Pungent Principle Research Articles

Capsaicin, The Vanilloid Receptor TRPV1 Agonist in Neuroprotection: Mechanisms Involved and Significance.

Hot peppers, also called chilli, chilli pepper, or paprika of the plant genus Capsicum (family Solanaceae), are one of the most used vegetables and spices worldwide. Capsaicin (8-methyl N-vanillyl-6-noneamide) is the main pungent principle of hot green and red peppers. By acting on the capsaicin receptor or transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1), capsaicin selectively stimulates and in high doses defunctionalizes capsaicin-sensitive chemonociceptors with C and Aδ afferent fibers. This channel, which is involved in a wide range of neuronal processes, is expressed in peripheral and central branches of capsaicin-sensitive nociceptive neurons, sensory ganglia, the spinal cord, and different brain regions in neuronal cell bodies, dendrites, astrocytes, and pericytes. Several experimental and clinical studies provided evidence that capsaicin protected against ischaemic or excitotoxic cerebral neuronal injury and may lower the risk of cerebral stroke. By preventing neuronal death, memory impairment and inhibiting the amyloidogenic process, capsaicin may also be beneficial in neurodegenerative disorders such as Parkinson's or Alzheimer's diseases. Capsaicin given in systemic inflammation/sepsis exerted beneficial antioxidant and anti-inflammatory effects while defunctionalization of capsaicin-sensitive vagal afferents has been demonstrated to increase brain oxidative stress. Capsaicin may act in the periphery via the vagal sensory fibers expressing TRPV1 receptors to reduce immune oxidative and inflammatory signalling to the brain. Capsaicin given in small doses has also been reported to inhibit the experimentally-induced epileptic seizures. The aim of this review is to provide a concise account on the most recent findings related to this topic. We attempted to delineate such mechanisms by which capsaicin exerts its neuronal protective effects. We also aimed to provide the reader with the current knowledge on the mechanism of action of capsaicin on sensory receptors.

Comparative evaluation of lipsticks developed using isolated pigments of Capsicum annuum and Lycopersicon esculentum fruits and various natural bases

Cosmetics have lured mankind from time immemorial. Colourant cosmetics have secured a respectable space at the dressing table or salon for their various benefits. Capsicum is widely cultivated across the globe for its pungent principle, capsaicin or capsanthin. However, the bright colour pigments are often neglected due to its pungency. Lycopersicon (tomatoes) also are rich in red colour because of the pigment lycopene. Objective of the current study was to integrate red pigments isolated from capsicum and lycopersicon fruits into lipstick. Major challenge was to nullify the pungency of the capsicum oleoresin. Lipstick bases were formulated using various combinations of waxes and fats. The capsicum oleoresin was treated with NaOH 10 % w/v to nullify the pungency. Lycopene rich extract was obtained from dried tomatoes and later incorporated into the lipsticks bases. The formulated sticks were evaluated and compared against the marketed lipsticks. Our findings reveal that both the lycopene and capsicum oleoresin rich extracts can be conveniently incorporated into the lipsticks and can prove to be a better natural and vegan substitute for synthetic carcinogenic dyes.

Piperine Improves Lipid Dysregulation by Modulating Circadian Genes Bmal1 and Clock in HepG2 Cells.

Metabolic disorders are closely associated with the dysregulation of circadian rhythms. Many bioactive components with lipid metabolism-regulating effects have been reported to function through circadian clock-related mechanisms. As the main pungent principle of black pepper, piperine (PIP) has been demonstrated to possess anti-obesity bioactivity by affecting hepatic lipid metabolism-related factors. However, whether the circadian clock genes Bmal1 and Clock are involved in the protective effect of PIP against lipid metabolism disorders remains unknown. In this work, oleic acid (OA) induced lipid accumulation in HepG2 cells. The effect of PIP on redox status, mitochondrial functions, and circadian rhythms of core clock genes were evaluated. Results revealed that PIP alleviated circadian desynchrony, ROS overproduction, and mitochondrial dysfunction. A mechanism study showed that PIP could activate the SREBP-1c/PPARγ and AMPK/AKT-mTOR signaling pathways in a Bmal1/Clock-dependent manner in HepG2 cells. These results indicated that Bmal1 and Clock played important roles in the regulating effect of PIP on hepatic lipid homeostasis.

Ginger Constituent 6-Shogaol Inhibits Inflammation- and Angiogenesis-Related Cell Functions in Primary Human Endothelial Cells.

