air injections (p = 0.003). Repeated esophageal infusion of capsaicin appears to attenuate heartburn perception and inhibit distension-induced secondary peristalsis in healthy adults. These results suggest capsaicin-sensitive afferents in modulating sensorimotor function of secondary peristalsis in human esophagus. © 2014 John Wiley & Sons Ltd.

Biotechnological enhancement of capsaicin biosynthesis in cell suspension cultures of Naga King Chili (Capsicum chinense Jacq.).

PubMed

Kehie, Mechuselie; Kumaria, Suman; Tandon, Pramod

2016-01-01

Cell suspension cultures were initiated from hypocotyl derived callus to induce capsaicin biosynthesis in suspension cultures of Naga King Chili (Capsicum chinense Jacq.). Efficient capsaicin production with high growth index (GI) was obtained by exposing cells to salicylic acid (SA) and calcium channel modulators in suspension cultures. The time course of capsaicin formation is related to the cell growth profile in a batch culture. Cells cultivated in the standard medium (SM) initially showed low level of capsaicin yield during active growth. When the cells approached stationary phase, cell growth and cell viability decreased whereas capsaicin production increased continuously. In the fed-batch cultures, the highest capsaicin yield (567.4 ± 8.1 μgg(1) fresh weight) (f.wt) was obtained by feeding the cells with 1 mM SA. However, SA feeding during cultivation repressed the cell growth. Enhanced cell growth (3.1 ± 0.1 GI/culture) and capsaicin yield (534 ± 7.8 μgg(-1)f.wt) were obtained when the cells were fed with calcium ionophore A23187 (0.5 mM) on day 25 as compared to the control. Addition of the calcium channel blocker verapamil hydrochloride (100 mM) inhibited cell growth and capsaicin production in Naga King Chili suspension cell cultures.

In vivo cough suppressive activity of pectic polysaccharide with arabinogalactan type II side chains of Piper nigrum fruits and its synergistic effect with piperine.

PubMed

Khawas, Sadhana; Nosáľová, Gabriela; Majee, Sujay Kumar; Ghosh, Kanika; Raja, Washim; Sivová, Veronika; Ray, Bimalendu

2017-06-01

Piper nigrum L. fruits are not only a prized spice, but also highly valued therapeutic agent that heals many ailments including asthma, cold and respiratory problems. Herein, we have investigated structural features and in vivo antitussive activity of three fractions isolated from Piper nigrum fruits. The water extract (PN-WE) upon fractionation with EtOH yielded two fractions: a soluble fraction (PN-eSf) and a precipitated (PN-ePf) one. The existence of a pectic polysaccharide with arabinogalactan type II side chains (147kDa) in PN-ePf and piperine in PN-eSf were revealed. Moreover, oligosaccharides providing fine structural details of side chains were generated from PN-ePf and then characterized. The parental water extract (PN-WE) that contained both pectic polysaccharide and piperine, after oral administration (50mgkg -1 body weight) to guinea pigs, showed antitussive activity comparable to codeine phosphate (10mgkg -1 body weight). The EtOH precipitated fraction (PN-ePf) containing pectic polysaccharide showed comparatively higher antitussive activity than EtOH soluble fraction (PN-eSf) that contained piperine, but their potencies are lower than the parental water extract. Significantly, the specific airway smooth muscle reactivity of all three fractions remained unchanged. Finally, pectic polysaccharide-piperine combination in parental extract synergistically enhances antitussive effect in guinea pigs. Copyright © 2017 Elsevier B.V. All rights reserved.

Capsaicin Cough Sensitivity and the Association with Clinical Parameters in Bronchiectasis

PubMed Central

Lin, Zhi-ya; Tang, Yan; Li, Hui-min; Lin, Zhi-min; Zheng, Jin-ping; Chen, Rong-chang; Zhong, Nan-shan

2014-01-01

Background Cough hypersensitivity has been common among respiratory diseases. Objective To determine associations of capsaicin cough sensitivity and clinical parameters in adults with clinically stable bronchiectasis. Methods We recruited 135 consecutive adult bronchiectasis patients and 22 healthy subjects. History inquiry, sputum culture, spirometry, chest high-resolution computed tomography (HRCT), Leicester Cough Questionnaire scoring, Bronchiectasis Severity Index (BSI) assessment and capsaicin inhalation challenge were performed. Cough sensitivity was measured as the capsaicin concentration eliciting at least 2 (C2) and 5 coughs (C5). Results Despite significant overlap between healthy subjects and bronchiectasis patients, both C2 and C5 were significantly lower in the latter group (all P<0.01). Lower levels of C5 were associated with a longer duration of bronchiectasis symptoms, worse HRCT score, higher 24-hour sputum volume, BSI and sputum purulence score, and sputum culture positive for P. aeruginosa. Determinants associated with increased capsaicin cough sensitivity, defined as C5 being 62.5 µmol/L or less, encompassed female gender (OR: 3.25, 95%CI: 1.35–7.83, P<0.01), HRCT total score between 7–12 (OR: 2.57, 95%CI: 1.07–6.173, P = 0.04), BSI between 5–8 (OR: 4.05, 95%CI: 1.48–11.06, P<0.01) and 9 or greater (OR: 4.38, 95%CI: 1.48–12.93, P<0.01). Conclusion Capsaicin cough sensitivity is heightened in a subgroup of bronchiectasis patients and associated with the disease severity. Gender and disease severity, but not sputum purulence, are independent determinants of heightened capsaicin cough sensitivity. Current testing for cough sensitivity diagnosis may be limited because of overlap with healthy subjects but might provide an objective index for assessment of cough in future clinical trials. PMID:25409316

Subthreshold concentration of endothelin-1-enhanced, capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs.

PubMed

Kanazawa, H; Fujiwara, H; Hirata, K; Yoshikawa, J

1998-12-01

An increasing number of studies have been performed to address a possible role for endothelin-1 (ET-1) as a significant mediator in asthma. However, the effects of subthreshold concentrations of ET-1, which cannot elicit bronchial smooth muscle contraction itself, in asthma has yet to be determined. This study determined these effects of ET-1 on capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs. Aerosolized ET-1 administered at doses of 10(-9) M and higher induced a dose-dependent increase in pulmonary resistance, but ET-1 at 10(-10) M did not have any bronchoconstrictive effect. However, this subthreshold concentration of ET-1 potentiated capsaicin-induced bronchoconstriction. In addition, the potentiation of capsaicin-induced bronchoconstriction by this subthreshold concentration of ET-1 was completely abolished by BQ788 (ET(B) receptor antagonist), but not BQ123 (ET(A) receptor antagonists). Immunoreactive substance P (SP) levels in bronchoalveolar lavage fluid after capsaicin administration were significantly higher than those after solvent administration. However, ET-1 alone did not significantly stimulate immunoreactive SP release and ET-1 (10(-10) M) did not potentiate capsaicin-induced immunoreactive SP release. In contrast, ET-1 (10(-10) M) potentiated exogenous neurokinin A- and SP-induced bronchoconstriction. These findings suggest that a subthreshold concentration of endothelin-1 does not potentiate the tachykinin release induced by capsaicin but the airway smooth muscle contraction through endothelin-B receptors.

Integrity of erythrocytes of hypercholesterolemic rats during spices treatment.

PubMed

Kempaiah, R K; Srinivasan, K

2002-07-01

In rats rendered hypercholesterolemic by maintaining them on a cholesterol-enriched diet (0.5%) for 8 weeks, inclusion of spice principles--curcumin (0.2%) or capsaicin (0.015%) or the spice--garlic powder (2.0%) in the diet, produced the expected hypolipidemic effect. Plasma cholesterol which was more than 200% that of basal control in hypercholesterolemic rats, was decreased by these dietary spice principles and garlic by 25-39%. Erythrocyte membranes of hypercholesterolemic rats were relatively enriched in cholesterol, which was about 120% of basal control, while membrane phospholipid was unaffected. This resulted in a significant alteration in cholesterol to phospholipid ratio of RBC membranes. Dietary curcumin, capsaicin and garlic were observed to counter this altered lipid profile of erythrocyte membranes in hypercholesterolemic situation by producing a significant 10-14% decrease in membrane cholesterol content. As a result of alteration in membrane structural lipids, the structural integrity of RBCs was also affected. An examination of the osmotic fragility of erythrocytes in various groups, indicated that RBCs of hypercholesterolemic rats were relatively fragile compared to normal controls. Dietary curcumin, capsaicin and garlic appeared to correct this increased fragility of erythrocytes.

Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

PubMed Central

Son, Dong Ju; Akiba, Satoshi; Hong, Jin Tae; Yun, Yeo Pyo; Hwang, Seock Yeon; Park, Young Hyun; Lee, Sung Eun

2014-01-01

PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum) and long pepper (Piper longum), was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX)-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA) metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2), COX-1, COX-2, and thromboxane A2 (TXA2) synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PG)E2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms. PMID:25153972

Facilitation and inhibition by capsaicin of cholinergic neurotransmission in the guinea-pig small intestine.

PubMed

Geber, Christian; Mang, Christian F; Kilbinger, Heinz

2006-01-01

The effects of capsaicin on [3H]acetylcholine release and muscle contraction were studied on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum preincubated with [3H]choline. Capsaicin concentration-dependently increased both basal [3H]acetylcholine release (pEC50 7.0) and muscle tone (pEC50 6.1). The facilitatory effects of capsaicin were antagonized by 1 microM capsazepine (pK (B) 7.0 and 7.6), and by the combined blockade of NK1 and NK3 tachykinin receptors with the antagonists CP99994 plus SR142801 (each 0.1 microM). This suggests that stimulation by capsaicin of TRPV1 receptors on primary afferent fibres causes a release of tachykinins which, in turn, mediate via NK1 and NK3 receptors an increase in acetylcholine release. The capsaicin-induced acetylcholine release was significantly enhanced by the NO synthase inhibitor L-NG-nitroarginine (100 microM). This indicates that tachykinins released from sensory neurons also stimulate nitrergic neurons and thus lead, via NO release, to inhibition of acetylcholine release. Capsaicin concentration-dependently reduced the electrically-evoked [3H]acetylcholine release (pEC50 6.4) and twitch contractions (pEC50 5.9). The inhibitory effects were not affected by either capsazepine, NK1 and NK3 receptor antagonists, the cannabinoid CB1 antagonist SR141716A or by L-NG-nitroarginine. Desensitization of TRPV1 receptors by a short exposure to 3 microM capsaicin abolished the facilitatory responses to a subsequent administration, but did not modify the inhibitory effects. In summary, capsaicin has a dual effect on cholinergic neurotransmission. The facilitatory effect is indirect and involves tachykinin release and excitation of NK1 and NK3 receptors on cholinergic neurons. The inhibition of acetylcholine release may be due to a decrease of Ca2+ influx into cholinergic neurons.

Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus.

PubMed

Kalia, Nitin Pal; Mahajan, Priya; Mehra, Rukmankesh; Nargotra, Amit; Sharma, Jai Parkash; Koul, Surrinder; Khan, Inshad Ali

2012-10-01

To delineate the role of capsaicin (8-methyl-N-vanillyl-6-nonenamide) as an inhibitor of the NorA efflux pump and its impact on invasion of macrophages by Staphylococcus aureus. Capsaicin in combination with ciprofloxacin was tested for activity against S. aureus SA-1199B (NorA overproducing), SA-1199 (wild-type) and SA-K1758 (norA knockout). The role of NorA in the intracellular invasion of S. aureus and the ability of capsaicin to inhibit this invasion was established in J774 macrophage cell lines. The three-dimensional structure of NorA was predicted using an in silico approach and docking studies of capsaicin were performed. Capsaicin significantly reduced the MIC of ciprofloxacin for S. aureus SA-1199 and SA-1199B. Furthermore, capsaicin also extended the post-antibiotic effect of ciprofloxacin by 1.1 h at MIC concentration. There was a decrease in mutation prevention concentration of ciprofloxacin when combined with capsaicin. Inhibition of ethidium bromide efflux by NorA-overproducing S. aureus SA-1199B confirmed the role of capsaicin as a NorA efflux pump inhibitor (EPI). The most significant finding of this study was the ability of capsaicin to reduce the intracellular invasion of S. aureus SA-1199B (NorA overproducing) in J774 macrophage cell lines by 2 log(10). This study, for the first time, has shown that capsaicin, a novel EPI, not only inhibits the NorA efflux pump of S. aureus but also reduces the invasiveness of S. aureus, thereby reducing its virulence.

Ca2+ and calpain mediate capsaicin-induced ablation of axonal terminals expressing transient receptor potential vanilloid 1.

PubMed

Wang, Sheng; Wang, Sen; Asgar, Jamila; Joseph, John; Ro, Jin Y; Wei, Feng; Campbell, James N; Chung, Man-Kyo

2017-05-19

Capsaicin is an ingredient in spicy peppers that produces burning pain by activating transient receptor potential vanilloid 1 (TRPV1), a Ca 2+ -permeable ion channel in nociceptors. Capsaicin has also been used as an analgesic, and its topical administration is approved for the treatment of certain pain conditions. The mechanisms underlying capsaicin-induced analgesia likely involve reversible ablation of nociceptor terminals. However, the mechanisms underlying these effects are not well understood. To visualize TRPV1-lineage axons, a genetically engineered mouse model was used in which a fluorophore is expressed under the TRPV1 promoter. Using a combination of these TRPV1-lineage reporter mice and primary afferent cultures, we monitored capsaicin-induced effects on afferent terminals in real time. We found that Ca 2+ influx through TRPV1 is necessary for capsaicin-induced ablation of nociceptive terminals. Although capsaicin-induced mitochondrial Ca 2+ uptake was TRPV1-dependent, dissipation of the mitochondrial membrane potential, inhibition of the mitochondrial transition permeability pore, and scavengers of reactive oxygen species did not attenuate capsaicin-induced ablation. In contrast, MDL28170, an inhibitor of the Ca 2+ -dependent protease calpain, diminished ablation. Furthermore, overexpression of calpastatin, an endogenous inhibitor of calpain, or knockdown of calpain 2 also decreased ablation. Quantitative assessment of TRPV1-lineage afferents in the epidermis of the hind paws of the reporter mice showed that EGTA and MDL28170 diminished capsaicin-induced ablation. Moreover, MDL28170 prevented capsaicin-induced thermal hypoalgesia. These results suggest that TRPV1/Ca 2+ /calpain-dependent signaling plays a dominant role in capsaicin-induced ablation of nociceptive terminals and further our understanding of the molecular mechanisms underlying the effects of capsaicin on nociceptors. © 2017 by The American Society for Biochemistry and Molecular Biology

Binding of Capsaicin to the TRPV1 Ion Channel.

PubMed

Darré, Leonardo; Domene, Carmen

2015-12-07

Transient receptor potential (TRP) ion channels constitute a notable family of cation channels involved in the ability of an organisms to detect noxious mechanical, thermal, and chemical stimuli that give rise to the perception of pain, taste, and changes in temperature. One of the most experimentally studied agonist of TRP channels is capsaicin, which is responsible for the burning sensation produced when chili pepper is in contact with organic tissues. Thus, understanding how this molecule interacts and regulates TRP channels is essential to high impact pharmacological applications, particularly those related to pain treatment. The recent publication of a three-dimensional structure of the vanilloid receptor 1 (TRPV1) in the absence and presence of capsaicin from single particle electron cryomicroscopy experiments provides the opportunity to explore these questions at the atomic level. In the present work, molecular docking and unbiased and biased molecular dynamics simulations were employed to generate a structural model of the capsaicin-channel complex. In addition, the standard free energy of binding was estimated using alchemical transformations coupled with conformational, translational, and orientational restraints on the ligand. Key binding modes consistent with previous experimental data are identified, and subtle but essential dynamical features of the binding site are characterized. These observations shed some light into how TRPV1 interacts with capsaicin, and may help to refine design parameters for new TRPV1 antagonists, and potentially guide further developments of TRP channel modulators.

Structural and Spectral Properties of Curcumin and Metal- Curcumin Complex Derived from Turmeric (Curcuma longa)

NASA Astrophysics Data System (ADS)

Bich, Vu Thi; Thuy, Nguyen Thi; Binh, Nguyen Thanh; Huong, Nguyen Thi Mai; Yen, Pham Nguyen Dong; Luong, Tran Thanh

Structural and spectral properties of curcumin and metal- curcumin complex derived from turmeric (Curcuma longa) were studied by SEM and vibrational (FTIR and Raman) techniques. By comparison between curcumin commercial, fresh turmeric and a yellow powder obtained via extraction and purification of turmeric, we have found that this insoluble powder in water is curcumin. The yellow compound could complex with certain ion metal and this metal-curcumin coloring complex is water soluble and capable of producing varying hues of the same colors and having antimicrobial, cytotoxicity activities for use in foodstuffs and pharmacy. The result also demonstrates that Micro-Raman spec-troscopy is a valuable non-destructive tool and fast for investigation of a natural plant even when occurring in low concentrations.

[Neuroprotective effects of curcumin].

PubMed

Li, Yong; Wang, Pengwen

2009-12-01

Traditionally, turmeric has been put to use as a food additive and herbal medicine in Asia. Curcumin is an active principle of the perennial herb curcuma longa (commonly known as turmeric). Recent evidence suggests that curcumin has activities with potential for neuroprotective efficacy, including anti-inflammatory, antioxidant, and antiprotein-aggregate activities. In the current review, we provide the newly evidence for the potential role of curcumin in the neuroprotective effects of neurodegenerative diseases like Alzheimer's disease (AD).

Novel Approaches to Extraction Methods in Recovery of Capsaicin from Habanero Pepper (CNPH 15.192).

PubMed

Martins, Frederico S; Borges, Leonardo L; Ribeiro, Claudia S C; Reifschneider, Francisco J B; Conceição, Edemilson C

2017-07-01

The objective of this study was to compare three capsaicin extraction methods: Shoxlet, Ultrasound-assisted Extraction (UAE), and Shaker-assisted Extraction (SAE) from Habanero pepper, CNPH 15.192. The different parameters evaluated were alcohol degree, time extraction, and solid-solvent ratio using response surface methodology (RSM). The three parameters found significant ( p < 0.05) were for UAE and solvent concentration and extraction time for SAE. The optimum conditions for the capsaicin UAE and SAE were similar 95% alcohol degree, 30 minutes and solid-liquid ratio 2 mg/mL. The Soxhlet increased the extraction in 10-25%; however, long extraction times (45 minutes) degraded 2% capsaicin. The extraction of capsaicin was influenced by extraction method and by the operating conditions chosen. The optimized conditions provided savings of time, solvent, and herbal material. Prudent choice of the extraction method is essential to ensure optimal yield of extract, thereby making the study relevant and the knowledge gained useful for further exploitation and application of this resource. Habanero pepper , line CNPH 15.192, possess capsaicin in higher levels when compared with others speciesHigher levels of ethanolic strength are more suitable to obtain a higher levels of capsaicinBox-Behnken design indicates to be useful to explore the best conditions of ultrasound assisted extraction of capsaicin. Abbreviations used: Nomenclature UAE: Ultrasound-assisted Extraction; SAE: Shaker-assisted Extraction.

Involvement of AMPK signaling cascade in capsaicin-induced apoptosis of HT-29 colon cancer cells.

PubMed

Kim, Young Min; Hwang, Jin-Taek; Kwak, Dong Wook; Lee, Yun Kyung; Park, Ock Jin

2007-01-01

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is activated during ATP-depleting metabolic states, such as hypoxia, heat shock, oxidative stress, and exercise. As a highly conserved heterotrimeric kinase that functions as a major metabolic switch to maintain energy homeostasis, AMPK has been shown to exert as an intrinsic regulator of mammalian cell cycle. Moreover, AMPK cascade has emerged as an important pathway implicated in cancer control. In this article, we have investigated the effects of capsaicin on apoptosis in relation to AMPK activation in colon cancer cell. Capsaicin-induced apoptosis was revealed by the presence of nucleobodies in the capsaicin-treated HT-29 colon cancer cells. Concomitantly, the activation of AMPK and the increased expression of the inactive form of acetyl-CoA carboxylase (ACC) were detected in capsaicin-treated colon cancer cells. We showed that both capsaicin and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR), an AMPK activator possess the AMPK-activating capacity as well as apoptosis-inducing properties. Evidence of the association between AMPK activation and the increased apoptosis in HT-29 colon cancer cells by capsaicin treatment, and further findings of the correlation of the activated AMPK and the elevated apoptosis by cotreatment of AICAR and capsaicin support AMPK as an important component of apoptosis, as well as a possible target of cancer control.

The functional genomic studies of curcumin.

PubMed

Huminiecki, Lukasz; Horbańczuk, Jarosław; Atanasov, Atanas G

2017-10-01

Curcumin is a natural plant-derived compound that has attracted a lot of attention for its anti-cancer activities. Curcumin can slow proliferation of and induce apoptosis in cancer cell lines, but the precise mechanisms of these effects are not fully understood. However, many lines of evidence suggested that curcumin has a potent impact on gene expression profiles; thus, functional genomics should be the key to understanding how curcumin exerts its anti-cancer activities. Here, we review the published functional genomic studies of curcumin focusing on cancer. Typically, a cancer cell line or a grafted tumor were exposed to curcumin and profiled with microarrays, methylation assays, or RNA-seq. Crucially, these studies are in agreement that curcumin has a powerful effect on gene expression. In the majority of the studies, among differentially expressed genes we found genes involved in cell signaling, apoptosis, and the control of cell cycle. Curcumin can also induce specific methylation changes, and is a powerful regulator of the expression of microRNAs which control oncogenesis. We also reflect on how the broader technological progress in transcriptomics has been reflected on the field of curcumin. We conclude by discussing the areas where more functional genomic studies are highly desirable. Integrated OMICS approaches will clearly be the key to understanding curcumin's anticancer and chemopreventive effects. Such strategies may become a template for elucidating the mode of action of other natural products; many natural products have pleiotropic effects that are well suited for a systems-level analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of reverse photoperiod on in vitro regeneration and piperine production in Piper nigrum L.

PubMed

Ahmad, Nisar; Abbasi, Bilal Haider; Fazal, Hina; Khan, Mubarak Ali; Afridi, Muhammad Siddique

2014-01-01

In this study, a novel approach for in vitro regeneration of Piper nigrum L. has been applied in order to increase healthy biomass, phytochemicals and piperine production via reverse photoperiod (16hD/8hL). Leaf portions of the seed-derived plants were placed on an MS-medium fortified with different PGRs. Under 16hD/8hL, thidiazuron (TDZ; 4.0 mg L⁻¹) and BA (1.5 mg L⁻¹) was found to be the most effective (<90%) in callus induction. Two concentrations (1.5, 2.0 mg L⁻¹) of the IBA produced>80% shoots from callus cultures. Healthy shoots were transferred to rooting medium and higher percentage of rooting (<90%) was observed on IBA (1.5 mg L⁻¹). These in vitro tissues were subjected to amino acid analysis, spectrophotometry, and HPLC. ARG, SER, THR, and TYR were the most abundant components out of 17 amino acids. Higher amino acid production was observed under normal photoperiod (16hL/8hD) than under reverse photoperiod (16hD/8hL). The highest total phenolic content (TPC; 9.91 mg/g-DW) and flavonoid content (7.38 mg/g-DW) were observed in callus cultures incubated under 16hL/8hD than other tissues incubated under 16hD/8hL photoperiod. Higher DPPH and PoMo activities were observed in tissues incubated under 16hL/8hD photoperiod, while ABTS and Fe²⁺ chelating activities were found higher in tissues incubated under reverse photoperiod. Significant quantities of piperine content were observed in all tissues except callus cultures. These results suggest that reverse photoperiod is a promising approach for callus induction, phytochemicals and piperine production for commercial applications. Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Autonomic Nervous Activity and Lipid Oxidation Postexercise with Capsaicin in the Humans

PubMed Central

Yeo, Nam Hwoeh; Kang, Sunghwun

2010-01-01

This study evaluated the synergistic effects of acute exercise with capsaicin (200mg) upon the restoration of cardiac autonomic functions and depolarization- repolarization interval as well as substrate oxidation. Nine healthy males [21.9(0.8) yrs] volunteered for this study. Cardiac autonomic activity, metabolic responses, and the ECG QT intervals were continuously measured during 5 min at rest and postexercise recovery after 30 min exercise at 50% VO2max on a stationary ergometer with placebo (ECON) or capsaicin intake (ECAP), and no exercise control (NCON) were randomized. Results indicated that the HF power reflecting parasympathetic activity significantly returned to the baseline much faster during ECAP than ECON trial during postexercise [122.1 (23.2) vs. 60.2 (11.7) %, p < 0.05]. The ECAP trial significantly decreased RQ [0.79(0.02) vs. 0.85 (0.03), p < 0.05] with significantly greater fat oxidation [69.3 (6.0) vs. 49.4 (10.8) %, p < 0.05] in comparison to NCON trial during 120 min postexercise recovery without any adverse effects on cardiac electrical stability as determined by trigger-averaged ECG QT interval analyses. We suggest that capsaicin before the exercise may contribute to the improvement of cardio-protective functions and metabolic responses as one of the beneficial supplements accelerating faster restoration of autonomic activity and enhanced lipolysis during postexercise recovery without any adverse effects on cardiac electrical stability. Key points Capsaicin before exercise may contribute to the improvement of cardio-protective functions as one of the beneficial supplements accelerating faster restoration of autonomic activity Capsaicin before exercise enhanced lipolysis during postexercise recovery period Capsaicin intake does not influence cardiac electrical stability during recovery period. PMID:24149693

Inducible nitric oxide synthase evoked nitric oxide counteracts capsaicin-induced airway smooth muscle contraction, but exacerbates plasma extravasation.

PubMed

Li, Ping-Chia; Shaw, Chen-Fu; Kuo, Tin-Fan; Chien, Chiang-Ting

2005-04-18

The contribution of nitric oxide (NO) to capsaicin-evoked airway responses was investigated in rats. The measurement of plasma NO level, airway dynamics, airway smooth muscle electromyogram, and plasma extravasation by India ink and Evans blue leakage technique was adapted. Capsaicin-evoked hypotension, bronchoconstriction, trachea plasma extravasation as well as increases in plasma NO level in a dose-dependent manner. L-732138 (NK1 receptor antagonist) or SR-48968 (NK2 receptor antagonist) pretreatment reduced capsaicin-enhanced hypotension, bronchoconstriction, plasma extravasation, and plasma NO level. N(G)-nitro-L-Arginine methyl ester (L-NAME, 10 mg/kg, i.v.), a non-selective NO synthase (NOS) inhibitor, or aminoguanidine (10 mg/kg, i.v.), a selective inducible NOS (iNOS) inhibitor, reduced capsaicin-induced increases in plasma NO level and protected against capsaicin-induced plasma extravasation, whereas L-arginine (150 mg/kg, i.v.), a NO precursor, enhanced capsaicin-evoked plasma NO level and plasma extravasation. L-Arginine pretreatment ameliorated capsaicin-induced bronchoconstriction, whereas L-NAME and aminoguanidine exaggerated capsaicin-induced bronchoconstriction. In summary, NK1 and NK2 receptors and iNOS play a role in NO formation and on capsaicin-induced bronchoconstriction and plasma extravasation. NO generated by iNOS counteracts tachykinin-mediated bronchoconstriction, but exacerbates tachykinin-mediated plasma extravasation.

The Essential Medicinal Chemistry of Curcumin.

PubMed

Nelson, Kathryn M; Dahlin, Jayme L; Bisson, Jonathan; Graham, James; Pauli, Guido F; Walters, Michael A

2017-03-09

Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

The Essential Medicinal Chemistry of Curcumin

PubMed Central

2017-01-01

Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed. PMID:28074653

Tacrolimus hydrate ointment inhibits skin plasma extravasation in rats induced by topical m-xylene but not capsaicin.

PubMed

Goto, Shiho; Kondo, Fumio; Ikai, Yoshitomo; Miyake, Mio; Futamura, Masaki; Ito, Komei; Sakamoto, Tatsuo

2009-04-17

Tacrolimus ointment is used to treat various chronic inflammatory skin diseases. However, the effect of this ointment on acute neurogenic inflammation in the skin remains to be fully elucidated. Topical capsaicin and m-xylene produce tachykinin release from sensory nerves in the skin, resulting in skin plasma leakage. We investigated the effect of tacrolimus ointment (0.1%) on skin microvascular leakage induced by topical capsaicin (10 mM) and m-xylene (neat), and intracutaneous compound 48/80 (c48/80) (10 microg/ml, 50 microl/site) in two groups of rats pretreated with excessive capsaicin or its vehicle. The amount of leaked Evans blue dye reflected skin plasma leakage. Capsaicin, m-xylene or c48/80 was applied to the shaved abdomens of rats 8 h after topical application of tacrolimus ointment or its base. Desensitization with capsaicin reduced the skin response to capsaicin and m-xylene by 100% and 65%, respectively, but not to c48/80. Tacrolimus ointment significantly inhibited the skin response induced by m-xylene and c48/80, regardless of pretreatment with capsaicin. However, topical tacrolimus did not influence the skin response induced by capsaicin. We also evaluated whether topical capsaicin and m-xylene, and intracutaneous c48/80 cause mast cell degranulation in skin treated with tacrolimus. Mast cell degranulation was microscopically assessed. Topical tacrolimus only significantly suppressed degranulation induced by m-xylene and c48/80. Our data shows that tacrolimus ointment partially inhibits plasma leakage and mast cell degranulation in rat skin induced by m-xylene and c48/80 but not capsaicin, suggesting that the inhibitory effect is not associated with a reduction in neurogenic-mediated mechanisms.

Recent developments in curcumin and curcumin based polymeric materials for biomedical applications: A review.

PubMed

Mahmood, Kashif; Zia, Khalid Mahmood; Zuber, Mohammad; Salman, Mahwish; Anjum, Muhammad Naveed

2015-11-01

Turmeric (Curcuma longa) is a popular Indian spice that has been used for centuries in herbal medicines for the treatment of a variety of ailments such as rheumatism, diabetic ulcers, anorexia, cough and sinusitis. Curcumin (diferuloylmethane) is the main curcuminoid present in turmeric and responsible for its yellow color. Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anticoagulant and anti-infective effects. This review summarizes and discusses recently published papers on the key biomedical applications of curcumin based materials. The highlighted studies in the review provide evidence of the ability of curcumin to show the significant vitro antioxidant, diabetic complication, antimicrobial, neuroprotective, anti-cancer activities and detection of hypochlorous acid, wound healing, treatment of major depression, healing of paracentesis, and treatment of carcinoma and optical detection of pyrrole properties. Hydrophobic nature of this polyphenolic compound along with its rapid metabolism, physicochemical and biological instability contribute to its poor bioavailability. To redress these problems several approaches have been proposed like encapsulation of curcumin in liposomes and polymeric micelles, inclusion complex formation with cyclodextrin, formation of polymer-curcumin conjugates, etc. Copyright © 2015 Elsevier B.V. All rights reserved.

Extraction and purification of capsaicin from capsicum oleoresin using an aqueous two-phase system combined with chromatography.

PubMed

Fan, Yong; Lu, Yan-Min; Yu, Bin; Tan, Cong-Ping; Cui, Bo

2017-09-15

Capsaicin was extracted from capsicum oleoresin using an aqueous two-phase system (ATPS) composed of an ethylene oxide-propylene oxide (EOPO) copolymer, salt and ethanol. Capsaicin was concentrated in the top polymer-rich phase. To determine the optimal conditions, the partitioning of capsaicin in the ATPS was investigated, considering a single-factor experiment including the salt concentration, polymer concentration, buffer pH, ethanol concentration, sample loading and extraction duration. Response surface methodology was applied to investigate the effects of the polymer concentration, buffer pH and sample loading on capsaicin partitioning. A capsaicin yield of 95.5% was obtained using the optimal extraction system, which consisted of 16.3% UCON 50-HB-5100/10% K 2 HPO 4 /1% ethanol, a buffer pH of 4.35 and 0.24g of capsicum oleoresin. Capsaicin was purified from the capsaicinoid extract using a two-step macroporous adsorption resin (MAR) method. After purification using non-polar MAR ADS-17, the recovery and purity of capsaicin were 83.7% and 50.3%, respectively. After purification using weakly polar MAR AB-8, the recovery and purity of capsaicin were 88.0% and 85.1%, respectively. Copyright © 2017. Published by Elsevier B.V.

The targets of curcumin.

PubMed

Zhou, Hongyu; Beevers, Christopher S; Huang, Shile

2011-03-01

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-kB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer's disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here.

An Amperometric Biosensor Utilizing a Ferrocene-Mediated Horseradish Peroxidase Reaction for the Determination of Capsaicin (Chili Hotness)

PubMed Central

Mohammad, Rosmawani; Ahmad, Musa; Heng, Lee Yook

2013-01-01

Chili hotness is very much dependent on the concentration of capsaicin present in the chili fruit. A new biosensor based on a horseradish peroxidase enzyme-capsaicin reaction mediated by ferrocene has been successfully developed for the amperometric determination of chili hotness. The amperometric biosensor is fabricated based on a single-step immobilization of both ferrocene and horseradish peroxidase in a photocurable hydrogel membrane, poly(2-hydroxyethyl methacrylate). With mediation by ferrocene, the biosensor could measure capsaicin concentrations at a potential 0.22 V (vs. Ag/AgCl), which prevented potential interference from other electroactive species in the sample. Thus a good selectivity towards capsaicin was demonstrated. The linear response range of the biosensor towards capsaicin was from 2.5–99.0 μM with detection limit of 1.94 μM. A good relative standard deviation (RSD) for reproducibility of 6.4%–9.9% was obtained. The capsaicin biosensor demonstrated long-term stability for up to seven months. The performance of the biosensor has been validated using a standard method for the analysis of capsaicin based on HPLC. PMID:23921830

Inhibition of Enveloped Viruses Infectivity by Curcumin

PubMed Central

Wen, Hsiao-Wei; Ou, Jun-Lin; Chiou, Shyan-Song; Chen, Jo-Mei; Wong, Min-Liang; Hsu, Wei-Li

2013-01-01

Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (HA) activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB)-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter) than for the pseudorabies virus (approximately 180 nm) and the vaccinia virus (roughly 335 × 200 × 200 nm). These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses. PMID:23658730

Neuroprotective effects of curcumin and highly bioavailable curcumin on oxidative stress induced by sodium nitroprusside in rat striatal cell culture.

PubMed

Nazari, Qand Agha; Kume, Toshiaki; Izuo, Naotaka; Takada-Takatori, Yuki; Imaizumi, Atsushi; Hashimoto, Tadashi; Izumi, Yasuhiko; Akaike, Akinori

2013-01-01

Curcumin, a polyphenolic compound extracted from Curcuma longa, has several pharmacological activities such as anticancer, anti-inflammatory, and antioxidant effects. The purpose of this study was to investigate the protective effects of curcumin and THERACURMIN, a highly bioavailable curcumin, against sodium nitroprusside (SNP)-induced oxidative damage in primary striatal cell culture. THERACURMIN as well as curcumin significantly prevented SNP-induced cytotoxicity. To elucidate the cytoprotective effects of curcumin and THERACURMIN, we measured the intracellular glutathione level in striatal cells. Curcumin and THERACURMIN significantly elevated the glutathione level, which was decreased by treatment with SNP. Moreover, curcumin showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging ability. Finally, a ferrozine assay showed that curcumin (10-100 µg/mL) has potent Fe(2+)-chelating ability. These results suggest that curcumin and THERACURMIN exert potent protective effects against SNP-induced cytotoxicity by free radical-scavenging and iron-chelating activities.

[Study on stability of curcumine, demethoxycurcumin and bisdemethoxycurcumin].

PubMed

Han, Gang; Cui, Jing-jing; Bi, Rui; Zhao, Lin-lin; Zhang, Wei-guo

2008-11-01

To investigate the stability of curcumin, demethoxycurcumin and bisdemethoxycurcumin in different buffer solution. To determine concentration of curcumin by HPLC when added curcumin, demethoxycurcumin and bisdemethoxycurcumin into the buffer solution the equation of degradation was established. The sequence of stability are bisdemethoxycurcumin > or = demethoxycurcumin > or =curcumin at the same condition. The demethoxycurcumin can stabilize curcumin more strong than the others. The demethoxycurcumin is a nature stabilizing agent for curcumin.

Effects of Capsaicin on Older Patients with Oropharyngeal Dysphagia: A Double-Blind, Placebo-Controlled, Crossover Study.

PubMed

Nakato, Rui; Manabe, Noriaki; Shimizu, Sayako; Hanayama, Kozo; Shiotani, Akiko; Hata, Jiro; Haruma, Ken

2017-01-01

The standard of care for older patients with oropharyngeal dysphagia (OD) is poor. Stimulation of transient receptor potential vanilloid 1 might become a pharmacological strategy for these patients. This study aimed to compare the therapeutic effect of film food containing 0.75 µg of capsaicin in these patients. In a crossover, randomized trial, 49 patients with OD were provided capsaicin or identical placebo at least 7 days apart. Patients' reported symptoms during repeated swallowing, the volume, pH and substance P (SP) concentrations in saliva, and cervical esophageal wall motion evaluated by ultrasonographic tissue Doppler imaging were obtained before and after capsaicin or placebo administration. Significantly more patients with OD who took capsaicin experienced improvement in symptoms than those who took placebo. Salivary SP levels were significantly increased after capsaicin administration compared with placebo in the effective group. The duration of cervical esophageal wall opening was significantly shorter in capsaicin administration in the effective group. Furthermore, a significant negative correlation was found between the duration of cervical esophageal wall opening and salivary SP levels. Elevated salivary SP concentrations stimulated by capsaicin greatly improve the safety and efficacy of swallowing, and shorten the swallow response in older patients with OD. © 2017 S. Karger AG, Basel.

