Pungent Component Of Chili Pepper Research Articles

Effects of Capsaicin on Migration and Alkaline Phosphatase Activity of Dental Pulp Cells.

Dental pulp, a specialized mesenchymal tissue within teeth, is pivotal in dental health and tissue repair. Capsaicin, the primary pungent component of chili peppers, is known for its diverse pharmacological properties. While capsaicin's effects on various cell types have been studied, its impact on dental pulp cells remains relatively unexplored. This study investigated the influence of pure capsaicin extract on dental pulp cell behavior, focusing on cell viability, proliferation, migration, and alkaline phosphatase (ALP) activity. Capsaicin solution was prepared and diluted to various concentrations (1 nM, 0.01 µM, 0.1 µM, 1 µM, 10 µM, and 100 µM), then was tested on rat dental pulp cells (RPC-C2A). Cell viability and proliferation were assessed using the MTT assay. Boyden chamber tests and wound healing were used for evaluating cell migration. The activity of ALP was determined to show cell function during dental pulp repair. The data were analyzed using a one-way analysis of variance or an independent-sample Kruskal-Wallis, followed by multiple comparison tests. Capsaicin of 100 µM exhibited cytotoxicity, whereas those with lower concentrations stimulated cell proliferation. Wound healing assays revealed increased cell migration, particularly when cultured with 1 nM capsaicin (p = 0.002). Boyden chamber assays demonstrated enhanced cell invasion without statistical significance. ALP activity of dental pulp cells increased significantly at 1 nM (p < 0.001) and 1 µM (p = 0.021) capsaicin concentrations, indicating potential dentinogenesis and pulp repair. Capsaicin of lower concentrations, less than 10 µM, is likely to promote proliferation, migration, and ALP activity of dental pulp cells. Our findings offer potential applications for capsaicin as a medication for dental pulp repair.

Capsaicin improves hypertension and cardiac hypertrophy via SIRT1/NF-κB/MAPKs pathway in the hypothalamic paraventricular nucleus

BackgroundHypertension has seriously affected a large part of the adult and elderly population. The complications caused by hypertension are important risk factors for cardiovascular disease accidents. Capsaicin, a pungent component of chili pepper has been revealed to improve hypertension. However, its potential mechanism in improving hypertension remains to be explored. PurposeIn the present study, we aimed to investigate whether capsaicin could attenuate the SIRT1/NF-κB/MAPKs pathway in the paraventricular nucleus of hypothalamus (PVN). MethodsWe used spontaneous hypertensive rats (SHRs) as animal model rats. Micro osmotic pump was used to give capsaicin through PVN for 28 days, starting from age12-week-old. ResultsThe results showed that capsaicin significantly reduced blood pressure from the 16th day of infusion onward. At the end of the experimental period, we measured cardiac hypertrophy index and the heart rate (HR), and the results showed that the cardiac hypertrophy and heart rate of rats was significantly improved upon capsaicin chronic infusion. Norepinephrine (NE) and epinephrine (EPI) in plasma of SHRs treated with capsaicin were also decreased. Additionally, capsaicin increased the protein expression and number of positive cells of SIRT1 and the 67-kDa isoform of glutamate decarboxylase (GAD67), decreased the production of reactive oxygen species (ROS), number of positive cells of NOX2, those of Angiotensin Converting Enzyme (ACE) and p-IKKβ, tyrosine hydroxylase (TH), the gene expression levels of NOX4 and pro-inflammatory cytokines. Capsaicin also decreased the relative protein expressions of protein in MAPKs pathway. ConclusionCurrent data indicated that capsaicin within the PVN improves hypertension and cardiac hypertrophy via SIRT1/NF-κB/MAPKs pathway in the PVN of SHRs, supporting its potential as candidate drug for preventing and improving hypertension.

Getting hot: Effect of chili pepper addition on sensory perception of liquid and solid foods.