Rhizomes from Zingiber officinale Roscoe are traditionally used for the treatment of a plethora of pathophysiological conditions such as diarrhea, nausea, or rheumatoid arthritis. While 6-gingerol is the pungent principle in fresh ginger, in dried rhizomes, 6-gingerol is dehydrated to 6-shogaol. 6-Shogaol has been demonstrated to exhibit anticancer, antioxidative, and anti-inflammatory actions more effectively than 6-gingerol due to the presence of an electrophilic Michael acceptor moiety. In vitro, 6-shogaol exhibits anti-inflammatory actions in a variety of cell types, including leukocytes. Our study focused on the effects of 6-shogaol on activated endothelial cells. We found that 6-shogaol significantly reduced the adhesion of leukocytes onto lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs), resulting in a significantly reduced transmigration of THP-1 cells through an endothelial cell monolayer. Analyzing the mediators of endothelial cell–leukocyte interactions, we found that 30 µM of 6-shogaol blocked the LPS-triggered mRNA and protein expression of cell adhesion molecules. In concert with this, our study demonstrates that the LPS-induced nuclear factor κB (NFκB) promoter activity was significantly reduced upon treatment with 6-shogaol. Interestingly, the nuclear translocation of p65 was slightly decreased, and protein levels of the LPS receptor Toll-like receptor 4 remained unimpaired. Analyzing the impact of 6-shogaol on angiogenesis-related cell functions in vitro, we found that 6-shogaol attenuated the proliferation as well as the directed and undirected migration of HUVECs. Of note, 6-shogaol also strongly reduced the chemotactic migration of endothelial cells in the direction of a serum gradient. Moreover, 30 µM of 6-shogaol blocked the formation of vascular endothelial growth factor (VEGF)-induced endothelial sprouts from HUVEC spheroids and from murine aortic rings. Importantly, this study shows for the first time that 6-shogaol exhibits a vascular-disruptive impact on angiogenic sprouts from murine aortae. Our study demonstrates that the main bioactive ingredient in dried ginger, 6-shogaol, exhibits beneficial characteristics as an inhibitor of inflammation- and angiogenesis-related processes in vascular endothelial cells.

Evidence for engagement of the nucleus of the solitary tract in processing intestinal chemonociceptive input irrespective of conscious pain response in healthy humans.

Neuroimaging studies have revealed important pathomechanisms related to disorders of brain-gut interactions, such as irritable bowel syndrome and functional dyspepsia. More detailed investigations aimed at neural processing in the brainstem, including the key relay station of the nucleus of the solitary tract (NTS), have hitherto been hampered by technical shortcomings. To ascertain these processes in more detail, we used multiecho multiband 7T functional magnetic resonance imaging and a novel translational experimental model based on a nutrient-derived intestinal chemonociceptive stimulus. In a randomized cross-over fashion, subjects received duodenal infusion of capsaicin (the pungent principle in red peppers) and placebo (saline). During infusion, functional magnetic resonance imaging data and concomitant symptom ratings were acquired. Of 26 healthy female volunteers included, 18 were included in the final analysis. Significantly increased brain activation over time during capsaicin infusion, as compared with placebo, was observed in brain regions implicated in pain processing, in particular the NTS. Brain activation in the thalamus, cingulate cortex, and insula was more pronounced in subjects who reported abdominal pain (visual analogue scale > 10 mm), as compared with subjects who experienced no pain. On the contrary, activations at the level of the NTS were independent of subjective pain ratings. The current experimental paradigm therefore allowed us to demonstrate activation of the principal relay station for visceral afferents in the brainstem, the NTS, which was engaged irrespective of the conscious pain response. These findings contribute to understanding the fundamental mechanism necessary for developing novel therapies aimed at correcting disturbances in visceral afferent pain processing.

Oral Capsaicinoid Administration Alters the Plasma Endocannabinoidome and Fecal Microbiota of Reproductive-Aged Women Living with Overweight and Obesity.