Influence of neonatally administered capsaicin on baroreceptor and chemoreceptor reflexes in the adult rat.

PubMed Central

Bond, S. M.; Cervero, F.; McQueen, D. S.

1982-01-01

1 Baroreceptor and chemoreceptor reflex activity was studied in anaesthetized adult rats which had been treated neonatally with a single injection of capsaicin (50 mg/kg s.c.). 2 Pressor responses to bilateral carotid artery occlusion were significantly lower in capsaicin-treated rats compared with vehicle-treated controls. Pressor responses to intravenously injected noradrenaline were similar in the two groups of rats. 3 Resting respiratory minute volume and tidal volume were lower in anaesthetized capsaicin-treated animals than in vehicle-treated controls, but there was no significant difference in respiratory frequency. 4 The increases in respiration evoked by intravenous administration of the peripheral arterial chemoreceptor stimulant, sodium cyanide, or by breathing a hypoxic gas mixture, were significantly lower in capsaicin-treated rats compared with the controls. 5 It is concluded that baroreceptor and chemoreceptor reflex activity are significantly reduced in anaesthetized adult rats which had been treated neonatally with capsaicin, and that this is likely to result from the destruction of unmyelinated baro- and chemoreceptor afferent fibres. PMID:6182938

Novel Approaches to Extraction Methods in Recovery of Capsaicin from Habanero Pepper (CNPH 15.192)

PubMed Central

Martins, Frederico S.; Borges, Leonardo L.; Ribeiro, Claudia S. C.; Reifschneider, Francisco J. B.; Conceição, Edemilson C.

2017-01-01

Introduction: The objective of this study was to compare three capsaicin extraction methods: Shoxlet, Ultrasound-assisted Extraction (UAE), and Shaker-assisted Extraction (SAE) from Habanero pepper, CNPH 15.192. Materials and Methods: The different parameters evaluated were alcohol degree, time extraction, and solid–solvent ratio using response surface methodology (RSM). Results: The three parameters found significant (p < 0.05) were for UAE and solvent concentration and extraction time for SAE. The optimum conditions for the capsaicin UAE and SAE were similar 95% alcohol degree, 30 minutes and solid–liquid ratio 2 mg/mL. The Soxhlet increased the extraction in 10–25%; however, long extraction times (45 minutes) degraded 2% capsaicin. Conclusion: The extraction of capsaicin was influenced by extraction method and by the operating conditions chosen. The optimized conditions provided savings of time, solvent, and herbal material. Prudent choice of the extraction method is essential to ensure optimal yield of extract, thereby making the study relevant and the knowledge gained useful for further exploitation and application of this resource. SUMMARY Habanero pepper, line CNPH 15.192, possess capsaicin in higher levels when compared with others speciesHigher levels of ethanolic strength are more suitable to obtain a higher levels of capsaicinBox-Behnken design indicates to be useful to explore the best conditions of ultrasound assisted extraction of capsaicin. Abbreviations used: Nomenclature UAE: Ultrasound-assisted Extraction; SAE: Shaker-assisted Extraction. PMID:28808409

The Effects of Curcumin and Curcumin-Phospholipid Complex on the Serum Pro-oxidant-Antioxidant Balance in Subjects with Metabolic Syndrome.

PubMed

Ghazimoradi, Maryam; Saberi-Karimian, Maryam; Mohammadi, Farzane; Sahebkar, Amirhossein; Tavallaie, Shima; Safarian, Hamideh; Ferns, Gordon A; Ghayour-Mobarhan, Majid; Moohebati, Mohsen; Esmaeili, Habibollah; Ahmadinejad, Malihe

2017-11-01

Metabolic syndrome (MetS) is defined by a clustering of metabolic and anthropometric abnormalities and is associated by an increased risk of cardiovascular disease. We have investigated the effect of curcumin supplementation on the serum pro-oxidant-antioxidant balance (PAB) in patients with MetS. This double-blind, randomized, placebo-controlled trial was conducted over 6 weeks. Subjects (n = 120) were randomly allocated to one of three groups (curcumin, phospholipidated curcumin, and placebo). The curcumin group received 1 g/day of simple curcumin, the phospholipidated curcumin group received 1 g/day of phospholipidated curcumin (containing 200 mg of pure curcumin), and the control group received 1 g/day of placebo. Serum PAB was measured before and after the intervention (at baseline and at 6 weeks). Data analyses were performed using spss software (version 16.0). Serum PAB increased significantly in the curcumin group (p < 0.001), but in the phospholipidated curcumin group, elevation of PAB level was not significant (p = 0.053). The results of our study did not suggest any improvement of PAB following supplementation with curcumin in MetS subjects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Anxiolytic efficacy of repeated oral capsaicin in rats with partial aberration of oral sensory relay to brain.

PubMed

Choi, Young-Jun; Kim, Jin Young; Jin, Wei-Peng; Kim, Yoon-Tae; Lee, Jong-Ho; Jahng, Jeong Won

2015-07-01

This study was conducted to examine if taste over load with oral capsaicin improves the adverse behavioural effects induced by partial aberration of oral sensory relays to brain with bilateral transections of the lingual and chorda tympani nerves. Male Sprague-Dawley rats received daily 1 ml of 0.02% capsaicin or water drop by drop into the oral cavity following the bilateral transections of the lingual and chorda tympani nerves. Rats were subjected to ambulatory activity, elevated plus maze and forced swim tests after 11th, 14th and 17th daily administration of capsaicin or water, respectively. The basal and stress-induced plasma corticosterone levels were examined after the end of behavioural tests. Ambulatory counts, distance travelled, centre zone activities and rearing were increased, and rostral grooming decreased, during the activity test in capsaicin treated rats. Behavioural scores of capsaicin rats during elevated plus maze test did not differ from control rats. Immobility during the swim test was decreased in capsaicin rats with near significance (P = 0.0547). Repeated oral capsaicin increased both the basal level and stress-induced elevation of plasma corticosterone in rats with bilateral transections of the lingual and chorda tympani nerves. It is concluded that repeated oral administration of capsaicin reduces anxiety-like behaviours in rats that received bilateral transections of the lingual and chorda tympani nerves, and that the increased corticosterone response, possibly modulating the hippocampal neural plasticity, may be implicated in the anxiolytic efficacy of oral capsaicin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Physiological and pathological characterization of capsaicin-induced reversible nerve degeneration and hyperalgesia.

PubMed

Chiang, H; Chang, K-C; Kan, H-W; Wu, S-W; Tseng, M-T; Hsueh, H-W; Lin, Y-H; Chao, C-C; Hsieh, S-T

2018-07-01

The study aimed to investigate the physiology, psychophysics, pathology and their relationship in reversible nociceptive nerve degeneration, and the physiology of acute hyperalgesia. We enrolled 15 normal subjects to investigate intraepidermal nerve fibre (IENF) density, contact heat-evoked potential (CHEP) and thermal thresholds during the capsaicin-induced skin nerve degeneration-regeneration; and CHEP and thermal thresholds at capsaicin-induced acute hyperalgesia. After 2-week capsaicin treatment, IENF density of skin was markedly reduced with reduced amplitude and prolonged latency of CHEP, and increased warm and heat pain thresholds. The time courses of skin nerve regeneration and reversal of physiology and psychophysics were different: IENF density was still lower at 10 weeks after capsaicin treatment than that at baseline, whereas CHEP amplitude and warm threshold became normalized within 3 weeks after capsaicin treatment. Although CHEP amplitude and IENF density were best correlated in a multiple linear regression model, a one-phase exponential association model showed better fit than a simple linear one, that is in the regeneration phase, the slope of the regression line between CHEP amplitude and IENF density was steeper in the subgroup with lower IENF densities than in the one with higher IENF densities. During capsaicin-induced hyperalgesia, recordable rate of CHEP to 43 °C heat stimulation was higher with enhanced CHEP amplitude and pain perception compared to baseline. There were differential restoration of IENF density, CHEP and thermal thresholds, and changed CHEP-IENF relationships during skin reinnervation. CHEP can be a physiological signature of acute hyperalgesia. These observations suggested the relationship between nociceptive nerve terminals and brain responses to thermal stimuli changed during different degree of skin denervation, and CHEP to low-intensity heat stimulus can reflect the physiology of hyperalgesia. © 2018 European Pain

Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series.

PubMed

Dezieck, Laurel; Hafez, Zachary; Conicella, Albert; Blohm, Eike; O'Connor, Mark J; Schwarz, Evan S; Mullins, Michael E

2017-09-01

Cannabinoid hyperemesis syndrome (CHS) is characterized by symptoms of cyclic abdominal pain, nausea, and vomiting in the setting of prolonged cannabis use. The transient receptor potential vanilloid 1 (TRPV1) receptor may be involved in this syndrome. Topical capsaicin is a proposed treatment for CHS; it binds TRPV1 with high specificity, impairing substance P signaling in the area postrema and nucleus tractus solitarius via overstimulation of TRPV1. This may explain its apparent antiemetic effect in this syndrome. We describe a series of thirteen cases of suspected cannabis hyperemesis syndrome treated with capsaicin in the emergency departments of two academic medical centers. A query of the electronic health record at both centers identified thirteen patients with documented daily cannabis use and symptoms consistent with CHS who were administered topical capsaicin cream for symptom management. All 13 patients experienced symptom relief after administration of capsaicin cream. Topical capsaicin was associated with improvement in symptoms of CHS after other treatments failed.

Challenges of curcumin bioavailability: novel aerosol remedies.

PubMed

Subramani, Parasuraman Aiya; Narala, Venkata R

2013-01-01

Nanoparticles are promising aids for drug delivery for previously challenging diseases, and many incurable ones. Curcumin (diferuloylmethane) is a pleiotropic molecule having various target molecules in the body. Despite its effects, curcumin-based drugs are not readily available in the market because of their low bioavailability. Although dietary intake and knowledge about the potential of curcumin are high in countries like India, studies indicate that the bioavailability problem still persists. However, administration of curcumin through inhalation has received little consideration. In this review we discuss the potential of curcumin, approaches made to overcome the bioavailability challenges, and novel approaches that could be applied in order to deliver curcumin in a pressurized metered dose inhaler (pMDI).

Advances in clinical study of curcumin.

PubMed

Yang, Chunfen; Su, Xun; Liu, Anchang; Zhang, Lin; Yu, Aihua; Xi, Yanwei; Zhai, Guangxi

2013-01-01

Curcumin has been estimated as a potential agent for many diseases and attracted great attention owing to its various pharmacological activities, including anti-cancer, and anti-inflammatory. Now curcumin is being applied to a number of patients with breast cancer, rheumatoid arthritis, Alzheimer's disease, colorectal cancer, psoriatic, etc. Several clinical trials have stated that curcumin is safe enough and effective. The objective of this article was to summarize the clinical studies of curcumin, and give a reference for future studies.

The influence of curcumin and manganese complex of curcumin on cadmium-induced oxidative damage and trace elements status in tissues of mice.

PubMed

Eybl, Vladislav; Kotyzová, Dana; Lesetický, Ladislav; Bludovská, Monika; Koutenský, Jaroslav

2006-01-01

Curcumin (diferuoyl methane) from turmeric is a well-known biologically active compound. It has been shown to ameliorate oxidative stress and it is considered to be a potent cancer chemopreventive agent. In our previous study the antioxidative effects of curcumin in cadmium exposed animals were demonstrated. Also manganese exerts protective effects in experimental cadmium intoxication. The present study examined the ability of the manganese complex of curcumin (Mn-curcumin) and curcumin to protect against oxidative damage and changes in trace element status in cadmium-intoxicated male mice. Curcumin or Mn-curcumin were administered at equimolar doses (0.14 mmol/kg b.w.) for 3 days, by gastric gavages, dispersed in methylcellulose. One hour after the last dose of antioxidants, cadmium chloride (33 micromol/kg) was administered subcutaneously. Both curcumin and Mn-curcumin prevented the increase of hepatic lipid peroxidation -- expressed as MDA level, induced by cadmium intoxication and attenuated the Cd-induced decrease of hepatic GSH level. No change in hepatic glutathione peroxidase or catalase activities was found in Cd-exposed mice. A decreased GSH-Px activity was measured in curcumin and Mn-curcumin alone treated mice. Neither curcumin nor Mn-curcumin treatment influenced cadmium distribution in the tissues and did not correct the changes in the balance of essential elements caused by Cd-treatment. The treatment with Mn-curcumin increased the Fe and Mn content in the kidneys of both control and Cd-treated mice and Fe and Cu content in the brain of control mice. In conclusion, regarding the antioxidative action, introducing manganese into the curcumin molecule does not potentiate the studied effects of curcumin. Copyright 2006 John Wiley & Sons, Ltd.

Application of a capsaicin rinse in the treatment of burning mouth syndrome

PubMed Central

Silvestre-Rangil, Javier; Tamarit-Santafé, Carmen; Bautista, Daniel

2012-01-01

Objective: To examine the efficacy of a new topical capsaicin presentation as an oral rinse in improving the symptoms of burning mouth syndrome (BMS). Study design: A prospective, double-blind, cross-over study was made of 30 patients with BMS. There were 7 dropouts; the final study series thus comprised 23 individuals. The patients were randomized to two groups: (A) capsaicin rinse (0.02%) or (B) placebo rinse, administered during one week. After a one-week washout period, the patients were then assigned to the opposite group. Burning discomfort was scored using a visual analog scale (VAS): in the morning before starting the treatment, in the afternoon on the first day of treatment, and at the end of the week of treatment in the morning and in the afternoon. The same scoring sequence was again applied one week later with the opposite rinse. Results: The mean patient age was 72.65 ± 12.10 years, and the duration of BMS was 5.43 ± 3.23 years on average. Significant differences in VAS score were recorded in the capsaicin group between baseline in the morning (AM1) or afternoon (AA1) and the end of the week of treatment (AA7)(p=0.003 and p=0.002, respectively). Conclusion: The topical application of capsaicin may be useful in treating the discomfort of BMS, but has some limitations. Key words: Burning mouth syndrome, stomatodynia, capsaicin, treatment, clinical management. PMID:21743415

Tachykinin antagonists and capsaicin-induced contraction of the rat isolated urinary bladder: evidence for tachykinin-mediated cotransmission.

PubMed

Maggi, C A; Patacchini, R; Santicioli, P; Giuliani, S

1991-06-01

1. The possible involvement of tachykinins (TKs) in the contraction produced by capsaicin in the rat isolated urinary bladder was addressed on the hypothesis that co-release of substance P (SP) and neurokinin A (NKA) occurs from sensory nerve terminals. 2. A low concentration of SP (30 nM) produced a rapid contraction which faded to baseline within 10 min. A low concentration of NKA (10 nM) produced a slowly developing contraction which was still evident at 10 min. Capsaicin (1 microM) produced a rapid phasic response and a tonic response (late response to capsaicin). Co-administration of SP and NKA mimicked the response to capsaicin more than each TK alone. 3. Fading of the response to SP was not caused by receptor desensitization and was partially prevented by peptidase inhibitors. 4. Spantide (3 microM) selectively antagonized the SP-induced contraction while L-659,877 (3-10 microM) or MEN 10,376 (10-30 microM) which are NK2 receptor selective antagonists selectively blocked the response to NKA. Co-administration of spantide and L-659,877 inhibited the response to both SP and NKA by an amount not greater than that produced by each antagonist alone. 5. Spantide selectively reduced the peak response to capsaicin, while leaving the late response unaffected. L-659,877 (3 microM) and MEN 10,376 (10 microM) selectively inhibited the late response to capsaicin while, at higher concentrations, also reduced the peak response to capsaicin. Co-administration of spantide and L-659,877 reduced the peak response to capsaicin more than that produced by each antagonist alone. 6. Bombesin (10 nM) produced a tonic contraction similar to that induced by NKA. The response to bombesin was not affected by spantide, L-659,877 or MEN 10,376. 7 P2. purinoceptor desensitization by repeated administration of alpha,betal-methylene ATP depressed the twitch response to electrical stimulation of postganglionic nerves but did not affect the peak or the late response to capsaicin. 8. We

Effect of sympathetic activity on capsaicin-evoked pain, hyperalgesia, and vasodilatation.

PubMed

Baron, R; Wasner, G; Borgstedt, R; Hastedt, E; Schulte, H; Binder, A; Kopper, F; Rowbotham, M; Levine, J D; Fields, H L

1999-03-23

Painful nerve and tissue injuries can be exacerbated by activity in sympathetic neurons. The mechanisms of sympathetically maintained pain (SMP) are unclear. To determine the effect of cutaneous sympathetic activity on pain induced by primary afferent C-nociceptor sensitization with capsaicin in humans. In healthy volunteers capsaicin was applied topically (n = 12) or injected into the forearm skin (n = 10) to induce spontaneous pain, dynamic and punctate mechanical hyperalgesia, and antidromic (axon reflex) vasodilatation (flare). Intensity of pain and hyperalgesia, axon reflex vasodilatation (laser Doppler), and flare size and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of high and low sympathetic skin activity induced by whole-body cooling and warming with a thermal suit. By this method sympathetic vasoconstrictor activity is modulated in the widest range that can be achieved physiologically. The degree of vasoconstrictor discharge was monitored by measuring skin blood flow (laser Doppler) and temperature (infrared thermometry) at the index finger. The intensity and spatial distribution of capsaicin-evoked spontaneous pain and dynamic and punctate mechanical hyperalgesia were identical during the presence of high and low sympathetic discharge. Antidromic vasodilatation and flare size were significantly diminished when sympathetic vasoconstrictor neurons were excited. Cutaneous sympathetic vasoconstrictor activity does not influence spontaneous pain and mechanical hyperalgesia after capsaicin-induced C-nociceptor sensitization. When using physiologic stimulation of sympathetic activity, the capsaicin model is not useful for elucidating mechanisms of SMP. In neuropathic pain states with SMP, different mechanisms may be present.

Capsicum and capsaicin--a review: case report of the use of hot peppers in child abuse.

PubMed

Tominack, R L; Spyker, D A

1987-01-01

Capsaicin, the active principle of hot peppers of the genus Capsicum, exhibits broad bioactivity. It targets neuronal structures which contain substance P, clinically seen as gastrointestinal and dermatologic irritation, bronchospasm and fibrinolysis. As a research tool, capsaicin profoundly alters neurologic anatomy and function. We review the toxicity of capsaicin and comment briefly on the use of hot peppers in child abuse.

The detection of capsaicin and dihydrocapsaicin in horse serum following long-term local administration.

PubMed

Zak, A; Siwinska, N; Slowikowska, M; Borowicz, H; Szpot, P; Zawadzki, M; Niedzwiedz, A

2018-06-19

Capsaicin and dihydrocapsaicin are alkaloids with analgesic effects in humans and animals. When used locally, both of them minimalise pain sensation by defunctionalising nerve endings. According to the Federation Equestrian International Prohibited Substances List, these are substance banned in horse competitions. The aim of the study was to determine the detection time of capsaicin in both plasma and serum after long-term use of a gel recommended for commercial use and applied as intended. The objective of the study was to select the best material for the detection of capsaicin as a doping substance in horses. Nine healthy mature horses were administered 0.1% capsaicin topically in the form of a commercial analgesic gel (15 g of the gel per limb) to the front limbs every 24 hours for five days with a polar fleece bandage. Blood serum and plasma were collected prior to gel application and in the 12th, 18th, 24th, 36th, 42nd, 48th, 60th, 84th, 108th, 132nd, 156th hour after the gel application. Qualitative and quantitative analysis was performed using ultra-high performance liquid chromatography coupled with a triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS). The concentration of capsaicin in the serum samples did not exceed the lower limit of quantification. Capsaicin was not detected in the plasma samples during the entire study period. Dihydrocapsaicin was not detected in blood serum or plasma. The presented results suggest that capsaicin is not detected in horse serum in the 24-hour-periodfollowing its last application according to the dosage regimen used by owners and veterinarians for therapy rather than doping, based on a five day gel application and a polar bandage.

Enkephalinase inhibitor potentiates substance P- and capsaicin-induced bronchial smooth muscle contractions in humans.

PubMed

Honda, I; Kohrogi, H; Yamaguchi, T; Ando, M; Araki, S

1991-06-01

To determine the roles of endogenously released tachykinins (substance P, neurokinins A and B) in human bronchial tissues, and to determine the roles of enkephalinase (neutral endopeptidase, E.C. 3.4.24.11) in regulating the effects of the tachykinins, we studied the effects of substance P and capsaicin, which releases tachykinins, on human bronchial smooth muscle contraction in the presence or absence of enkephalinase inhibitor phosphoramidon in vitro. Substance P alone caused human bronchial smooth muscle contraction at 10(-6) M or more. Phosphoramidon (10(-7) to 10(-5) M) potentiated the substance P-induced contraction in a dose-dependent fashion, and phosphoramidon shifted the dose-response curve to lower concentrations. Capsaicin (10(-5) or 10(-4) M) alone caused bronchial smooth muscle contraction in four tissues from nine patients. After the contraction by capsaicin reached a plateau, phosphoramidon (10(-5) M) increased and prolonged the contraction significantly. Furthermore, pretreatment of bronchial tissues with phosphoramidon (10(-5) M) potentiated capsaicin-induced contraction in all tissues from five patients. Phosphoramidon (10(-5) M) shifted the dose-response curve to capsaicin to lower concentrations more than 1 log unit. Captopril did not alter the contractile response to substance P, suggesting that angiotensin-converting enzyme does not regulate the contractile response to substance P in human bronchial smooth muscle in vitro. These results suggest that enkephalinase regulates the contractile effects of exogenous substance P and endogenous substances, probably tachykinins, released by capsaicin in the human bronchus.

Determination of process parameters for curcumin - dextrose cocrystallization

NASA Astrophysics Data System (ADS)

Katherine; Nugroho, Denny; Sugih, Asaf K.

2018-01-01

Curcumin is a polyphenol that could act as anti-oxidant and anti - inflammation agent. It is usually isolated from rhizome plants such as turmeric and temulawak. Despite its many favorable properties, curcumin is practically insoluble in water, thus limiting its application. In the present investigation, variables affecting preparation of curcumin-dextrose cocrystal were examined with the aim to increase the solubility of curcumin. The effect of different processing conditions, such as water to dextrose ratio, final heating temperature and water bath temperature to the formation of cocrystal, were studied and the yield and solubility of curcumin - dextrose cocrystal products were analyzed. The morphology of the cocrystals were also analyzed using SEM and fluorescence microscopy.. Curcumin - dextrose cocrystals showed a significant increase in solubility up to 25 mg curcumin per mL water compared to pure curcumin.

Bioavailability of a Sustained Release Formulation of Curcumin

PubMed Central

Madhavi, Doddabele; Kagan, Daniel

2014-01-01

Context Curcumin has a number of beneficial effects, such as functioning as a potent antioxidant,1 anti-inflammatory, 2 and anticancer agent. Because of its poor oral bioavailability, very high oral doses and repeated dosing have been used to obtain effective plasma levels, with mixed results. High doses of curcumin may cause gastric disturbance, often resulting in poor patient compliance. Objective The objective of this study was to compare the relative bioavailability of MicroActive Curcumin—an advanced, micronized formulation of curcumin that is 25% curcuminoids in a sustained release matrix—with that of an unformulated, 95% pure curcumin powder. Design A dissolution study compared the solubility of the formulated and the unformulated curcumin. The research team also performed a single-dose, 12-h, crossover uptake study with 10 participants and a high-dose tolerability and accumulation study with 3 participants, comparing the 2 forms of curcumin. Setting The study was done in MAZE Laboratories (Purchase, NY, USA). Participants Ten healthy male and female volunteers, aged 21–66 y, took part in the single-dose study. Three participants, 2 female and 1 male aged 40–55 y, took part in the tolerability and accumulation study. The participants were people from the community. Intervention For the dissolution study, the research team filled hard gelatin capsules with unformulated 95% curcumin powder and the MicroActive Curcumin powder to the equivalent of 25 mg curcuminoids. For the single-dose study, participants received 500 mg of curcumin in 2 forms. MicroActive Curcumin capsules were administered after breakfast, and blood samples were drawn at 1, 2, 4, 8, and 12 h postdose. After a 7-d washout period, the protocol was repeated for unformulated, 95% curcumin powder capsules. For the tolerability study, the unformulated, 95% curcumin powder was given at a dose that provided 2 g of curcumin for 7 d followed by 5 g of curcumin for an additional 7 d. After a

Theoretical study on physicochemical properties of curcumin

NASA Astrophysics Data System (ADS)

Shen, Liang; Ji, Hong-Fang

2007-07-01

Curcumin is a yellow-orange pigment, which has attracted considerable attention due to its wide spectrum of biological and pharmacological activities. In spite of much effort devoted on curcumin, there still exist some open questions concerning its fundamental physicochemical properties. The present study suggests that the DFT and TD-DFT calculations are useful to answer these questions. Firstly, the thermodynamic as well as spectral parameters support that curcumin exists predominantly in enol form in solution. Secondly, the calculated absorption spectra of curcumin anions provides direct evidence that the lowest p Ka of curcumin corresponds to the dissociation of enolic proton, which not only reconciles the controversy on this topic, but also has important implications on the proton-transfer/dissociation-associated radical-scavenging mechanisms of curcumin.

Induction of abnormal respiratory sounds by capsaicin in rats previously infected with Bordetella pertussis.

PubMed

Parton, R; Hall, E; Wardlaw, A C

1998-02-01

Sprague Dawley rats, previously infected with Phase-I Bordetella pertussis, developed more severe abnormal respiratory sounds than normal animals, but not coughing, when exposed to aerosolized capsaicin, one of several cough-inducing agents tested. Stethoscope examination suggested that greater production of pulmonary mucus might be occurring after capsaicin challenge of the infected animals, compared to the uninfected controls. Rats of three other strains gave characteristically different responses from the Sprague Dawleys. The administration of capsaicin to B. pertussis-infected rats may provide useful insights into the pathophysiology of excess mucus secretion in human pertussis.

Curcumin β-D-Glucuronide Plays an Important Role to Keep High Levels of Free-Form Curcumin in the Blood.

PubMed

Ozawa, Hitomi; Imaizumi, Atsushi; Sumi, Yoshihiko; Hashimoto, Tadashi; Kanai, Masashi; Makino, Yuji; Tsuda, Takanori; Takahashi, Nobuaki; Kakeya, Hideaki

2017-01-01

Curcumin, a polyphenol derived from the rhizome of the naturally occurring plant Curcuma longa, has various pharmacological actions such as antioxidant and anti-inflammatory effects. In this paper, we evaluated the role of its internal metabolite, curcumin β-D-glucuronide (curcumin monoglucuronide, CMG), by investigating curcumin kinetics and metabolism in the blood. Firstly, we orally administered highly bioavailable curcumin to rats to elucidate its kinetics, and observed not only the free-form of curcumin, but also, curcumin in a conjugated form, within the portal vein. We confirmed that curcumin is conjugated when it passes through the intestinal wall. CMG, one of the metabolites, was then orally administered to rats. Despite its high aqueous solubility compared to free-form curcumin, it was not well absorbed. In addition, CMG was injected intravenously into rats in order to assess its metabolic behavior in the blood. Interestingly, high levels of free-form curcumin, thought to be sufficiently high to be pharmacologically active, were observed. The in vivo antitumor effects of CMG following intravenous injection were then evaluated in tumor-bearing mice with the HCT116 human colon cancer cell line. The tumor volume within the CMG group was significantly less than that of the control group. Moreover, there was no significant loss of body weight in the CMG group compared to the control group. These results suggest that CMG could be used as an anticancer agent without the serious side effects that most anticancer agents have.

Effects of curcumin on HDL functionality.

PubMed

Ganjali, Shiva; Blesso, Christopher N; Banach, Maciej; Pirro, Matteo; Majeed, Muhammed; Sahebkar, Amirhossein

2017-05-01

Curcumin, a bioactive polyphenol, is a yellow pigment of the Curcuma longa (turmeric) plant. Curcumin has many pharmacologic effects including antioxidant, anti-carcinogenic, anti-obesity, anti-angiogenic and anti-inflammatory properties. Recently, it has been found that curcumin affects lipid metabolism, and subsequently, may alleviate hyperlipidemia and atherosclerosis. Plasma HDL cholesterol (HDL-C) is an independent negative risk predictor of cardiovascular disease (CVD). However, numerous clinical and genetic studies have yielded disappointing results about the therapeutic benefit of raising plasma HDL-C levels. Therefore, research efforts are now focused on improving HDL functionality, independent of HDL-C levels. The quality of HDL particles can vary considerably due to heterogeneity in composition. Consistent with its complexity in composition and metabolism, a wide range of biological activities is reported for HDL, including antioxidant, anti-glycation, anti-inflammatory, anti-thrombotic, anti-apoptotic and immune modulatory activities. Protective properties of curcumin may influence HDL functionality; therefore, we reviewed the literature to determine whether curcumin can augment HDL function. In this review, we concluded that curcumin may modulate markers of HDL function, such as apo-AI, CETP, LCAT, PON1, MPO activities and levels. Curcumin may subsequently improve conditions in which HDL is dysfunctional and may have potential as a therapeutic drug in future. Further clinical trials with bioavailability-improved formulations of curcumin are warranted to examine its effects on lipid metabolism and HDL function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neonatal capsaicin treatment in rats affects TRPV1-related noxious heat sensation and circadian body temperature rhythm.

PubMed

Jeong, Keun-Yeong; Seong, Jinsil

2014-06-15

The transient receptor potential vanilloid 1 (TRPV1) is a cation channel that serves as a polymodal detector of noxious stimuli such as capsaicin. Therefore, capsaicin treatment has been used to investigate the physiological function of TRPV1. Here, we report physiological changes induced by treating neonatal rats with capsaicin. Capsaicin (50mg/kg) (cap-treated) or vehicle (vehicle-treated) was systemically administered to newborn SD rat pups within 48 h after birth. TRPV1 expression, intake volume of capsaicin water, and noxious heat sensation were measured 6 weeks after capsaicin treatment. Circadian body temperature and locomotion were recorded by biotelemetry. Expression of Per1, Per2, Bmal1 and Hsf1 (clock genes) was also investigated. Neonatal capsaicin treatment not only decreased TRPV1 expression but also induced desensitization to noxious heat stimuli. Circadian body temperature of cap-treated rats increased significantly compared with that of vehicle-treated rats. Additionally, the amplitude of the circadian body temperature was reversed in cap-treated rats. Expression of the hypothalamic Hsf1 and liver Per2 clock genes followed a similar trend. Therefore, we suggest that these findings will be useful in studying various physiological mechanisms related to TRPV1. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects and distribution of vagal capsaicin-sensitive substance P neurons with special reference to the trachea and lungs.

PubMed

Lundberg, J M; Brodin, E; Saria, A

1983-11-01

The origin of substance P (SP)-immunoreactive neurons in the lower respiratory tract, esophagus and heart of guinea-pigs was demonstrated by surgical denervation or capsaicin pretreatment with subsequent determination of the tissue levels of SP by radioimmunoassay. In other experiments the effect of vagal nerve stimulation on the SP levels in these tissues was studied. The effects of capsaicin-sensitive afferents in the respiratory tract mucosa and bronchial smooth muscle was also studied by analysis of vascular permeability to Evans blue and insufflation-pressure changes. Our present data indicate that all SP nerves in the trachea and lung are afferent and capsaicin-sensitive. The trachea and stem bronchi receive SP afferents mainly from the right vagus nerve with cell bodies located in both the nodose and jugular ganglia. The SP innervation of the lung seems to have a dual origin: 1. Afferents from both vagal nerves with a crossed type of innervation pattern. 2. A non-vagal source which consists of about 40% of the SP nerves in the lung. These nerves probably originate from thoracic spinal ganglia. The effects of ether and capsaicin on insufflation pressure and increase in vascular permeability were dependent on the integrity of capsaicin-sensitive afferents of both vagal and non-vagal origin. In the guinea pig, systemic capsaicin pretreatment to adult animals seemed to result in irreversible changes in the respiratory tract, while in the rat a successive recovery of the functional response of capsaicin-sensitive afferents occurred. Different regimes of systemic capsaicin pretreatment induced different effects on the cholinergic (atropine-sensitive) insufflation-pressure response. Capsaicin pretreatment, using multiple injections over two days, depressed the cholinergic insufflation-pressure increase, while the cholinergic vagal component was unaffected in animals which received a single dose of capsaicin or local pretreatment with capsaicin on the vagal nerves

Capsaicin sensitizes TRAIL-induced apoptosis through Sp1-mediated DR5 up-regulation: Involvement of Ca{sup 2+} influx

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

Moon, Dong-Oh; Kang, Chang-Hee; Kang, Sang-Hyuck

2012-02-15

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various malignant cells, several cancers including human hepatocellular carcinoma (HCC) exhibit potent resistance to TRAIL-induced cell death. The aim of this study is to evaluate the anti-cancer potential of capsaicin in TRAIL-induced cancer cell death. As indicated by assays that measure phosphatidylserine exposure, mitochondrial activity and activation of caspases, capsaicin potentiated TRAIL-resistant cells to lead to cell death. In addition, we found that capsaicin induces the cell surface expression of TRAIL receptor DR5, but not DR4 through the activation Sp1 on its promoter region. Furthermore, we investigated that capsaicin-induced DR5more » expression and apoptosis are inhibited by calcium chelator or inhibitors for calmodulin-dependent protein kinase. Taken together, our data suggest that capsaicin sensitizes TRAIL-mediated HCC cell apoptosis by DR5 up-regulation via calcium influx-dependent Sp1 activation. Highlights: ► Capsaicin sensitizes TRAIL-induced apoptosis through activation of caspases. ► Capsaicin induces expression of DR5 through Sp1 activation. ► Capsaicin activates calcium signaling pathway.« less

Nanotechnology-Applied Curcumin for Different Diseases Therapy

PubMed Central

Ghalandarlaki, Negar; Ashkani-Esfahani, Soheil

2014-01-01

Curcumin is a lipophilic molecule with an active ingredient in the herbal remedy and dietary spice turmeric. It is used by different folks for treatment of many diseases. Recent studies have discussed poor bioavailability of curcumin because of poor absorption, rapid metabolism, and rapid systemic elimination. Nanotechnology is an emerging field that is potentially changing the way we can treat diseases through drug delivery with curcumin. The recent investigations established several approaches to improve the bioavailability, to increase the plasma concentration, and to enhance the cellular permeability processes of curcumin. Several types of nanoparticles have been found to be suitable for the encapsulation or loading of curcumin to improve its therapeutic effects in different diseases. Nanoparticles such as liposomes, polymeric nanoparticles, micelles, nanogels, niosomes, cyclodextrins, dendrimers, silvers, and solid lipids are emerging as one of the useful alternatives that have been shown to deliver therapeutic concentrations of curcumin. This review shows that curcumin's therapeutic effects may increase to some extent in the presence of nanotechnology. The presented board of evidence focuses on the valuable special effects of curcumin on different diseases and candidates it for future clinical studies in the realm of these diseases. PMID:24995293

Curcumin Modulates α-Synuclein Aggregation and Toxicity

PubMed Central

2012-01-01

In human beings, Parkinson’s disease (PD) is associated with the oligomerization and amyloid formation of α-synuclein (α-Syn). The polyphenolic Asian food ingredient curcumin has proven to be effective against a wide range of human diseases including cancers and neurological disorders. While curcumin has been shown to significantly reduce cell toxicity of α-Syn aggregates, its mechanism of action remains unexplored. Here, using a series of biophysical techniques, we demonstrate that curcumin reduces toxicity by binding to preformed oligomers and fibrils and altering their hydrophobic surface exposure. Further, our fluorescence and two-dimensional nuclear magnetic resonance (2D-NMR) data indicate that curcumin does not bind to monomeric α-Syn but binds specifically to oligomeric intermediates. The degree of curcumin binding correlates with the extent of α-Syn oligomerization, suggesting that the ordered structure of protein is required for effective curcumin binding. The acceleration of aggregation by curcumin may decrease the population of toxic oligomeric intermediates of α-Syn. Collectively; our results suggest that curcumin and related polyphenolic compounds can be pursued as candidate drug targets for treatment of PD and other neurological diseases. PMID:23509976

Cytoprotective mechanism of action of curcumin against cataract.