The impact of trigeminal oral burn and pungency on taste, flavor, and mouth-feel perception of commercially available foods is underexplored. This study aimed to determine the effect of oral burn sensations evoked by the addition of chili powder to tomato soup, beef burger patties, and curried rice on taste, flavor, and mouth-feel perception. Chili powder was added to tomato soups, beef burger patties, and curried rice at four concentrations. A consumer panel comprising n=66 participants (49 women, 25.5±5.8 years, BMI 22.9±2.8kg/m2 ) assessed taste, flavor, trigeminal, and mouth-feel intensity of all samples using Rate-All-That-Apply methodology. Food matrix consistency strongly impacted oral burn sensations with solid food matrices (beef burger patties and curried rice) suppressing oral burn intensity compared to liquid food matrices (tomato soup). With increasing oral burn intensity, perceived intensity of beef flavor decreased significantly for beef burger patties. Tomato flavor, sweetness, and sourness intensity decreased significantly with increasing oral burn intensity for tomato soups. Perceived burn intensity of all food matrices and beef flavor intensity of beef burger patties differed between infrequent and frequent chili pepper consumers. We conclude that increasing oral burn intensity by the addition of chili pepper powder led to only small reductions in taste and flavor intensity of tomato soups and to little or no changes in flavor and mouth-feel perception of beef burger patties and curried rice. We suggest that reductions in taste, flavor, and mouth-feel intensity caused by oral burn might be more pronounced in liquid (tomato soup) than solid foods (beef burger patties and curried rice). PRACTICAL APPLICATION: There is a growing public and scientific interest in the development of strategies to increase the sensory appeal of healthy foods and beverages. Incorporation of trigeminal stimuli, such as chili peppers or capsaicin (pungent component of chili peppers), can be a strategy to increase sensory appeal of foods and beverages. Little is known about how trigeminal oral burn and pungency influence taste, flavor, and mouth-feel perception of commercially available foods, although it has been well established that taste, flavor, mouth-feel, and trigeminal sensations contribute to product acceptance. By investigating the sensory impact of oral burn on flavor and mouth-feel perception of foods, this study may help to better understand how trigeminal stimuli can be applied to moderate flavor and mouth-feel perception of foods to optimize sensory appeal.

Beyond Thermal Sensation: Roles of Transient Receptor Potential Vanilloid Subfamily Member 1 and Spicy Food in Cardiometabolic Diseases

Beyond Thermal Sensation: Roles of Transient Receptor Potential Vanilloid Subfamily Member 1 and Spicy Food in Cardiometabolic Diseases

The science of “smell” and the noble for “hugs:” making “sense?”

David Julius and Ardem Patapoutian were jointly awarded the 2021 Nobel Prize in Physiology and Medicine for their discoveries of receptors for temperature and touch. It was a phenomenal moment for the scientific community, more for the discovery that forms the basic fabric of our everyday life—ever imagined how life would have been without feeling the aroma around? Or even the dangers of accidentally touching a heated object. Dr Julius and Dr Patapoutian, independently discovered key mechanisms of how living organisms sense heat, cold, and touch. The journey started when Dr Julius, at the University of California, San Francisco, used a key ingredient in hot chili peppers to identify a protein in nerve cells that respond to these stimuli. Using capsaicin, the pungent component of chili peppers, he provided fundamental insights into mechanisms of pain. Then using a meticulous cDNA library-based functional screening from sensory neurons to search for the gene(s) that could confer capsaicin sensitivity, Dr Julius identified for the first time a novel ion channel (now called transient receptor potential [TRP] vanilloid 1) belonging to the family of TRP ion channels associated with the pain sensitivity. A painful exercise indeed! While Prof Julius was exploring the oceans and skies to hunt for sensory pain pathways, quite independently, Dr Patapoutian of Scripps Research Institute La Jolla, California, was searching for a similar thing that seemed to bother him equally. How do we sense touches? After all, there are so many emotions packaged in this small five-letter word, touch. The mother’s touch is the first sensation that every single of us always cherishes. Dr Patapoutian research is centered around finding candidate genes in a mechanosensitive cell line that could respond to mechanical stimuli. After a thorough search, the team identified two mechanically-activated ion channels, PIEZO1 and PIEZO2, representing an entirely novel class of mechanical sensors-based ion channels. What is fascinating is the idea that discovery of the smell and touch receptor stretches far beyond just touch and temperature sensations only. Mutations in other TRP channels are involved in neurodegenerative disorders and skeletal dysplasia, while mutations in PIEZO channels help control critical functions such as respiration and blood pressure regulation. So now, the mysterious world surrounding us looks more transparent and clearer. The molecular landscape is defined with precision. We now have a chemical entity behind all these emotions and intuition. The warm hug that makes our day is now millions of ions crisscrossing the ion channels. There is a different side to this too. How will the world look if everything is defined as a chemical entity? Won’t we lose the charm? After all, so much within the subtleness remains charmful when wrapped within the veil of ignorance. Knowing too much about something steals the show.