Capsaicinoids, the pungent principles of chili peppers and prototypical activators of the transient receptor potential of the vanilloid type-1 (TRPV1) channel, which is a member of the expanded endocannabinoid system known as the endocannabinoidome (eCBome), counteract food intake and obesity. In this exploratory study, we examined the blood and stools from a subset of the participants in a cohort of reproductive-aged women with overweight/obesity who underwent a 12-week caloric restriction of 500 kcal/day with the administration of capsaicinoids (two capsules containing 100 mg of a capsicum annuum extract (CAE) each for a daily dose of 4 mg of capsaicinoids) or a placebo. Samples were collected immediately before and after the intervention, and plasma eCBome mediator levels (from 23 participants in total, 13 placebo and 10 CAE) and fecal microbiota taxa (from 15 participants in total, 9 placebo and 6 CAE) were profiled using LC–MS/MS and 16S metagenomic sequencing, respectively. CAE prevented the reduced caloric-intake-induced decrease in beneficial eCBome mediators, i.e., the TRPV1, GPR119 and/or PPARα agonists, N-oleoyl-ethanolamine, N-linoleoyl-ethanolamine and 2-oleoyl-glycerol, as well as the anti-inflammatory N-acyl-ethanolamines N-docosapentaenyl-ethanolamine and N-docosahexaenoyl-ethanolamine. CAE produced few but important alterations in the fecal microbiota, such as an increased relative abundance of the genus Flavonifractor, which is known to be inversely associated with obesity. Correlations between eCBome mediators and other potentially beneficial taxa were also observed, thus reinforcing the hypothesis of the existence of a link between the eCBome and the gut microbiome in obesity.

Effectiveness of Ginger in Treating Nausea and Vomiting of Pregnancy

Nausea and vomiting in pregnancy (NVP) is one of the common main complaint in pregnancy. NVP can be a significant burden to the patient, make a decrease in quality of life, pregnancy threatening or even worse can lead to nutritional loss and death. NVP diagnosed when in first trimester of pregnancy and the other possible cause of NVP is excluded. Management of NVP is included maintaining hydration, nutrition, and lifestyle modification. Also avoiding the smells, food, or activity that can cause nause are necessary. There are some methods to treat NVP including pharmalogical or non-pharmalogical. The non-pharmalogical approach is change nutritional habits, lifestyle and medications. Several pharmalogical agents that can be used to relief the symptoms of NVP are pyridoxine, anti- histamines, metoclopramide, pyridoxine/doxylamine, promethazine and metoclopramide. Some patients also want to try more “natural” medications for NVP like ginger. The pharmacological activity is thought to stand in the pungent principles (gingerols and shogaols) and volatile oils (sesquiterpenes and monoterpenes). The true mechanism of action of ginger is probable to be a gastric effect, to increase tone and peristaltic due to anticholinergic and antiserotonin act. Ginger acts straight to the digestive tract and avoids the CNS side effects common to centrally acting antiemetics. Ginger is available in capsule or syrup form or in candy, cookies, beer, tinctures, teas, sodas, and jam. Nowadays, true dosing is available only if one uses standardized extracts; however, women may choose to use another form of ginger.

Front Cover: Co‐Oxidative Transformation of Piperine to Piperonal and 3,4‐Methylenedioxycinnamaldehyde by a Lipoxygenase from Pleurotus sapidus (ChemBioChem 19/2021)

Biotransformation of piperine, the pungent principle of black pepper (Piper nigrum), by the fungus Pleurotus sapidus resulted in the formation of two vanilla-like aroma compounds: The highly valuable piperonal, which is used for the aromatization of different sweets and dairy products, such as chocolate and ice cream, and 3,4-methylenedioxycinnamaldehyde. The conversion was identified as the result of a co-oxidative reaction catalyzed by a lipoxygenase of P. sapidus in the presence of polyunsaturated fatty acids. More information can be found in the Communication by N.-K. Krahe et al.

Co-Oxidative Transformation of Piperine to Piperonal and 3,4-Methylenedioxycinnamaldehyde by a Lipoxygenase from Pleurotus sapidus.

The valuable aroma compound piperonal with its vanilla‐like olfactory properties is of high interest for the fragrance and flavor industry. A lipoxygenase (LOXPsa1) of the basidiomycete Pleurotus sapidus was identified to convert piperine, the abundant pungent principle of black pepper (Piper nigrum), to piperonal and a second volatile product, 3,4‐methylenedioxycinnamaldehyde, with a vanilla‐like odor through an alkene cleavage. The reaction principle was co‐oxidation, as proven by its dependence on the presence of linoleic or α‐linolenic acid, common substrates of lipoxygenases. Optimization of the reaction conditions (substrate concentrations, reaction temperature and time) led to a 24‐fold and 15‐fold increase of the piperonal and 3,4‐methylenedioxycinnamaldehyde concentration using the recombinant enzyme. Monokaryotic strains showed different concentrations of and ratios between the two reaction products.