PubMed

Raman, Thiagarajan; Ramar, Manikandan; Arumugam, Munusamy; Nabavi, Seyed Mohammad; Varsha, Mosur Kumaraswamy Nagarajan Sai

2016-06-01

This review discusses the relationship between oxidative stress and cataract formation, molecular mechanism of curcumin action and potential benefits of treatment with the antioxidant curcumin. The first section deals with curcumin and endogenous antioxidants. The second section focuses on the action of curcumin on lipid peroxidation. Calcium homeostasis and curcumin will be discussed in the third section. The fourth section discusses the role of crystallin proteins that are responsible for maintaining lens transparency and the role of curcumin in regulating crystallin expression. The interaction of curcumin with transcription factors will be dealt in the fifth section. The final section will focus on the effect of curcumin on aldose reductase, which is associated with hyperglycemia and cataract. One of the strongest antioxidants is curcumin which has been shown to be very effective against cataract. This compound is better than other antioxidants in preventing cataract but its limited bioavailability can be addressed by employing nanotechnology. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Novel dipeptide nanoparticles for effective curcumin delivery

PubMed Central

Alam, Shadab; Panda, Jiban J; Chauhan, Virander S

2012-01-01

Background: Curcumin, the principal curcuminoid of the popular Indian spice turmeric, has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin is a major challenge in its development as a useful drug. To enhance the aqueous solubility and bioavailability of curcumin, attempts have been made to encapsulate it in liposomes, polymeric nanoparticles (NPs), lipid-based NPs, biodegradable microspheres, cyclodextrin, and hydrogels. Methods: In this work, we attempted to entrap curcumin in novel self-assembled dipeptide NPs containing a nonprotein amino acid, α, β-dehydrophenylalanine, and investigated the biological activity of dipeptide-curcumin NPs in cancer models both in vitro and in vivo. Results: Of the several dehydrodipeptides tested, methionine-dehydrophenylalanine was the most suitable one for loading and release of curcumin. Loading of curcumin in the dipeptide NPs increased its solubility, improved cellular availability, enhanced its toxicity towards different cancerous cell lines, and enhanced curcumin’s efficacy towards inhibiting tumor growth in Balb/c mice bearing a B6F10 melanoma tumor. Conclusion: These novel, highly biocompatible, and easy to construct dipeptide NPs with a capacity to load and release curcumin in a sustained manner significantly improved curcumin’s cellular uptake without altering its anticancer or other therapeutic properties. Curcumin-dipeptide NPs also showed improved in vitro and in vivo chemotherapeutic efficacy compared to curcumin alone. Such dipeptide-NPs may also improve the delivery of other potent hydrophobic drug molecules that show poor cellular uptake, bioavailability, and efficacy. PMID:22915849

The Effectiveness and Safety of Topical Capsaicin in Postherpetic Neuralgia: A Systematic Review and Meta-analysis

PubMed Central

Yong, Yi Lai; Tan, Loh Teng-Hern; Ming, Long Chiau; Chan, Kok-Gan; Lee, Learn-Han; Goh, Bey-Hing; Khan, Tahir Mehmood

2017-01-01

In particular, neuropathic pain is a major form of chronic pain. This type of pain results from dysfunction or lesions in the central and peripheral nervous system. Capsaicin has been traditionally utilized as a medicine to remedy pain. However, the effectiveness and safety of this practice is still elusive. Therefore, this systematic review aimed to investigate the effect of topical capsaicin as a pain-relieving agent that is frequently used in pain management. In brief, all the double-blinded, randomized placebo- or vehicle-controlled trials that were published in English addressing postherpetic neuralgia were included. Meta-analysis was performed using Revman® version 5.3. Upon application of the inclusion and exclusion criteria, only six trials fulfilled all the criteria and were included in the review for qualitative analysis. The difference in mean percentage change in numeric pain rating scale score ranges from -31 to -4.3. This demonstrated high efficacy of topical capsaicin application and implies that capsaicin could result in pain reduction. Furthermore, meta-analysis was performed on five of the included studies. All the results of studies are in favor of the treatment using capsaicin. The incidence of side effects from using topical capsaicin is consistently higher in all included studies, but the significance of safety data cannot be quantified due to a lack of p-values in the original studies. Nevertheless, topical capsaicin is a promising treatment option for specific patient groups or certain neuropathic pain conditions such as postherpetic neuralgia. PMID:28119613

Telomerase: A Target for Therapeutic Effects of Curcumin and a Curcumin Derivative in Aβ1-42 Insult In Vitro

PubMed Central

Lin, Jianwen; Zheng, Zhenyang; Shi, Xiaolei; Di, Wei; Qi, Weiwei; Zhu, Yingting; Zhou, Guijuan; Fang, Yannan

2014-01-01

This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer's disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aβ1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aβ1–42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1. PMID:24983737

Bidirectional interactions between dietary curcumin and gut microbiota.

PubMed

Shen, Liang; Ji, Hong-Fang

2018-05-21

Curcumin is a polyphenolic compound with a long history of use as an herbal remedy, dietary spice and food-coloring agent. Despite curcumin possesses a wide range of biological and pharmacological activities, it exhibits extremely poor bioavailability, which makes its pharmacology intriguing and also hinders its clinical application. In recent years, there is ample evidence supporting the associations between the alteration of gut microbiota and many diseases. Interestingly, after oral administration, curcumin shows its preferential distribution and accumulation in the intestine. In view of the above aspects, we reviewed the updated knowledge regarding the bidirectional interactions between curcumin and gut microbiota from two perspectives: i) gut microbiota regulation by curcumin and ii) curcumin biotransformation by digestive microbiota. Besides the study deals with 3 potential pharmacological implications: i) identification of metabolites being more active and bioavaliable than parent curcumin; ii) assessment of contribution of gut microbiota regulation of curcumin to its pharmacological effects and iii) development of gut microbiota regulation-based disease prevention/treatment strategy for curcumin in view of its clinical safety. This review is important to deepen our understanding of the mechanisms of action of curcumin and to provide future directions about how to use this natural compound to combat human diseases.

Recent progress on curcumin-based therapeutics: a patent review (2012-2016). Part I: Curcumin.

PubMed

Di Martino, Rita Maria Concetta; Luppi, Barbara; Bisi, Alessandra; Gobbi, Silvia; Rampa, Angela; Abruzzo, Angela; Belluti, Federica

2017-05-01

curcumin is the main bioactive component contained in Curcuma Longa, largely employed in traditional medicine. Recently, beneficial properties, useful for prevention and treatment of several disorders, have been discovered for this compound. Peculiar structural feature is an α,β-unsaturated carbonyl system essential for establishing contacts with critical cysteine residues of several targets. This distinctive mechanism of action imparts to the molecule the ability to affect a large number of targets, accounting for its pleiotropic behaviour and definition of "privileged structure". Areas covered: The objective of the review is an examination of the recent developments in the field of the anti-cancer applications of curcumin, together with formulation issues, considering the patent literature in the years 2012-2016. Expert opinion: The wide therapeutic efficacy of curcumin is related to synergistic interactions with several biological targets, along with the modulation of several signaling pathways. This peculiar behaviour could be useful in the treatment of multifactorial diseases such as cancer. Combination of curcumin with a first line antineoplastic drug proved to be a valuable strategy to obtain an amplified response with minimized side effects. Innovative curcumin formulations based on the nanotechnology approach allowed improving both bioavailability and therapeutic efficacy.

Analgesic effect of topical oral capsaicin gel in burning mouth syndrome.

PubMed

Jørgensen, Mette Rose; Pedersen, Anne Marie Lynge

2017-03-01

To investigate the effectiveness of repeated topical application of oral capsaicin gel in two different concentrations for relief of burning/stinging sensations in patients with burning mouth syndrome (BMS). This randomized double-blind cross-over study included 22 female patients with BMS. The patients were randomized for topical application of either 0.01% or 0.025% oral capsaicin gel on the dorsal part of tongue three times daily for 14 days, followed by 14 days wash-out period, and finally treatment with the other concentration of oral gel three times daily for 14 days. A visual analogue scale (VAS) was used to assess the severity of pain five times during the intervention period. 18 patients completed the intervention. Their VAS score at baseline was 5.5 ± 0.6 cm (mean ± SD). Treatment with the two concentrations of capsaicin gels significantly improved the burning/stinging symptoms assessed on VAS compared with baseline (p = 0.002). There was no statistically significant difference between the two concentrations of the gels on relieving symptoms. Four patients dropped out during the intervention period due to gastrointestinal side-effects. Topical capsaicin might be an alternative for the short-term treatment of BMS. However, further studies are needed to investigate especially the gastro-intestinal side-effects which may limit its long-term use.

Curcumin directly inhibits the transport activity of GLUT1

PubMed Central

Gunnink, Leesha K.; Alabi, Ola D.; Kuiper, Benjamin D.; Gunnink, Stephen M.; Schuiteman, Sam J.; Strohbehn, Lauren E.; Hamilton, Kathryn E.; Wrobel, Kathryn E.; Louters, Larry L.

2016-01-01

Curcumin, a major ingredient in turmeric, has a long history of medicinal applications in a wide array of maladies including treatment for diabetes and cancer. Seemingly counterintuitive to the documented hypoglycemic effects of curcumin, however, a recent report indicates that curcumin directly inhibits glucose uptake in adipocytes. The major glucose transporter in adipocytes is GLUT4. Therefore, this study investigates the effects of curcumin in cell lines where the major transporter is GLUT1. We report that curcumin has an immediate inhibitory effect on basal glucose uptake in L929 fibroblast cells with a maximum inhibition of 80% achieved at 75 μM curcumin. Curcumin also blocks activation of glucose uptake by azide, glucose deprivation, hydroxylamine, or phenylarsine oxide. Inhibition does not increase with exposure time and the inhibitory effects reverse within an hour. Inhibition does not appear to involve a reaction between curcumin and the thiol side chain of a cysteine residue since neither prior treatment of cells with iodoacetamide nor curcumin with cysteine alters curcumin’s inhibitory effects. Curcumin is a mixed inhibitor reducing the Vmax of 2DG transport by about half with little effect on the Km. The inhibitory effects of curcumin are not additive to the effects of cytochalasin B and 75 μM curcumin actually reduces specific cytochalasin B binding by 80%. Taken together, the data suggest that curcumin binds directly to GLUT1 at a site that overlaps with the cytochalasin B binding site and thereby inhibits glucose transport. A direct inhibition of GLUT proteins in intestinal epithelial cells would likely reduce absorption of dietary glucose and contribute to a hypoglycemic effect of curcumin. Also, inhibition of GLUT1 activity might compromise cancer cells that overexpress GLUT1 and be another possible mechanism for the documented anticancer effects of curcumin. PMID:27039889

Curcumin as potential therapeutic natural product: a nanobiotechnological perspective.

PubMed

Shome, Soumitra; Talukdar, Anupam Das; Choudhury, Manabendra Dutta; Bhattacharya, Mrinal Kanti; Upadhyaya, Hrishikesh

2016-12-01

Nanotechnology-based drug delivery systems can resolve the poor bioavailability issue allied with curcumin. The therapeutic potential of curcumin can be enhanced by making nanocomposite preparation of curcumin with metal oxide nanoparticles, poly lactic-co-glycolic acid (PLGA) nanoparticles and solid lipid nanoparticles that increases its bioavailability in the tissue. Curcumin has manifold therapeutic effects which include antidiabetic, antihypertensive, anticancer, anti-inflammatory and antimicrobial properties. Curcumin can inhibit diabetes, heavy metal and stress-induced hypertension with its antioxidant, chelating and inhibitory effects on the pathways that lead to hypertension. Curcumin is an anticancer agent that can prevent abnormal cell proliferation. Nanocurcumin is an improved form of curcumin with enhanced therapeutic properties due to improved delivery to the diseased tissue, better internalization and reduced systemic elimination. Curcumin has multiple pharmacologic effects, but its poor bioavailability reduces its therapeutic effects. By conjugating curcumin to metal oxide nanoparticles or encapsulation in lipid nanoparticles, dendrimers, nanogels and polymeric nanoparticles, the water solubility and bioavailability of curcumin can be improved and thus increase its pharmacological effectiveness. © 2016 Royal Pharmaceutical Society.

Binding of curcumin with bovine serum albumin in the presence of ι-carrageenan and implications on the stability and antioxidant activity of curcumin.

PubMed

Yang, Mingling; Wu, Yue; Li, Jinbing; Zhou, Haibo; Wang, Xiaoyong

2013-07-24

This work studied the influences of formation of BSA/ι-carrageenan complexes on the binding, stability, and antioxidant activity of curcumin. In the presence of BSA and ι-carrageenan, curcumin gives higher intensities of absorption and fluorescence than free curcumin and curcumin only combined with BSA. The added ι-carrageenan is observed to promote curcumin for quenching the instrinsic fluorescence of BSA. These results are explained in terms of the formation of BSA/ι-carrageenan complexes, which help to stabilize the folded structure of BSA for providing curcumin with a more hydrophobic microenvironment. The small difference in anisotropy values of curcumin with BSA alone and of BSA/ι-carrageenan complexes suggests that ι-carrageenan acts as outer stretch conformation in BSA/ι-carrageenan complexes but does not directly disturb the hydrophobic pockets inside BSA, where curcumin is hydrophobically located. The determined values of the binding constant are higher for curcumin with BSA/ι-carrageenan complexes than with BSA alone. Moreover, BSA/ι-carrageenan complexes are found to be superior to single BSA for enhancing the stability and DPPH radical-scavenging ability of curcumin.

Oral bioavailability of curcumin: problems and advancements.

PubMed

Liu, Weidong; Zhai, Yingjie; Heng, Xueyuan; Che, Feng Yuan; Chen, Wenjun; Sun, Dezhong; Zhai, Guangxi

2016-09-01

Curcumin is a natural compound of Curcuma longa L. and has shown many pharmacological activities such as anti-inflammatory, anti-oxidant in both preclinical and clinical studies. Moreover, curcumin has hepatoprotective, neuroprotective activities and protects against myocardial infarction. Particularly, curcumin has also demonstrated favorite anticancer efficacy. But limiting factors such as its extremely low oral bioavailability hampers its application as therapeutic agent. Therefore, many technologies have been developed and applied to overcome this limitation. This review described the main physicochemical properties of curcumin and summarized the recent studies in the design and development of oral delivery systems for curcumin to enhance the solubility and oral bioavailability, including liposomes, nanoparticles and polymeric micelles, phospholipid complexes, and microemulsions.

A comparative study of the spectral, fluorometric properties and photostability of natural curcumin, iron- and boron- complexed curcumin

NASA Astrophysics Data System (ADS)

Mohammed, Fatima; Rashid-Doubell, Fiza; Cassidy, Seamas; Henari, Fryad

2017-08-01

Curcumin is a yellow phenolic compound with a wide range of reported biological effects. However, two main obstacles hinder the use of curcumin therapeutically, namely its poor bioavailability and photostability. We have synthesized two curcumin complexes, the first a boron curcumin complex (B-Cur2) and the second an iron (Fe-Cur3) complex of curcumin. Both derivatives showed high fluorescence efficiency (quantum yield) and greater photostability in solution. The improved photostability could be attributed to the coordination structures and the removal of β-diketone group from curcumin. The fluorescence and ultra violet/visible absorption spectra of curcumin, B-Cur2 and Fe-Cur3 all have a similar spectral pattern when dissolved in the same organic solvent. However, a shift towards a lower wavelength was observed when moving from polar to non-polar solvents, possibly due to differences in solvent polarity. A plot of Stokes' shift vs the orientation polarity parameter (Δf) or vs the solvent polarity parameter (ET 30) showed an improved correlation between the solvent polarity parameter than with the orientation polarity parameter and indicating that the red shift observed could be due to hydrogen-bonding between the solvent molecules. A similar association was obtained when Stokes' shift was replaced by maximum synchronous fluorescence. Both B-Cur2 and Fe-Cur3 had larger quantum yields than curcumin, suggesting they may be good candidates for medical imaging and in vitro studies.

Mesoscopic Modeling of the Encapsulation of Capsaicin by Lecithin/Chitosan Liposomal Nanoparticles.

PubMed

Terrón-Mejía, Ketzasmin A; Martínez-Benavidez, Evelin; Higuera-Ciapara, Inocencio; Virués, Claudia; Hernández, Javier; Domínguez, Zaira; Argüelles-Monal, Waldo; Goycoolea, Francisco M; López-Rendón, Roberto; Gama Goicochea, Armando

2018-06-12

The transport of hydrophobic drugs in the human body exhibits complications due to the low solubility of these compounds. With the purpose of enhancing the bioavailability and biodistribution of such drugs, recent studies have reported the use of amphiphilic molecules, such as phospholipids, for the synthesis of nanoparticles or nanocapsules. Given that phospholipids can self-assemble in liposomes or micellar structures, they are ideal candidates to function as vehicles of hydrophobic molecules. In this work, we report mesoscopic simulations of nanoliposomes, constituted by lecithin and coated with a shell of chitosan. The stability of such structures and the efficiency of the encapsulation of capsaicin, as well as the internal and superficial distribution of capsaicin and chitosan inside the nanoliposome, were analyzed. The characterization of the system was carried out through density maps and the potentials of mean force for the lecithin-capsaicin, lecithin-chitosan, and capsaicin-chitosan interactions. The results of these simulations show that chitosan is deposited on the surface of the nanoliposome, as has been reported in some experimental works. It was also observed that a nanoliposome of approximately 18 nm in diameter is stable during the simulation. The deposition behavior was found to be influenced by a pattern of N-acetylation of chitosan.

[Pharmacological studies on ginger. V. Pharmacological comparison between (6)-shogaol and capsaicin].

PubMed

Suekawa, M; Sone, H; Sakakibara, I; Ikeya, Y; Aburada, M; Hosoya, E

1986-11-01

Pharmacological actions of (6)-shogaol and capsaicin were studied. Both (6)-shogaol (0.5 mg/kg, i.v.) and capsaicin (0.1 mg/kg, i.v.) caused a triad such as a rapid fall in blood pressure, bradycardia and aponea in rats. Both drugs-induced marked pressor responses in blood pressure, which occurred after the rapid fall, were markedly reduced by a spinal destruction. In pithed rats, both drugs-induced peripheral pressor responses were markedly reduced with the combined treatment of [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (0.5 mg/kg, i.v.), phentolamine (10 mg/kg, i.v.) and the section of sciatic nerves. In isolated guinea-pig trachea, (6)-shogaol (100 microM) and capsaicin (10 microM) induced contractile responses which were slightly inhibited by substance P antagonist (10 microM), but exhibited also a tachyphylaxis. Furthermore, although (6)-shogaol (3.6 microM) showed positive inotropic and chronotropic actions on isolated atria in rats, this effect of (6)-shogaol disappeared by repeated injections or pretreatment (100 mg/kg, s.c.) of (6)-shogaol. These results suggest that (6)-shogaol and capsaicin have similar actions, and that both drugs may cause a peripheral action by releasing an unknown active substance from nerve ends.

Eliminating the Heart from the Curcumin Molecule: Monocarbonyl Curcumin Mimics (MACs)

PubMed Central

Shetty, Dinesh; Kim, Yong Joon; Shim, Hyunsuk; Snyder, James P.

2015-01-01

Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin’s Achilles heel lies in its poor aqueous solubility and rapid degradation at pH ~ 7.4. Researchers have sought to unlock curcumin’s assets by chemical manipulation. One class of molecules under scrutiny are the monocarbonyl analogs of curcumin (MACs). A thousand plus such agents have been created and tested primarily against cancer and inflammation. The outcome is clear. In vitro, MACs furnish a 10–20 fold potency gain vs. curcumin for numerous cancer cell lines and cellular proteins. Similarly, MACs have successfully demonstrated better pharmacokinetic (PK) profiles in mice and greater tumor regression in cancer xenografts in vivo than curcumin. The compounds reveal limited toxicity as measured by murine weight gain and histopathological assessment. To our knowledge, MAC members have not yet been monitored in larger animals or humans. However, Phase 1 clinical trials are certainly on the horizon. The present review focuses on the large and evolving body of work in cancer and inflammation, but also covers MAC structural diversity and early discovery for treatment of bacteria, tuberculosis, Alzheimer’s disease and malaria. PMID:25547726

Glutamate Receptor GluA1 Subunit Is Implicated in Capsaicin Induced Modulation of Amygdala LTP but Not LTD

ERIC Educational Resources Information Center

Gebhardt, Christine; Albrecht, Doris

2018-01-01

Capsaicin has been shown to modulate synaptic plasticity in various brain regions including the amygdala. Whereas in the lateral amygdala the modulatory effect of capsaicin on long-term potentiation (LA-LTP) is mediated by TRPV1 channels, we have recently shown that capsaicin-induced enhancement of long term depression (LA-LTD) is mediated by…

TRPV1 recapitulates native capsaicin receptor in sensory neurons in association with Fas-associated factor 1.

PubMed

Kim, Sangsung; Kang, Changjoong; Shin, Chan Young; Hwang, Sun Wook; Yang, Young Duk; Shim, Won Sik; Park, Min-Young; Kim, Eunhee; Kim, Misook; Kim, Byung-Moon; Cho, Hawon; Shin, Youngki; Oh, Uhtaek

2006-03-01

TRPV1, a cloned capsaicin receptor, is a molecular sensor for detecting adverse stimuli and a key element for inflammatory nociception and represents biophysical properties of native channel. However, there seems to be a marked difference between TRPV1 and native capsaicin receptors in the pharmacological response profiles to vanilloids or acid. One plausible explanation for this overt discrepancy is the presence of regulatory proteins associated with TRPV1. Here, we identify Fas-associated factor 1 (FAF1) as a regulatory factor, which is coexpressed with and binds to TRPV1 in sensory neurons. When expressed heterologously, FAF1 reduces the responses of TRPV1 to capsaicin, acid, and heat, to the pharmacological level of native capsaicin receptor in sensory neurons. Furthermore, silencing FAF1 by RNA interference augments capsaicin-sensitive current in native sensory neurons. We therefore conclude that FAF1 forms an integral component of the vanilloid receptor complex and that it constitutively modulates the sensitivity of TRPV1 to various noxious stimuli in sensory neurons.

Dose-dependent protective effect of BPC 157 on capsaicin-induced rhinitis in rats.

PubMed

Kalogjera, L; Ries, M; Baudoin, T; Ferencic, Z; Trotic, R; Pegan, B

1997-01-01

Protection of BPC 157 on capsaicin-induced rhinitis was studied in Wistar rats for its effect on mastocyte infiltration, degranulation and inflammatory cell infiltration. Animals were pretreated with 10 microg/kg, 10 ng/kg or 2 ml saline i.p. and capsaicin (0.05 ml/nostril of 1750 nmol/l sol.) was applied intranasally. They were then euthanized at 1, 3 and 12 h after capsaicin provocation. Nasal mucosa was analyzed and scored for mastocyte infiltration, degranulation and inflammatory cell infiltration. BPC 157 pretreatment significantly prevented mastocyte infiltration at 1 h. Polymorphonuclear leukocyte infiltration was significantly reduced in rats pretreated with 10 microg/kg BPC 157. A dose-dependent effect of BPC 157 pretreatment was demonstrated only for polymorphonuclear leukocyte infiltration at 12 h.

Molecular complexation of curcumin with pH sensitive cationic copolymer enhances the aqueous solubility, stability and bioavailability of curcumin.

PubMed

Kumar, Sunny; Kesharwani, Siddharth S; Mathur, Himanshi; Tyagi, Mohit; Bhat, G Jayarama; Tummala, Hemachand

2016-01-20

Curcumin is a natural dietary compound with demonstrated potential in preventing/treating several chronic diseases in animal models. However, this success is yet to be translated to humans mainly because of its poor oral bioavailability caused by extremely low water solubility. This manuscript demonstrates that water insoluble curcumin (~1μg/ml) forms highly aqueous soluble complexes (>2mg/ml) with a safe pH sensitive polymer, poly(butyl-methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl-methacrylate) when precipitated together in water. The complexation process was optimized to enhance curcumin loading by varying several formulation factors. Acetone as a solvent and polyvinyl alcohol as a stabilizer with 1:2 ratio of drug to polymer yielded complexes with relatively high loading (~280μg/ml) and enhanced solubility (>2mg/ml). The complexes were amorphous in solid and were soluble only in buffers with pHs less than 5.0. Hydrogen bond formation and hydrophobic interactions between curcumin and the polymer were recorded by infrared spectroscopy and nuclear magnetic resonance spectroscopy, respectively. Molecular complexes of curcumin were more stable at various pHs compared to unformulated curcumin. In mice, these complexes increased peak plasma concentration of curcumin by 6 times and oral bioavailability by ~20 times. This is a simple, economic and safer strategy of enhancing the oral bioavailability of curcumin. Copyright © 2015 Elsevier B.V. All rights reserved.

Involvement of the phosphoinositide 3-kinase/Akt pathway in apoptosis induced by capsaicin in the human pancreatic cancer cell line PANC-1.

PubMed

Zhang, Jian-Hong; Lai, Fu-Ji; Chen, Hui; Luo, Jiang; Zhang, Ri-Yuan; Bu, He-Qi; Wang, Zhao-Hong; Lin, Hong-Hai; Lin, Sheng-Zhang

2013-01-01

Capsaicin, one of the major pungent ingredients found in red peppers, has been recently demonstrated to induce apoptosis in various malignant cell lines through an unclear mechanism. In this study, the effect of capsaicin on proliferation and apoptosis in the human pancreatic cancer cell line PANC-1 and its possible mechanism(s) of action were investigated. The results of a Cell Counting Kit-8 (CCK-8) assay revealed that capsaicin significantly decreased the viability of PANC-1 cells in a dose-dependent manner. Capsaicin induced G0/G1 phase cell cycle arrest and apoptosis in PANC-1 cells as demonstrated by a flow cytometric assessment. Caspase-3 expression at both the protein and mRNA level was promoted following capsaicin treatment. Furthermore, we revealed that phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473) in PANC-1 cells were downregulated in response to capsaicin. Moreover, capsaicin gavage significantly inhibited the growth of pancreatic cancer PANC-1 cell xenografts in athymic nude mice. An increased number of TUNEL-positive cells and cleaved caspase-3 were observed in capsaicin-treated mice. In vivo, capsaicin downregulated the expression of phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473). In conclusion, we have demonstrated that capsaicin is an inhibitor of growth of PANC-1 cells, and downregulation of the phosphoinositide 3-kinase/Akt pathway may be involved in capsaicin-induced apoptosis in vitro and in vivo.

Curcumin-Free Turmeric Exhibits Activity against Human HCT-116 Colon Tumor Xenograft: Comparison with Curcumin and Whole Turmeric

PubMed Central

Prasad, Sahdeo; Tyagi, Amit K.; Siddik, Zahid H.; Aggarwal, Bharat B.

2017-01-01

Extensive research within last two decades has indicated that curcumin extracted from turmeric (Curcuma longa), exhibits anticancer potential, in part through the modulation of inflammatory pathways. However, the residual antitumor activity of curcumin-free turmeric (CFT) relative to curcumin or turmeric is not well-understood. In the present study, therefore, we determined activities of these agents in both in vitro and in vivo models of human HCT-116 colorectal cancer (CRC). When examined in an in vitro antiproliferative, clonogenic or anti-inflammatory assay system, we found that curcumin was highly active whereas turmeric and CFT had relatively poor activity against CRC cells. However, when examined in vivo at an oral dose of either 100 or 500 mg/kg given to nude mice bearing CRC xenografts, all three preparations of curcumin, turmeric, and CFT similarly suppressed the growth of the xenograft. The effect of CFT on suppression of tumor growth was dose-dependent, with 500 mg/kg tending to be more effective than 100 mg/kg. Interestingly, 100 mg/kg curcumin or turmeric was found to be more effective than 500 mg/kg. When examined in vivo for the expression of biomarkers associated with cell survival (cIAP-1, Bcl-2, and survivin), proliferation (Ki-67 and cyclin D1) and metastasis (ICAM-1 and VEGF), all were down-modulated. These agents also suppressed inflammatory transcription factors (NF-κB and STAT3) in tumor cells. Overall, our results with CFT provide evidence that turmeric must contain additional bioactive compounds other than curcumin that, in contrast to curcumin, exhibit greater anticancer potential in vivo than in vitro against human CRC. Moreover, our study highlights the fact that the beneficial effects of turmeric and curcumin in humans may be more effectively realized at lower doses, whereas CFT could be given at higher doses without loss in favorable activity. PMID:29311914

Bioavailability enhancement of curcumin by complexation with phosphatidyl choline.

PubMed

Gupta, Nishant Kumar; Dixit, Vinod Kumar

2011-05-01

Curcumin is a major constituent of rhizomes of Curcuma longa. Pharmacokinetic studies of curcumin reveal its poor absorption through intestine. Objective of the present study was to enhance bioavailability of curcumin by its complexation with phosphatidyl choline (PC). Complex of curcumin was prepared with PC and characterized on the basis of solubility, melting point, differential scanning calorimetry, thin layer chromatography, and infrared spectroscopic analysis. Everted intestine sac technique was used to study ex vivo drug absorption of curcumin-PC (CU-PC) complex and plain curcumin. Pharmacokinetic studies were performed in rats, and hepatoprotective activity of CU-PC complex was also compared with curcumin and CU-PC physical mixture in isolated rat hepatocytes. Analytical reports along with spectroscopic data revealed the formation of complex. The results of ex vivo study show that CU-PC complex has significantly increased absorption compared with curcumin, when given in equimolar doses. Complex showed enhanced bioavailability, improved pharmacokinetics, and increased hepatoprotective activity as compared with curcumin or CU-PC physical mixture. Enhanced bioavailability of CU-PC complex may be due to the amphiphilic nature of the complex, which greatly enhance the water and lipid solubility of the curcumin. The present study clearly indicates the superiority of complex over curcumin, in terms of better absorption, enhanced bioavailability, and improved pharmacokinetics. Copyright © 2010 Wiley-Liss, Inc.

Curcumin and autoimmune disease.

PubMed

Bright, John J

2007-01-01

The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

Curcumin: A Contact Allergen.

PubMed

Chaudhari, Soham P; Tam, Alison Y; Barr, Jason A

2015-11-01

Herbal medicines are used by thousands of patients all over the world. However, they can often cause adverse effects. Turmeric, made from the root of Curcuma, longa, is a yellow spice used throughout South Asia for its flavor as well as for its medicinal properties. Curcumin is the main ingredient in turmeric. It is known for downregulating the expression of various proinflammatory cytokines and has been studied for its antiinflammatory mechanism. However, it has also been reported to cause contact dermatitis. Kumkum, a turmeric-based powder applied by Hindu women on their foreheads, has also been found as an allergen. The authors have reviewed the anti-inflammatory properties of curcumin and reports of contact dermatitis to understand the possible harmful effects of this commonly used spice, while also examining its beneficial role in dermatologic conditions. They aim to increase awareness regarding this common herb and its prevalent use not only in South Asia, but also in North America. A thorough literature search of the PubMed database was conducted to identify studies that examined the antiinflammatory role of curcumin and its role in contact dermatitis. Eleven studies demonstrate that although curcumin does have antiinflammatory properties, it is an allergen. Curcumin has many valuable properties that can be exploited to treat dermatologic conditions. However, patients and dermatologists must be keen of possible allergic reactions. Further studies are needed to completely understand this widely used herb and its efficacy in dermatology.

Curcumin therapeutic promises and bioavailability in colorectal cancer.

PubMed

Shehzad, A; Khan, S; Shehzad, O; Lee, Y S

2010-07-01

Curcumin, a polyphenol and derivative of turmeric is one of the most commonly used and highly researched phytochemicals. Several research studies have provided interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancers, including colorectal cancer. Curcumin has the ability to inhibit carcinogenic promotion of colorectal cancer through the modulation of multiple molecular targets such as transcription factors, enzymes, cell cycle proteins, cell surface adhesion proteins, survival pathways and cytokines. A number of clinical trials dealing with curcumin's efficacy and safety revealed poor absorption and low bioavailability. Different factors contributing to the low bioavailability include low plasma level, tissue distribution, rapid metabolism and elimination from the body. Although, curcumin poor absorption and low systemic bioavailability limit its translation into clinics, some of the methods for its use can be approached to enhance the absorption and achieve a therapeutic level of curcumin. Recent clinical trials suggest a potential role for curcumin in regards to colorectal cancer therapy.

Capsaicin affects brain function in a model of hepatic encephalopathy associated with fulminant hepatic failure in mice

PubMed Central

Avraham, Y; Grigoriadis, NC; Magen, I; Poutahidis, T; Vorobiav, L; Zolotarev, O; Ilan, Y; Mechoulam, R; Berry, EM

2009-01-01

Background and purpose: Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver failure. In view of the effects of cannabinoids in a thioacetamide-induced model of hepatic encephalopathy and liver disease and the beneficial effect of capsaicin (a TRPV1 agonist) in liver disease, we assumed that capsaicin may also affect hepatic encephalopathy. Experimental approach: Fulminant hepatic failure was induced in mice by thioacetamide and 24 h later, the animals were injected with one of the following compound(s): 2-arachidonoylglycerol (CB1, CB2 and TRPV1 receptor agonist); HU308 (CB2 receptor agonist), SR141716A (CB1 receptor antagonist); SR141716A+2-arachidonoylglycerol; SR144528 (CB2 receptor antagonist); capsaicin; and capsazepine (TRPV1 receptor agonist and antagonist respectively). Their neurological effects were evaluated on the basis of activity in the open field, cognitive function in an eight-arm maze and a neurological severity score. The mice were killed 3 or 14 days after thioacetamide administration. 2-arachidonoylglycerol and 5-hydroxytryptamine (5-HT) levels were determined by gas chromatography-mass spectrometry and high-performance liquid chromatography with electrochemical detection, respectively. Results: Capsaicin had a neuroprotective effect in this animal model as shown by the neurological score, activity and cognitive function. The effect of capsaicin was blocked by capsazepine. Thioacetamide induced astrogliosis in the hippocampus and the cerebellum and raised brain 5-hydroxytryptamine levels, which were decreased by capsaicin, SR141716A and HU-308. Thioacetamide lowered brain 2-arachidonoylglycerol levels, an effect reversed by capsaicin. Conclusions: Capsaicin improved both liver and brain dysfunction caused by thioacetamide, suggesting that both the endocannabinoid and the vanilloid systems play important roles in hepatic encephalopathy. Modulation of these systems may have therapeutic value. PMID:19764982

Tachykinin antagonists and capsaicin-induced contraction of the rat isolated urinary bladder: evidence for tachykinin-mediated cotransmission.

PubMed Central

Maggi, C. A.; Patacchini, R.; Santicioli, P.; Giuliani, S.

1991-01-01

1. The possible involvement of tachykinins (TKs) in the contraction produced by capsaicin in the rat isolated urinary bladder was addressed on the hypothesis that co-release of substance P (SP) and neurokinin A (NKA) occurs from sensory nerve terminals. 2. A low concentration of SP (30 nM) produced a rapid contraction which faded to baseline within 10 min. A low concentration of NKA (10 nM) produced a slowly developing contraction which was still evident at 10 min. Capsaicin (1 microM) produced a rapid phasic response and a tonic response (late response to capsaicin). Co-administration of SP and NKA mimicked the response to capsaicin more than each TK alone. 3. Fading of the response to SP was not caused by receptor desensitization and was partially prevented by peptidase inhibitors. 4. Spantide (3 microM) selectively antagonized the SP-induced contraction while L-659,877 (3-10 microM) or MEN 10,376 (10-30 microM) which are NK2 receptor selective antagonists selectively blocked the response to NKA. Co-administration of spantide and L-659,877 inhibited the response to both SP and NKA by an amount not greater than that produced by each antagonist alone. 5. Spantide selectively reduced the peak response to capsaicin, while leaving the late response unaffected. L-659,877 (3 microM) and MEN 10,376 (10 microM) selectively inhibited the late response to capsaicin while, at higher concentrations, also reduced the peak response to capsaicin. Co-administration of spantide and L-659,877 reduced the peak response to capsaicin more than that produced by each antagonist alone. 6. Bombesin (10 nM) produced a tonic contraction similar to that induced by NKA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1715797

Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice.

PubMed

Liu, Zhaoguo; Zhu, Pingting; Tao, Yu; Shen, Cunsi; Wang, Siliang; Zhao, Lingang; Wu, Hongyan; Fan, Fangtian; Lin, Chao; Chen, Chen; Zhu, Zhijie; Wei, Zhonghong; Sun, Lihua; Liu, Yuping; Wang, Aiyun; Lu, Yin

2015-07-01

Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-κB), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular mechanisms of curcumin action: gene expression.

PubMed

Shishodia, Shishir

2013-01-01

Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Supramolecular curcumin-barium prodrugs for formulating with ceramic particles.

PubMed

Kamalasanan, Kaladhar; Anupriya; Deepa, M K; Sharma, Chandra P

2014-10-01

A simple and stable curcumin-ceramic combined formulation was developed with an aim to improve curcumin stability and release profile in the presence of reactive ceramic particles for potential dental and orthopedic applications. For that, curcumin was complexed with barium (Ba(2+)) to prepare curcumin-barium (BaCur) complex. Upon removal of the unbound curcumin and Ba(2+) by dialysis, a water-soluble BaCur complex was obtained. The complex was showing [M+1](+) peak at 10,000-20,000 with multiple fractionation peaks of MALDI-TOF-MS studies, showed that the complex was a supramolecular multimer. The (1)H NMR and FTIR studies revealed that, divalent Ba(2+) interacted predominantly through di-phenolic groups of curcumin to form an end-to-end complex resulted in supramolecular multimer. The overall crystallinity of the BaCur was lower than curcumin as per XRD analysis. The complexation of Ba(2+) to curcumin did not degrade curcumin as per HPLC studies. The fluorescence spectrum was blue shifted upon Ba(2+) complexation with curcumin. Monodisperse nanoparticles with size less than 200dnm was formed, out of the supramolecular complex upon dialysis, as per DLS, and upon loading into pluronic micelles the size was remaining in similar order of magnitude as per DLS and AFM studies. Stability of the curcumin was improved greater than 50% after complexation with Ba(2+) as per UV/Vis spectroscopy. Loading of the supramloecular nanoparticles into pluronic micelles had further improved the stability of curcumin to approx. 70% in water. These BaCur supramolecule nanoparticles can be considered as a new class of prodrugs with improved solubility and stability. Subsequently, ceramic nanoparticles with varying chemical composition were prepared for changing the material surface reactivity in terms of the increase in, degradability, surface pH and protein adsorption. Further, these ceramic particles were combined with curcumin prodrug formulations and optimized the curcumin release

Chronic Oral Capsaicin Exposure During Development Leads to Adult Rats with Reduced Taste Bud Volumes.