A simple and affordable method for estimating the fluid volume a mosquito sucks using food dyes

BackgroundBlood-sucking by mosquitoes is an inevitable behavior when pathogens are transmitted among humans. Adenine nucleotides such as ATP are known as phagostimulants for mosquitoes and are widely used to induce and enhance the blood-sucking activity in an artificial manner. Although using ATP solution is convenient to introduce a variety of substances (for example chemicals and pathogens) into the mosquito body via sucking, establishing an easy and cost-effective method to quantify the amount of solution ingested has yet to be reported.ResultsA set of commercial food dyes (green, blue, yellow, and red) was employed in this study. Each dye was added to ATP solution used to colorize the abdomen of Ae. aegypti female mosquitoes after ingestion. The intake of food dyes did not show any toxicity to the mosquitoes, affecting neither ATP-sucking behavior nor survival of the mosquitoes. We observed that quantifying the color intensity of green dye in the mosquito abdomen by spectral analysis, as well as distinguishing the size of the colored abdomen using the naked eye, allowed the estimation of the amount of ingested solution. Using this method, capsaicin, a pungent component of chili peppers, was identified as an aversive tastant that can discourage mosquitoes from sucking the ATP solution.ConclusionsEmploying commercially available, non-toxic food dyes converted ATP-driven membrane feeding into an easy-to-use method to estimate the amount of solution ingested by mosquitoes. This method can be further applied for a variety of experiments such as introducing a certain quantity of chemical compounds or microbes into the mosquito body.

The third dimension of flavor: A chemesthetic approach to healthier eating (a review)

AbstractObesity and obesity‐related illness are an increasingly prevalent problem globally, especially in Western society. One of the largest contributing factors to the obesity pandemic is the modern food environment and food culture. It is necessary to identify and develop strategies to increase the sensory appeal of healthy food and beverage options in order to provide healthy options to consumers without sacrificing the fundamental sensory enjoyment of eating. Since flavor is the largest driver of food intake and choice, it follows that flavor ought to be part of the solution. This paper reviews the potential of chili pepper or capsaicin (the pungent component of chili pepper) as a healthy eating strategy, by increasing energy expenditure, decreasing intake, decreasing eating rate, and enhancing flavor and satisfaction. Furthermore, we suggest a holistic chemesthetic approach to weight management, by using the sensory impact of trigeminal stimulation (spiciness or heat) in foods, rather than medicinally, in order to cross‐modally enhance tastes and odors, increase perceived complexity and overall flavor, increase sensory satisfaction, and decrease salt and caloric intake. Future research directions are discussed.Practical ApplicationIt is necessary to provide strategies, such as trigeminal stimulation, global culinary practices, and flavor complexity, to consumers to maintain sensory satisfaction derived from healthier foods and beverages. Healthy does not have to equate to flavorless or unappealing, although it is commonly believed that unhealthy = tasty in the United States. Food can be both healthy and flavorful if we harness our collective sensory and culinary knowledge to generate a satisfying sensory experience. Incorporation of trigeminal stimulation, the third dimension of flavor in addition to taste and aroma, such as capsaicin or hot pepper, is an excellent example of drawing from global cuisines, increasing flavor complexity, and increasing overall flavor impression, in order to boost the sensory appeal, nutrition content, and nutrient absorption of healthy foods and to promote healthier eating.