Piper nigrum CYP719A37 Catalyzes the Decisive Methylenedioxy Bridge Formation in Piperine Biosynthesis.

Black pepper (Piper nigrum) is among the world’s most popular spices. Its pungent principle, piperine, has already been identified 200 years ago, yet the biosynthesis of piperine in black pepper remains largely enigmatic. In this report we analyzed the characteristic methylenedioxy bridge formation of the aromatic part of piperine by a combination of RNA-sequencing, functional expression in yeast, and LC-MS based analysis of substrate and product profiles. We identified a single cytochrome P450 transcript, specifically expressed in black pepper immature fruits. The corresponding gene was functionally expressed in yeast (Saccharomyces cerevisiae) and characterized for substrate specificity with a series of putative aromatic precursors with an aromatic vanilloid structure. Methylenedioxy bridge formation was only detected when feruperic acid (5-(4-hydroxy-3-methoxyphenyl)-2,4-pentadienoic acid) was used as a substrate, and the corresponding product was identified as piperic acid. Two alternative precursors, ferulic acid and feruperine, were not accepted. Our data provide experimental evidence that formation of the piperine methylenedioxy bridge takes place in young black pepper fruits after a currently hypothetical chain elongation of ferulic acid and before the formation of the amide bond. The partially characterized enzyme was classified as CYP719A37 and is discussed in terms of specificity, storage, and phylogenetic origin of CYP719 catalyzed reactions in magnoliids and eudicots.

Quality control and long-term stability study of ginger from different geographical origins using chemometrics.

Ginger rhizome (Zingiber officinale) is a well-known spice and medicinal plant that is widely used in the Egyptian market as a spice, flavor and medicinal herb for different diseases. Since it is not cultivated as rhizomes in Egypt, ginger is imported from other countries, which may impact its quality. In this study, UV spectroscopy and high-performance liquid chromatography (HPLC) were applied as efficient available techniques for the discrimination and quality control of ginger collected from different geographical origins in combination with chemometrics. In addition, HPLC was applied to investigate the stability of ginger samples upon storage for 3 years to trace the changes in their main active constituents. Data obtained from both UV and HPLC in combination with Principal Component Analysis (PCA) displayed proper discrimination of the samples according to their geographical origins. Regarding the stability study, ginger samples showed a significant decrease in quality after storage for 3 years, in which significant variation in the main pungent principles (6-, 8-, 10-gingerols and 6-shogaol) were observed. PCA failed to discriminate between ginger samples after long-time storage, so the applied model could discriminate between ginger samples before and after storage. UV and HPLC in combination with chemometrics can be applied as a successful tool for the study of quality, stability and geographical discrimination of ginger. © 2020 Society of Chemical Industry.

Botany, phytochemistry and antimicrobial activity of ginger (Zingiber officinale): A review

Antibiotic resistance in every corner of the planet is growing to dangerously high levels. New mechanisms of resistance are emerging and spreading globally which threatens our ability to treat common infectious diseases. Many scientists documented some plants having antimicrobial properties. Zingiber officinale Roscoe (ZO), the most recognised member of Zingiber, is one of them. This review aims to validate the antimicrobial activity of ginger. The information and data on ZO were collated from various resources like ethnobotanical textbooks, Pub Med, Google Scholar, Science Direct, Web of Science, and Scopus. ZO has many medicinal, nutritional and ethnomedical values and is commonly used as a spice, flavouring agent and herbal remedy worldwide. In addition to giving ginger its pungent aroma, volatile oil gingerol and other pungent principles are the most medically potent since they inhibit the production of prostaglandin and leukotriene, which are chemicals that affect blood flow and inflammation. Traditionally, it has been used as an herbal remedy for centuries in Ayurvedic, Tibb-Unani, Chinese, Islamic, Africans, the Caribbean and many other medicinal systems to cure a variety of diseases like throat infections, asthma, inflammation, dyspepsia, loss of appetite, palpitation, constipation and indigestion, colds, arthritis, nausea, hypertension, migraines, and many more. It has a high proportion of α-Zingiberene, β-sesquiphellandrene, (E,E)- α-farnesene, geranial and ar-curcumene. The ZO extracts, essential oil and chemical constituents exhibited antimicrobial, anticonvulsant, analgesic, anti-inflammatory, antiulcer, immunomodulatory, and other beneficial activities. The research suggests that there are marked antimicrobial activities in the ginger that could be beneficial and applied in various research areas, such as the pharmaceutical and food industries. To understand the molecular mechanisms by which these effects are exerted, more research may be required.