PubMed

Omelian, Jacquelyn M; Samson, Kaeli K; Sollars, Suzanne I

2016-09-01

Cross-sensory interaction between gustatory and trigeminal nerves occurs in the anterior tongue. Surgical manipulations have demonstrated that the strength of this relationship varies across development. Capsaicin is a neurotoxin that affects fibers of the somatosensory lingual nerve surrounding taste buds, but not fibers of the gustatory chorda tympani nerve which synapse with taste receptor cells. Since capsaicin is commonly consumed by many species, including humans, experimental use of this neurotoxin provides a naturalistic perturbation of the lingual trigeminal system. Neonatal or adults rats consumed oral capsaicin for 40 days and we examined the cross-sensory effect on the morphology of taste buds across development. Rats received moderate doses of oral capsaicin, with chronic treatments occurring either before or after taste system maturation. Tongue morphology was examined either 2 or 50 days after treatment cessation. Edema, which has been previously suggested as a cause of changes in capsaicin-related gustatory function, was also assessed. Reductions in taste bud volume occurred 50 days, but not 2 days post-treatment for rats treated as neonates. Adult rats at either time post-treatment were unaffected. Edema was not found to occur with the 5 ppm concentration of capsaicin we used. Results further elucidate the cooperative relationship between these discrete sensory systems and highlight the developmentally mediated aspect of this interaction. Chronic exposure to even moderate levels of noxious stimuli during development has the ability to impact the orosensory environment, and these changes may not be evident until long after exposure has ceased.

Therapeutic applications of curcumin for patients with pancreatic cancer

PubMed Central

Kanai, Masashi

2014-01-01

A number of preclinical studies have demonstrated anticancer effects for curcumin in various types of tumors, including pancreatic cancer. Curcumin has anticancer effects both alone and in combination with other anticancer drugs (e.g., gemcitabine, 5-fluorouracil, and oxaliplatin), and it has been shown to modulate a variety of molecular targets in preclinical models, with more than 30 molecular targets identified to date. Of these various molecules, NF-κB is thought to be one of the primary targets of curcumin activity. Based on these promising preclinical results, several research groups, including our own, have progressed to testing the anticancer effects of curcumin in clinical trials; however, the poor bioavailability of this agent has been the major challenge for its clinical application. Despite the ingestion of gram-level doses of curcumin, plasma curcumin levels remain at low (ng/mL) levels in patients, which is insufficient to yield the anticancer benefits of curcumin. This problem has been solved by the development of highly bioavailable forms of curcumin (THERACURMIN®), and higher plasma curcumin levels can now be achieved without increased toxicity in patients with pancreatic cancer. In this article, we review possible therapeutic applications of curcumin in patients with pancreatic cancer. PMID:25071333

Curcumin inhibits aggregation of alpha-synuclein.

PubMed

Pandey, Neeraj; Strider, Jeffrey; Nolan, William C; Yan, Sherry X; Galvin, James E

2008-04-01

Aggregation of amyloid-beta protein (Abeta) is a key pathogenic event in Alzheimer's disease (AD). Curcumin, a constituent of the Indian spice Turmeric is structurally similar to Congo Red and has been demonstrated to bind Abeta amyloid and prevent further oligomerization of Abeta monomers onto growing amyloid beta-sheets. Reasoning that oligomerization kinetics and mechanism of amyloid formation are similar in Parkinson's disease (PD) and AD, we investigated the effect of curcumin on alpha-synuclein (AS) protein aggregation. In vitro model of AS aggregation was developed by treatment of purified AS protein (wild-type) with 1 mM Fe3+ (Fenton reaction). It was observed that the addition of curcumin inhibited aggregation in a dose-dependent manner and increased AS solubility. The aggregation-inhibiting effect of curcumin was next investigated in cell culture utilizing catecholaminergic SH-SY5Y cell line. A model system was developed in which the red fluorescent protein (DsRed2) was fused with A53T mutant of AS and its aggregation examined under different concentrations of curcumin. To estimate aggregation in an unbiased manner, a protocol was developed in which the images were captured automatically through a high-throughput cell-based screening microscope. The obtained images were processed automatically for aggregates within a defined dimension of 1-6 microm. Greater than 32% decrease in mutant alpha-synuclein aggregation was observed within 48 h subsequent to curcumin addition. Our data suggest that curcumin inhibits AS oligomerization into higher molecular weight aggregates and therefore should be further explored as a potential therapeutic compound for PD and related disorders.

New perspectives of curcumin in cancer prevention

PubMed Central

Park, Wungki; Amin, A.R.M Ruhul; Chen, Zhuo Georgia; Shin, Dong M.

2013-01-01

Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications. PMID:23466484

Neuronal activity related to spontaneous and capsaicin-induced rhythmical jaw movements in the rat.

PubMed

Ohta, M; Sasamoto, K; Kobayashi, J

1998-02-01

Intraoral capsaicin induced rhythmical jaw movements (RJM) in anesthetized rats. Neurons in the trigeminal spinal nucleus caudalis or the cortico-peduncular (CP) axons were extracellularly recorded. Capsaicin excited dose-dependently most caudalis neurons, which were activated by stimulation of the oral cavity and/or the tooth pulp and activated during spontaneous or induced RJM. Ten of 55 CP axons were antidromically activated by stimulation of the contralateral trigeminal motor nucleus. All antidromic and 29 other CP axons discharged prior to the spontaneous RJM, but most of them did not during capsaicin-induced RJM. These neuronal activities possibly initiate spontaneous RJM although the activities of caudalis neurons are necessary for capsicin-induced RJM.

Manipulation of culture strategies to enhance capsaicin biosynthesis in suspension and immobilized cell cultures of Capsicum chinense Jacq. cv. Naga King Chili.

PubMed

Kehie, Mechuselie; Kumaria, Suman; Tandon, Pramod

2014-06-01

Manipulation of culture strategies was adopted to study the influence of nutrient stress, pH stress and precursor feeding on the biosynthesis of capsaicin in suspension and immobilized cell cultures of C. chinense. Cells cultured in the absence of one of the four nutrients (ammonium and potassium nitrate for nitrate and potassium stress, potassium dihydrogen orthophosphate for phosphorus stress, and sucrose for sugar stress) influenced the accumulation of capsaicin. Among the stress factors studied, nitrate stress showed maximal capsaicin production on day 20 (505.9 ± 2.8 μg g(-1) f.wt) in immobilized cell, whereas in suspension cultures the maximum accumulation (345.5 ± 2.9 μg g(-1) f.wt) was obtained on day 10. Different pH affected capsaicin accumulation; enhanced accumulation of capsaicin (261.6 ± 3.4 μg g(-1) f.wt) was observed in suspension cultures at pH 6 on day 15, whereas in case of immobilized cultures the highest capsaicin content (433.3 ± 3.3 μg g(-1) f.wt) was obtained at pH 5 on day 10. Addition of capsaicin precursors and intermediates significantly enhanced the biosynthesis of capsaicin, incorporation of vanillin at 100 μM in both suspension and immobilized cell cultures resulted in maximum capsaicin content with 499.1 ± 5.5 μg g(-1) f.wt on day 20 and 1,315.3 ± 10 μg g(-1) f.wt on day 10, respectively. Among the different culture strategies adopted to enhance capsaicin biosynthesis in cell cultures of C. chinense, cells fed with vanillin resulted in the maximum capsaicin accumulation. The rate of capsaicin production was significantly higher in immobilized cells as compared to freely suspended cells.

The Effects of Capsaicin and Capsiate on Energy Balance: Critical Review and Meta-analyses of Studies in Humans

PubMed Central

Ludy, Mary-Jon; Moore, George E.

2012-01-01

Consumption of spicy foods containing capsaicin, the major pungent principle in hot peppers, reportedly promotes negative energy balance. However, many individuals abstain from spicy foods due to the sensory burn and pain elicited by the capsaicin molecule. A potential alternative for nonusers of spicy foods who wish to exploit this energy balance property is consumption of nonpungent peppers rich in capsiate, a recently identified nonpungent capsaicin analog contained in CH-19 Sweet peppers. Capsiate activates transient receptor potential vanilloid subtype 1 (TRPV1) receptors in the gut but not in the oral cavity. This paper critically evaluates current knowledge on the thermogenic and appetitive effects of capsaicin and capsiate from foods and in supplemental form. Meta-analyses were performed on thermogenic outcomes, with a systematic review conducted for both thermogenic and appetitive outcomes. Evidence indicates that capsaicin and capsiate both augment energy expenditure and enhance fat oxidation, especially at high doses. Furthermore, the balance of the literature suggests that capsaicin and capsiate suppress orexigenic sensations. The magnitude of these effects is small. Purposeful inclusion of these compounds in the diet may aid weight management, albeit modestly. PMID:22038945

Understanding curcumin-induced modulation of protein aggregation.

PubMed

Ahmad, Basir; Borana, Mohanish S; Chaudhary, Ankur P

2017-07-01

Curcumin, a diarylheptanoid compound, found in spice turmeric is known to alter the aggregation of proteins and reduce the toxicity of the aggregates. This review looks at the molecular basis of modulating protein aggregation and toxicity of the aggregates. Foremost, we identify the interaction of curcumin and its derivatives with proteins/peptides and the effect of their interaction on the conformational stability and unfolding/folding pathway(s). The unfolding/folding processes generate partially folded/unfolded intermediate, which serve as aggregation precursor state. Secondly, we discuss the effect of curcumin binding on the kinetics parameters of the aggregation process, which give information about the mechanism of the aggregation inhibition. We describe, in addition, that curcumin can accelerate/promote fibril formation by binding to oligomeric intermediate(s) accumulated in the aggregation pathway. Finally, we discuss the correlation of curcumin-induced monomeric and/or oligomeric precursor states with aggregate structure and toxicity. On the basis of these discussions, we propose a model describing curcumin-induced inhibition/promotion of formation of amyloid-like fibrils. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel delivery system for natural products: Nano-curcumin formulations.

PubMed

Rahimi, Hamid Reza; Nedaeinia, Reza; Sepehri Shamloo, Alireza; Nikdoust, Shima; Kazemi Oskuee, Reza

2016-01-01

Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA) and messengers (RNA). A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rheumatoid arthritis, Alzheimer's, inflammatory bowel disease (IBD), and even it has wound healing. Oral bioavailability of curcumin is rather poor, which would certainly put some boundaries in the employment of this drug. Bibliographical searches were performed using MEDLINE/ScienceDirect/OVID up to February 2015 using the following keywords (all fields): ("Curcumin" OR "Curcuma longa") AND [(nanoparticles) OR (Nanomicelles) OR (micro emulsions) OR (liposome) OR (phospholipid). Consequently, for any developments of curcumin in the future, analogues of curcumin that have better bioavailability or substitute formulations are needed crucially. These studies indicated that nanotechnology can formulate curcumin effectively, and this nano-formulated curcumin with a potent ability against various cancer cells, were represented to have better efficacy and bioavailability under in vivo conditions.

Dietary spices as beneficial modulators of lipid profile in conditions of metabolic disorders and diseases.

PubMed

Srinivasan, Krishnapura

2013-04-25

Spices are valued for their medicinal properties besides their use as food adjuncts to enhance the sensory quality of food. Dietary garlic, onion, fenugreek, red pepper, turmeric, and ginger have been proven to be effective hypocholesterolemics in experimentally induced hypercholesterolemia. The hypolipidemic potential of fenugreek in diabetic subjects and of garlic and onion in humans with induced lipemia has been demonstrated. Capsaicin and curcumin - the bioactive compounds of red pepper and turmeric - are documented to be efficacious at doses comparable to usual human intake. Capsaicin and curcumin have been shown to be hypotriglyceridemic, thus preventing accumulation of fat in the liver under adverse situations by enhancing triglyceride transport out of the liver. Capsaicin, curcumin, fenugreek, ginger, and onion enhance secretion of bile acids into bile. These hypocholesterolemic spices/spice principles reduce blood and liver cholesterol by enhancing cholesterol conversion to bile acids through activation of hepatic cholesterol-7α-hydroxylase. Many human trials have been carried out with garlic, onion, and fenugreek. The mechanism underlying the hypocholesterolemic and hypotriglyceridemic influence of spices is fairly well understood. Health implications of the hypocholesterolemic effect of spices experimentally documented are cardio-protection, protection of the structural integrity of erythrocytes by restoration of membrane cholesterol/phospholipid profile and prevention of cholesterol gallstones by modulation of the cholesterol saturation index in bile.

Curcumin (Turmeric) and cancer.

PubMed

Unlu, Ahmet; Nayir, Erdinc; Dogukan Kalenderoglu, Muhammed; Kirca, Onder; Ozdogan, Mustafa

2016-01-01

Curcumin is a substance obtained from the root of the turmeric plant, which has the feature of being a yellow or orange pigment. It is also the main component of curry powder commonly used in Asian cuisine. Curcumin, a substance that has had an important place in traditional Indian and Chinese medicines for thousands of years, has been the center of interest for scientific studies especially in the field of cancer treatment for several years. Laboratory studies have presented some favorable results in terms of curcumin's antioxidant, antiinflammatory and anticancer properties in particular. However, since such findings have yet to be confirmed in clinical studies, its effect on humans is not clearly known. Therefore, when its advantages in terms of toxicity, cost and availability as well as the favorable results achieved in laboratory studies are considered, it would not be wrong to say that curcumin is a substance worth being studied. However, for now the most correct approach is to abstain from its use for medical purposes due to lack of adequate reliable evidence obtained from clinical studies, and because of its potential to interfere with other drugs.

Curcumin-functionalized silk biomaterials for anti-aging utility.

PubMed

Yang, Lei; Zheng, Zhaozhu; Qian, Cheng; Wu, Jianbing; Liu, Yawen; Guo, Shaozhe; Li, Gang; Liu, Meng; Wang, Xiaoqin; Kaplan, David L

2017-06-15

Curcumin is a natural antioxidant that is isolated from turmeric (Curcuma longa) and exhibits strong free radical scavenging activity, thus functional for anti-aging. However, poor stability and low solubility of curcumin in aqueous conditions limit its biomedical applications. Previous studies have shown that the anti-oxidation activity of curcumin embedded in silk fibroin films could be well preserved, resulting in the promoted adipogenesis from human mesenchymal stem cells (hMSCs) cultured on the surface of the films. In the present study, curcumin was encapsulated in both silk fibroin films (silk/cur films) and nanoparticles (silk/cur NPs), and their anti-aging effects were compared with free curcumin in solution, with an aim to elucidate the mechanism of anti-aging of silk-associated curcumin and to better serve biomedical applications in the future. The morphology and structure of silk/cur film and silk/cur NP were characterized using SEM, FTIR and DSC, indicating characteristic stable beta-sheet structure formation in the materials. Strong binding of curcumin molecules to the beta-sheet domains of silk fibroin resulted in the slow release of curcumin with well-preserved activity from the materials. For cell aging studies, rat bone marrow mesenchymal stem cells (rBMSCs) were cultured in the presence of free curcumin (FC), silk/cur film and silk/cur NP, and cell proliferation and markers of aging (P53, P16, HSP70 gene expression and β-Galactosidase activity) were examined. The results indicated that cell aging was retarded in all FC, silk/cur NP and silk/cur film samples, with the silk-associated curcumin superior to the FC. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of a water-soluble curcumin protein conjugate vs. pure curcumin in a diabetic model of erectile dysfunction.

PubMed

Abdel Aziz, Mohamed Talaat; Motawi, Tarek; Rezq, Ameen; Mostafa, Taymour; Fouad, Hanan H; Ahmed, Hanan H; Rashed, Laila; Sabry, Dina; Senbel, Amira; Al-Malki, A; El-Shafiey, Raghda

2012-07-01

Curcumin is involved in erectile signaling via elevation of cyclic guanosine monophosphate (cGMP). Assessment of the effects of water-soluble curcumin in erectile dysfunction (ED). One hundred twenty male white albino rats were divided into: 1st and 2nd control groups with or without administration of Zinc protoporphyrin (ZnPP), 3rd and 4th diabetic groups with or without ZnPP, 5th diabetic group on single oral dose of pure curcumin, 6th diabetic group on pure curcumin administered daily for 12 weeks, 7th and 8th diabetic groups on single dose of water-soluble curcumin administered with or without ZnPP, 9th and 10th diabetic groups on water-soluble curcumin administered daily for 12 weeks with or without ZnPP. All curcumin dosage schedules were administered after induction of diabetes. Quantitative gene expression of endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), heme oxygenase-1 (HO-1), nuclear transcription factor-erythroid2 (Nrf2), NF-Кβ, and p38. Cavernous tissue levels of HO and NOS enzyme activities, cGMP and intracavernosal pressure (ICP). Twelve weeks after induction of diabetes, ED was confirmed by the significant decrease in ICP. There was a significant decrease in cGMP, NOS, HO enzymes, a significant decrease in eNOS, nNOS, HO-1 genes and a significant elevation of NF-Кβ, p38, iNOS genes. Administration of pure curcumin or its water-soluble conjugate led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in eNOS, nNOS, HO-1, and Nrf2 genes, and a significant decrease in NF-Кβ, p38, and iNOS genes. Water-soluble curcumin showed significant superiority and more prolonged duration of action. Repeated doses regimens were superior to single dose regimen. Administration of ZnPP significantly reduced HO enzyme, cGMP, ICP/ mean arterial pressure (MAP), HO-1 genes in diabetic groups. Water-soluble curcumin could enhance erectile function with more

Perceptual and Affective Responses to Sampled Capsaicin Differ by Reported Intake

PubMed Central

Nolden, Alissa A.; Hayes, John E.

2016-01-01

The present study was conducted to a) generate suprathresold dose-response functions for multiple qualities evoked by capsaicin across a wide range of concentrations, and b) revisit how intensity ratings and liking may differ as a function of self reported intake. Individuals rated eight samples of capsaicin for perceived burn and bitterness, as well as disliking/liking. Measures of reported preference for chili peppers, chili intake frequency, prior experience and personality measures were also assessed. Here, we confirm prior findings showing that burn in the laboratory differs with reported chili intake, with infrequent consumers reporting more burn. We extend these findings by exploring how capsaicin perception varies by reported liking, and measures of variety seeking. We also address the question of whether differences in burn ratings may potentially be an artifact of differential scale usage across groups due to prior experience, and not chronic desensitization, as is typically assumed. By using generalized scaling methods and recalled sensations, we conclude the differences observed here and elsewhere are not likely due to differences in how participants use rating scales. PMID:28392628

Curcumin as "Curecumin": from kitchen to clinic.

PubMed

Goel, Ajay; Kunnumakkara, Ajaikumar B; Aggarwal, Bharat B

2008-02-15

Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".

Photodynamic effect of curcumin on Vibrio parahaemolyticus.

PubMed

Wu, Juan; Mou, Haijin; Xue, Changhu; Leung, Albert Wingnang; Xu, Chuanshan; Tang, Qing-Juan

2016-09-01

Vibrio parahaemolyticus (V. parahaemolyticus) is currently a major cause of bacterial diarrhoea associated with seafood consumption. The objective of this study was to determine the inactivation effect of curcumin-mediated photodynamic action on V. parahaemolyticus. First of all, V. parahaemolyticus suspended in PBS buffer was irradiated by a visible light from a LED light source with an energy density of 3.6J/cm(2). Colony forming units (CFU) were counted and the viability of V. parahaemolyticus cells was calculated after treatment. Singlet oxygen ((1)O2) production after photodynamic action of curcumin was evaluated using 9,10-Anthracenediyl-bis (methylene) dimalonic acid (ADMA). Bacterial outer membrane protein was extracted and analyzed using electrophoresis SDS-PAGE. DNA and RNA of V. parahaemolyticus were also extracted and analyzed using agarose gel electrophoresis after photodynamic treatment. Finally, the efficacy of photodynamic action of curcumin was preliminarily evaluated in the decontamination of V. parahaemolyticus in oyster. Results showed that the viability of V. parahaemolyticus was significantly decreased to non-detectable levels over 6.5-log reductions with the curcumin concentration of 10 and 20μM. Photodynamic action of curcumin significantly increased the singlet oxygen level with the curcumin concentration of 10μM. Notable damage was found to bacterial outer membrane proteins and genetic materials after photodynamic treatment. Photodynamic action of curcumin reduced the number of V. parahaemolyticus contaminating in oyster to non-detectable level. Our findings demonstrated that photodynamic action of curcumin could be a potentially good method to inactivate Vibrio parahaemolyticus contaminating in oyster. Copyright © 2016 Elsevier B.V. All rights reserved.

Determining whether curcumin degradation/condensation is actually bioactivation (Review).

PubMed

Jankun, Jerzy; Wyganowska-Świątkowska, Marzena; Dettlaff, Katarzyna; Jelińska, Anna; Surdacka, Anna; Wątróbska-Świetlikowska, Dorota; Skrzypczak-Jankun, Ewa

2016-05-01

Curcumin has been shown to exert therapeutic or protective effects against a variety of diseases, such as cancer, pulmonary diseases, neurological, liver, metabolic, autoimmune, cardiovascular diseases and numerous other chronic ailments. Over 116 clinical studies on curcumin in humans were registered with the US National Institutes of Health in 2015. However, it is mystifying how curcumin can be so effective in the treatment of many diseases since it has very low water solubility and bioavailability. Furthermore, curcumin is not stable under various conditions; its degradation or condensation into different bioactive compounds may be responsible for its biological activities rather than curcumin itself. In this review, we provide evidence of curcumin degradation and condensation into different compounds which have or may have health benefits themselves. Literature reviews strongly suggest that these molecules contribute to the observed health benefits, rather than curcumin itself.

Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

PubMed

Wu, Xiang; Chen, Huixin; Huang, Chunhui; Gu, Xinmei; Wang, Jialing; Xu, Dilin; Yu, Xin; Shuai, Chu; Chen, Liping; Li, Shun; Xu, Yiguo; Gao, Tao; Ye, Mingrui; Su, Wei; Liu, Haixiong; Zhang, Jinrong; Wang, Chuang; Chen, Junping; Wang, Qinwen; Cui, Wei

2017-06-01

Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

Comparison of topical capsaicin and betamethasone in the treatment of chronic skin lesions due to sulfur mustard exposure.

PubMed

Panahi, Yunes; Davoudi, Seyyed Masoud; Moharamzad, Yashar; Beiraghdar, Fatemeh; Naghizadeh, Mohammad Mehdi

2008-01-01

Chronic pruritic skin lesions are considered to be one of the late complications of sulfur mustard exposure. The purpose of this study was to compare the efficacy of topical capsaicin with that of betamethasone in the treatment of these lesions. In this investigator-blinded, randomized clinical trial, patients applied capsaicin cream 0.025% (n=32) or betamethasone cream 0.1% (n=32) 2 times a day for 6 weeks. Efficacy was based on a dermatologist assessment. The severity of the pruritus was assessed by pruritic score questionnaire and a visual analog scale before and after treatment. All patients complained of pruritus. Both groups showed a significant decrease in pruritus, scaling, and skin dryness (p<0.05), but burning sensation was not improved significantly in the capsaicin group. The mean (+/- standard deviation [SD]) baseline pruritic scores in the capsaicin and betamethasone groups were 29.4 (13.1) and 33.6 (7.2), respectively (p=0.1). The mean (SD) pruritus score change from baseline to after the treatment was significantly higher (p<0.001) in the betamethasone group than in the capsaicin group, 12.7 (6.4) vs. 6.9 (5.6). Fourteen (35%) patients in the capsaicin group reported a burning sensation and intolerable odor, but these effects were not serious enough to necessitate discontinuing the treatment. Topical capsaicin cream 0.025% was much less well tolerated than betamethasone and inferior to betamethasone in reducing chronic skin lesions and symptoms from sulfur mustard exposure.

Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies.

PubMed

Mirzaei, Hamed; Shakeri, Abolfazl; Rashidi, Bahman; Jalili, Amin; Banikazemi, Zarrin; Sahebkar, Amirhossein

2017-01-01

Curcumin, a hydrophobic polyphenol, is the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric). Curcumin is known as a strong anti-oxidant and anti-inflammatory agent that has different pharmacological effects. In addition, several studies have demonstrated that curcumin is safe even at dosages as high as 8g per day; however, instability at physiological pH, low solubility in water and rapid metabolism results in a low oral bioavailability of curcumin. The phytosomal formulation of curcumin (a complex of curcumin with phosphatidylcholine) has been shown to improve curcumin bioavailability. Existence of phospholipids in phytosomes leads to specific physicochemical properties such as amphiphilic nature that allows dispersion in both hydrophilic and lipophilic media. The efficacy and safety of curcumin phytosomes have been shown against several human diseases including cancer, osteoarthritis, diabetic microangiopathy and retinopathy, and inflammatory diseases. This review focuses on the pharmacokinetics as well as pharmacological and clinical effects of phytosomal curcumin. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Polymeric Curcumin Nanoparticle Pharmacokinetics and Metabolism in Bile Duct Cannulated Rats

PubMed Central

Zou, Peng; Helson, Lawrence; Maitra, Anirban; Stern, Stephan T.; McNeil, Scott E.

2013-01-01

The objective of this study was to compare the pharmacokinetics and metabolism of polymeric nanoparticle encapsulated (nanocurcumin), and solvent solubilized curcumin formulations in Sprague Dawley (SD) rats. Nanocurcumin is currently under development for cancer therapy. Since free, unencapsulated curcumin is rapidly metabolized and excreted in rats, upon i.v. administration of nanocurcumin only nanoparticle encapsulated curcumin can be detected in plasma samples. Hence, the second objective of this study was to utilize the metabolic instability of curcumin to assess in vivo drug release from nanocurcumin. Nanocurcumin and solvent solubilized curcumin were administered at 10 mg curcumin/kg by jugular vein to bile duct-cannulated male SD rats (n = 5). Nanocurcumin increased the plasma Cmax of curcumin 1749 fold relative to the solvent solubilized curcumin. Nanocurcumin also increased the relative abundance of curcumin and glucuronides in bile, but did not dramatically alter urine and tissue metabolite profiles. The observed increase in biliary and urinary excretion of both curcumin and metabolites for the nanocurcumin formulation suggested rapid, “burst” release of curcumin. Although the burst release observed in this study is a limitation for targeted tumor delivery, nanocurcumin still exhibits major advantages over solvent solubilized curcumin, as the nanoformulation does not result in the lung accumulation observed for the solvent solubilized curcumin and increases overall systemic curcumin exposure. Additionally, the remaining encapsulated curcumin fraction following burst release is available for tumor delivery via the enhanced permeation and retention effect commonly observed for nanoparticle formulations. PMID:23534919

Preparation of curcumin nanoparticle by using reinforcement ionic gelation technique

NASA Astrophysics Data System (ADS)

Suryani, Halid, Nur Hatidjah Awaliyah; Akib, Nur Illiyyin; Rahmanpiu, Mutmainnah, Nina

2017-05-01

Curcumin, a polyphenolic compound present in curcuma longa has a wide range of activities including anti-inflammatory properties. The potency of curcumin is limited by its poor oral bioavailability because of its poor solubility in aqueous. Various methods have been tried to solve the problem including its encapsulation into nanoparticle. The aim of this study is to develop curcumin nanoparticle by using reinforcement ionic gelation technique and to evaluate the stability of curcumin nanoparticles in gastrointestinal fluid. Curcumin nanoparticles were prepared by using reinforcement ionic gelation technique with different concentrations of chitosan, trypolyphosphate, natrium alginate and calcium chloride. Curcumin nanoparticles were then characterized including particle size and zeta potential by using particle size analyzer and morphology using a transmission electron microscope, entrapment efficiency using UV-Vis Spectrophotometer and chemical structure analysis by Infra Red Spectrophotometer (FTIR). Furthermore, the stability of curcumin nanoparticles were evaluated on artificial gastric fluid and artificial intestinal fluids by measuring the amount of curcumin released in the medium at a time interval. The result revealed that curcumin nanoparticles can be prepared by reinforcement ionic gelation technique, the entrapment efficiency of curcumin nanoparticles were from 86.08 to 91.41%. The average of particle size was 272.9 nm and zeta potential was 12.05 mV. The morphology examination showed that the curcumin nanoparticles have spherical shape. The stability evaluation of curcumin nanoparticles showed that the nanoparticles were stable on artificial gastric fluid and artificial intestinal fluid. This result indicates that curcumin nanoparticles have the potential to be developed for oral delivery.

Novel capsaicin-induced parameters of microcirculation in migraine patients revealed by imaging photoplethysmography.

PubMed

Kamshilin, Alexei A; Volynsky, Maxim A; Khayrutdinova, Olga; Nurkhametova, Dilyara; Babayan, Laura; Amelin, Alexander V; Mamontov, Oleg V; Giniatullin, Rashid

2018-06-18

The non-invasive biomarkers of migraine can help to develop the personalized medication of this disorder. In testing of the antimigraine drugs the capsaicin-induced skin redness with activated TRPV1 receptors in sensory neurons associated with the release of the migraine mediator CGRP has already been widely used. Fourteen migraine patients (mean age 34.6 ± 10.2 years) and 14 healthy volunteers (mean age 29.9 ± 9.7 years) participated in the experiment. A new arrangement of imaging photoplethysmography recently developed by us was used here to discover novel sensitive parameters of dermal blood flow during capsaicin applications in migraine patients. Blood pulsation amplitude (BPA) observed as optical-intensity waveform varying synchronously with heartbeat was used for detailed exploration of microcirculatory perfusion induced by capsicum patch application. The BPA signals, once having appeared after certain latent period, were progressively rising until being saturated. Capsaicin-induced high BPA areas were distributed unevenly under the patch, forming "hot spots." Interestingly the hot spots were much more variable in migraine patients than in the control group. In contrast to BPA, a slow component of waveforms related to the skin redness changed significantly less than BPA highlighting the latter parameter as the potential sensitive biomarker of capsaicin-induced activation of the blood flow. Thus, in migraine patients, there is a non-uniform (both in space and in time) reaction to capsaicin, resulting in highly variable openings of skin capillaries. BPA dynamics measured by imaging photoplethysmography could serve as a novel sensitive non-invasive biomarker of migraine-associated changes in microcirculation.

Curcumin Quantum Dots Mediated Degradation of Bacterial Biofilms.

PubMed

Singh, Ashish K; Prakash, Pradyot; Singh, Ranjana; Nandy, Nabarun; Firdaus, Zeba; Bansal, Monika; Singh, Ranjan K; Srivastava, Anchal; Roy, Jagat K; Mishra, Brahmeshwar; Singh, Rakesh K

2017-01-01

Bacterial biofilm has been reported to be associated with more than 80% of bacterial infections. Curcumin, a hydrophobic polyphenol compound, has anti-quorum sensing activity apart from having antimicrobial action. However, its use is limited by its poor aqueous solubility and rapid degradation. In this study, we attempted to prepare quantum dots of the drug curcumin in order to achieve enhanced solubility and stability and investigated for its antimicrobial and antibiofilm activity. We utilized a newer two-step bottom up wet milling approach to prepare Curcumin Quantum Dots (CurQDs) using acetone as a primary solvent. Minimum inhibitory concentration against select Gram-positive and Gram-negative bacteria was performed. The antibiofilm assay was performed at first using 96-well tissue culture plate and subsequently validated by Confocal Laser Scanning Microscopy. Further, biofilm matrix protein was isolated using formaldehyde sludge and TCA/Acetone precipitation method. Protein extracted was incubated with varying concentration of CurQDs for 4 h and was subjected to SDS-PAGE. Molecular docking study was performed to observe interaction between curcumin and phenol soluble modulins as well as curli proteins. The biophysical evidences obtained from TEM, SEM, UV-VIS, fluorescence, Raman spectroscopy, and zeta potential analysis confirmed the formation of curcumin quantum dots with increased stability and solubility. The MICs of curcumin quantum dots, as observed against both select gram positive and negative bacterial isolates, was observed to be significantly lower than native curcumin particles. On TCP assay, Curcumin observed to be having antibiofilm as well as biofilm degrading activity. Results of SDS-PAGE and molecular docking have shown interaction between biofilm matrix proteins and curcumin. The results indicate that aqueous solubility and stability of Curcumin can be achieved by preparing its quantum dots. The study also demonstrates that by sizing down the

Transdermal delivery of curcumin via microemulsion.

PubMed

Sintov, Amnon C

2015-03-15

The objective of this study was to evaluate the transdermal delivery potential of a new curcumin-containing microemulsion system. Three series of experiments were carried out to comprehend the system characteristics: (a) examining the influence of water content on curcumin permeation, (b) studying the effect of curcumin loading on its permeability, and (c) assessing the contribution of the vesicular nature of the microemulsion on permeability. The skin permeability of curcumin from microemulsions, which contained 5%, 10%, and 20% of water content (1% curcumin), was measured in vitro using excised rat skin. It has been shown that the permeability coefficient of CUR in a formulation containing 10% aqueous phase (ME-10) was twofold higher than the values obtained for formulations with 5% and 20% water (Papp=0.116 × 10(-3)± 0.052 × 10(-3)vs. 0.043 × 10(-3)± 0.022 × 10(-3) and 0.047 × 10(-3)± 0.025 × 10(-3)cm/h, respectively. A reasonable explanation for this phenomenon may be the reduction of both droplet size and droplets' concentration in the microemulsion as the aqueous phase decreased from 20% to 5%. It has also been shown that a linear correlation exists between the decrease in droplet size and the increase of curcumin loading in the microemulsion. In addition, it has been demonstrated that a micellar system, S/O-mix, and a plain solution of curcumin resulted in a significantly lower curcumin permeation relative to that presented by the microemulsion, Papp=0.018 × 10(-3)± 0.011 × 10(-3), 0.005 × 10(-3)± 0.002 × 10(-3), and 0.002 × 10(-3)± 0.000 × 10(-3)cm/h, respectively, vs. 0.110 × 10(-3)± 0.021 × 10(-3)cm/h for the microemulsion. The enhancement ratio (ER=Jss-ME/Jss-solution) of CUR permeated via 1% loaded microemulsion was 55. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of vehicle properties and excipients on hydrolytic and photochemical stability of curcumin in preparations containing Pluronics: studies of curcumin and curcuminoids XLVIII.

PubMed

Singh, R; Kristensen, S; Tønnesen, H H

2013-03-01

The influence of vehicle properties and excipients on the hydrolytic and photochemical stability of curcumin in Pluronic preparations, and the interactions between curcumin and Pluronics was investigated. Curcumin was found to be degraded by general acid-base catalyzed hydrolytic degradation in alkaline preparations. The degradation rate of curcumin was higher in carbonate buffer than in phosphate buffer (pH 8.8), while it was higher in phosphate buffer than in citrate buffer (pH 7.8). At pH 8.0-8.8 the degradation rate of curcumin increased compared to preparations with pH <8.0. The stabilizing effect of the Pluronics against hydrolytic degradation of curcumin was only detectable at pH 8.0-8.8, and it was highest for F127 and lowest for P85, in phosphate buffer pH 8.8. An increase in the ionic strength increased the stabilization against hydrolytic degradation of curcumin by all Pluronics. Addition of ethanol decreased the hydrolytic stability of curcumin in all Pluronics. Addition of PEG 400 decreased the hydrolytic stability in preparation with either P123 or F127 while the degradation in preparations with P85 remained the same as in P85 preparations without PEG 400. Vehicle properties and excipients did not to any large degree influence the spectroscopic properties or the photostability of curcumin in Pluronic preparations. Photochemical half life of curcumin was in the minutes range. Spectrophotometric data indicate that Pluronic aggregates most likely solubilize curcumin through hydrophobic interactions, although hydrogen-bonding may also be involved.