Dietary capsaicin-mediated attenuation of hypertension in a rat model of renovascular hypertension

ABSTRACTBackground: Capsaicin, a pungent component of chili pepper, has been reported to decrease blood pressure (BP) and to cause vasorelaxation via nitric oxide (NO) production. However, it is still unclear how dietary capsaicin effects on renovascular hypertension. To examine this, we observed the effects of dietary capsaicin on BP in 2-kidney, 1-clip renovascular hypertension (2K1C) rats, and investigated the participation of NO in the mechanism.Methods: Rats with 2K1C or sham-operated rats (SHAM) were treated with 0.006% capsaicin diet (CAP) or control diet (CTL) for 6 weeks. Systolic BP (SBP) was measured by tail-cuff method once a week. In the end, mean arterial BP (MAP) was measured in the rats under anesthesia. These observations were performed also in the rats taking a NO synthase (NOS) inhibitor (LN). After rats were euthanized, thoracic aortas were collected and used for western blot analyses to evaluate the phosphorylated ratio of endothelial NOS (eNOS), protein kinase A (PKA) and B (Akt), in order to explore a mechanism of the effects on BP by dietary capsaicin.Results: SBP and MAP in 2K1C rats were significantly higher than in SHAM rats when fed CTL, but not when fed CAP. Those in 2K1C-CAP rats were significantly lower than in 2K1C-CTL rats. LN suppressed the effect of dietary capsaicin. The ratios of phosphorylated (p-) eNOS/eNOS and p-Akt/Akt, but not p-PKA/PKA, were significantly increased in rats fed CAP compared with rats fed CTL.Conclusion: Dietary capsaicin may alleviate 2K1C renovascular hypertension, probably via enhancing phosphorylation of Akt and eNOS.Abbreviations: 2K1C: 2-kidney, 1-clip hypertension model; Akt: protein kinase B; Ang II: angiotensin II; ANOVA: measures analysis of variance; BP: blood pressure; EC: endothelial cell; eNOS: endothelial nitric oxide synthase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; L-NAME, LN: Nω-Nitro-L-arginine methyl ester hydrochloride; MA: mesenteric arteries; MAP: mean arterial blood pressure; NO: nitric oxide; PKA: protein kinase A; PVDF: polyvinylidene difluoride; SBP: Systolic blood pressure; SHR: spontaneously hypertensive rats; SN: sympathetic nervous; TRPV1: transient receptor potential vanilloid type 1; WKY: Wistar Kyoto rats.

Capsaicin Induces Apoptosis in KSHV-Positive Primary Effusion Lymphoma by Suppressing ERK and p38 MAPK Signaling and IL-6 Expression.

Primary effusion lymphoma (PEL) is defined as a rare subtype of non-Hodgkin's B-cell lymphoma which is caused by Kaposi's sarcoma-associated herpesvirus (KSHV) in immunosuppressed patients. PEL is an aggressive lymphoma and is frequently resistant to conventional chemotherapies. Therefore, it is critical to investigate novel therapeutic options for PEL. Capsaicin is a pungent component of chili pepper and possesses unique pharmacological effects, such as pain relief, anti-microbial and anti-cancer properties. Here, we demonstrate that capsaicin markedly inhibited the growth of KSHV latently infected PEL cells by inhibiting ERK, p38 MAPK and expression hIL-6, which are known to contribute to PEL growth and survival. The underlying mechanism of action by capsaicin was through the inhibition of ERK and p38 MAPK phosphorylation and signaling that affected hIL-6 expression. As a result, capsaicin induced apoptosis in PEL cells in a caspase-9 dependent manner. In line with these results, ERK (U0126) and p38 MAPK (SB203580) specific signaling inhibitors suppressed hIL-6 expression and attenuated cell growth in PEL cells. Furthermore, the addition of hIL-6 neutralizing antibody to culture medium suppressed the growth of PEL cells. We also demonstrate that capsaicin suppressed PEL cell growth in the absence of nascent viral replication. Finally, we confirmed ex vivo treatment of capsaicin attenuated PEL development in SCID mice. Taken together, capsaicin could represent a lead compound for PEL therapy without the risk of de novo KSHV infection.

Capsaicin-enriched diet ameliorates autoimmune neuritis in rats

BackgroundAutoimmune 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.MethodsWe 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.ResultsWe 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.ConclusionThis is the first report about the immunomodulatory effect of the common nutrient, capsaicin, in an experimental model for autoimmune neuropathies.