Analgesic and Anti- Inflammatory Effect of Zingiber Officinale in Albino Mice

Zingiber officinale (ginger) is common part of the diet in many parts of the world, Recent research has found ginger to have various pharmacological properties due to a variety of active constituents, including shogoals and gingerols. It is a member of zingiberaceae family originated in Southeast Asia and has been introduced to many parts of the globe where it proliferates in suitable environment. Ginger contain constituents with anti-inflammatory properties. The fresh and dried ginger both contains active 6 – gingerol and gingerdion along with other resinous pungent principle, extracted with n- hexane and methanol that are responsible for inhibition of inflammatory metabolite's production by lipooxygenase and cyclooxyganse. The present paper aimed to determine anti- inflammatory effects of Zingiber officinale extract in experimental animals .The anti-inflammatory activity was assessed by using carrageenan it showed that the plant extract has anti-inflammatory effect in rats by using acetic acid model. The present paper indicated that plant extract has analgesic activity in dose dependent pattern.

A sensitive 1 H NMR spectroscopic method for the quantification of capsaicin and capsaicinoid: morpho-chemical characterisation of chili land races from northeast India.

Proton (1 H) nuclear magnetic resonance (NMR) spectroscopy based analytical method for the quantification of capsaicin (major pungent principle of chili) has certain advantages including short data acquisition time and better structural authentication. Earlier NMR methods are associated with either of the bottlenecks such as low or lack of information on the sensitivity and scope for the quantification of total capsaicinoid. To develop a sensitive 1 H quantitative NMR (qNMR) technique for capsaicin and total capsaicinoid in dry chili and chili oleoresin and to demonstrate its applicability in a real sample set. A 1 H qNMR method was developed using benzene as the internal standard for the quantification of capsaicin (terminal methyl signal) as well as total capsaicinoid (benzyl methylene signal) in dry chili and oleoresin and validated in terms of specificity, linearity, sensitivity, accuracy and precision. The developed 1 H qNMR method was specific, sensitive (limit of detection 4.4 μg/mL and limit of quantitation 14.8 μg/mL), linear in the range 0.083-8.33 mg/mL of capsaicin, accurate and precise. The credibility of the developed method was showcased in the morpho-chemical characterisation of commercially available 15 chili land races from northeast India. The analysis identified the land races with a wide range of capsaicin (trace to 1.49% in the dry fruit and trace to 6.21% in the oleoresin w/w) and oleoresin content (3.35-26.78% w/w). The standardized 1 H qNMR method facilitated the findings of chemical basis for the selection of chili land races from this region, capable of producing high-yielding oleoresin with intended degree of pungency.

Distinct Drimane Chemotypes in Tasmanian Mountain Pepper (Tasmannia lanceolata): Differences in the Profiles of Pungent Leaf Phytochemicals Associated with Altitudinal Cline.

This study assesses whether the distinct altitudinal cline in leaf morphology (decreased leaf width and length with increased altitude) in Tasmanian mountain pepper (Tasmannia lanceolata) is associated with changes in the leaf chemistry of wild populations from different ecological landscapes and altitudes. The presence of distinct pungent drimane sesquiterpenoid chemotypes was identified: subalpine woodland and wet sclerophyll forest chemotypes. Isolation studies and analysis of extracts revealed that wet sclerophyll forest T. lanceolata populations featured polygodial as the principal terpenoid, with profiles similar to the commercial cultivars sampled. In contrast, the subalpine woodland populations contained the drimane sesquiterpenoids 1β-acetoxy-9-deoxyisomuzigadial and 3β-acetoxydrimenin and the conspicuous absence of the pungent principle polygodial.

Study on the Pungent Principle and Its Related Compounds of Myoga, Zingiber mioga Roscoe

Study on the Pungent Principle and Its Related Compounds of Myoga, <i>Zingiber mioga</i> Roscoe

Synergistic inhibitory effect of capsaicin and dihydrocapsaicin on in-vitro platelet aggregation and thromboxane formation.