Capsaicin induces browning of white adipose tissue and counters obesity by activating TRPV1 channel‐dependent mechanisms

PubMed Central

Baskaran, Padmamalini; Krishnan, Vivek; Ren, Jun

2016-01-01

Background and Purpose The growing epidemic of obesity and metabolic diseases necessitates the development of novel strategies to prevent and treat such diseases. Current research suggests that browning of white adipose tissue (WAT) promotes energy expenditure to counter obesity. Recent research suggests that activation of the TRPV1 channels counters obesity. However, the mechanism by which activation of TRPV1 channels counters obesity still remains unclear. Experimental Approach We evaluated the effect of dietary capsaicin to induce a browning program in WAT by activating TRPV1 channels to prevent diet‐induced obesity using wild‐type and TRPV1−/− mouse models. We performed experiments using preadipocytes and fat pads from these mice. Key Results Capsaicin stimulated the expression of brown fat‐specific thermogenic uncoupling protein‐1 and bone morphogenetic protein‐8b in WAT. Capsaicin triggered browning of WAT by promoting sirtuin‐1 expression and activity via TRPV1 channel‐dependent elevation of intracellular Ca2 + and phosphorylation of Ca2 +/calmodulin‐activated protein kinase II and AMP‐activated kinase. Capsaicin increased the expression of PPARγ 1 coactivator α and enhanced metabolic and ambulatory activity. Further, capsaicin stimulated sirtuin‐1‐dependent deacetylation of PPARγ and the transcription factor PRDM‐16 and facilitated PPARγ–PRDM‐16 interaction to induce browning of WAT. Dietary capsaicin did not protect TRPV1−/− mice from obesity. Conclusions and Interpretations Our results show for the first time that activation of TRPV1 channels by dietary capsaicin triggers browning of WAT to counteract obesity. Our results suggest that activation of TRPV1 channels is a promising strategy to counter obesity. PMID:27174467

Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations

PubMed Central

Cui, Yuanyuan; Yang, Fan; Cao, Xu; Yarov-Yarovoy, Vladimir

2012-01-01

The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly heat-sensitive ion channel. Although chemical activation and heat activation of TRPV1 elicit similar pungent, painful sensation, the molecular mechanism underlying synergistic activation remains mysterious. In particular, where the temperature sensor is located and whether heat and capsaicin share a common activation pathway are debated. To address these fundamental issues, we searched for channel mutations that selectively affected one form of activation. We found that deletion of the first 10 amino acids of the pore turret significantly reduced the heat response amplitude and shifted the heat activation threshold, whereas capsaicin activation remained unchanged. Removing larger portions of the turret disrupted channel function. Introducing an artificial sequence to replace the deleted region restored sensitive capsaicin activation in these nonfunctional channels. The heat activation, however, remained significantly impaired, with the current exhibiting diminishing heat sensitivity to a level indistinguishable from that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that heat and capsaicin activation of TRPV1 are structurally and mechanistically distinct processes, and the pore turret is an indispensible channel structure involved in the heat activation process but is not part of the capsaicin activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate. PMID:22412190

Curcumin as a potential protective compound against cardiac diseases.

PubMed

Jiang, Shuai; Han, Jing; Li, Tian; Xin, Zhenlong; Ma, Zhiqiang; Di, Wencheng; Hu, Wei; Gong, Bing; Di, Shouyin; Wang, Dongjin; Yang, Yang

2017-05-01

Curcumin, which was first used 3000 years ago as an anti-inflammatory agent, is a well-known bioactive compound derived from the active ingredient of turmeric (Curcuma longa). Previous research has demonstrated that curcumin has immense therapeutic potential in a variety of diseases via anti-oxidative, anti-apoptotic, and anti-inflammatory pathways. Cardiac diseases are the leading cause of mortality worldwide and cause considerable harm to human beings. Numerous studies have suggested that curcumin exerts a protective role in the human body whereas its actions in cardiac diseases remain elusive and poorly understood. On the basis of the current evidence, we first give a brief introduction of cardiac diseases and curcumin, especially regarding the effects of curcumin in embryonic heart development. Secondly, we analyze the basic roles of curcumin in pathways that are dysregulated in cardiac diseases, including oxidative stress, apoptosis, and inflammation. Thirdly, actions of curcumin in different cardiac diseases will be discussed, as will relevant clinical trials. Eventually, we would like to discuss the existing controversial opinions and provide a detailed analysis followed by the remaining obstacles, advancement, and further prospects of the clinical application of curcumin. The information compiled here may serve as a comprehensive reference of the protective effects of curcumin in the heart, which is significant to the further research and design of curcumin analogs as therapeutic options for cardiac diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Curcumin inhibits amygdaloid kindled seizures in rats.

PubMed

DU, Peng; Li, Xin; Lin, Hao-Jie; Peng, Wei-Feng; Liu, Jian-Ying; Ma, Yu; Fan, Wei; Wang, Xin

2009-06-20

Curcumin can reduce the severity of seizures induced by kainate acid (KA), but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats. With an amygdaloid kindled Sprague-Dawley (SD) rat model and an electrophysiological method, different doses of curcumin (10 mgxkg(-1)xd(-1) and 30 mgxkg(-1)xd(-1) as low dose groups, 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1) as high dose groups) were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge (AD) thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher's least significant difference post hoc test were used for statistical analyses. Curcumin (both 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1)) significantly inhibited the behavioral seizure development in the (19.80 +/- 2.25) and (21.70 +/- 2.21) stimulations respectively required to reach the kindled state. Rats treated with 100 mgxkg(-1)xd(-1) curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from (703.3 +/- 85.9) microA to (960.0 +/- 116.5) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin showed a significant increase in the stimulation current intensity required to evoke AD from (735.0 +/- 65.2) microA to (867.0 +/- 93.4) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class both IV (as (199.83 +/- 12.47) seconds) and V seizures (as (210.66 +/- 10.68) seconds). Rats treated with 100 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class V seizures (as (219.56 +/- 18.24) seconds). Our study suggests that curcumin has

Photodecomposition Profile of Curcumin in the Existence of Tungsten Trioxide Particles

NASA Astrophysics Data System (ADS)

Nandiyanto, A. B. D.; Zaen, R.; Oktiani, R.; Abdullah, A. G.

2018-02-01

The purpose of this study was to investigate the stability of curcumin solution in the existence of tungsten trioxide (WO3) particles under light illumination. In the experimental method, curcumin extracted from Indonesian local turmeric was added with WO3 microparticles and put into the photoreactor system. The photostability performance of curcumin was conducted for 22 hours using 100 W of Neon Lamp. The results showed that the curcumin solution was relatively stable. When curcumin without existence of WO3 was irradiated, no change in the curcumin concentration was found. However, when curcumin solution was mixed with WO3 particles, decreases in the concentration of curcumin was found. The concentration of curcumin with WO3 after light irradiation was about 73.58%. Based on the results, we concluded that the curcumin is relatively stable against light. However, its lightirradiation stability decreases with additional inorganic material.

The effect of Pro NanoLipospheres (PNL) formulation containing natural absorption enhancers on the oral bioavailability of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a rat model.

PubMed

Cherniakov, Irina; Izgelov, Dvora; Domb, Abraham J; Hoffman, Amnon

2017-11-15

The lipophilic phytocannabinoids cannabidiol (CBD) and Δ 9 -tetrahydrocannabinol (THC) show therapeutic efficacy in various medical conditions. Both molecules are poorly water soluble and subjected to extensive first pass metabolism in the gastrointestinal tract, leading to a limited oral bioavailability of approximately 9%. We have developed an advanced lipid based Self-Emulsifying Drug Delivery System termed Advanced Pro-NanoLiposphere (PNL) pre-concentrate. The PNL is composed of lipid and emulsifying excipients of GRAS status and are known to increase solubility and reduce Phase I metabolism of lipophilic active compounds. Advanced PNLs are PNLs with an incorporated natural absorption enhancers. These molecules are natural alkaloids and phenolic compounds which were reported to inhibit certain phase I and phase II metabolism processes. Here we use piperine, curcumin and resveratrol to formulate the Advanced-PNL formulations. Consequently, we have explored the utility of these Advanced-PNLs on CBD and THC oral bioavailability. Oral administration of CBD-piperine-PNL resulted in 6-fold increase in AUC compared to CBD solution, proving to be the most effective of the screened formulations. The same trend was found in pharmacokinetic experiments of THC-piperine-PNL which resulted in a 9.3-fold increase in AUC as compared to THC solution. Our Piperine-PNL can be used as a platform for synchronized delivery of piperine and CBD or THC to the enterocyte site. This co-localization provides an increase in CBD and THC bioavailability by its effect at the pre-enterocyte and the enterocyte levels of the absorption process. The extra augmentation in the absorption of CBD and THC by incorporating piperine into PNL is attributed to the inhibition of Phase I and phase II metabolism by piperine in addition to the Phase I metabolism and P-gp inhibition by PNL. These novel results pave the way to utilize piperine-PNL delivery system for other poorly soluble, highly metabolized

Enhanced solubilization of curcumin in mixed surfactant vesicles.

PubMed

Kumar, Arun; Kaur, Gurpreet; Kansal, S K; Chaudhary, Ganga Ram; Mehta, S K

2016-05-15

Self-assemblies of equimolar double and single chain mixed ionic surfactants, with increasing numbers of carbon atoms of double chain surfactant, were analyzed on the basis of fluorescence and conductivity results. Attempts were also made to enhance the solubilization of curcumin in aqueous equimolar mixed surfactant systems. Mixed surfactant assembly was successful in retarding the degradation of curcumin in alkaline media (only 25-28 40% degraded in 10h at pH 13). Fluorescence spectroscopy and fluorescence quenching methods were employed to predict the binding position and mechanism of curcumin with self-assemblies. Results indicate that the interactions take place according to both dynamic and static quenching mechanisms and curcumin was distributed in a palisade layer of mixed aggregates. Antioxidant activity (using DPPH radical) and biocompatibility (using calf-thymus DNA) of curcumin-loaded mixed surfactant formulations were also evaluated. The prepared systems improved the stability, solubility and antioxidant activity of curcumin and additionally are biocompatible. Copyright © 2015 Elsevier Ltd. All rights reserved.

Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway.

PubMed

Lin, Yu-Tsai; Wang, Hung-Chen; Hsu, Yi-Chiang; Cho, Chung-Lung; Yang, Ming-Yu; Chien, Chih-Yen

2017-06-23

Capsaicin is a potential chemotherapeutic agent for different human cancers. In Southeast China, nasopharyngeal carcinoma (NPC) has the highest incidence of all cancers, but final treatment outcomes are unsatisfactory. However, there is a lack of information regarding the anticancer activity of capsaicin in NPC cells, and its effects on the signaling transduction pathways related to apoptosis and autophagy remain unclear. In the present study, the precise mechanisms by which capsaicin exerts anti-proliferative effects, cell cycle arrest, autophagy and apoptosis were investigated in NPC-TW01 cells. Exposure to capsaicin inhibited cancer cell growth and increased G1 phase cell cycle arrest. Western blotting and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) were used to measure capsaicin-induced autophagy via involvement of the class III PI3K/Beclin-1/Bcl-2 signaling pathway. Capsaicin induced autophagy by increasing levels of the autophagy markers LC3-II and Atg5, enhancing p62 and Fap-1 degradation and increasing caspase-3 activity to induce apoptosis, suggesting a correlation of blocking the PI3K/Akt/mTOR pathway with the above-mentioned anticancer activities. Taken together, these data confirm that capsaicin inhibited the growth of human NPC cells and induced autophagy, supporting its potential as a therapeutic agent for cancer.

Curcumin phytosomal softgel formulation: Development, optimization and physicochemical characterization.

PubMed

Allam, Ahmed N; Komeil, Ibrahim A; Abdallah, Ossama Y

2015-09-01

Curcumin, a naturally occurring lipophilic molecule can exert multiple and diverse bioactivities. However, its limited aqueous solubility and extensive presystemic metabolism restrict its bioavailability. Curcumin phytosomes were prepared by a simple solvent evaporation method where free flowing powder was obtained in addition to a newly developed semisolid formulation to increase curcumin content in softgels. Phytosomal powder was characterized in terms of drug content and zeta potential. Thirteen different softgel formulations were developed using oils such as Miglyol 812, castor oil and oleic acid, a hydrophilic vehicle such as PEG 400 and bioactive surfactants such as Cremophor EL and KLS P 124. Selected formulations were characterized in terms of curcumin in vitro dissolution. TEM analysis revealed good stability and a spherical, self-closed structure of curcumin phytosomes in complex formulations. Stability studies of chosen formulations prepared using the hydrophilic vehicle revealed a stable curcumin dissolution pattern. In contrast, a dramatic decrease in curcumin dissolution was observed in case of phytosomes formulated in oily vehicles.

Novel delivery system for natural products: Nano-curcumin formulations

PubMed Central

Rahimi, Hamid Reza; Nedaeinia, Reza; Sepehri Shamloo, Alireza; Nikdoust, Shima; Kazemi Oskuee, Reza

2016-01-01

Objective: Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA) and messengers (RNA). A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rheumatoid arthritis, Alzheimer’s, inflammatory bowel disease (IBD), and even it has wound healing. Oral bioavailability of curcumin is rather poor, which would certainly put some boundaries in the employment of this drug. Materials and Methods: Bibliographical searches were performed using MEDLINE/ScienceDirect/OVID up to February 2015 using the following keywords (all fields): (“Curcumin” OR “Curcuma longa”) AND [(nanoparticles) OR (Nanomicelles) OR (micro emulsions) OR (liposome) OR (phospholipid). Results: Consequently, for any developments of curcumin in the future, analogues of curcumin that have better bioavailability or substitute formulations are needed crucially. Conclusion: These studies indicated that nanotechnology can formulate curcumin effectively, and this nano-formulated curcumin with a potent ability against various cancer cells, were represented to have better efficacy and bioavailability under in vivo conditions. PMID:27516979

Modulation of transcription factors by curcumin.

PubMed

Shishodia, Shishir; Singh, Tulika; Chaturvedi, Madan M

2007-01-01

Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors. Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action.

Degradation of curcumin: From mechanism to biological implications

PubMed Central

Schneider, Claus; Gordon, Odaine N.; Edwards, Rebecca L.; Luis, Paula B.

2016-01-01

Curcumin is the main bioactive ingredient in turmeric extract and widely consumed as part of the spice mix curry or as dietary supplement. Turmeric has a long history of therapeutic application in traditional Asian medicine. Biomedical studies conducted in the past two decades have identified a large number of cellular targets and effects of curcumin. In vitro curcumin rapidly degrades in an autoxidative transformation to diverse chemical species, formation of which has only recently been appreciated. We discuss how degradation and metabolism of curcumin, through products and their mechanism of formation, provide a basis for the interpretation of preclinical data and clinical studies. We suggest that the previously unrecognized diversity of its degradation products could be an important factor in explaining the polypharmacology of curcumin. PMID:25817068

Renoprotective effect of the antioxidant curcumin: Recent findings☆

PubMed Central

Trujillo, Joyce; Chirino, Yolanda Irasema; Molina-Jijón, Eduardo; Andérica-Romero, Ana Cristina; Tapia, Edilia; Pedraza-Chaverrí, José

2013-01-01

For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2), inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury. PMID:24191240

Cough reflex testing with inhaled capsaicin and TRPV1 activation in asthma and comorbid conditions.

PubMed

Couto, M; de Diego, A; Perpiñi, M; Delgado, L; Moreira, A

2013-01-01

A high parasympathetic tone leading to bronchoconstriction and neurogenic inflammation is thought to have a major role in the pathogenesis of asthma. Transient receptor potential vanilloid 1 (TRPV1) is the hub of almost all neuronal inflammatory signaling pathways. A critical determinant of neurogenic inflammation, TRPV1 functions as a sensor for detecting irritants in the lung by transmitting noxious stimuli to the central nervous system and inducing the release of a variety of proinflammatory neuropeptides at the peripheral terminals. Challenge with inhaled capsaicin, an exogenous agonist of TRPV1, has been used to measure the sensitivity of the cough reflex. However, inhalation of capsaicin is also associated with parasympathetic bronchoconstriction, mucus hypersecretion, vasodilatation, and the sensation of dyspnea. Therefore, inhaled capsaicin challenge is expected to have other potential applications in asthma and comorbid conditions, such as rhinitis and gastroesophageal reflux disease, both of which produce cough. Capsaicin challenge has established itself as a useful objective method for evaluating airway hypersensitivity; however, it is potentially valuable in many other situations, which will be reviewed in this paper.

Investigation on Curcumin nanocomposite for wound dressing.

PubMed

Venkatasubbu, G Devanand; Anusuya, T

2017-05-01

Curcuma longa (turmeric) has a long history of use in medicine as a treatment for inflammatory conditions. The primary active constituent of turmeric and the one responsible for its vibrant yellow color is curcumin. Curcumin is used for treatment of wound and inflammation. It had antimicrobial and antioxidant property. It has low intrinsic toxicity and magnificent properties like with comparatively lesser side-effects. Cotton cloth is one of the most successful wound dressings which utilize the intrinsic properties of cotton fibers. Modern wound dressings, however, require other properties such as antibacterial and moisture maintaining capabilities. In this study, conventional cotton cloth was coated with Curcumin composite for achieving modern wound dressing properties. Curcumin nanocomposite is characterized. The results show that coated cotton cloth with Curcumin nanocomposite has increased drying time (74%) and water absorbency (50%). Furthermore, they show antibacterial efficiency against bacterial species present in wounds. Copyright © 2017 Elsevier B.V. All rights reserved.

Solvent dependent photophysical properties of dimethoxy curcumin

NASA Astrophysics Data System (ADS)

Barik, Atanu; Indira Priyadarsini, K.

2013-03-01

Dimethoxy curcumin (DMC) is a methylated derivative of curcumin. In order to know the effect of ring substitution on photophysical properties of curcumin, steady state absorption and fluorescence spectra of DMC were recorded in organic solvents with different polarity and compared with those of curcumin. The absorption and fluorescence spectra of DMC, like curcumin, are strongly dependent on solvent polarity and the maxima of DMC showed red shift with increase in solvent polarity function (Δf), but the above effect is prominently observed in case of fluorescence maxima. From the dependence of Stokes' shift on solvent polarity function the difference between the excited state and ground state dipole moment was estimated as 4.9 D. Fluorescence quantum yield (ϕf) and fluorescence lifetime (τf) of DMC were also measured in different solvents at room temperature. The results indicated that with increasing solvent polarity, ϕf increased linearly, which has been accounted for the decrease in non-radiative rate by intersystem crossing (ISC) processes.

N-Glycosylation Determines Ionic Permeability and Desensitization of the TRPV1 Capsaicin Receptor*

PubMed Central

Veldhuis, Nicholas A.; Lew, Michael J.; Abogadie, Fe C.; Poole, Daniel P.; Jennings, Ernest A.; Ivanusic, Jason J.; Eilers, Helge; Bunnett, Nigel W.; McIntyre, Peter

2012-01-01

The balance of glycosylation and deglycosylation of ion channels can markedly influence their function and regulation. However, the functional importance of glycosylation of the TRPV1 receptor, a key sensor of pain-sensing nerves, is not well understood, and whether TRPV1 is glycosylated in neurons is unclear. We report that TRPV1 is N-glycosylated and that N-glycosylation is a major determinant of capsaicin-evoked desensitization and ionic permeability. Both N-glycosylated and unglycosylated TRPV1 was detected in extracts of peripheral sensory nerves by Western blotting. TRPV1 expressed in HEK-293 cells exhibited various degrees of glycosylation. A mutant of asparagine 604 (N604T) was not glycosylated but did not alter plasma membrane expression of TRPV1. Capsaicin-evoked increases in intracellular calcium ([Ca2+]i) were sustained in wild-type TRPV1 HEK-293 cells but were rapidly desensitized in N604T TRPV1 cells. There was marked cell-to-cell variability in capsaicin responses and desensitization between individual cells expressing wild-type TRPV1 but highly uniform responses in cells expressing N604T TRPV1, consistent with variable levels of glycosylation of the wild-type channel. These differences were also apparent when wild-type or N604T TRPV1-GFP fusion proteins were expressed in neurons from trpv1−/− mice. Capsaicin evoked a marked, concentration-dependent increase in uptake of the large cationic dye YO-PRO-1 in cells expressing wild-type TRPV1, indicative of loss of ion selectivity, that was completely absent in cells expressing N604T TRPV1. Thus, TRPV1 is variably N-glycosylated and glycosylation is a key determinant of capsaicin regulation of TRPV1 desensitization and permeability. Our findings suggest that physiological or pathological alterations in TRPV1 glycosylation would affect TRPV1 function and pain transmission. PMID:22570472

Capsaicin-evoked cough responses in asthmatic patients: Evidence for airway neuronal dysfunction.

PubMed

Satia, Imran; Tsamandouras, Nikolaos; Holt, Kimberley; Badri, Huda; Woodhead, Mark; Ogungbenro, Kayode; Felton, Timothy W; O'Byrne, Paul M; Fowler, Stephen J; Smith, Jaclyn A

2017-03-01

Cough in asthmatic patients is a common and troublesome symptom. It is generally assumed coughing occurs as a consequence of bronchial hyperresponsiveness and inflammation, but the possibility that airway nerves are dysfunctional has not been fully explored. We sought to investigate capsaicin-evoked cough responses in a group of patients with well-characterized mild-to-moderate asthma compared with healthy volunteers and assess the influences of sex, atopy, lung physiology, inflammation, and asthma control on these responses. Capsaicin inhalational challenge was performed, and cough responses were analyzed by using nonlinear mixed-effects modeling to estimate the maximum cough response evoked by any concentration of capsaicin (E max ) and the capsaicin dose inducing half-maximal response (ED 50 ). Ninety-seven patients with stable asthma (median age, 23 years [interquartile range, 21-27 years]; 60% female) and 47 healthy volunteers (median age, 38 years [interquartile range, 29-47 years]; 64% female) were recruited. Asthmatic patients had higher E max and lower ED 50 values than healthy volunteers. E max values were 27% higher in female subjects (P = .006) and 46% higher in patients with nonatopic asthma (P = .003) compared with healthy volunteers. Also, patients with atopic asthma had a 21% lower E max value than nonatopic asthmatic patients (P = .04). The ED 50 value was 65% lower in female patients (P = .0001) and 71% lower in all asthmatic patients (P = .0008). ED 50 values were also influenced by asthma control and serum IgE levels, whereas E max values were related to 24-hour cough frequency. Age, body mass index, FEV 1 , PC 20 , fraction of exhaled nitric oxide, blood eosinophil counts, and inhaled steroid treatment did not influence cough parameters. Patients with stable asthma exhibited exaggerated capsaicin-evoked cough responses consistent with neuronal dysfunction. Nonatopic asthmatic patients had the highest cough responses, suggesting

Curcumin Alleviates Diabetic Retinopathy in Experimental Diabetic Rats.

PubMed

Yang, Fang; Yu, Jinqiang; Ke, Feng; Lan, Mei; Li, Dekun; Tan, Ke; Ling, Jiaojiao; Wang, Ying; Wu, Kaili; Li, Dai

2018-03-29

To investigate the potential protective effects of curcumin on the retina in diabetic rats. An experimental diabetic rat model was induced by a low dose of streptozotocin combined with a high-energy diet. Rats which had blood glucose levels ≥11.6 mmol/L were used as diabetic rats. The diabetic rats were randomly divided into 3 groups: diabetic rats with no treatment (DM), diabetic rats treated with 100 mg/kg curcumin (DM + Cur 100 mg/kg), and diabetic rats treated with 200 mg/kg curcumin (DM + Cur 200 mg/kg). Curcumin was orally administered daily for 16 weeks. After 16 weeks of administration, the rats were euthanized, and eyes were dissected. Retinal histology was examined, and the thickness of the retina was measured. Ultrastructural changes of retinal ganglion cells, inner layer cells, retinal capillary, and membranous disks were observed by electron microscopy. Malondialdehyde, superoxide dismutase, and total antioxidant capacity were measured by ELISA. Expression levels of vascular endothelial growth factor (VEGF) in retina tissues were examined by immunohistochemical staining and ELISA. Expression levels of Bax and Bcl-2 in retina tissues were determined by immunohistochemical staining and Western blotting. Curcumin reduced the blood glucose levels of diabetic rats and decreased diabetes-induced body weight loss. Curcumin prevented attenuation of the retina in diabetic rats and ameliorated diabetes-induced ultrastructure changes of the retina, including thinning of the retina, apoptosis of the retinal ganglion cells and inner nuclear layer cells, thickening of retinal capillary basement membrane and disturbance of photoreceptor cell membranous disks. We also found that curcumin has a strong antioxidative ability in the retina of diabetic rats. It was observed that curcumin attenuated the expression of VEGF in the retina of diabetic rats. We also discovered that curcumin had an antiapoptotic effect by upregulating the expression of Bcl-2 and downregulating

Topical Mannitol Reduces Capsaicin-Induced Pain: Results of a Pilot-Level, Double-Blind, Randomized Controlled Trial.

PubMed

Bertrand, Helene; Kyriazis, Marylene; Reeves, K Dean; Lyftogt, John; Rabago, David

2015-11-01

Capsaicin specifically activates, and then gradually exhausts, the transient receptor potential vanilloid type 1 (TRPV1) receptor, a key receptor in neuropathic pain. Activation of the TRPV-1 receptor is accompanied by burning pain. A natural substance or medication that can reduce the burning pain resulting from capsaicin application may have therapeutic potential in neuropathic pain. To assess the pain-relieving effects of a mannitol-containing cream in a capsaicin-based pain model. Randomized, placebo-controlled, double-blind clinical trial. Outpatient pain clinic. Twenty-five adults with pain-free lips. Capsaicin .075% cream was applied to both halves of each participant's upper lip, inducing pain via stimulation of the transient receptor potential vanilloid 1 (TRPV1, capsaicin) receptor, then removed after 5 minutes or when participants reported a burning pain of 8/10, whichever came first. A cream containing mannitol and the same cream without mannitol (control) were then immediately applied, 1 on each side of the lip, in an allocation-masked manner. Participants self-recorded a numeric rating scale (NRS, 0-10) pain score for each side of the lip per minute for 10 minutes. A t-test was performed to evaluate the pain score change from baseline between each side of the lip at each recording. Area under the curve (AUC) analysis was used to determine the overall difference between groups. Participants reached a capsaicin-induced pain level of 7.8 ± 1.0 points in 3.3 ± 1.6 minutes that was equal on both sides of the lip. Both groups reported progressive diminution of pain over the 10-minute study period. However, participants reported significantly reduced pain scores on the mannitol cream half-lip compared to control at 3 through 10 minutes (P < .05) and in AUC analysis (P < .001). Mannitol cream reduced self-reported pain scores in a capsaicin pain model more rapidly than a control cream, potentially via a TRPV1 receptor effect. Copyright © 2015 American

Capsaicin-sensitive sensory neurons are involved in the plasma catecholamine response of rats to selective stressors.

PubMed Central

Zhou, X F; Livett, B G

1991-01-01

1. The effect of capsaicin pre-treatment on adrenal catecholamine (CA) secretion in response to stress is controversial. In earlier experiments performed under pentobarbitone anaesthesia, the release of CA in response to stress was complicated by the effects of the barbiturate anaesthesia. 2. In the present study we have used conscious freely moving rats with indwelling cannulae to study the effect of neonatal capsaicin pre-treatment on the plasma CA response to different types of stressors (swimming stress, hypovolaemic stress, immobilization stress and cold stress). 3. After swimming for 20 min, plasma noradrenaline (NA) levels increased by 8-fold and adrenaline by 2-fold in control rats. The increase in plasma NA levels in the capsaicin group was attenuated at 10 min of swimming compared with the vehicle group (P < 0.05). 4. With hypovolaemic stress, there were no differences in plasma CA levels, blood pressure and heart rate between the capsaicin group and the vehicle group. There were also no differences in plasma CA levels after immobilization stress between the two groups. 5. With cold stress, plasma NA levels increased 5-fold and adrenaline levels by 3-fold over basal at 45 min in the vehicle pre-treated rats. This increase was not observed in the capsaicin group. 6. Immunoreactive substance P was depleted by only 68% in the splanchnic nerve following capsaicin pre-treatment. If the remaining 32% was biologically active substance P then it could account for the maintenance of the response to hypovolaemic and immobilization stress. However, it might be possible that the responses to hypovolaemic and immobilization stresses could be attenuated if a more complete depletion were achieved. 7. These results in conscious rats indicate that capsaicin-sensitive sensory neurons are required for plasma CA response to selective stressors. They are required for CA output in response to cold stress and to the early phase of swimming stress, but not to hypovolaemic stress

Cost-effectiveness analysis of a new 8% capsaicin patch compared to existing therapies for postherpetic neuralgia.

PubMed

Armstrong, Edward P; Malone, Daniel C; McCarberg, Bill; Panarites, Christopher J; Pham, Sissi V

2011-05-01

The purpose of this study was to compare the cost effectiveness of a new 8% capsaicin patch, compared to the current treatments for postherpetic neuralgia (PHN), including tricyclic antidepressants (TCAs), topical lidocaine patches, duloxetine, gabapentin, and pregabalin. A 1-year Markov model was constructed for PHN with monthly cycles, including dose titration and management of adverse events. The perspective of the analysis was from a payer perspective, managed-care organization. Clinical trials were used to determine the proportion of patients achieving at least a 30% improvement in PHN pain, the efficacy parameter. The outcome was cost per quality-adjusted life-year (QALY); second-order probabilistic sensitivity analyses were conducted. The effectiveness results indicated that 8% capsaicin patch and topical lidocaine patch were significantly more effective than the oral PHN products. TCAs were least costly and significantly less costly than duloxetine, pregabalin, topical lidocaine patch, 8% capsaicin patch, but not gabapentin. The incremental cost-effectiveness ratio for the 8% capsaicin patch overlapped with the topical lidocaine patch and was within the accepted threshold of cost per QALY gained compared to TCAs, duloxetine, gabapentin, and pregablin. The frequency of the 8% capsaicin patch retreatment assumption significantly impacts its cost-effectiveness results. There are several limitations to this analysis. Since no head-to-head studies were identified, this model used inputs from multiple clinical trials. Also, a last observation carried forward process was assumed to have continued for the duration of the model. Additionally, the trials with duloxetine may have over-predicted its efficacy in PHN. Although a 30% improvement in pain is often an endpoint in clinical trials, some patients may require greater or less improvement in pain to be considered a clinical success. The effectiveness results demonstrated that 8% capsaicin and topical lidocaine

Curcumin nanoformulations: a future nanomedicine for cancer

PubMed Central

Yallapu, Murali M; Jaggi, Meena; Chauhan, Subhash C

2011-01-01

Curcumin, a natural diphenolic compound derived from turmeric Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion, apoptosis and cell death, revealing its anticancer potential. In this review, we focus on the design and development of nanoparticles, self-assemblies, nanogels, liposomes and complex fabrication for sustained and efficient curcumin delivery. We also discuss the anticancer applications and clinical benefits of nanocurcumin formulations. Only a few novel multifunctional and composite nanosystem strategies offer simultaneous therapy as well as imaging characteristics. We also summarize the challenges to developing curcumin delivery platforms and up-to-date solutions for improving curcumin bioavailability and anticancer potential for therapy. PMID:21959306

Curcumin: the spicy modulator of breast carcinogenesis.

PubMed

Banik, Urmila; Parasuraman, Subramani; Adhikary, Arun Kumar; Othman, Nor Hayati

2017-07-19

Worldwide breast cancer is the most common cancer in women. For many years clinicians and the researchers are examining and exploring various therapeutic modalities for breast cancer. Yet the disease has remained unconquered and the quest for cure is still going on. Present-day strategy of breast cancer therapy and prevention is either combination of a number of drugs or a drug that modulates multiple targets. In this regard natural products are now becoming significant options. Curcumin exemplifies a promising natural anticancer agent for this purpose. This review primarily underscores the modulatory effect of curcumin on the cancer hallmarks. The focus is its anticancer effect in the complex pathways of breast carcinogenesis. Curcumin modulates breast carcinogenesis through its effect on cell cycle and proliferation, apoptosis, senescence, cancer spread and angiogenesis. Largely the NFkB, PI3K/Akt/mTOR, MAPK and JAK/STAT are the key signaling pathways involved. The review also highlights the curcumin mediated modulation of tumor microenvironment, cancer immunity, breast cancer stem cells and cancer related miRNAs. Using curcumin as a therapeutic and preventive agent in breast cancer is perplexed by its diverse biological activity, much of which remains inexplicable. The information reviewed here should point toward potential scope of future curcumin research in breast cancer.

Direct regulation of IL-2 by curcumin.

PubMed

Oh, Jin-Gyo; Hwang, Da-Jeong; Heo, Tae-Hwe

2018-01-01

Interleukin-2 (IL-2) is a crucial growth factor for both regulatory and effector T cells. Thus, IL-2 plays a critical role in the stimulation and suppression of immune responses. Recently, anti-IL-2 antibodies (Abs) have been shown to possess strong IL-2 modulatory activities by affecting the interaction between IL-2 and IL-2 receptors. In this study, we screened an herbal library to identify a compound that regulates IL-2, which resulted in the identification of curcumin as a direct binder and inhibitor of IL-2. Curcumin is a phytochemical with well-known anti-cancer properties. In this study, curcumin mimicked or altered the binding pattern of anti-IL-2 Abs against IL-2 and remarkably inhibited the interaction of recombinant IL-2 with the IL-2 receptor α, CD25. Interestingly, curcumin neutralized the biological activities of IL-2 both in vitro and in vivo. In this report, we elucidated the unsolved mechanism of the anti-cancer effect of curcumin by identifying IL-2 as a direct molecular target. Curcumin, as a small molecule IL-2 modulator, has the potential to be used to treat IL-2 related pathologic conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhancing curcumin anticancer efficacy through di-block copolymer micelle encapsulation.

PubMed

Lv, Li; Shen, Yuanyuan; Liu, Jieying; Wang, Feihu; Li, Min; Li, Min; Guo, Aijie; Wang, Yun; Zhou, Dejian; Guo, Shengrong

2014-02-01

We report herein the development of a novel aqueous formulation and improved antitumor activity for curcumin by encapsulating it into a biocompatible and biodegradable poly(L-lactic acid) based poly(anhydride-ester)-b-poly(ethylene glycol) (PAE-b-PEG) micelle. The resulting curcumin loaded micelles were completely water-dispersible, overcoming the problem of poor water solubility that limited its efficacy and bioavailability. In vitro cellular studies revealed that the curcumin-loaded micelles were taken up mainly via endocytosis route and exhibited higher cytotoxicities toward model cancer cell lines (HeLa and EMT6) than free curcumin. An in vivo biodistribution study revealed that the curcumin-loaded micelles displayed significantly enhanced accumulation inside the tumor of EMT6 breast tumor-bearing mice. More impressively, the curcumin-loaded micelles showed stronger antitumor activity, higher anti-angiogenesis effects and induced apoptosis on the EMT6 breast tumor model bearing mice than free curcumin. Furthermore, the curcumin-loaded micelles showed no significant toxicity towards hemotological system, major organs or tissues in mice. Combined with a high antitumor activity and low toxic side-effects, the curcumin-loaded micelles developed here thus appear to be a highly attractive nanomedicine for effective, targeted cancer therapy.

Curcumin: the Indian solid gold.

PubMed

Aggarwal, Bharat B; Sundaram, Chitra; Malani, Nikita; Ichikawa, Haruyo

2007-01-01

Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".

Curcumin, a potential therapeutic candidate for retinal diseases.

PubMed

Wang, Lei-Lei; Sun, Yue; Huang, Kun; Zheng, Ling

2013-09-01

Curcumin, the major extraction of turmeric, has been widely used in many countries for centuries both as a spice and as a medicine. In the last decade, researchers have found the beneficial effects of curcumin on multiple disorders are due to its antioxidative, anti-inflammatory, and antiproliferative properties, as well as its novel function as an inhibitor of histone aectyltransferases. In this review, we summarize the recent progress made on studying the beneficial effects of curcumin on multiple retinal diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent clinical trials on the effectiveness of phosphatidylcholine formulated curcumin in treating eye diseases have also shown promising results, making curcumin a potent therapeutic drug candidate for inflammatory and degenerative retinal and eye diseases. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Curcumin suppresses proliferation of colon cancer cells by targeting CDK2.

PubMed

Lim, Tae-Gyu; Lee, Sung-Young; Huang, Zunnan; Lim, Do Young; Chen, Hanyong; Jung, Sung Keun; Bode, Ann M; Lee, Ki Won; Dong, Zigang

2014-04-01

Curcumin, the yellow pigment of turmeric found in Southeast Indian food, is one of the most popular phytochemicals for cancer prevention. Numerous reports have demonstrated modulation of multiple cellular signaling pathways by curcumin and its molecular targets in various cancer cell lines. To identify a new molecular target of curcumin, we used shape screening and reverse docking to screen the Protein Data Bank against curcumin. Cyclin-dependent kinase 2 (CDK2), a major cell-cycle protein, was identified as a potential molecular target of curcumin. Indeed, in vitro and ex vivo kinase assay data revealed a dramatic suppressive effect of curcumin on CDK2 kinase activity. Furthermore, curcumin induced G1 cell-cycle arrest, which is regulated by CDK2 in HCT116 cells. Although the expression levels of CDK2 and its regulatory subunit, cyclin E, were not changed, the phosphorylation of retinoblastoma (Rb), a well-known CDK2 substrate, was reduced by curcumin. Because curcumin induced cell-cycle arrest, we investigated the antiproliferative effect of curcumin on HCT116 colon cancer cells. In this experiment, curcumin suppressed HCT116 cell proliferation effectively. To determine whether CDK2 is a direct target of curcumin, CDK2 expression was knocked down in HCT116 cells. As expected, HCT116 sh-CDK2 cells exhibited G1 arrest and reduced proliferation. Because of the low levels of CDK2 in HCT116 sh-CDK2 cells, the effects of curcumin on G1 arrest and cell proliferation were not substantially relative to HCT116 sh-control cells. From these results, we identified CDK2 as a direct target of curcumin in colon cancer cells.