Rapid determination of capsaicinoids by colorimetric method

Capsaicinoids, the pungent component of chili peppers, are generally analyzed by precise analytical techniques, such as gas chromatography and high-performance liquid chromatography (HPLC), but these are not practical for the mass analyses of samples. To analyze mass samples rapidly, a colorimetric method was suggested. In this work, pigments and capsaicinoids were efficiently separated from chili pepper extract by sequential solid–liquid extraction and liquid–liquid extraction in test tubes followed by a colorimetric analysis on the capsaicinoids by a selective chromogenic reaction with Gibbs reagent (2,6-dichloroquinone-4-chloroimide). In the comparison of the capsaicinoid content by the colorimetric method and HPLC using acetone extracts of fresh pepper and dry red pepper as samples, R2 was 0.9973 and 0.9816, respectively, which shows a high linear correlation. In addition, a minimum of 1 μg/mL capsaicinoids can be detected and it was therefore determined that the method can efficiently analyze a great quantity of samples in a short time.

Capsaicin reactivates hMOF in gastric cancer cells and induces cell growth inhibition

ABSTRACTCapsaicin (CAP) is the major pungent component of chili pepper and is being evaluated for use against numerous types of tumors. Although CAP is indicated to target multiple signaling pathways, exact mechanisms of how it disturb cancer cell metablism remain obscure. Recent studies revealed Sirtuin 1 (SIRT1) serves as a potential target of CAP in cancer cells, indicating a direct regulation of cancer cell histone acetylation by capsaicin. The present study evaluated the effect of CAP on gastric cancer (GC) cell lines to understand the mechanism of cell growth inhibition. The results showed that CAP could significantly suppress cell growth, while altering histone acetylation in GC cell lines. Further studies found that hMOF, a major histone acetyltranferase for H4K16, is central to CAP-induced epigenetic changes. Reduced hMOF activity was detected in GC tissues, which could be restored by CAP both in vivo and in vitro. These findings revealed an important role of hMOF-mediated histone acetylation in CAP-directed anti-cancer processes, and suggested CAP as a potential drug for use in gastric cancer prevention and therapy.

The Effects of Dietary Capsaicin on Ventilation in Aging Mice

Capsaicin (CAP), the main pungent component of chili peppers, is a selective agonist for transient receptor potential vanilloid 1 (TRPV1). Stimulation of TRPV1 receptors with low doses of CAP results in augmented ventilatory output in anesthetized mice (Wang, 2006 JAP). We tested the hypothesis that dietary intake of CAP in older mice would augment ventilation compared to a control diet. Male mice were tested using unrestrained barometric plethysmography to quantify ventilation before initiation of a specialized diet and after 4‐weeks of AIN‐93G diet (Harlan Teklad) enhanced with either CAP dissolved in lecithin (50 mg/kg food weight: CAP; n=13) or lecithin only (CON; n=12). Mice were acclimated to the chamber (30 min – 180 min) and a 10‐min baseline was collected with room air. Data were analyzed using a multi‐variate linear model and are presented as MEAN±SEM; p &lt; 0.05. At 23‐mon, mice displayed a similar pattern of quiet breathing (data combined; Freq 124±4 bpm, tidal volume (TV) 0.33±0.01 mL/breath, minute ventilation (MV) 40.7±2.1 mL/min). Following 4 weeks of AIN‐93G diet, CON vs. CAP groups demonstrated no differences when exposed to room air for Freq (119±9 vs. 146±13 bpm), TV (0.34±0.02 vs. 0.32±0.01 mL/breath) or MV (39.3±2.6 vs. 47.1±4.7). These responses indicate that dietary CAP does not alter quiet breathing in aging mice. Both groups were exposed to acute hypoxia (15 minutes; 10% O2); these data may provide additional insight regarding the pattern of breathing following dietary CAP. Funding: LMC Student Research Committee; McDevitt Center Research Fellowships in Natural Science to AL and SR.

High-Dose Capsaicin for the Treatment of Neuropathic Pain: What We Know and What We Need to Know.