: Capsaicinoids, including capsaicin (CAP) and dihydrocapsaicin (DHC), the pungent principles of pepper fruits, individually inhibit in-vitro platelet aggregation. However, their effects, when present together, are not known. The aims of this study were to compare the effects of CAP and DHC alone, and in combination in the ratio that they are found in chilies (∼60% CAP : 40% DHC), on in-vitro platelet aggregation, platelet count and thromboxane B2 (TXB2) formation. The effects of 12.5 and 6.25 μmol/l CAP and DHC individually, and in combination (CAP : DHC, 60 : 40) on arachidonic acid-induced, ADP-induced and collagen-induced aggregation, were investigated. Platelet count was determined preincubation and postincubation with CAP and DHC and in combination. TXB2 formation from platelets treated with arachidonic acid in the absence and presence of CAP and DHC individually, and in combination, was measured. Compared with control, CAP and DHC (12.5 μmol/l) inhibited arachidonic acid-induced aggregation by 23.2 and 25.3%, respectively (both P < 0.01). In combination, CAP and DHC exhibited further inhibition in arachidonic acid-induced aggregation (CAP : DHC, 3.75 : 2.5 μmol/l, 36.5%, P = 0.01; 7.5 : 5 μmol/l, 57.5%, P < 0.001), compared with control. Incubation of platelets with caspaicinoids did not significantly affect the platelet count. In addition, the CAP : DHC (7.5 : 5 μmol/l) combination significantly inhibited (P < 0.001) TXB2 formation, compared with the individual capsaicinoids. Capsaicinoids had no effect ADP-induced or collagen-induced aggregation. The combination of CAP and DHC produces a significantly greater inhibitory effect on arachidonic acid-induced platelet aggregation and subsequent TXB2 formation, compared with the individual capsaicinoids.

Capsaicin, the pungent principle of peppers, ameliorates alcohol-induced acute liver injury in mice via modulation of matrix metalloproteinases.

Alcohol, the most common cause for hepatic injury, may further deteriorate the hepatic tissue when left unattended. Capsaicin, the pungent principle of chilli peppers, possesses antioxidant and anti-inflammatory properties and is a proven dietary antioxidant in various ailments. However, its role in alcohol-induced hepatic injury is unclear. In this study, we investigated the effects of capsaicin on the hepatic tissue of mice treated with alcohol. Acute liver injury was induced in mice by oral gavage of 5 doses of 10 mL/kg of 50% ethyl alcohol at an interval of 12 h. The tissue antioxidant levels along with the mitochondrial functional parameters and matrix metalloproteinase levels were evaluated in the hepatic tissues of mice following alcohol challenge. The results showed that alcohol intake significantly attenuated the hepatic antioxidant levels and mitochondrial function. These changes were accompanied by enhanced serum hepatic injury markers and matrix metalloproteinases. However, capsaicin treatment (10 and 20 mg/kg, oral) throughout the experimental period caused a drastic improvement in the hepatic tissue of the alcohol-treated mice, reflected by the normalization of hepatic enzyme and protein levels along with restored histological alterations. These results indicate that capsaicin, as a dietary intervention, may prevent alcohol-induced acute liver injury.

Capsaicin pretreatment enhanced the bioavailability of fexofenadine in rats by P-glycoprotein modulation: in vitro, in situ and in vivo evaluation

Background and objective: 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.Methods: 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.Results: The intestinal transport and apparent permeability (Papp) 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 (Ka), fraction absorbed (Fab) and effective permeability (Peff) 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 (Cmax) 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.Conclusions: 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.

An updated review on molecular mechanisms underlying the anticancer effects of capsaicin.

The quest for developing anticancer principles from natural sources has a long historical track record and remarkable success stories. The pungent principle of hot chili pepper, capsaicin, has been a subject of research for anticancer drug discovery for more than three decades. However, the majority of research has revealed that capsaicin interferes with various hallmarks of cancer, such as increased cell proliferation, evasion from apoptosis, inflammation, tumor angiogenesis and metastasis, and tumor immune escape. Moreover, the compound has been reported to inhibit carcinogen activation and chemically induced experimental tumor growth. Capsaicin has also been reported to inhibit the activation of various kinases and transcription that are involved in tumor promotion and progression. The compound activated mitochondria-dependent and death receptor-mediated tumor cell apoptosis. Considering the growing interest in capsaicin, this review provides an update on the molecular targets of capsaicin in modulating oncogenic signaling.