Curcumin suppresses proliferation of colon cancer cells by targeting CDK2

PubMed Central

Lim, Tae-Gyu; Lee, Sung-Young; Huang, Zunnan; Lim, Do Young; Chen, Hanyong; Jung, Sung Keun; Bode, Ann M.; Lee, Ki Won; Dong, Zigang

2014-01-01

Curcumin, the yellow pigment of turmeric found in Southeast Indian food, is one of the most popular phytochemicals for cancer prevention. Numerous reports have demonstrated modulation of multiple cellular signaling pathways by curcumin and its molecular targets in various cancer cell lines. To identify a new molecular target of curcumin, we used shape screening and reverse docking to screen the protein data bank against curcumin. Cyclin dependent kinase 2 (CDK2), a major cell cycle protein, was identified as a potential molecular target of curcumin. Indeed, in vitro and ex vivo kinase assay data revealed a dramatic suppressive effect of curcumin on CDK2 kinase activity. Furthermore, curcumin induced G1 cell cycle arrest, which is regulated by CDK2 in HCT116 cells. Although the expression levels of CDK2 and its regulatory subunit, cyclin E, were not changed, the phosphorylation of Rb, a well-known CDK2 substrate, was reduced by curcumin. Because curcumin induced cell cycle arrest, we investigated the anti-proliferative effect of curcumin on HCT116 colon cancer cells. In this experiment, curcumin suppressed HCT116 cell proliferation effectively. To determine if CDK2 is a direct target of curcumin, CDK2 expression was knocked down in HCT116 cells. As expected, HCT116 sh-CDK2 cells exhibited G1 arrest and reduced proliferation. Because of the low levels of CDK2 in HCT116 sh-CDK2 cells, the effects of curcumin on G1 arrest and cell proliferation were not substantial relative to HCT116 sh-control cells. From these results, we identified CDK2 as a direct target of curcumin in colon cancer cells. PMID:24550143

Cannabinoid hyperemesis syndrome: potential mechanisms for the benefit of capsaicin and hot water hydrotherapy in treatment.

PubMed

Richards, John R; Lapoint, Jeff M; Burillo-Putze, Guillermo

2018-01-01

Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation. Putative mechanisms responsible for the benefit of hot water hydrotherapy are also investigated. An extensive search of PubMed, OpenGrey, and Google Scholar from inception to April 2017 was performed to identify known and theoretical thermoregulatory mechanisms associated with the endocannabinoid system. The searches resulted in 2417 articles. These articles were screened for relevant mechanisms behind capsaicin and heat activation having potential antiemetic effects. References from the selected articles were also hand-searched. A total of 137 articles were considered relevant and included. Capsaicin: Topical capsaicin is primarily used for treatment of neuropathic pain, but it has also been used successfully in some 20 cases of cannabinoid hyperemesis syndrome. The pharmacokinetics and pharmacodynamics of capsaicin as a transient receptor potential vanilloid 1 agonist may explain this effect. Topical capsaicin has a longer half-life than oral administration, thus its potential duration of benefit is longer. Capsaicin and transient receptor potential vanilloid 1: Topical capsaicin binds and activates the transient receptor potential vanilloid 1 receptor, triggering influx of calcium and sodium, as well as release of inflammatory neuropeptides leading to transient burning, stinging, and itching. This elicits

Development of 68Ga-SCN-DOTA-Capsaicin as an Imaging Agent Targeting Apoptosis and Cell Cycle Arrest in Breast Cancer.

PubMed

Lee, Jun Young; Lee, Sang-Yeun; Kim, Gun Gyun; Hur, Min Goo; Yang, Seung Dae; Park, Jeong-Hoon; Kim, Sang Wook

2017-06-01

68 Ga-labeled capsaicin using a DOTA (1,4,7,10-tetraazocyclododecane-N,N',N″,N'″-tetraacetic acid) derivative [ 68 Ga-SCN-Benzyl(Bn)-DOTA-capsaicin] was studied for the diagnosis of breast cancers, such as MCF-7 and SK-BR-3. The standard compound, 69 Ga-SCN-Bn-DOTA-capsaicin, was also prepared and characterized by spectroscopic analysis. The binding affinity of 68 Ga-SCN-Bn-DOTA-capsaicin was evaluated by using breast cancer cell lines (MCF-7, SK-BR-3) and colon cancer cell (CT-26); the biodistribution was carried out by using MCF-7-bearing nude mice, after which the positron emission tomography (PET) images were obtained at different time intervals (15-120 minutes). 68 Ga-SCN-Bn-DOTA-capsaicin showed a cellular uptake of 0.93% Injected Dose (ID) after 30 minutes of incubation, whereas 68 Ga-SCN-Bn-DOTA showed a lower uptake of 0.25% ID. The tumor-to-blood ID/g% ratios increased and were found to be 0.49, 0.22, and 0.77 for 15, 30, and 60 minutes, respectively. The small-animal PET study showed that the uptake of 68 Ga-SCN-Bn-DOTA-capsaicin was higher in the tumor regions even at 30 minutes after injection. These results suggest that 68 Ga-SCN-Bn-DOTA-capsaicin is a potential targeting agent for PET imaging of MCF-7.

Dietary capsaicin and its anti-obesity potency: from mechanism to clinical implications

PubMed Central

Zheng, Jia; Zheng, Sheng; Feng, Qianyun; Zhang, Qian

2017-01-01

Obesity is a growing public health problem, which has now been considered as a pandemic non-communicable disease. However, the efficacy of several approaches for weight loss is limited and variable. Thus, alternative anti-obesity treatments are urgently warranted, which should be effective, safe, and widely available. Active compounds isolated from herbs are similar with the practice of Traditional Chinese Medicine, which has a holistic approach that can target to several organs and tissues in the whole body. Capsaicin, a major active compound from chili peppers, has been clearly demonstrated for its numerous beneficial roles in health. In this review, we will focus on the less highlighted aspect, in particular how dietary chili peppers and capsaicin consumption reduce body weight and its potential mechanisms of its anti-obesity effects. With the widespread pandemic of overweight and obesity, the development of more strategies for the treatment of obesity is urgent. Therefore, a better understanding of the role and mechanism of dietary capsaicin consumption and metabolic health can provide critical implications for the early prevention and treatment of obesity. PMID:28424369

Design, synthesis and biological evaluation of novel hydrogen sulfide releasing capsaicin derivatives.

PubMed

Gao, Mingxiang; Li, Jinyu; Nie, Cunbin; Song, Beibei; Yan, Lin; Qian, Hai

2018-05-15

Capsaicin (CAP), the prototypical TRPV1 agonist, is the major active component in chili peppers with health-promoting benefits. However, its use is limited by the low bioavailability and irritating quality. In this study, for improving the activity of CAP and alleviating its irritating effects, a series of H 2 S-releasing CAPs were designed and synthesized by combining capsaicin and dihydro capsaicin with various hydrogen sulfide donors. The resulting compounds were evaluated their TRPV1 agonist activity, analgesic activity, anticancer activities, H 2 S-releasing ability, and gastric mucosa irritation. Biological evaluation indicated that the most active compound B 9 , containing 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H 2 S donor, had better analgesic activity and displayed more potent cytotoxic effects on the test cell lines than the lead compound CAP. Furthermore, the preferred compound, B 9 reduced rat gastric mucosa irritation caused by CAP. Notably, the improved properties of this derivative are associated with its H 2 S-releasing capability. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enhanced bioavailability and bioefficacy of an amorphous solid dispersion of curcumin.

PubMed

Chuah, Ai Mey; Jacob, Bindya; Jie, Zhang; Ramesh, Subbarayan; Mandal, Shibajee; Puthan, Jithesh K; Deshpande, Parag; Vaidyanathan, Vadakkanchery V; Gelling, Richard W; Patel, Gaurav; Das, Tapas; Shreeram, Sathyavageeswaran

2014-08-01

Curcumin has been shown to have a wide variety of biological activities for various human diseases including inflammation, diabetes and cancer. However, the poor oral bioavailability of curcumin poses a significant pharmacological barrier to its use therapeutically and/or as a functional food. Here we report the evaluation of the bioavailability and bio-efficacy of curcumin as an amorphous solid dispersion (ASD) in a matrix consisting of hydroxypropyl methyl cellulose (HPMC), lecithin and isomalt using hot melt extrusion for application in food products. Oral pharmacokinetic studies in rats showed that ASD curcumin was ∼13-fold more bioavailable compared to unformulated curcumin. Evaluation of the anti-inflammatory activity of ASD curcumin in vivo demonstrated enhanced bio-efficacy compared to unformulated curcumin at 10-fold lower dose. Thus ASD curcumin provides a more potent and efficacious formulation of curcumin which may also help in masking the colour, taste and smell which currently limit its application as a functional food ingredient. Copyright © 2014 Elsevier Ltd. All rights reserved.

Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates

PubMed Central

Asad, Abu Bakar Ali; Seah, Stephanie; Baumgartner, Richard; Feng, Dai; Jensen, Andres; Manigbas, Elaine; Henry, Brian; Houghton, Andrea; Evelhoch, Jeffrey L.; Derbyshire, Stuart W. G.; Chin, Chih-Liang

2016-01-01

Background Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored. Methodology Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8). BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle) at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm) application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail). Principal Findings Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the ‘pain matrix’, including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8), while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures. Conclusions These findings provide insights into the specific brain regions involved with aversive, ‘pain-like’, responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain

Enhancement of Curcumin Bioavailability Via the Prodrug Approach: Challenges and Prospects.

PubMed

Ratnatilaka Na Bhuket, Pahweenvaj; El-Magboub, Asma; Haworth, Ian S; Rojsitthisak, Pornchai

2017-06-01

Curcumin is a natural product with many interesting pharmacological properties. However, these are offset by the particularly poor biopharmaceutical properties. The oral bioavailability of curcumin in humans is very low, mainly due to low solubility, poor stability, and extensive metabolism. This has led to multiple approaches to improve bioavailability, including administration of curcumin with metabolism inhibitors, formulation into nanoparticles, modification of the curcumin structure, and development of curcumin prodrugs. In this paper, we focus on the pharmacokinetic outcomes of these approaches. Pharmacokinetic parameters of curcumin after release from prodrugs are dependent on the linker between curcumin and the promoiety, and the release itself may depend on the physiological and enzymatic environment at the site of cleavage. This is an area in which more data are required for rational design of improved linkers. Cytotoxicity of curcumin prodrugs seems to correlate well with cellular uptake in vitro, but the in vivo relevance is uncertain. We conclude that improved experimental and theoretical models of absorption of curcumin prodrugs, development of accurate analytical methods for simultaneous measurement of plasma levels of prodrug and released curcumin, and acquisition of more pharmacokinetic data in animal models for dose prediction in humans are required to facilitate movement of curcumin prodrugs into clinical trials.

Enhanced solubility and targeted delivery of curcumin by lipopeptide micelles.

PubMed

Liang, Ju; Wu, Wenlan; Lai, Danyu; Li, Junbo; Fang, Cailin

2015-01-01

A lipopeptide (LP)-containing KKGRGDS as the hydrophilic heads and lauric acid (C12) as the hydrophobic tails has been designed and prepared by standard solid-phase peptide synthesis technique. LP can self-assemble into spherical micelles with the size of ~30 nm in PBS (phosphate buffer saline) (pH 7.4). Curcumin-loaded LP micelles were prepared in order to increase the water solubility, sustain the releasing rate, and improve the tumor targeted delivery of curcumin. Water solubility, cytotoxicity, in vitro release behavior, and intracellular uptake of curcumin-loaded LP micelles were investigated. The results showed that LP micelles can increase the water solubility of curcumin 1.1 × 10(3) times and sustain the release of curcumin in a low rate. Curcumin-loaded LP micelles showed much higher cell inhibition than free curcumin on human cervix carcinoma (HeLa) and HepG2 cells. When incubating these curcumin-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD (functionalized peptide sequences: Arg-Gly-Asp) sequence to deliver the drug into HeLa cells, and better efficiency of the self-assembled LP micelles for curcumin delivery than crude curcumin was also confirmed by LCSM (laser confocal scanning microscope) assays. Combined with the enhanced solubility and higher cell inhibition, LP micelles reported in this study may be promising in clinical application for targeted curcumin delivery.

Use of the TRPV1 Agonist Capsaicin to Provide Long-Term Analgesia in a Rat Limb Fracture/Open Repair, Internal Fixation Model

DTIC Science & Technology

2012-10-01

W81XWH-10-2-0093 TITLE: Use of the TRPV1 Agonist Capsaicin to Provide Long-Term Analgesia in a Rat Limb Fracture/Open Repair, Internal Fixation Model...2. REPORT TYPE Final 3. DATES COVERED (From - To) 30September2010-29September2012 4. TITLE AND SUBTITLE Use of the TRPV1 Agonist Capsaicin to...capsaicin around the fracture site. 15. SUBJECT TERMS Femur fracture, Rat Model, Pain, Capsaicin, Trauma, TRPV1 16. SECURITY CLASSIFICATION OF

Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aβ40 Insult.

PubMed

Qi, Zhangyang; Wu, Meihao; Fu, Yun; Huang, Tengfei; Wang, Tingting; Sun, Yanjie; Feng, Zhibo; Li, Changzheng

2017-01-01

The generation of reactive oxygen species (ROS) caused by amyloid-β (Aβ) is considered to be one of mechanisms underlying the development of Alzheimer's disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aβ. P-curcumin was prepared through chemical synthesis. Its structure was determined via nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). An MTT assay was used to assess Aβ cytotoxicity and the protective effect of P-curcumin on SH-SY5Y cells. The effect of P-curcumin on Aβ-induced ROS production in vitro and in vivo were assessed based on changes in dichlorofluorescein (DCF) fluorescence. A spectrophotometric method was employed to detect lipid peroxidation. To mimic the interaction of P-curcumin on cell membranes with Aβ, liposomes were prepared by thin film method. Finally, the interactions between free P-curcumin and P-curcumin cultivated on liposomes and Aβ were determined via spectrophotometry. A novel derivative, palmitic acid curcumin ester was prepared and characterized. This curcumin, cultivated on the membranes of neurocytes, may prevent Aβ-mediated ROS production and may inhibit the direct interaction between Aβ and the cellular membrane. Furthermore, P-curcumin could scavenge Aβ-mediated ROS as curcumin in vitro and in vivo, and had the potential to prevent lipid peroxidation. Morphological analyses showed that P-curcumin was better than curcumin at protecting cell shape. To examine P-curcumin's ability to attenuate direct interaction between Aβ and cell membranes, the binding affinity of Aβ to curcumin and P-curcumin was determined. The association

Curcumin Pyrazole and its derivative (N-(3-Nitrophenylpyrazole) Curcumin inhibit aggregation, disrupt fibrils and modulate toxicity of Wild type and Mutant α-Synuclein

PubMed Central

Ahsan, Nuzhat; Mishra, Satyendra; Jain, Manish Kumar; Surolia, Avadhesha; Gupta, Sarika

2015-01-01

Accumulating evidence suggests that deposition of neurotoxic α-synuclein aggregates in the brain during the development of neurodegenerative diseases like Parkinson’s disease can be curbed by anti-aggregation strategies that either disrupt or eliminate toxic aggregates. Curcumin, a dietary polyphenol exhibits anti-amyloid activity but the use of this polyphenol is limited owing to its instability. As chemical modifications in curcumin confiscate this limitation, such efforts are intensively performed to discover molecules with similar but enhanced stability and superior properties. This study focuses on the inhibitory effect of two stable analogs of curcumin viz. curcumin pyrazole and curcumin isoxazole and their derivatives against α-synuclein aggregation, fibrillization and toxicity. Employing biochemical, biophysical and cell based assays we discovered that curcumin pyrazole (3) and its derivative N-(3-Nitrophenylpyrazole) curcumin (15) exhibit remarkable potency in not only arresting fibrillization and disrupting preformed fibrils but also preventing formation of A11 conformation in the protein that imparts toxic effects. Compounds 3 and 15 also decreased neurotoxicity associated with fast aggregating A53T mutant form of α-synuclein. These two analogues of curcumin described here may therefore be useful therapeutic inhibitors for the treatment of α-synuclein amyloidosis and toxicity in Parkinson’s disease and other synucleinopathies. PMID:25985292

Piperine-like alkamides from Piper nigrum induce BDNF promoter and promote neurite outgrowth in Neuro-2a cells.

PubMed

Yun, Young Sook; Noda, Sachie; Takahashi, Shigeru; Takahashi, Yuji; Inoue, Hideshi

2018-01-01

Black pepper (Piper nigrum) contains a variety of alkamides. Among them, piperine has been reported to have antidepressant-like effects in chronically stressed mice, but little is known about the biological activity of other alkamides. In this study, we investigated the effects of alkamides from white pepper (P. nigrum) on neuronal cells. Twelve alkamides were isolated from white pepper MeOH extracts, and their chemical structures were identified by NMR and MS analyses. The compounds were subjected to assays using the luciferase-reporter gene under the control of the BDNF promoter or cAMP response element in mouse neuroblastoma Neuro-2a cells. In both assays, marked reporter-inducing activity was observed for piperine (1), piperettine (2) and piperylin (7), all of which have in common an (E)-5-(buta-1,3-dien-1-yl)benzo[d] [1, 3] dioxole moiety. Piperettine (2) and piperylin (7) tended to increase endogenous BDNF protein levels. Furthermore, piperylin (7) promoted retinoic acid-induced neurite outgrowth. These results suggest that piperylin (7), or analogues thereof, may have a beneficial effect on disorders associated with dysregulation of BDNF expression, such as depression.

Curcumin: getting back to the roots.

PubMed

Shishodia, Shishir; Sethi, Gautam; Aggarwal, Bharat B

2005-11-01

The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots."

Capsaicin induces cystatin S-like substances in submandibular saliva of the rat.

PubMed

Katsukawa, H; Ninomiya, Y

1999-10-01

Irritating dietary substances such as tannin and papain have been reported to alter the morphology of salivary glands and their secretions. Such alterations can be one line of protection from toxic or irritating substances in food. We investigated the effects of dietary capsaicin (a pungent ingredient of hot red pepper) on the rat submandibular gland and its secretions. Several groups of animals were offered either control diets or diets containing capsaicin (from 0.0001 to 0.1%) for seven days. Higher concentrations suppressed food consumption for two days, after which only the highest concentration continued to reduce intake. The relative weight of the salivary glands in capsaicin-diet groups increased in a dose-dependent fashion, and new proteins appeared in the submandibular saliva. Chromatographic and electrophoretic properties of these proteins were identical or similar to those of isoproterenol-induced proteins. After affinity chromatography of the new protein fraction on a Cm-papain Sepharose 4B column, SDS-electrophoresis of the eluate revealed three major bands (15,500, 16,500, and 28,000 kDa). Hydrolysis of N-benzoyl-D,L-arginine-p-nitroanilide by papain (a cysteine protease) decreased in the presence of the new protein fraction, suggesting that these proteins have cystatin-like activity (inhibition of cysteine protease). Denervation of the glossopharyngeal nerve suppressed induction of these proteins. The results suggest that dietary capsaicin induces cystatin S-like substances in submandibular saliva by stimulating the reflex arc involving the glossopharyngeal nerve. These proteins likely facilitate ingestion of diets containing the irritating substance.

Mechanism of curcumin-induced trypsin inhibition: Computational and experimental studies

NASA Astrophysics Data System (ADS)

Wang, Yan-Qing; Zhang, Hong-Mei; Kang, Yi-Jun; Gu, Yun-Lan; Cao, Jian

2016-03-01

In the present study, the experimental and theoretical methods were used to analyze the binding interaction of food dye, curcumin with trypsin. The results of fluorescence spectroscopic measurements indicated that curcumin binding resulted in the obviously intrinsic fluorescence quenching with the increase concentration of curcumin. This binding interaction is a spontaneous process with the estimated enthalpy and entropy changes being -15.70 kJ mol-1 and 40.25 J mol-1 K-1, respectively. Hydrogen bonds and hydrophobic forces played an important role in the complex formation between curcumin and trypsin. Moreover, curcumin could enter into the primary substrate-binding pocket and makes the activity of trypsin decrease remarkably with the increasing concentration of curcumin.

Neutral endopeptidase inhibitors potentiate substance P- and capsaicin-induced cough in awake guinea pigs.

PubMed

Kohrogi, H; Graf, P D; Sekizawa, K; Borson, D B; Nadel, J A

1988-12-01

To study the roles of substance P and endogenous neutral endopeptidase in mediating cough, we measured cough responses in awake guinea pigs in response to exogenous substance P and capsaicin aerosols in the presence and absence of the neutral endopeptidase inhibitors leucine-thiorphan and phosphoramidon. Substance P stimulated cough in very low concentrations (10(-17)-10(-16) M). In a second study where the investigator did not know whether substance P or diluent alone was aerosolized, substance P (10(-16) M) caused cough. Leucine-thiorphan (10(-5) M) and phosphoramidon (10(-5) M) potentiated substance P-induced cough; NEP inhibitors also potentiated capsaicin-induced cough significantly. These findings suggest that substance P is a potent stimulator of cough responses, that capsaicin-induced cough is mediated by substance P or another similar neuropeptide, and that cough responses are modulated by endogenous neutral endopeptidase.

Effect of frusemide on bradykinin- and capsaicin-induced contraction of the guinea-pig trachea.

PubMed

Molimard, M; Advenier, C

1993-03-01

Frusemide, a loop diuretic, inhibits the bronchial response to various bronchoconstrictor stimuli in asthmatic subjects. The underlying mechanisms remain unclear. In order to determine whether frusemide inhibits pharmacologically induced C-fibre stimulation, we investigated the effect of frusemide on bradykinin-, capsaicin-, neurokinin A-, and substance P-induced contraction of the guinea-pig isolated trachea. Frusemide 10(-5) and 10(-4) M produced a significant inhibition of concentration-response curves to bradykinin, which was markedly reduced by indomethacin 10(-6) M. Frusemide significantly reduced capsaicin-induced contraction only in the presence of indomethacin 10(-6) M. Neurokinin A- and substance P-induced contractions were not affected by frusemide and/or indomethacin. Our data suggest that a cyclo-oxygenase pathway is involved in the inhibition by frusemide of the bradykinin-induced contraction, but not in the inhibition of the capsaicin-induced contraction.

[Pharmacological researches of curcumin solid dispersions in treatment of cancer].

PubMed

Mei, Xue-Ting; Xu, Dong-Hui; He, Xue-Ni; Lu, Yong-Chang

2012-10-01

To investigate the anticancer effect of curcumin Solid Dispersions (SDs). Curcumin SDs were prepared by patent technology. The anticancer effect of curcumin SDs were investigated by vivo and vitro tests of SCG-7901, BEL-7402, S-180 and Ehrlich ascites tumor models. The results showed that Curcumin SDs had markedly anticancer effect and could improve the anticancer effect of cisplatin. Curcumin SDs could be developed into one kind of adjuvant drug for anticancer, as it has markedly anticancer effect, and could improve the anticancer effects of cisplatin.

Curcumin Inhibits Tau Aggregation and Disintegrates Preformed Tau Filaments in vitro.

PubMed

Rane, Jitendra Subhash; Bhaumik, Prasenjit; Panda, Dulal

2017-01-01

The pathological aggregation of tau is a common feature of most of the neuronal disorders including frontotemporal dementia, Parkinson's disease, and Alzheimer's disease. The inhibition of tau aggregation is considered to be one of the important strategies for treating these neurodegenerative diseases. Curcumin, a natural polyphenolic molecule, has been reported to have neuroprotective ability. In this work, curcumin was found to bind to adult tau and fetal tau with a dissociation constant of 3.3±0.4 and 8±1 μM, respectively. Molecular docking studies indicated a putative binding site of curcumin in the microtubule-binding region of tau. Using several complementary techniques, including dynamic light scattering, thioflavin S fluorescence, 90° light scattering, electron microscopy, and atomic force microscopy, curcumin was found to inhibit the aggregation of tau. The dynamic light scattering analysis and atomic force microscopic images revealed that curcumin inhibits the oligomerization of tau. Curcumin also disintegrated preformed tau oligomers. Using Far-UV circular dichroism, curcumin was found to inhibit the β-sheets formation in tau indicating that curcumin inhibits an initial step of tau aggregation. In addition, curcumin inhibited tau fibril formation. Furthermore, the effect of curcumin on the preformed tau filaments was analyzed by atomic force microscopy, transmission electron microscopy, and 90° light scattering. Curcumin treatment disintegrated preformed tau filaments. The results indicated that curcumin inhibited the oligomerization of tau and could disaggregate tau filaments.

Capsaicin Displays Anti-Proliferative Activity against Human Small Cell Lung Cancer in Cell Culture and Nude Mice Models via the E2F Pathway

PubMed Central

Hardman, W. Elaine; Luo, Haitao; Chen, Yi C.; Carpenter, A. Betts; Lau, Jamie K.; Dasgupta, Piyali

2010-01-01

Background Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays anti-proliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo. Methodology/Principal Findings BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently suppressed the growth of H69 human SCLC tumors in vivo as ascertained by CAM assays and nude mice models. The second part of our study attempted to provide insight into molecular mechanisms underlying the anti-proliferative activity of capsaicin. We found that the anti-proliferative activity of capsaicin is correlated with a decrease in the expression of E2F-responsive proliferative genes like cyclin E, thymidylate synthase, cdc25A and cdc6, both at mRNA and protein levels. The transcription factor E2F4 mediated the anti-proliferative activity of capsaicin. Ablation of E2F4 levels by siRNA methodology suppressed capsaicin-induced G1 arrest. ChIP assays demonstrated that capsaicin caused the recruitment of E2F4 and p130 on E2F-responsive proliferative promoters, thereby inhibiting cell proliferation. Conclusions/Significance Our findings suggest that the anti-proliferative effects of capsaicin could be useful in the therapy of human SCLCs. PMID:20421925

Thiol Reactivity of Curcumin and Its Oxidation Products.

PubMed

Luis, Paula B; Boeglin, William E; Schneider, Claus

2018-04-16

The polypharmacological effects of the turmeric compound curcumin may be partly mediated by covalent adduction to cellular protein. Covalent binding to small molecule and protein thiols is thought to occur through a Michael-type addition at the enone moiety of the heptadienedione chain connecting the two methoxyphenol rings of curcumin. Here we show that curcumin forms the predicted thiol-Michael adducts with three model thiols, glutathione, N-acetylcysteine, and β-mercaptoethanol. More abundant, however, are respective thiol adducts of the dioxygenated spiroepoxide intermediate of curcumin autoxidation. Two electrophilic sites at the quinone-like ring of the spiroepoxide are identified. Addition of β-mercaptoethanol at the 5'-position of the ring gives a 1,7-dihydroxycyclopentadione-5' thioether, and addition at the 1'-position results in cleavage of the aromatic ring from the molecule, forming methoxyphenol-thioether and a tentatively identified cyclopentadione aldehyde. The curcuminoids demethoxy- and bisdemethoxycurcumin do not form all of the possible thioether adducts, corresponding with their increased stability toward autoxidation. RAW264.7 macrophage-like cells activated with phorbol ester form curcumin-glutathionyl and the 1,7-dihydroxycyclopentadione-5'-glutathionyl adducts. These studies indicate that the enone of the parent compound is not the only functional electrophile in curcumin, and that its oxidation products provide additional electrophilic sites. This suggests that protein binding by curcumin may involve oxidative activation into reactive quinone methide and spiroepoxide electrophiles.

Biological and therapeutic activities, and anticancer properties of curcumin.

PubMed

Perrone, Donatella; Ardito, Fatima; Giannatempo, Giovanni; Dioguardi, Mario; Troiano, Giuseppe; Lo Russo, Lucio; DE Lillo, Alfredo; Laino, Luigi; Lo Muzio, Lorenzo

2015-11-01

Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Curcumin has been used extensively in Ayurvedic medicine, as it is nontoxic and exhibits a variety of therapeutic properties, including antioxidant, analgesic, anti-inflammatory and antiseptic activities. Recently, certain studies have indicated that curcumin may exert anticancer effects in a variety of biological pathways involved in mutagenesis, apoptosis, tumorigenesis, cell cycle regulation and metastasis. The present study reviewed previous studies in the literature, which support the therapeutic activity of curcumin in cancer. In addition, the present study elucidated a number of the challenges concerning the use of curcumin as an adjuvant chemotherapeutic agent. All the studies reviewed herein suggest that curcumin is able to exert anti-inflammatory, antiplatelet, antioxidative, hepatoprotective and antitumor activities, particularly against cancers of the liver, skin, pancreas, prostate, ovary, lung and head neck, as well as having a positive effect in the treatment of arthritis.

Vasomotor response to cold stimulation in human capsaicin-induced hyperalgesic area.

PubMed

Pud, Dorit; Andersen, Ole Kaeseler; Arendt-Nielsen, Lars; Eisenberg, Elon; Yarnitsky, David

2005-07-01

Cooling the skin induces sympathetically driven vasoconstriction, with some vasoparalytic dilatation at the lowest temperatures. Neurogenic inflammation, on the other hand, entails vasodilatation. In this study we investigated the balance between vasoconstriction and vasodilatation in an area of experimentally induced secondary hyperalgesia (2 degrees HA), in response to low-temperature stimulations. Fourteen healthy volunteers were exposed to three 30-s long cold stimuli (20, 10, and 0 degrees C) applied, at three adjacent sites, before (baseline) and 8 min after intradermal injection of 50 microg capsaicin to the volar forearm. The cold stimuli were applied distally to the injection site within the 2 degrees HA. Blood flux (BF) and skin temperatures were measured at four different regions (proximally, and distally to the capsaicin injection and at the 0, 10, and 20 degrees C thermode sites) all within the 2 degrees HA. The vascular measurements were conducted five times. Results showed a marked increase in BF after baseline cold stimulation (P<0.001) at the 0 degrees C compared with the three other sites. In addition, vasodilatory effect (elevated BF) was found following the capsaicin injection compared with baseline for all regions (P<0.001): the non-cooled area was dilated by 450+/-5.1%; The vasoconstrictive effect for the 10 and 20 degrees C did not overcome the capsaicin vasodilatation, but did reduce it, with dilatation of 364+/-7.0% and 329+/-7.3%, respectively. For 0 degrees C, a dilatation of 407+/-6.5% was seen. It is concluded that in this experimental model, and potentially in the equivalent clinical syndromes, vasodilatation induced by the inflammation is only slightly reduced by cold stimulation such that it is still dominant, despite some cold-induced vasoconstriction.

Contribution of capsaicin-sensitive primary afferents to mechanical hyperalgesia induced by ventral root transection in rats: the possible role of BDNF.

PubMed

Li, Wei; Wang, Jian-Xiu; Zhou, Zhong-He; Lu, Yao; Li, Xiao-Qiu; Liu, Bao-Jun; Chen, Hui-Sheng

2016-01-01

A recent study showed that brain-derived neurotrophic factor (BDNF) may play a role in the development of the neuropathic pain resulting from injury to motor efferent fibres, such as that in the ventral root transection (VRT) model. Capsaicin stimulation of afferent fibres was also shown to result in the release of BDNF into the spinal cord. Here, the effects of ablation of capsaicin-sensitive primary afferents (CSPAs) by local application of capsaicin on the sciatic nerve on VRT-induced mechanical hyperalgesia were observed. The paw withdrawal mechanical threshold (PWMT) was measured before and then 1 and 3 days and 1, 2, 3, 4 and 6 weeks after VRT. The results showed that local application of capsaicin significantly inhibited the decrease in the PWMT induced by VRT, suggesting the inhibitory effect of locally delivered capsaicin. Furthermore, intrathecal administration of exogenous BDNF not only produced mechanical hyperalgesia but also significantly blocked the inhibitory effect of capsaicin. Taken together, the results of this study suggest that CSPA fibres may contribute to mechanical hyperalgesia in the VRT model.

Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs.

PubMed

Muñoz-Islas, Enriqueta; González-Hernández, Abimael; Lozano-Cuenca, Jair; Ramírez-Rosas, Martha Beatríz; Medina-Santillán, Roberto; Centurión, David; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

2015-10-01

During migraine, capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Moreover, 5-HT is involved in the pathophysiology of migraine and depression. Interestingly, some limited lines of evidence suggest that fluoxetine may be effective in migraine prophylaxis, but the underlying mechanisms are uncertain. Hence, this study investigated the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine before and after acute and chronic oral treatment with fluoxetine. Forty-eight vagosympathectomised male mongrel dogs were prepared to measure blood pressure, heart rate and external carotid blood flow. The thyroid artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal cannula was inserted (C1-C3) for infusions of 5-HT. The external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine remained unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine, were inhibited after chronic oral treatment with fluoxetine (300 µg/kg; for 90 days) or intrathecal 5-HT. Chronic oral fluoxetine inhibited capsaicin-induced external carotid vasodilatation, and this inhibition could partly explain its potential prophylactic antimigraine action. © International Headache Society 2015.

Preparative separation of capsaicin and dihydrocapsaicin from Capsicum frutescens by high-speed counter-current chromatography.

PubMed

Peng, Aihua; Ye, Haoyu; Li, Xia; Chen, Lijuan

2009-09-01

Capsaicin and dihydrocapsaicin are two main bioactive components of Capsicum frutescens and are widely used as food additives and drugs in China and India. Due to their similarity in structures, isolation of capsaicin and dihydrocapsaicin with traditional methods such as silica gel column chromatography, normal-phase thin-layer chromatography (TLC) becomes difficult. This study involves separating capsaicin and dihydrocapsaicin with sufficient purity and recovery using high-speed counter-current chromatography (HSCCC) with a solvent system composed of n-hexane-ethyl acetate-methanol-water-acetic acid (20:20:20:20:2, v/v/v/v/v). Separation parameters such as sample volume, and sample concentration were first optimized on analytical HSCCC, and then scaled up to preparative HSCCC. 0.65 g capsaicin and 0.28 g dihydrocapsaicin were obtained from 1.2 g crude extract and their purities were 98.5 and 97.8%, respectively. The recoveries of the two compounds were 86.3 and 85.4%, respectively. The purity of the isolated compounds was analyzed by high-performance liquid chromatography (HPLC) and their structures were identified by (1)H nuclear magnetic resonance (NMR) and (13)C NMR analysis.

Curcumin Alleviates the Functional Gastrointestinal Disorders of Mice In Vivo.

PubMed

Yu, Jing; Xu, Wen-Hua; Sun, Wei; Sun, Yi; Guo, Zhi-Li; Yu, Xiao-Ling

2017-12-01

Curcumin is a natural polyphenol extracted from the turmeric rhizome, which has a wide range of biological activities, but until now the effects of curcumin on the gastrointestinal peristalsis have not been fully understood. In vivo study, we observed the effects of curcumin on gastric emptying and intestinal propulsion rates of mice in normal state and in delayed state by atropine (ATR) or nitric oxide precursor L-arginine (L-Arg). An in vitro study explored the direct effects of curcumin on the intestinal contractility, but were studied through measuring spontaneous contraction of isolated jejunum of mice. Our results showed that intragastric administration of curcumin (200 mg/kg/day) for 10-20 days significantly improved gastric emptying and intestinal propulsion rates of mice delayed by ATR. Moreover, intragastric administration of curcumin (200 mg/kg/day) for 15 days also significantly improved mice gastric emptying and intestinal propulsion rates delayed by L-Arg. There was no significant effect on normal gastrointestinal propulsion of mice after intragastric administration of curcumin (200 mg/kg/day) for 1-20 days. When normal isolated jejunum of mice were incubated with curcumin in vitro, the amplitude of the spontaneous contractile waves of jejunum was reduced in a concentration-dependent manner. Moreover, curcumin reduced the amplitude of the contractile waves of jejunum in both contracted and relaxed state induced by acetylcholine or ATR individually. Taken together, our results suggest that curcumin has quite different effects on gastrointestinal peristalsis in vivo and in vitro. Moderate dose of curcumin by intragastric administration for more than 10 days can alleviate the functional gastrointestinal disorders of mice, but cannot affect normal gastrointestinal propulsion.

Curcumin inhibits interferon-γ signaling in colonic epithelial cells

PubMed Central

Midura-Kiela, Monica T.; Radhakrishnan, Vijayababu M.; Larmonier, Claire B.; Laubitz, Daniel; Ghishan, Fayez K.