Neuropathic pain is a frequent and disabling condition with diverse underlying etiologies and is often difficult to treat. Systemic drug treatment is often limited in efficacy. Furthermore, adverse effects may be a limiting factor when trying to reach the necessary dose. Analgesics that can be applied topically have the potential to largely overcome this problem. They may be of particular advantage in localized neuropathic pain syndromes such as postherpetic neuralgia or small fiber neuropathy. Capsaicin, the pungent component of chili peppers, is a natural ligand of the transient receptor potential vanilloid 1 channel and has long been used as topically applicable cream with concentrations of 0.025 to 0.075%. In 2009, a high-concentration transdermal capsaicin 8% patch (Qutenza®; Acorda Therapeutics, Inc., Ardsley, NY, USA; Astellas Pharma Europe Ltd., Chertsey, Surrey, UK) was introduced for the treatment of peripheral neuropathic pain syndromes other than of diabetic origin in adults. It has since been widely used in diverse neuropathic pain disorders. In this review article, we summarize current knowledge on Qutenza, its advantages and problems, and expose unmet needs.Electronic supplementary materialThe online version of this article (doi:10.1007/s40122-014-0027-1) contains supplementary material, which is available to authorized users.

Vanilloid receptor-1 as a regulator of gut homeostasis (MUC8P.800)

Abstract The intestinal mucosa is exposed to myriads of foreign antigens. Hence the immune responses elicited to innocuous antigens in the gut are highly regulated to avoid overt inflammation. CX3CR1hi macrophages , also known as regulatory macrophages, play a critical role in maintenance of immune homeostasis in the gut. Thus therapeutic strategies leading to increase in CX3CR1hi macrophages would be beneficial for treatment of inflammatory diseases. Our present study demonstrates that Vanilloid receptor 1 (VR1), an ion channel previously identified on sensory neurons, is specifically expressed in the CD64+CX3CR1hi macrophages in intestinal lamina propria (LP). VR1-/- mice under normal steady state conditions have significantly reduced number of CX3CR1hi macrophages as compared to wild type counterpart. This data indicates a homeostatic role of VR1 and its endogenous ligands in regulating inflammation and maintaining immune tolerance in the gut. Interestingly, engagement of VR1 by orally administering its exogenous ligand Capsaicin (CP), the pungent component of chili peppers, increases the frequency of CD64+CX3CR1hi macrophages in LP. Furthermore we have shown that CP administration plays a key role in promotion of tolerance via the induction of immune-suppressive CD4+IL10+ IFN- γ+FoxP3- Tr1 cells in IL27 dependent manner. The therapeutic relevance of this phenomenon is highlighted by our study that oral administration of CP to NOD mice provides protection from Type 1 diabetes.

Modulation of intestinal macrophages for control of Type 1 diabetes (P3183)

Abstract We have previously reported that oral administration of Capsaicin (CP), the pungent component of chili peppers inhibits proliferation and activation of auto-reactive T cells and protects mice from development of Type-1 diabetes (T1D) in a dose dependent manner. Here, we demonstrate that orally administered CP leads to induction of CX3CR1+ macrophages specifically in lamina propria and in the pancreatic lymph nodes. CX3CR1+ macrophages also known as regulatory macrophages (Mregs) play a critical role in maintenance of immune homeostasis in the gut. Inflammation hampers the differentiation of monocytes into CX3CR1+ macrophages in the gut. However, the factors responsible for facilitating the differentiation into Mregs remain elusive. Using mice deficient in Vanilloid Receptor 1 (VR1), the receptor for CP, we report that VR1 is important for the differentiation of macrophages into Mregs, which subsequently play a key role in tolerance induction via the induction of immune-suppressive CD4+IL10+FoxP3- Tr1 cells. This process culminates in providing protection from T1D in NOD mice. This study elucidates how a common food additive, CP, can act as a potent immune-modulatory agent and ameliorate autoimmune disease like T1D.