2012-01-01

Curcumin (diferulolylmethane) is an anti-inflammatory phenolic compound found effective in preclinical models of inflammatory bowel diseases (IBD) and in ulcerative colitis patients. Pharmacokinetics of curcumin and its poor systemic bioavailability suggest that it targets preferentially intestinal epithelial cells. The intestinal epithelium, an essential component of the gut innate defense mechanisms, is profoundly affected by IFN-γ, which can disrupt the epithelial barrier function, prevent epithelial cell migration and wound healing, and prime epithelial cells to express major histocompatibility complex class II (MHC-II) molecules and to serve as nonprofessional antigen-presenting cells. In this report we demonstrate that curcumin inhibits IFN-γ signaling in human and mouse colonocytes. Curcumin inhibited IFN-γ-induced gene transcription, including CII-TA, MHC-II genes (HLA-DRα, HLA-DPα1, HLA-DRβ1), and T cell chemokines (CXCL9, 10, and 11). Acutely, curcumin inhibited Stat1 binding to the GAS cis-element, prevented Stat1 nuclear translocation, and reduced Jak1 phosphorylation and phosphorylation of Stat1 at Tyr701. Longer exposure to curcumin led to endocytic internalization of IFNγRα followed by lysosomal fusion and degradation. In summary, curcumin acts as an IFN-γ signaling inhibitor in colonocytes with biphasic mechanisms of action, a phenomenon that may partially account for the beneficial effects of curcumin in experimental colitis and in human IBD. PMID:22038826

The Effects of Pregabalin and the Glial Attenuator Minocycline on the Response to Intradermal Capsaicin in Patients with Unilateral Sciatica

PubMed Central

Sumracki, Nicole M.; Hutchinson, Mark R.; Gentgall, Melanie; Briggs, Nancy; Williams, Desmond B.; Rolan, Paul

2012-01-01

Background Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes. Aim This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg. Methods/Results Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (−38% in affected leg, 95% CI for difference −19% to −52%). Both hand dominance and sex were significant covariates of response to capsaicin. Conclusions It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may

Nanoparticles Containing Curcumin Useful for Suppressing Macrophages In Vivo in Mice

PubMed Central

Amano, Chie; Minematsu, Hideki; Fujita, Kazuyo; Iwashita, Shinki; Adachi, Masaki; Igarashi, Koichi; Hinuma, Shuji

2015-01-01

To explore a novel method using liposomes to suppress macrophages, we screened food constituents through cell culture assays. Curcumin was one of the strongest compounds exhibiting suppressive effects on macrophages. We subsequently tried various methods to prepare liposomal curcumin, and eventually succeeded in preparing liposomes with sufficient amounts of curcumin to suppress macrophages by incorporating a complex of curcumin and bovine serum albumin. The diameter of the resultant nanoparticles, the liposomes containing curcumin, ranged from 60 to 100 nm. Flow cytometric analyses revealed that after intraperitoneal administration of the liposomes containing curcumin into mice, these were incorporated mainly by macrophages positive for F4/80, CD36, and CD11b antigens. Peritoneal cells prepared from mice injected in vivo with the liposomes containing curcumin apparently decreased interleukin-6-producing activities. Major changes in body weight and survival rates in the mice were not observed after administrating the liposomes containing curcumin. These results indicate that the liposomes containing curcumin are safe and useful for the selective suppression of macrophages in vivo in mice. PMID:26361331

Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin.

PubMed

Ji, Hongyu; Tang, Jingling; Li, Mengting; Ren, Jinmei; Zheng, Nannan; Wu, Linhua

2016-01-01

The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin. The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin. The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of -24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2) of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p < 0.01). The in situ intestinal absorption study revealed that the effective permeability (Peff) value of curcumin for SLNs was significantly improved (p < 0.01) comparing to curcumin solution. Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.

Capsaicin pretreatment enhanced the bioavailability of fexofenadine in rats by P-glycoprotein modulation: in vitro, in situ and in vivo evaluation.

PubMed

Bedada, Satish Kumar; Appani, Ramgopal; Boga, Praveen Kumar

2017-06-01

Capsaicin is the main pungent principle present in chili peppers has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro, which may have the potential to modulate bioavailability of P-gp substrates. Therefore, purpose of this study was to evaluate the effect of capsaicin on intestinal absorption and bioavailability of fexofenadine, a P-gp substrate in rats. The mechanistic evaluation was determined by non-everted sac and intestinal perfusion studies to explore the intestinal absorption of fexofenadine. These results were confirmed by an in vivo pharmacokinetic study of oral administered fexofenadine in rats. The intestinal transport and apparent permeability (P app ) of fexofenadine were increased significantly by 2.8 and 2.6 fold, respectively, in ileum of capsaicin treated rats when compared to control group. Similarly, absorption rate constant (K a ), fraction absorbed (F ab ) and effective permeability (P eff ) of fexofenadine were increased significantly by 2.8, 2.9 and 3.4 fold, respectively, in ileum of rats pretreated with capsaicin when compared to control group. In addition, maximum plasma concentration (C max ) and area under the concentration-time curve (AUC) were increased significantly by 2.3 and 2.4 fold, respectively, in rats pretreated with capsaicin as compared to control group. Furthermore, obtained results in rats pretreated with capsaicin were comparable to verapamil (positive control) treated rats. Capsaicin pretreatment significantly enhanced the intestinal absorption and bioavailability of fexofenadine in rats likely by inhibition of P-gp mediated cellular efflux, suggesting that the combined use of capsaicin with P-gp substrates may require close monitoring for potential drug interactions.

Identification of proteins regulated by curcumin in cerebral ischemia.

PubMed

Shah, Fawad-Ali; Gim, Sang-Ah; Sung, Jin-Hee; Jeon, Seong-Jun; Kim, Myeong-Ok; Koh, Phil-Ok

2016-03-01

Curcumin is known to have a neuroprotective effect against cerebral ischemia. The objective of this study was to identify various proteins that are differentially expressed by curcumin treatment in focal cerebral ischemia using a proteomic approach. Adult male rats were treated with vehicle or curcumin 1 h after middle cerebral artery occlusion. Brain tissues were collected 24 h after the onset of middle cerebral artery occlusion, and cerebral cortices proteins were identified by two-dimensional gel electrophoresis and mass spectrometry. We detected several proteins with altered expression levels between vehicle- and curcumin-treated animals. Among these proteins, ubiquitin carboxy-terminal hydrolase L1, isocitrate dehydrogenase, adenosylhomocysteinase, and eukaryotic initiation factor 4A were decreased in the vehicle-treated animal, and curcumin treatment attenuated the injury-induced decreases of these proteins. Conversely, pyridoxal phosphate phosphatase was increased in the vehicle-treated animal, and curcumin treatment prevented decreases in this protein. The identified altered proteins are associated with cellular metabolism and differentiation. The results of this study suggest that curcumin exerts a neuroprotective effect by regulating the expression of various proteins in focal cerebral ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Curcumin Attenuation of Lipopolysaccharide Induced Cardiac Hypertrophy in Rodents

PubMed Central

Graham, Thomas; Reddy, Gopal

2013-01-01

To study the ameliorating effects of curcumin in lipopolysaccharide (LPS) induced cardiac hypertrophy, mice were assigned to 4 groups (3 males and 3 females in each group): (A) control, (B) curcumin: 100 μg/kg of body weight by intraperitoneal route (IP), (C) LPS: 60 mg/kg (IP), and (D) LPS + curcumin: both at previously stated concentrations by IP route. All mice were sacrificed as 12 hr and 24 hrs groups accordingly after LPS injection. The hearts were collected, photographed for cardiomegaly, and weighed to compare heart weight/brain weight (HW/BW) in mg/mg. For immunohistochemistry, the tissue sections were exposed to histone H3, H4 and acetylated histone H3, H4 antibody. LPS induced a significant increase in histone acetylation as shown by intense staining. In curcumin + LPS treated mice nuclear staining was similar to the control group indicating that curcumin traversed the histone acetylation activity of the LPS. To further check the mechanism of action of curcumin, p300 protein acetylation levels were analyzed. This study suggests that the probable mechanism of action of curcumin is via the reduction of p300 HAT activity. PMID:24236240

Knee joint mobilization reduces secondary mechanical hyperalgesia induced by capsaicin injection into the ankle joint.

PubMed

Sluka, K A; Wright, A

2001-01-01

Joint mobilization is a treatment approach commonly used by physical therapists for the management of a variety of painful conditions. However, the clinical effectiveness when compared to placebo and the neurophysiological mechanism of action are not known. The purpose of this study was to establish that application of a manual therapy technique will produce antihyperalgesia in an animal model of joint inflammation and that the antihyperalgesia produced by joint mobilization depends on the time of treatment application. Capsaicin (0.2%, 50 microl) was injected into the lateral aspect of the left ankle joint and mechanical withdrawal threshold assessed before and after capsaicin injection in Sprague-Dawley rats. Joint mobilization of the ipsilateral knee joint was performed 2 h after capsaicin injection for a total of 3 min, 9 min or 15 min under halothane anaesthesia. Control groups included animals that received halothane for the same time as the group that received joint mobilization and those whose limbs were held for the same duration as the mobilization (no halothane). Capsaicin resulted in a decreased mechanical withdrawal threshold by 2 h after injection that was maintained through 4 h. Both 9 and 15 min of mobilization, but not 3 min of mobilization, increased the withdrawal threshold to mechanical stimuli to baseline values when compared with control groups. The antihyperalgesic effect of joint mobilization lasted 30 min. Thus, joint mobilization (9 or 15 min duration) produces a significant reversal of secondary mechanical hyperalgesia induced by intra-articular injection of capsaicin. Copyright 2001 European Federation of Chapters of the International Association for the Study of Pain.

Tachykinin substance P depletion by capsaicin exacerbates inflammatory response to sidestream cigarette smoke in rats.

PubMed

Sun, Nina N; Wong, Simon S; Keith, Ingegerd; Witten, Mark L

2004-09-01

To evaluate the role of substance P (SP)-containing C-fiber nerves in the development of the inflammatory responses to sidestream cigarette smoke (SSCS), female Fischer 344 rats were randomly assigned into vehicle and capsaicin groups, respectively. Then, half the number in each group (N = 24) was nose-only exposed to air or 0.4 mg/m3 total particulate matter of SSCS for 4 h/day for 7 days. Exposure of the vehicle rats to SSCS induced obvious pulmonary neurogenic inflammation as indicated by elevations in plasma extravasation and proinflammatory cytokine secretions [interieukin (IL)-1beta and IL-12]. In addition, except for SP release, SSCS exposure significantly induced the tachykininergic toxicities at the gene level: upregulation of beta-preprotachykinin-I (beta-PPT-I) mRNA. However, neither SSCS exposure nor capsaicin pretreatment affects the immunolabeling density of neurokinin-1 receptor (NK-1R) in airway epithelium. SSCS also significantly inactivated pulmonary neutral endopeptidase (NEP) in lung tissue. Moreover, pretreatment with capsaicin significantly exacerbated the SSCS-induced inflammatory responses mentioned above as well as the release of plasma protein. Considering that capsaicin did not affect the normal control baselines of these parameters except for a decrease in NK-1R mRNA, we conclude that the degree of SSCS-induced inflammatory response was exacerbated because of the depletion of stored SP and/or inactivation of capsaicin-sensitive C-fiber nerves. Our data suggest the loss of afferent tachykinin SP signaling may lead to dysfunction of the sensory C-fiber nerve reflexes during exposure to SSCS, suggesting that SP serves a protective role.

Depletion of substance P and glutamate by capsaicin blocks respiratory rhythm in neonatal rat in vitro

PubMed Central

Morgado-Valle, Consuelo; Feldman, Jack L

2004-01-01

The specific role of the neuromodulator substance P (SP) and its target, the neurokinin 1 receptor (NK1R), in the generation and regulation of respiratory activity is not known. The preBötzinger complex (preBötC), an essential site for respiratory rhythm generation, contains glutamatergic NK1R-expressing neurones that are strongly modulated by exogenously applied SP or acute pharmacological blockade of NK1Rs. We investigated the effects of capsaicin, which depletes neuropeptides (including SP) and glutamate from presynaptic terminals, on respiratory motor output in medullary slice preparations of neonatal rat that generate respiratory-related activity. Bath application of capsaicin slowed respiratory motor output in a dose- and time-dependent manner. Respiratory rhythm could be restored by bath application of SP or glutamate transporter blockers. Capsaicin also evoked dose-dependent glutamate release and depleted SP in fibres within the preBötC. Our results suggest that depletion of SP (or other peptides) and/or glutamate by capsaicin causes a cessation of respiratory rhythm in neonatal rat slices. PMID:14724197

Depletion of substance P and glutamate by capsaicin blocks respiratory rhythm in neonatal rat in vitro.

PubMed

Morgado-Valle, Consuelo; Feldman, Jack L

2004-03-16

The specific role of the neuromodulator substance P (SP) and its target, the neurokinin 1 receptor (NK1R), in the generation and regulation of respiratory activity is not known. The preBötzinger complex (preBötC), an essential site for respiratory rhythm generation, contains glutamatergic NK1R-expressing neurones that are strongly modulated by exogenously applied SP or acute pharmacological blockade of NK1Rs. We investigated the effects of capsaicin, which depletes neuropeptides (including SP) and glutamate from presynaptic terminals, on respiratory motor output in medullary slice preparations of neonatal rat that generate respiratory-related activity. Bath application of capsaicin slowed respiratory motor output in a dose- and time-dependent manner. Respiratory rhythm could be restored by bath application of SP or glutamate transporter blockers. Capsaicin also evoked dose-dependent glutamate release and depleted SP in fibres within the preBötC. Our results suggest that depletion of SP (or other peptides) and/or glutamate by capsaicin causes a cessation of respiratory rhythm in neonatal rat slices.

Strategies to enhance the bioavailability of curcumin: a potential antitumor drug

NASA Astrophysics Data System (ADS)

Kumar, Abhishek; Chittigori, Joshna; Li, Lian; Samuelson, Lynne; Sandman, Daniel; Kumar, Jayant

2012-02-01

Curcumin is a polyphenol which has elicited considerable interest for its antioxidant and anti tumor properties. Although curcumin may be used as potential therapeutic drug, it is very sparingly soluble in water which makes it less bioavailable under physiological conditions. We report two approaches to make curcumin more bioavailable. The first approach involves fabricating colloidal dispersions of curcumin in the range of tens of nanometers. The second approach involves functionalization of curcumin with polyethylene glycol (PEG) to render it water dispersible or soluble. Since curcumin is a fluorescent molecule as well as a potential drug, its interactions with cells have been investigated using one and two photon confocal fluorescence imaging. We have also observed strong interaction between curcumin and metal ions, which may have physiological implications.

Curcumin as a clinically-promising anti-cancer agent: pharmacokinetics and drug interactions.

PubMed

Adiwidjaja, Jeffry; McLachlan, Andrew J; Boddy, Alan V

2017-09-01

Curcumin has been extensively studied for its anti-cancer properties. While a diverse array of in vitro and preclinical research support the prospect of curcumin use as an anti-cancer therapeutic, most human studies have failed to meet the intended clinical expectation. Poor systemic availability of orally-administered curcumin may account for this disparity. Areas covered: This descriptive review aims to concisely summarise available clinical studies investigating curcumin pharmacokinetics when administered in different formulations. A critical analysis of pharmacokinetic- and pharmacodynamic-based interactions of curcumin with concomitantly administered drugs is also provided. Expert opinion: The encouraging clinical results of curcumin administration are currently limited to people with colorectal cancer, given that sufficient curcumin concentrations persist in colonic mucosa. Higher parent curcumin systemic exposure, which can be achieved by several newer formulations, has important implications for optimal treatment of cancers other than those in gastrointestinal tract. Curcumin-drug pharmacokinetic interactions are also almost exclusively in the enterocytes, owing to extensive first pass metabolism and poor curcumin bioavailability. Greater scope of these interactions, i.e. modulation of the systemic elimination of co-administered drugs, may be expected from more-bioavailable curcumin formulations. Further studies are still warranted, especially with newer formulations to support the inclusion of curcumin in cancer therapy regimens.

Synthetic and Medicinal Prospective of Structurally Modified Curcumins.

PubMed

Kumar, Bhupinder; Singh, Virender; Shankar, Ravi; Kumar, Kapil; Rawal, Ravindra K

2017-01-01

Curcumin, a natural yellow phenolic compound, is present in various types of herbs, particularly in Turmeric, Curcuma longa Linn. (Zingiberaceae family) rhizomes. Curcumin is a polyphenolic natural compound with diverse and attractive biological activities. In the last decade curcumine and its various synthetic analogues have been prepared and evaluated for various pharmacological activities that prove it as a lead molecule against several biological targets. It is a natural antioxidant and exhibited many pharmacological activities such as anti-inflammatory, anti-microbial, anticancer, anti-Alzheimer in both preclinical and clinical studies. Moreover, Curcumin and its analogues have anti-tubercular, cardioprotective, anti-diabetic, hepatoprotective, neuroprotective, nephroprotective, antirheumatic and anti-viral activities. The substitutions of 1,6-heptadiene linkage moiety via carbonyl group sustituion and addition of heterocyclic linker; isoxazole, 1H-pyrazole, cyclopentanone, piperidin-4-one, N-methylpiperidin-4-one enhance biological activities. The structure activity relationship of various curcumin analogues is studied for medicinal purposes and it reveals that monocarbonyl linkage analogues have anticancer properties. The current review gives an insight of the history, chemistry, analogues and most interesting in vitro and in vivo studies on the biological effects of Curcumin and its analogues.

Wound Healing Effects of Curcumin: A Short Review.

PubMed

Tejada, Silvia; Manayi, Azadeh; Daglia, Maria; Nabavi, Seyed F; Sureda, Antoni; Hajheydari, Zohreh; Gortzi, Olga; Pazoki-Toroudi, Hamidreza; Nabavi, Seyed M

Wound healing is a complex process that consists of several phases that range from coagulation, inflammation, accumulation of radical substances, to proliferation, formation of fibrous tissues and collagen, contraction of wound with formation of granulation tissue and scar. Since antiquity, vegetable substances have been used as phytotherapeutic agents for wound healing, and more recently natural substances of vegetable origin have been studied with the attempt to show their beneficial effect on wound treatment. Curcumin, the most active component of rhizome of Curcuma longa L. (common name: turmeric), has been studied for many years due to its bio-functional properties, especially antioxidant, radical scavenger, antimicrobial and anti-inflammatory activities, which play a crucial role in the wound healing process. Moreover, curcumin stimulated the production of the growth factors involved in the wound healing process, and so curcumin also accelerated the management of wound restoration. The aim of the present review is collecting and evaluating the literature data regarding curcumin properties potentially relevant for wound healing. Moreover, the investigations on the wound healing effects of curcumin are reported. In order to produce a more complete picture, the chemistry and sources of curcumin are also discussed.

Curcumin as an amyloid-indicator dye in E. coli.

PubMed

McCrate, Oscar A; Zhou, Xiaoxue; Cegelski, Lynette

2013-05-14

We have demonstrated that curcumin is an amyloid-specific dye in E. coli. Curcumin binds to curliated whole cells and to isolated curli amyloid fibers. Similar to Congo red, curcumin exhibits a red-shift in absorbance and a significant increase in fluorescence upon binding to isolated curli.

Curcumin-loaded polymeric nanoparticles for enhanced anti-colorectal cancer applications.

PubMed

Udompornmongkol, Panisa; Chiang, Been-Huang

2015-11-01

The purpose of the present study was to fabricate polymeric nanoparticles as drug carriers for encapsulated curcumin with enhanced anti-colorectal cancer applications. Nanoparticles were formulated from chitosan and gum arabic, natural polysaccharides, via an emulsification solvent diffusion method. The formation of curcumin nanoparticles was confirmed by Fourier transform infrared spectroscopy and differential scanning calorimeter. The results show that curcumin was entrapped in carriers with +48 mV, 136 nm size, and high encapsulation efficiency (95%). Based on an in vitro release study, we inferred that curcumin nanoparticles could tolerate hydrolysis due to gastric juice or small intestinal enzymes, and therefore, it should reach the colon largely intact. In addition, curcumin nanoparticles had higher anti-colorectal cancer properties than free curcumin due to greater cellular uptake. Therefore, we concluded that curcumin was successfully encapsulated in chitosan-gum arabic nanoparticles with superior anti-colorectal cancer activity. © The Author(s) 2015.

Curcumin prevents human dendritic cell response to immune stimulants

PubMed Central

Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

2012-01-01

Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14+ monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing naïve CD4+ T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant. PMID:18639521

Curcumin prevents human dendritic cell response to immune stimulants

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

Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.

2008-09-26

Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14{sup +} monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays weremore » performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4{sup +} T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant.« less

Curcumin Treatment Improves Motor Behavior in α-Synuclein Transgenic Mice

PubMed Central

Spinelli, Kateri J.; Osterberg, Valerie R.; Meshul, Charles K.; Soumyanath, Amala; Unni, Vivek K.

2015-01-01

The curry spice curcumin plays a protective role in mouse models of neurodegenerative diseases, and can also directly modulate aggregation of α-synuclein protein in vitro, yet no studies have described the interaction of curcumin and α-synuclein in genetic synucleinopathy mouse models. Here we examined the effect of chronic and acute curcumin treatment in the Syn-GFP mouse line, which overexpresses wild-type human α-synuclein protein. We discovered that curcumin diet intervention significantly improved gait impairments and resulted in an increase in phosphorylated forms of α-synuclein at cortical presynaptic terminals. Acute curcumin treatment also caused an increase in phosphorylated α-synuclein in terminals, but had no direct effect on α-synuclein aggregation, as measured by in vivo multiphoton imaging and Proteinase-K digestion. Using LC-MS/MS, we detected ~5 ng/mL and ~12 ng/mL free curcumin in the plasma of chronic or acutely treated mice, with a glucuronidation rate of 94% and 97%, respectively. Despite the low plasma levels and extensive metabolism of curcumin, these results show that dietary curcumin intervention correlates with significant behavioral and molecular changes in a genetic synucleinopathy mouse model that mimics human disease. PMID:26035833

Neuroprotective properties of curcumin in Alzheimer's disease--merits and limitations.

PubMed

Chin, Dawn; Huebbe, Patricia; Pallauf, Kathrin; Rimbach, Gerald

2013-01-01

As demographics in developed nations shift towards an aging population, neurodegenerative pathologies, especially dementias such as Alzheimer's disease, pose one of the largest challenges to the modern health care system. Since there is yet no cure for dementia, there is great pressure to discover potential therapeutics for these diseases. One popular candidate is curcumin or diferuloylmethane, a polyphenolic compound that is the main curcuminoid found in Curcuma longa (family Zingiberaceae). In recent years, curcumin has been reported to possess anti-amyloidogenic, antiinflammatory, anti-oxidative, and metal chelating properties that may result in potential neuroprotective effects. Particularly, the hydrophobicity of the curcumin molecule hints at the possibility of blood-brain barrier penetration and accumulation in the brain. However, curcumin exhibits extremely low bioavailability, mainly due to its poor aqueous solubility, poor stability in solution, and rapid intestinal first-pass and hepatic metabolism. Despite the many efforts that are currently being made to improve the bioavailability of curcumin, brain concentration of curcumin remains low. Furthermore, although many have reported that curcumin possesses a relatively low toxicity profile, curcumin applied at high doses, which is not uncommon practice in many in vivo and clinical studies, may present certain dangers that in our opinion have not been addressed sufficiently. Herein, the neuroprotective potential of curcumin, with emphasis on Alzheimer's disease, as well as its limitations will be discussed in detail.

Photodynamic inactivation of Listeria innocua biofilms with food-grade photosensitizers: a curcumin-rich extract of Curcuma longa vs commercial curcumin.

PubMed

Bonifácio, D; Martins, C; David, B; Lemos, C; Neves, M G P M S; Almeida, A; Pinto, D C G A; Faustino, M A F; Cunha, Â

2018-03-22

The aim of this work is to assess the potential of curcumin in the photosensitization of biofilms of Listeria. Biofilms of Listeria innocua, were irradiated with blue light in the presence of a curcumin-rich extract of Curcuma longa or commercial curcumin. Similar experiments were conducted with planktonic cells, for comparison. A reduction of 4·9 log in the concentration of viable biofilm cells was obtained with 3·7 mg l -1 of commercial curcumin. Planktonic cells were much more susceptible (6·1 log reduction). A tetracationic porphyrin, used as a reference photosensitizer (PS), caused a very modest inactivation of the biofilm (1·1 log) and complete inactivation of the planktonic form (>8 log). Curcumin is an effective PS for the photodynamic control of Listeria biofilms and the inactivation efficiency attained with this natural compound is higher than with the porphyrin. This result may point to a better performance of type I PSs against bacterial biofilms by circumventing the limitations to singlet-oxygen diffusion imposed by the extracellular matrix. Curcumin represents a promising alternative to the control of bacteria and bacterial biofilms in food products particularly in the case of meat products in which turmeric is used as spice. © 2018 The Society for Applied Microbiology.

Beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress, ethanol, indomethacin, and capsaicin neurotoxicity.

PubMed

Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Gjurasin, M; Konjevoda, P; Separović, J; Ljubanović, D; Artuković, B; Bratulić, M; Tisljar, M; Jurina, L; Buljat, G; Miklić, P; Marović, A

1996-08-01

Very recently, the integrity of capsaicin somatosensory neurons and their protection were suggested to be related to the activity in nociception of a newly discovered 15-amino acid peptide, BPC 157, shown to have strong beneficial effect on intestinal and liver lesions. Therefore, from this viewpoint, we have studied the gastroprotective effect of the pentadecapeptide BPC 157, on gastric lesions produced in rats by 96% ethanol, restraint stress, and indomethacin. The possible involvement of sensory neurons in the salutary actions of BPC 157 (10 micrograms/kg, 10 ng/kg intraperitoneally) was studied with capsaicin, which has differential effects on sensory neurons: a high dose in adult (125 mg/kg subcutaneously, 3 months old) or administration (50 mg/kg subcutaneously) to neonatal animals (age of the 7 days) destroys sensory fibers, whereas a low dose (500 micrograms/kg intraperitoneally) activates neurotransmitter release and protective effects on the mucosa. In the absence of capsaicin, BPC 157 protected gastric mucosa against ethanol, restraint, and indomethacin application. In the presence of neurotoxic doses of capsaicin, the negative influence of capsaicin on restraint, ethanol, or indomethacin lesions consistently affected salutary activity of BPC 157. However, BPC 157 protection was still evident in the capsaicin-treated rats (either treated as adults or as newborns) in all of these assays. Interestingly, after neonatal capsaicin treatment, a complete abolition of BPC gastroprotection was noted if BPC 157 was applied as a single nanogram-regimen, but the mucosal protection was fully reversed when the same dose was used daily. In line with the excitatory dose of capsaicin the beneficial effectiveness of BPC 157 appears to be increased as well. Taken together, these data provide evidence for complex synergistic interaction between the beneficial effectiveness of BPC 157 and peptidergic sensory afferent neuron activity.

Curcumin modulates DNA methylation in colorectal cancer cells.

PubMed

Link, Alexander; Balaguer, Francesc; Shen, Yan; Lozano, Juan Jose; Leung, Hon-Chiu E; Boland, C Richard; Goel, Ajay

2013-01-01

Recent evidence suggests that several dietary polyphenols may exert their chemopreventive effect through epigenetic modifications. Curcumin is one of the most widely studied dietary chemopreventive agents for colon cancer prevention, however, its effects on epigenetic alterations, particularly DNA methylation, remain unclear. Using systematic genome-wide approaches, we aimed to elucidate the effect of curcumin on DNA methylation alterations in colorectal cancer cells. To evaluate the effect of curcumin on DNA methylation, three CRC cell lines, HCT116, HT29 and RKO, were treated with curcumin. 5-aza-2'-deoxycytidine (5-aza-CdR) and trichostatin A treated cells were used as positive and negative controls for DNA methylation changes, respectively. Methylation status of LINE-1 repeat elements, DNA promoter methylation microarrays and gene expression arrays were used to assess global methylation and gene expression changes. Validation was performed using independent microarrays, quantitative bisulfite pyrosequencing, and qPCR. As expected, genome-wide methylation microarrays revealed significant DNA hypomethylation in 5-aza-CdR-treated cells (mean β-values of 0.12), however, non-significant changes in mean β-values were observed in curcumin-treated cells. In comparison to mock-treated cells, curcumin-induced DNA methylation alterations occurred in a time-dependent manner. In contrast to the generalized, non-specific global hypomethylation observed with 5-aza-CdR, curcumin treatment resulted in methylation changes at selected, partially-methylated loci, instead of fully-methylated CpG sites. DNA methylation alterations were supported by corresponding changes in gene expression at both up- and down-regulated genes in various CRC cell lines. Our data provide previously unrecognized evidence for curcumin-mediated DNA methylation alterations as a potential mechanism of colon cancer chemoprevention. In contrast to non-specific global hypomethylation induced by 5-aza

Novel water-soluble curcumin derivative mediating erectile signaling.

PubMed

Abdel Aziz, Mohamed Talaat; El Asmer, Mohammed F; Rezq, Ameen; Kumosani, Taha Abdullah; Mostafa, Samya; Mostafa, Taymour; Atta, Hazem; Abdel Aziz Wassef, Mohamed; Fouad, Hanan H; Rashed, Laila; Sabry, Dina; Hassouna, Amira A; Senbel, Amira; Abdel Aziz, Ahmed

2010-08-01

Curcumin is an inducer of heme oxygenase enzyme-1 (HO-1) that is involved in erectile signaling via elevating cyclic guanosine monophosphate (cGMP)levels. To assess the effect of oral administration of a water-soluble long-acting curcumin derivative on erectile signaling. Two hundred and thirty six male white albino rats were divided into four groups; group 1 (N = 20) includes control. Group 2 (N = 72) was equally divided into four subgroups; subgroup 1 received pure curcumin (10 mg/kg), subgroup 2 received the long-acting curcumin derivative (2 mg/kg), subgroup 3 received the long-acting curcumin derivative (10 mg/kg), and subgroup 4 received sildenafil (4 mg/kg). Subgroups were sacrificed after the first, second, and third hour. Group 3 (N = 72) was equally divided into the same four subgroups already mentioned and were sacrificed after 24 hours, 48 hours, and 1 week. Group 4 (N = 72) was subjected to intracavernosal pressure (ICP) measurements 1 hour following oral administration of the same previous doses in the same rat subgroups. Cavernous tissue HO enzyme activity, cGMP, and ICP. In group 2, there was a significant progressive maintained elevation of HO activity and cGMP tissue levels starting from the first hour in subgroups 3 and 4, whereas, the rise in HO activity and cGMP started from second hour regarding the other rat subgroups. Sildenafil effect decreased after 3 hours. In group 3, there was a significant maintained elevation of HO activity and cGMP tissue levels extended to 1 week as compared to controls for all rat subgroups that received both forms of curcumin. In group 4, long-acting curcumin derivative exhibited more significant potentiation of intracavernosal pressure as compared to control and to the pure curcumin. Water-soluble long-acting curcumin derivative could mediate erectile function via upregulating cavernous tissue cGMP. © 2009 International Society for Sexual Medicine.

Curcumin Modulates DNA Methylation in Colorectal Cancer Cells

PubMed Central

Link, Alexander; Balaguer, Francesc; Shen, Yan; Lozano, Juan Jose; Leung, Hon-Chiu E.; Boland, C. Richard; Goel, Ajay

2013-01-01

Aim Recent evidence suggests that several dietary polyphenols may exert their chemopreventive effect through epigenetic modifications. Curcumin is one of the most widely studied dietary chemopreventive agents for colon cancer prevention, however, its effects on epigenetic alterations, particularly DNA methylation, remain unclear. Using systematic genome-wide approaches, we aimed to elucidate the effect of curcumin on DNA methylation alterations in colorectal cancer cells. Materials and Methods To evaluate the effect of curcumin on DNA methylation, three CRC cell lines, HCT116, HT29 and RKO, were treated with curcumin. 5-aza-2′-deoxycytidine (5-aza-CdR) and trichostatin A treated cells were used as positive and negative controls for DNA methylation changes, respectively. Methylation status of LINE-1 repeat elements, DNA promoter methylation microarrays and gene expression arrays were used to assess global methylation and gene expression changes. Validation was performed using independent microarrays, quantitative bisulfite pyrosequencing, and qPCR. Results As expected, genome-wide methylation microarrays revealed significant DNA hypomethylation in 5-aza-CdR-treated cells (mean β-values of 0.12), however, non-significant changes in mean β-values were observed in curcumin-treated cells. In comparison to mock-treated cells, curcumin-induced DNA methylation alterations occurred in a time-dependent manner. In contrast to the generalized, non-specific global hypomethylation observed with 5-aza-CdR, curcumin treatment resulted in methylation changes at selected, partially-methylated loci, instead of fully-methylated CpG sites. DNA methylation alterations were supported by corresponding changes in gene expression at both up- and down-regulated genes in various CRC cell lines. Conclusions Our data provide previously unrecognized evidence for curcumin-mediated DNA methylation alterations as a potential mechanism of colon cancer chemoprevention. In contrast to non

Neutral endopeptidase inhibitors potentiate substance P- and capsaicin-induced cough in awake guinea pigs.

PubMed Central

Kohrogi, H; Graf, P D; Sekizawa, K; Borson, D B; Nadel, J A

1988-01-01

To study the roles of substance P and endogenous neutral endopeptidase in mediating cough, we measured cough responses in awake guinea pigs in response to exogenous substance P and capsaicin aerosols in the presence and absence of the neutral endopeptidase inhibitors leucine-thiorphan and phosphoramidon. Substance P stimulated cough in very low concentrations (10(-17)-10(-16) M). In a second study where the investigator did not know whether substance P or diluent alone was aerosolized, substance P (10(-16) M) caused cough. Leucine-thiorphan (10(-5) M) and phosphoramidon (10(-5) M) potentiated substance P-induced cough; NEP inhibitors also potentiated capsaicin-induced cough significantly. These findings suggest that substance P is a potent stimulator of cough responses, that capsaicin-induced cough is mediated by substance P or another similar neuropeptide, and that cough responses are modulated by endogenous neutral endopeptidase. PMID:2461967

Potency and Stability of Intradermal Capsaicin: Implications for Use as a Human Model of Pain in Multicenter Clinical Trials

PubMed Central

Balabathula, Pavan; Bhattacharjee, Himanshu; Thoma, Laura A; Nolly, Robert J; Horton, Frank P; Stornes, Gwendolyn D; Wan, Jim Y; Brooks, Ian M; Bachmann, Gloria A; Foster, David C; Brown, Candace S

2014-01-01

Intradermally injected capsaicin has been used extensively both as a human pain model and to assess analgesic efficacy. Factors such as dose, formulation, route, and site are known to affect its sensitivity. We determined whether potency and stability of capsaicin solutions were further sources of variability when following strict manufacturing guidelines. Capsaicin solution (1.0 mg/mL) was prepared according to Current Good Manufacturing Practice (cGMP) guidelines and aseptically filled into sterile amber borosilicate vials and stored at 5°C, 25°C, and 30°C. All samples were analyzed at one, three, six, and twelve months. Chemical stability was determined using HPLC and physical stability was evaluated by visual inspection of color changes, clarity, particulate matter, and product/ container closure abnormalities during each sampling time. Capsaicin intradermal injection was found to be sterile and retained 95% of the initial concentration for at least one year, regardless of studied storage temperatures (P<0.0001). Visual inspection indicated no changes in color, clarity, particulate matter, and product/ container closure abnormalities in all samples. These data show that capsaicin solutions (1.0 mg/mL) maintain their potency and stability over one year when manufactured according to cGMP guidelines. These results suggest that in clinical trials manufacturing of capsaicin solutions is recommended over extemporaneous compounding. PMID:25105064

Curcumin and its topical formulations for wound healing applications.

PubMed

Mohanty, Chandana; Sahoo, Sanjeeb K

2017-10-01

Oxidative damage and inflammation have been identified, through clinical and preclinical studies, as the main causes of nonhealing chronic wounds. Reduction of persistent chronic inflammation by application of antioxidant and anti-inflammatory agents such as curcumin has been well studied. However, low aqueous solubility, poor tissue absorption, rapid metabolism and short plasma half-life have made curcumin unsuitable for systemic administration for better wound healing. Recently, various topical formulations of curcumin such as films, fibers, emulsion, hydrogels and different nanoformulations have been developed for targeted delivery of curcumin at wounded sites. In this review, we summarize and discuss different topical formulations of curcumin with emphasis on their wound-healing properties in animal models. Copyright © 2017 Elsevier Ltd. All rights reserved.

The time course of brief and prolonged topical 8% capsaicin-induced desensitization in healthy volunteers evaluated by quantitative sensory testing and vasomotor imaging.

PubMed

Lo Vecchio, Silvia; Andersen, Hjalte Holm; Arendt-Nielsen, Lars

2018-05-29

Topically applied high-concentration capsaicin induces reversible dermo-epidermal denervation and depletion of capsaicin-sensitive nociceptors. This causes desensitization of distinct sensory modalities and is used to treat peripheral neuropathic pain and itch. For high-concentration capsaicin, the selectivity of loss of function and functional recovery rates of various afferent fibers subpopulations are unknown. This study used comprehensive quantitative sensory testing and vasomotor imaging to assess effectiveness, duration and sensory selectivity of high-concentration 8% capsaicin-ablation. Skin areas in 14 healthy volunteers were randomized to treatment with 8% capsaicin/vehicle patches for 1 and 24 h and underwent comprehensive sensory and vasomotor testing at 1, 7 and 21 days postpatch removal. Tests consisted of thermal detection and pain thresholds, tactile and vibration detection thresholds, mechanical pain threshold and mechanical pain sensitivity as well as micro-vascular and itch reactivity to histamine provocations. The 24 h capsaicin drastically inhibited warmth detection (P < 0.001), heat pain (P < 0.001) as well as histamine-induced itch (P < 0.05) and neurogenic flare (P < 0.001), but had no impact on tactile sensitivity, cold detection and cold pain. A marginal decrease in mechanical pain sensitivity was observed (P < 0.05). Capsaicin for 1 h had limited and transient sensory effects only affecting warmth and heat sensations. Time-dependent functional recovery was almost complete 21 days after the 24 h capsaicin exposure, while recovery of neurogenic inflammatory responsiveness remained partial. The psychophysically assessed sensory deficiencies induced by the used 8% capsaicin-ablation correspond well with a predominant effect on TRPV1 + -cutaneous fibers. The method is easy to apply, well tolerated, and utilizable for studies on, e.g., interactions between skin barrier, inflammation and capsaicin-sensitive afferents.

Potential anticancer properties and mechanisms of action of curcumin.