Capsaicin may slow PSA doubling time: case report and literature review

Capsaicin is the main pungent component of chili peppers. This is the first case, to our knowledge, that describes prostate-specific antigen (PSA) stabilization in a patient with prostate cancer, who had biochemical failure after radiation therapy. A 66-year-old male underwent radiotherapy treatment for a T2b, Gleason 7 (3+4) adenocarcinoma of the prostate, with a PSA level of 13.3 ng/mL in April 2001. He had 3-dimensional conformal radiotherapy of 46 Gy in 23 fractions to the prostate and pelvis, and a prostate boost of 30 Gy in 15 fractions. Radiotherapy was completed in May 2001 and PSA nadired in January 2002 (0.57). Due to the continued PSA rise, the patient was started on bicalutamide (50 mg orally, daily) and leuprolide acetate (1 dose of 22.5 mg intramuscularly) in July 2005 when PSA was 38.5 ng/mL. Due to poor tolerance of androgen ablation therapy, the patient discontinued treatment and started taking 2.5 mL of habaneros chili sauce, containing capsaicin, 1 to 2 times a week in April 2006. Prostate-specific antigen doubling time (PSAdt) increased from 4 weeks before capsaicin to 7.3 months by October 2006. From October 2006 until November 2007, the patient remained on capsaicin (2.5 to 15 mL daily) and his PSA was stable (between 11 to 14 ng/mL). By January 2008, his PSA rose to 22.3 and he has maintained a PSAdt between 4 and 5 months, where it presently remains. Due to the patient's continued PSA rise, he was restarted on bicalutamide (12.5 mg daily). Apart from PSA relapse, the patient remains free of signs or symptoms of recurrence.

TRPV1 Activation in Primary Cortical Neurons Induces Calcium-Dependent Programmed Cell Death

Transient receptor potential cation channel, subfamily V, member 1 (TRPV1, also known as vanilloid receptor 1) is a receptor that detects capsaicin, a pungent component of chili peppers, and noxious heat. Although its function in the primary nociceptor as a pain receptor is well established, whether TRPV1 is expressed in the brain is still under debate. In this study, the responses of primary cortical neurons were investigated. Here, we report that 1) capsaicin induces caspase-3-dependent programmed cell death, which coincides with increased production of nitric oxide and peroxynitrite ; that 2) the prolonged capsaicin treatment induces a steady increase in the degree of capase-3 activation, which is prevented by the removal of capsaicin; 3) and that blocking calcium entry and calcium-mediated signaling prevents capsaicin-induced cell death. These results indicate that cortical neurons express TRPV1 whose prolonged activation causes cell death.

Oral administration of Capsaicin, a ligand of VR1, can modulate dendritic cell population and induces CD4+FoxP3- Tr-1 cells in the GALT (178.14)

Abstract VR1 is a non-selective cation channel, highly expressed by sensory neurons and cells of the immune system e.g. dendritic cells (DCs) and macrophages. Capsaicin (CP), the pungent component of chili peppers is a chemical ligand of VR1. We have recently reported that oral administration of CP inhibits proliferation and activation of auto-reactive T cells and protects mice from development of Type-1 diabetes (T1D) in a dose dependent manner. Here we demonstrate that orally administered CP can lead to an increase in IL-27 producing DCs, and IL10 producing CD4+/FoxP3- T cells (Tr1) but decrease in the frequency of CD4+/IL17+ T cells (TH17) in the pancreatic lymph node (PLN). We also demonstrate that splenocytes and PLN cells when adoptively transferred from capsaicin fed mouse to a naïve NOD mouse leads to protection of the recipient mouse from T1D. Our results thus demonstrate that engagement of VR1 on immune cells can have profound effect on gut mediated immune tolerance and autoimmunity.

20-Hydroxyeicosatetraenoic Acid (20-HETE) Is a Novel Activator of Transient Receptor Potential Vanilloid 1 (TRPV1) Channel

TRPV1 is a member of the transient receptor potential ion channel family and is gated by capsaicin, the pungent component of chili pepper. It is expressed predominantly in small diameter peripheral nerve fibers and is activated by noxious temperatures >42 °C. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 4A/4F-derived metabolite of the membrane phospholipid arachidonic acid. It is a powerful vasoconstrictor and has structural similarities with other TRPV1 agonists, e.g. the hydroperoxyeicosatetraenoic acid 12-HPETE, and we hypothesized that it may be an endogenous ligand for TRPV1 in sensory neurons innervating the vasculature. Here, we demonstrate that 20-HETE both activates and sensitizes mouse and human TRPV1, in a kinase-dependent manner, involving the residue Ser(502) in heterologously expressed hTRPV1, at physiologically relevant concentrations.