PubMed

Vallianou, Natalia G; Evangelopoulos, Angelos; Schizas, Nikos; Kazazis, Christos

2015-02-01

Curcumin, a yellow substance belonging to the polyphenols superfamily, is the active component of turmeric, a common Indian spice, which is derived from the dried rhizome of the Curcuma longa plant. Numerous studies have demonstrated that curcumin possesses anti-oxidant, anti-inflammatory and anticancerous properties. The purpose of this review is to focus on the anti-tumor effects of curcumin. Curcumin inhibits the STAT3 and NF-κB signaling pathways, which play key-roles in cancer development and progression. Also, inhibition of Sp-1 and its housekeeping gene expressions may serve as an important hypothesis to prevent cancer formation, migration, and invasion. Recent data have suggested that curcumin may act by suppressing the Sp-1 activation and its downstream genes, including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in a concentration-dependent manner in colorectal cancer cell lines; these results are consistent with other studies, which have reported that curcumin could suppress the Sp-1 activity in bladder cancer and could decrease DNA binding activity of Sp-1 in non-small cell lung carcinoma cells. Recent data advocate that ER stress and autophagy may as well play a role in the apoptosis process, which is induced by the curcumin analogue B19 in an epithelial ovarian tumor cell line and that autophagy inhibition could increase curcumin analogue-induced apoptosis by inducing severe ER stress. The ability of curcumin to induce apoptosis in tumor cells and its anti-angiogenic potential will be discussed in this review. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Curcumin Binding to Beta Amyloid: A Computational Study.

PubMed

Rao, Praveen P N; Mohamed, Tarek; Teckwani, Karan; Tin, Gary

2015-10-01

Curcumin, a chemical constituent present in the spice turmeric, is known to prevent the aggregation of amyloid peptide implicated in the pathophysiology of Alzheimer's disease. While curcumin is known to bind directly to various amyloid aggregates, no systematic investigations have been carried out to understand its ability to bind to the amyloid aggregates including oligomers and fibrils. In this study, we constructed computational models of (i) Aβ hexapeptide (16) KLVFFA(21) octamer steric-zipper β-sheet assembly and (ii) full-length Aβ fibril β-sheet assembly. Curcumin binding in these models was evaluated by molecular docking and molecular dynamics (MD) simulation studies. In both the models, curcumin was oriented in a linear extended conformation parallel to fiber axis and exhibited better stability in the Aβ hexapeptide (16) KLVFFA(21) octamer steric-zipper model (Ebinding  = -10.05 kcal/mol) compared to full-length Aβ fibril model (Ebinding  = -3.47 kcal/mol). Analysis of MD trajectories of curcumin bound to full-length Aβ fibril shows good stability with minimum Cα-atom RMSD shifts. Interestingly, curcumin binding led to marked fluctuations in the (14) HQKLVFFA(21) region that constitute the fibril spine with RMSF values ranging from 1.4 to 3.6 Å. These results show that curcumin binding to Aβ shifts the equilibrium in the aggregation pathway by promoting the formation of non-toxic aggregates. © 2015 John Wiley & Sons A/S.

A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin

PubMed Central

Zorofchian Moghadamtousi, Soheil; Abdul Kadir, Habsah; Hassandarvish, Pouya; Tajik, Hassan; Abubakar, Sazaly; Zandi, Keivan

2014-01-01

Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent. PMID:24877064

Oxidative Metabolites of Curcumin Poison Human Type II Topoisomerases†

PubMed Central

Ketron, Adam C.; Gordon, Odaine N.; Schneider, Claus; Osheroff, Neil

2013-01-01

The polyphenol curcumin is the principal flavor and color component of the spice turmeric. Beyond its culinary uses, curcumin is believed to positively impact human health and displays antioxidant, anti-inflammatory, antibacterial, and chemopreventive properties. It also is in clinical trials as an anticancer agent. In aqueous solution at physiological pH, curcumin undergoes spontaneous autoxidation that is enhanced by oxidizing agents. The reaction proceeds through a series of quinone methide and other reactive intermediates to form a final dioxygenated bicyclopentadione product. Several naturally occurring polyphenols that can form quinones have been shown to act as topoisomerase II poisons (i.e., increase levels of topoisomerase II-mediated DNA cleavage). Because several of these compounds have chemopreventive properties, we determined the effects of curcumin, its oxidative metabolites, and structurally related degradation products (vanillin, ferulic acid, and feruloylmethane), on the DNA cleavage activities of human topoisomerase IIα and IIβ. Intermediates in the curcumin oxidation pathway increased DNA scission mediated by both enzymes ~4-5–fold. In contrast, curcumin and the bicyclopentadione, as well as vanillin, ferulic acid, and feruloylmethane, had no effect on DNA cleavage. As found for other quinone-based compounds, curcumin oxidation intermediates acted as redox-dependent (as opposed to interfacial) topoisomerase II poisons. Finally, under conditions that promote oxidation, the dietary spice turmeric enhanced topoisomerase II-mediated DNA cleavage. Thus, even within the more complex spice formulation, oxidized curcumin intermediates appear to function as topoisomerase II poisons. PMID:23253398

Biocompatible Lipid Nanoparticles as Carriers To Improve Curcumin Efficacy in Ovarian Cancer Treatment.

PubMed

Bondì, Maria Luisa; Emma, Maria Rita; Botto, Chiara; Augello, Giuseppa; Azzolina, Antonina; Di Gaudio, Francesca; Craparo, Emanuela Fabiola; Cavallaro, Gennara; Bachvarov, Dimcho; Cervello, Melchiorre

2017-02-22

Curcumin is a natural molecule with proved anticancer efficacy on several human cancer cell lines. However, its clinical application has been limited due to its poor bioavailability. Nanocarrier-based drug delivery approaches could make curcumin dispersible in aqueous media, thus overtaking the limits of its low solubility. The aim of this study was to increase the bioavailability and the antitumoral activity of curcumin, by entrapping it into nanostructured lipid carriers (NLCs). For this purpose here we describe the preparation and characterization of three kinds of curcumin-loaded NLCs. The nanosystems allowed the achievement of a controlled release of curcumin, the amounts of curcumin released after 24 h from Compritol-Captex, Compritol-Miglyol, and Compritol NLCs being, respectively, equal to 33, 28, and 18% w/w on the total entrapped curcumin. Considering the slower curcumin release profile, Compritol NLCs were chosen to perform successive in vitro studies on ovarian cancer cell lines. The results show that curcumin-loaded NLCs maintain anticancer activity, and reduce cell colony survival more effectively than free curcumin. As an example, the ability of A2780S cells to form colonies was decreased after treatment with 5 μM free curcumin by 50% ± 6, whereas, at the same concentration, the delivery of curcumin with NLC significantly (p < 0.05) inhibited colony formation to approximately 88% ± 1, therefore potentiating the activity of curcumin to inhibit A2780S cell growth. The obtained results clearly suggest that the entrapment of curcumin into NLCs increases curcumin efficacy in vitro, indicating the potential use of NLCs as curcumin delivery systems.

Biological actions of curcumin on articular chondrocytes.

PubMed

Henrotin, Y; Clutterbuck, A L; Allaway, D; Lodwig, E M; Harris, P; Mathy-Hartert, M; Shakibaei, M; Mobasheri, A

2010-02-01

Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.

Curcumin AntiCancer Studies in Pancreatic Cancer.

PubMed

Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco

2016-07-16

Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.

Curcumin AntiCancer Studies in Pancreatic Cancer

PubMed Central

Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco

2016-01-01

Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC. PMID:27438851

Capsaicin stimulates the non-store-operated Ca{sup 2+} entry but inhibits the store-operated Ca{sup 2+} entry in neutrophils

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

Wang, J.-P.; Tseng, C.-S.; Sun, S.-P.

2005-12-01

Rat neutrophils express the mRNA encoding for transient receptor potential (TRP) V1. However, capsaicin-stimulated [Ca{sup 2+}]{sub i} elevation occurred only at high concentrations ({>=}100 {mu}M). This response was substantially decreased in a Ca{sup 2+}-free medium. Vanilloids displayed similar patterns of Ca{sup 2+} response with the rank order of potency as follows: scutigeral>resiniferatoxin>capsazepine>capsaicin=olvanil>isovelleral. Arachidonyl dopamine (AAD), an endogenous ligand for TRPV1, failed to desensitize the subsequent capsaicin challenge. Capsaicin-induced Ca{sup 2+} response was not affected by 8-bromo-cyclic ADP-ribose (8-Br-cADPR), the ryanodine receptor blocker, but was slightly attenuated by 1-[6-[17{beta}-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,= 5-dione (U-73122), the inhibitor of phospholipase C-coupled processes, 1-[{beta}-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365), the blockermore » of receptor-gated and store-operated Ca{sup 2+} (SOC) channels, 2-aminoethyldiphenyl borate (2-APB), the blocker of D-myo-inositol 1,4,5-trisphospahte (IP{sub 3}) receptor and Ca{sup 2+} influx, and by ruthenium red, a blocker of TRPV channels, and enhanced by the Ca{sup 2+} channels blocker, cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL-12330A) and Na{sup +}-deprivation. In addition, capsaicin had no effect on the plasma membrane Ca{sup 2+}-ATPase activity or the production of nitric oxide (NO) and reactive oxygen intermediates (ROI) or on the total thiols content. Capsaicin ({>=}100 {mu}M) inhibited the cyclopiazonic acid (CPA)-induced store-operated Ca{sup 2+} entry (SOCE). In the absence of external Ca{sup 2+}, the robust Ca{sup 2+} entry after subsequent addition of Ca{sup 2+} was decreased by capsaicin in CPA-activated cells. Capsaicin alone increased the actin cytoskeleton, and also increased the actin filament content in cell activation with CPA. These results indicate that capsaicin

Curcumin Modulates Pancreatic Adenocarcinoma Cell-Derived Exosomal Function

PubMed Central

Osterman, Carlos J. Diaz; Lynch, James C.; Leaf, Patrick; Gonda, Amber; Ferguson Bennit, Heather R.; Griffiths, Duncan; Wall, Nathan R.

2015-01-01

Pancreatic cancer has the highest mortality rates of all cancer types. One potential explanation for the aggressiveness of this disease is that cancer cells have been found to communicate with one another using membrane-bound vesicles known as exosomes. These exosomes carry pro-survival molecules and increase the proliferation, survival, and metastatic potential of recipient cells, suggesting that tumor-derived exosomes are powerful drivers of tumor progression. Thus, to successfully address and eradicate pancreatic cancer, it is imperative to develop therapeutic strategies that neutralize cancer cells and exosomes simultaneously. Curcumin, a turmeric root derivative, has been shown to have potent anti-cancer and anti-inflammatory effects in vitro and in vivo. Recent studies have suggested that exosomal curcumin exerts anti-inflammatory properties on recipient cells. However, curcumin’s effects on exosomal pro-tumor function have yet to be determined. We hypothesize that curcumin will alter the pro-survival role of exosomes from pancreatic cancer cells toward a pro-death role, resulting in reduced cell viability of recipient pancreatic cancer cells. The main objective of this study was to determine the functional alterations of exosomes released by pancreatic cancer cells exposed to curcumin compared to exosomes from untreated pancreatic cancer cells. We demonstrate, using an in vitro cell culture model involving pancreatic adenocarcinoma cell lines PANC-1 and MIA PaCa-2, that curcumin is incorporated into exosomes isolated from curcumin-treated pancreatic cancer cells as observed by spectral studies and fluorescence microscopy. Furthermore, curcumin is delivered to recipient pancreatic cancer cells via exosomes, promoting cytotoxicity as demonstrated by Hoffman modulation contrast microscopy as well as AlamarBlue and Trypan blue exclusion assays. Collectively, these data suggest that the efficacy of curcumin may be enhanced in pancreatic cancer cells through

Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells

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

Cai, Wenqing; Zhang, Baoxin; Duan, Dongzhu

2012-08-01

The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH, is ubiquitous in all cells and involved in many redox-dependent signaling pathways. Curcumin, a naturally occurring pigment that gives a specific yellow color in curry food, is consumed in normal diet up to 100 mg per day. This molecule has also been used in traditional medicine for the treatment of a variety of diseases. Curcumin has numerous biological functions, and many of these functions are related to induction of oxidative stress. However, how curcumin elicits oxidative stress in cells is unclear. Our previous work has demonstrated the waymore » by which curcumin interacts with recombinant TrxR1 and alters the antioxidant enzyme into a reactive oxygen species (ROS) generator in vitro. Herein we reported that curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells. Curcumin-modified TrxR1 dose-dependently and quantitatively transfers electrons from NADPH to oxygen with the production of ROS. Also, curcumin can drastically down-regulate Trx1 protein level as well as its enzyme activity in HeLa cells, which in turn remarkably decreases intracellular free thiols, shifting the intracellular redox balance to a more oxidative state, and subsequently induces DNA oxidative damage. Furthermore, curcumin-pretreated HeLa cells are more sensitive to oxidative stress. Knockdown of TrxR1 sensitizes HeLa cells to curcumin cytotoxicity, highlighting the physiological significance of targeting TrxR1 by curcumin. Taken together, our data disclose a previously unrecognized prooxidant mechanism of curcumin in cells, and provide a deep insight in understanding how curcumin works in vivo. -- Highlights: ► Curcumin induces oxidative stress by targeting the thioredoxin system. ► Curcumin-modified TrxR quantitatively oxidizes NADPH to generate ROS. ► Knockdown of TrxR1 augments curcumin's cytotoxicity in HeLa cells. �

Role of curcumin in health and disease.

PubMed

Pari, Leelavinothan; Tewas, Daniel; Eckel, Juergen

2008-04-01

Curcumin (diferuloylmethane) is an orange-yellow component of turmeric (Curcuma longa), a spice often found in curry powder. In recent years, considerable interest has been focused on curcumin due to its use to treat a wide variety of disorders without any side effects. It is one of the major curcuminoids of turmeric, which impart its characteristic yellow colour. It was used in ancient times on the Indian subcontinent to treat various illnesses such as rheumatism, body ache, skin diseases, intestinal worms, diarrhoea, intermittent fevers, hepatic disorders, biliousness, urinary discharges, dyspepsia, inflammations, constipation, leukoderma, amenorrhea, and colic. Curcumin has the potential to treat a wide variety of inflammatory diseases including cancer, diabetes, cardiovascular diseases, arthritis, Alzheimer's disease, psoriasis, etc, through modulation of numerous molecular targets. This article reviews the use of curcumin for the chemoprevention and treatment of various diseases.

Nanoparticle Self-Assembled Grain Like Curcumin Conjugated ZnO: Curcumin Conjugation Enhances Removal of Perylene, Fluoranthene, and Chrysene by ZnO

PubMed Central

Moussawi, Rasha N.; Patra, Digambara

2016-01-01

Curcumin conjugated ZnO, referred as Zn(cur)O, nanostructures have been successfully synthesized, these sub-micro grain-like structures are actually self-assemblies of individual needle-shaped nanoparticles. The nanostructures as synthesized possess the wurtzite hexagonal crystal structure of ZnO and exhibit very good crystalline quality. FT-Raman and TGA analysis establish that Zn(cur)O is different from curcumin anchored ZnO (ZnO@cur), which is prepared by physically adsorbing curcumin on ZnO surfaces. Chemically Zn(cur)O is more stable than ZnO@cur. Diffuse reflectance spectroscopy indicates Zn(cur)O have more impurities compared to ZnO@cur. The solid-state photoluminescence of Zn(cur)O has been investigated, which demonstrates that increase of curcumin concentration in Zn(cur)O suppresses visible emission of ZnO prepared through the same method, this implies filling ZnO defects by curcumin. However, at excitation wavelength 425 nm the emission is dominated by fluorescence from curcumin. The study reveals that Zn(cur)O can remove to a far extent high concentrations of perylene, fluoranthene, and chrysene faster than ZnO. The removal depends on the extent of curcumin conjugation and is found to be faster for PAHs having smaller number of aromatic rings, particularly, it is exceptional for fluoranthene with 93% removal after 10 minutes in the present conditions. The high rate of removal is related to photo-degradation and a mechanism has been proposed. PMID:27080002

Design and synthesis of dimethylaminomethyl-substituted curcumin derivatives/analogues: potent antitumor and antioxidant activity, improved stability and aqueous solubility compared with curcumin.

PubMed

Fang, Xubin; Fang, Lei; Gou, Shaohua; Cheng, Lin

2013-03-01

A series of dimethylaminomethyl-substituted curcumin derivatives/analogues were designed and synthesized. All compounds effectively inhibited HepG2, SGC-7901, A549 and HCT-116 tumor cell lines proliferation in MTT assay. Particularly, compounds 2a and 3d showed much better activity than curcumin against all of the four tumor cell lines. Antioxidant test revealed that these compounds had higher free radical scavenging activity than curcumin towards both DPPH and galvinoxyl radicals. Furthermore, the aqueous solubility and stability of the target compounds were also significantly improved compared with curcumin. Copyright © 2013 Elsevier Ltd. All rights reserved.

The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice.

PubMed

Kadekawa, Katsumi; Majima, Tsuyoshi; Shimizu, Takahiro; Wada, Naoki; de Groat, William C; Kanai, Anthony J; Goto, Momokazu; Yoshiyama, Mitsuharu; Sugaya, Kimio; Yoshimura, Naoki

2017-09-01

We examined bladder and urethral sphincter activity in mice with or without spinal cord injury (SCI) after C-fiber afferent desensitization induced by capsaicin pretreatment and changes in electrophysiological properties of mouse bladder afferent neurons 4 wk after SCI. Female C57BL/6N mice were divided into four groups: 1 ) spinal intact (SI)-control, 2 ) SI-capsaicin pretreatment (Cap), 3 ) SCI-control, and 4 ) SCI-Cap groups. Continuous cystometry and external urethral sphincter (EUS)-electromyogram (EMG) were conducted under an awake condition. In the Cap groups, capsaicin (25, 50, or 100 mg/kg) was injected subcutaneously 4 days before the experiments. In the SI-Cap group, 100 mg/kg capsaicin pretreatment significantly increased bladder capacity and decreased the silent period duration of EUS/EMG compared with the SI-control group. In the SCI-Cap group, 50 and 100 mg/kg capsaicin pretreatment decreased the number of nonvoiding contractions (NVCs) and the duration of reduced EUS activity during voiding, respectively, compared with the SCI-control group. In SCI mice, hexamethonium, a ganglionic blocker, almost completely blocked NVCs, suggesting that they are of neurogenic origin. Patch-clamp recordings in capsaicin-sensitive bladder afferent neurons from SCI mice showed hyperexcitability, which was evidenced by decreased spike thresholds and increased firing rate compared with SI mice. These results indicate that capsaicin-sensitive C-fiber afferent pathways, which become hyperexcitable after SCI, can modulate bladder and urethral sphincter activity in awake SI and SCI mice. Detrusor overactivity as shown by NVCs in SCI mice is significantly but partially dependent on capsaicin-sensitive C-fiber afferents, whereas the EUS relaxation during voiding is enhanced by capsaicin-sensitive C-fiber bladder afferents in SI and SCI mice. Copyright © 2017 the American Physiological Society.

Synthesis and antioxidant activity of curcumin analogs.

PubMed

Zheng, Qu-Tong; Yang, Ze-Hua; Yu, Liu-Ying; Ren, Yu-Yan; Huang, Qiu-Xia; Liu, Qiu; Ma, Xiang-Yu; Chen, Zi-Kang; Wang, Zong-Bao; Zheng, Xing

2017-05-01

Numerous biological activities including antioxidant, antitumor, anti-inflammation, and antivirus of the natural product curcumin were reported. However, the clinical application of it was significantly limited by its instability, poor solubility, less body absorbing, and low bioavailability. This review focuses on the structure modification and antioxidant activity evaluation of curcumin. To study the structure-activity relationship (SAR), five series of curcumin analogs were synthesized and their antioxidant activity were evaluated in vitro. The results showed that electron-donating groups, especially the phenolic hydroxyl group are an essential component to improve the antioxidant activity.

Multitargeting by curcumin as revealed by molecular interaction studies

PubMed Central

Gupta, Subash C.; Prasad, Sahdeo; Kim, Ji Hye; Patchva, Sridevi; Webb, Lauren J.; Priyadarsini, Indira K.

2012-01-01

Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca2+ ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its β-diketone moiety, curcumin undergoes keto–enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the α, β-unsaturated β-diketone moiety, carbonyl and enolic groups of the β-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8-naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting

Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia

PubMed Central

Newson, Penny; Lynch-Frame, Ann; Roach, Rebecca; Bennett, Sarah; Carr, Vaughan; Chahl, Loris A

2005-01-01

Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin-sensitive primary afferent neurons might be abnormal in schizophrenia. This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg−1 subcutaneously, or vehicle (control) at 24–36 h of life. At 5–7 weeks behavioural observations were made, and brains removed, fixed and sectioned. The mean body weight of capsaicin-treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control. Capsaicin-treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol. Coronal brain sections of capsaicin-treated rats had smaller cross-sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex. It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia. PMID:16041396

Gingerol Reverses the Cancer-Promoting Effect of Capsaicin by Increased TRPV1 Level in a Urethane-Induced Lung Carcinogenic Model.

PubMed

Geng, Shengnan; Zheng, Yaqiu; Meng, Mingjing; Guo, Zhenzhen; Cao, Ning; Ma, Xiaofang; Du, Zhenhua; Li, Jiahuan; Duan, Yongjian; Du, Gangjun

2016-08-10

Both gingerol and capsaicin are agonists of TRPV1, which can negatively control tumor progression. This study observed the long-term effects of oral administration of 6-gingerol alone or in combination with capsaicin for 20 weeks in a urethane-induced lung carcinogenic model. We showed that lung carcinoma incidence and multiplicity were 70% and 21.2 ± 3.6, respectively, in the control versus 100% and 35.6 ± 5.2 in the capsaicin group (P < 0.01) and 50% and 10.8 ± 3.1 in the 6-gingerol group (P < 0.01). The combination of 6-gingerol and capsaicin reversed the cancer-promoting effect of capsaicin (carcinoma incidence of 100% versus 20% and multiplicity of 35.6 ± 5.2 versus 4.7 ± 2.3; P < 0.001). The cancer-promoting effect of capsaicin was due to increased epidermal growth-factor receptor (EGFR) level by decreased transient receptor potential vanilloid type-1 (TRPV1) level (P < 0.01) . The capsaicin-decreased EGFR level subsequently reduced levels of nuclear factor-κB (NF-κB) and cyclin D1 that favored enhanced lung epithelial proliferation and epithelial-mesenchymal transition (EMT) during lung carcinogenesis (P < 0.01). In contrast, 6-gingerol promoted TRPV1 level and drastically decreased the levels of EGFR, NF-κB, and cyclin D1 that favored reduced lung epithelial proliferation and EMT (P < 0.01). This study provides valuable information for the long-term consumption of chili-pepper-rich diets to decrease the risk of cancer development.

Protective Effects of Curcumin on Manganese-Induced BV-2 Microglial Cell Death.

PubMed

Park, Euteum; Chun, Hong Sung

2017-08-01

Curcumin, a bioactive component in tumeric, has been shown to exert antioxidant, anti-inflammatory, anticarcinogenic, hepatoprotective, and neuroprotective effects, but the effects of curcumin against manganese (Mn)-mediated neurotoxicity have not been studied. This study examined the protective effects of curcumin on Mn-induced cytotoxicity in BV-2 microglial cells. Curcumin (0.1-10 µM) dose-dependently prevented Mn (250 µM)-induced cell death. Mn-induced mitochondria-related apoptotic characteristics, such as caspase-3 and -9 activation, cytochrome c release, Bax increase, and Bcl-2 decrease, were significantly suppressed by curcumin. In addition, curcumin significantly increased intracellular glutathione (GSH) and moderately potentiated superoxide dismutase (SOD), both which were diminished by Mn treatment. Curcumin pretreatment effectively suppressed Mn-induced upregulation of malondialdehyde (MDA), total reactive oxygen species (ROS). Moreover, curcumin markedly inhibited the Mn-induced mitochondrial membrane potential (MMP) loss. Furthermore, curcumin was able to induce heme oxygenase (HO)-1 expression. Curcumin-mediated inhibition of ROS, down-regulation of caspases, restoration of MMP, and recovery of cell viability were partially reversed by HO-1 inhibitor (SnPP). These results suggest the first evidence that curcumin can prevent Mn-induced microglial cell death through the induction of HO-1 and regulation of oxidative stress, mitochondrial dysfunction, and apoptotic events.

Dose-dependent bioavailability indicators for curcumin and two of its novel derivatives.

PubMed

Abd el Aziz, Mohamed; El-Asmer, Mohamed; Rezq, Ameen; Al-Malki, Abdulrahman; Kumosani, Taha; Fouad, Hanan; Ahmed, Hanan; Taha, Fatma; Hassouna, Amira; Hafez, Hafez

2014-01-01

Novel water-soluble curcumin derivatives have been developed to overcome low in vivo bioavailability of curcumin. The aim of this work is to assess the potential utility of certain downstream targets as bioavailability indicators of systemic activity of pure curcumin and two novel water-soluble curcumin derivatives (NCD) by constructing dose-dependent response curves and to prove whether this novel curcumin derivatives retained, improved, or abolished biological activity of pure curcumin when applied in vivo. Pure curcumin (CUR), curcumin-carboxy derivative (NCD-1), and curcumin protein conjugate (NCD-2) were administered orally to rats at escalating doses: 37, 74, 148, and 296 μM/kg body weight, respectively. Plasma levels of GST activity, cavernous tissue levels of cGMP, and enzymatic activity of both HO-1 and GST were assessed one and half and 24 hours after oral administration of curcumin formulae. This study showed that there was a progressive elevation of cavernous tissue levels of cGMP and enzymatic activity of both HO-1 and GST in a dose-dependent manner that was maintained for 24 h with CUR, NCD-1, and NCD-2. Plasma GST activity was decreased by the lowest doses on the curve. The three dose-dependent bioavailability indicators as surrogates of curcumin and two of its novel derivatives are valid in the studied range of concentration and extended time. The novel curcumin derivatives still conserve with improvement the biological activity of natural curcumin when applied in vivo. © 2013 International Union of Biochemistry and Molecular Biology.

Preparation and anti-cancer activity of polymer-encapsulated curcumin nanoparticles

NASA Astrophysics Data System (ADS)

Thu Ha, Phuong; Huong Le, Mai; Nhung Hoang, Thi My; Thu Huong Le, Thi; Quang Duong, Tuan; Tran, Thi Hong Ha; Tran, Dai Lam; Phuc Nguyen, Xuan

2012-09-01

Curcumin (Cur) is a yellow compound isolated from rhizome of the herb curcuma longa. Curcumin possesses antioxidant, anti-inflammatory, anti-carcinogenic and antimicrobial properties, and suppresses proliferation of many tumor cells. However, the clinical application of curcumin in cancer treatment is considerably limited due to its serious poor delivery characteristics. In order to increase the hydrophilicity and drug delivery capability, we encapsulated curcumin into copolymer PLA-TPGS, 1,3-beta-glucan (Glu), O-carboxymethyl chitosan (OCMCs) and folate-conjugated OCMCs (OCMCs-Fol). These polymer-encapsulated curcumin nanoparticles (Cur-PLA-TPGS, Cur-Glu, Cur-OCMCs and Cur-OCMCs-Fol) were characterized by infrared (IR), fluorescence (FL), photoluminescence (PL) spectra, field emission scanning electron microscopy (FE-SEM), and found to be spherical particles with an average size of 50-100 nm, being suitable for drug delivery applications. They were much more soluble in water than not only free curcumin but also other biodegradable polymer-encapsulated curcumin nanoparticles. The anti-tumor promoting assay was carried out, showing the positive effects of Cur-Glu and Cur-PLA-TPGS on tumor promotion of Hep-G2 cell line in vitro. Confocal microscopy revealed that the nano-sized curcumin encapsulated by polymers OCMCs and OCMCs-Fol significantly enhanced the cellular uptake (cancer cell HT29 and HeLa).

[Preliminary study on molecular mechanism of curcumine anti-mouse melanoma].

PubMed

Gui, Fei; Ma, Wei-Feng; Cai, Shao-Hui; Li, Xiao-Kun; Tan, Yi; Zhou, Chun-Ling; Chen, Hong-Yuan

2008-11-01

To investigate the effects of curcumine on mouse B16 melanoma growth and possible mechanism of Bcl-2, P53 and glutathione in tumor cells. The inhibitory effect on growth of melanoma in vivo were examined by mice melanoma models transplanted B16 cells to C57BL/6J mice. MTT method was used to assay the contribution of curcumine to B16 cells in vitro. The apoptosis and expression of Bcl-2, P53 gene of B16 cells were analyzed by flow cytometry, and HPLC assay was used to detect the change of GSH in B16 melanom tissues of C57BL/6J mouse caused by curcumine. Curcumine had obvious inhibitory effect on the growth of mouse B16 melanoma in time and dose dependent manner and the gene expression of bcl-2 in B16 cells decreased after 24 hours supplied with curcumine, whereas P53 protein expression increased; Curcumine depressed the GSH quantity in melanoma tissues. The growth inhibitory effect of curcumine on mouse melanom is proved in vivo and in vitro respectively. Curcumine can induce some cells to apoptosis which may be relevant to downregulation of bcl-2 expression and upregulation of P53 expression as well as exhaustion of GSH in tumor organization.

Curcumin inhibits cancer progression through regulating expression of microRNAs.

PubMed

Zhou, Siying; Zhang, Sijie; Shen, Hongyu; Chen, Wei; Xu, Hanzi; Chen, Xiu; Sun, Dawei; Zhong, Shanliang; Zhao, Jianhua; Tang, Jinhai

2017-02-01

Curcumin, a major yellow pigment and spice in turmeric and curry, is a powerful anti-cancer agent. The anti-tumor activities of curcumin include inhibition of tumor proliferation, angiogenesis, invasion and metastasis, induction of tumor apoptosis, increase of chemotherapy sensitivity, and regulation of cell cycle and cancer stem cell, indicating that curcumin maybe a strong therapeutic potential through modulating various cancer progression. It has been reported that microRNAs as small noncoding RNA molecules are related to cancer progression, which can be regulated by curcumin. Dysregulated microRNAs play vital roles in tumor biology via regulating expressions of target genes and then influencing multiple cancer-related signaling pathways. In this review, we focused on the inhibition effect of curcumin on various cancer progression by regulating expression of multiple microRNAs. Curcumin-induced dysregulation of microRNAs may activate or inactivate a set of signaling pathways, such as Akt, Bcl-2, PTEN, p53, Notch, and Erbb signaling pathways. A better understanding of the relation between curcumin and microRNAs may provide a potential therapeutic target for various cancers.

Amoebicidal activity of curcumin on Entamoeba histolytica trophozoites.

PubMed

Rangel-Castañeda, Itzia Azucena; Hernández-Hernández, José Manuel; Pérez-Rangel, Armando; González-Pozos, Sirenia; Carranza-Rosales, Pilar; Charles-Niño, Claudia Lisette; Tapia-Pastrana, Gabriela; Ramírez-Herrera, Mario Alberto; Castillo-Romero, Araceli

2018-03-01

This study was undertaken to investigate the amoebicidal potential of curcumin on Entamoeba histolytica, as well as its synergistic effect with metronidazole. Entamoeba histolytica trophozoites were exposed to 100, 200 and 300 μm of curcumin, for 6, 12 and 24 h. Consequently, the viability of cells was determined by trypan blue exclusion test. All specimens were further analysed by scanning electron microscopy. For drug combination experiment, the Chou-Talalay method was used. Curcumin affected the growth and cell viability in a time- and dose-dependent manner. The higher inhibitory effects were observed with 300 μm at 24 h; 65.5% of growth inhibition and only 28.8% of trophozoites were viable. Additionally, curcumin also altered adhesion and the morphology of the trophozoites. Scanning electron microscopy revealed treated trophozoites with damages on the membrane, size alterations and parasites with loss of cellular integrity. In addition, the combination of curcumin + metronidazole exhibited a synergistic effect; the activity of both drugs was improved. This is the first report evaluating the effectiveness of curcumin against E. histolytica. Our results suggest that CUR could be considered for evaluation in future pharmacological studies as a promising amoebicidal agent or as complementary therapy. © 2018 Royal Pharmaceutical Society.

The photo- and electrophysical properties of curcumin in aqueous solution

NASA Astrophysics Data System (ADS)

Kim, Sung-Hoon; Gwon, Seon-Yeong; Burkinshaw, S. M.; Son, Young-A.

2010-08-01

An investigation of the photo- and electrophysical properties of curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione) revealed well-defined color changes upon the addition of Hg 2+ or OH -. Curcumin exhibited high selectivity for Hg 2+ ions, as compared with Cu 2+, Fe 2+, Fe 3+, Zn 2+, Na + and Ni 2+ ions in DMSO/H 2O (5:1, v/v) which was attributed to the formation of a 4:1 Hg 2+-curcumin coordination complex. Spectral responses at λmax = 434 nm revealed that curcumin can function as a NOR logic gate with OH - and Hg 2+ as input variables. The electrochromic properties of curcumin were studied using an ITO/curcumin-Bu 4NClO 4/ITO cell. The electrochromic cell colored red at 3 V, but changed to yellow in open-circuit condition.

Effects of Stable Degradation Products of Curcumin on Cancer Cell Proliferation and Inflammation.

PubMed

Sanidad, Katherine Z; Zhu, Julia; Wang, Weicang; Du, Zheyuan; Zhang, Guodong

2016-12-07

Curcumin is among the most promising dietary compounds for cancer prevention. However, curcumin rapidly degrades in aqueous buffer at physiological pH, making it difficult to understand whether the effects of curcumin are from curcumin itself or its degradation products. Here we studied the antiproliferative and anti-inflammatory effects of curcumin degradation products, including its total degradation products (a mixture containing all stable degradation products of curcumin) and bicyclopentadione (a dominant stable degradation compound of curcumin). Curcumin potently modulated cell proliferation, progression of cell cycle, and apoptosis in MC38 colon cancer cells and inhibited lipopolysaccharide (LPS)-induced inflammatory responses and NF-κB signaling in RAW 264.7 macrophage cells. In contrast, neither the total degradation products of curcumin nor bicyclopentadione had such effects. For example, after 24 h of treatment in MC38 colon cancer cells, 5 μg/mL curcumin inhibited 39.2 ± 1.8% of cell proliferation, whereas its degradation products were inactive. Together, these results suggest that the stable chemical degradation products of curcumin are not likely to play a major role in mediating the biological activities of curcumin.

Estimation of capsaicin through scanning densitometry and evaluation of different varieties of capsicum in India.

PubMed

Gantait, Arunava; Maji, Amal; Barman, Tapu; Banerji, Pratim; Venkatesh, P; Mukherjee, Pulok K

2012-01-01

Capsicum annuum L. (family: Solanaceae) possesses therapeutic benefits for the treatment of rheumatism, neuropathy, psoriasis, flatulence and so on. In this study fruits of four different varieties of C. annuum from four different geographical regions in India were evaluated based on their total content of capsaicin. Ethanol extracts of the fruits were used. HPTLC plates were developed in a mobile phase containing benzene, ethyl acetate and methanol (75:20:5). Densitometric scanning was performed at a wavelength of 283 nm in the absorbance mode. The calibration curve was described by the equation Y=393.587+3.836*X with a correlation coefficient (r) of 0.99890. The content of capsaicin in Nagaland, Manipur, West Bengal and Shimla varieties was found to be 3.71%, 1.78%, 0.54% and 0.06%, respectively. The developed densitometric method was found to be specific, accurate and precise. A recovery study and precision showed low levels of %RSD values. The linearity range of the curve for capsaicin was found to be 300-900 ng per spot. The limit of detection and the limit of quantification values were determined to be 31 and 94 ng, respectively, proving the sensitivity of the method. Thus the method can be used to control the total content of capsaicin on an industrial scale.

Tachykinin antagonist FK224 inhibits neurokinin A-, substance P- and capsaicin-induced human bronchial contraction.

PubMed

Honda, I; Kohrogi, H; Yamaguchi, T; Hamamoto, J; Hirata, N; Iwagoe, H; Fujii, K; Goto, E; Ando, M

1997-01-01

To determine the roles of endogenously released tachykinins (substance P [SP] and neurokinin A [NKA]) in the human bronchial tissues, we studied the effects of tachykinin antagonist FK224 on bronchial smooth muscle contraction induced by SP, NKA and capsaicin in an organ bath. FK224 (10(-6) M and 10(-5) M, respectively) significantly inhibited NKA-induced contraction and 10(-5) M FK224 shifted the dose-response curve to more than one log unit higher concentration. Because SP- and capsaicin-induced contractions were small, we pretreated the tissues with the neutral endopeptidase inhibitor phosphoramidon (10(-5) M), which inhibits degradation of exogenous tachykinins in order to potentiate the contractions. FK224 (10(-5) M) significantly inhibited SP-induced contraction and it shifted the dose-response curves to about one log unit higher concentration. FK224 (10(-5) M) also significantly inhibited capsaicin-induced contraction and it shifted the dose-response curves to more than one log unit higher concentration. In contrast, FK224 (10(-5) M) did not affect on acetylcholine-, histamine-, and leukotriene D4-induced contraction. These results suggest that FK224 is a tachykinin receptor antagonist in the human bronchial smooth muscle, and that capsaicin-induced contraction is due to endogenously released tachykinin-like substances in the human bronchus.

Capsaicin-induced reactivation of latent herpes simplex virus type 1 in sensory neurons in culture.

PubMed