Effects Of Capsaicin Research Articles

More spice, less salt: How capsaicin affects liking for and perceived saltiness of foods in people with smell loss

People who lose their sense of smell self-report consuming more salt to compensate for a lack of flavor and enhance eating enjoyment. However, this may contribute to excess sodium intake. Capsaicin may help increase salt taste intensity and eating enjoyment in people with smell loss, but this has not been studied in this population. The purpose of this study was to determine 1) whether salt intake in those with smell loss differs from population averages, 2) whether capsaicin increases flavor and salt taste intensity, and 3) if adding spice to foods increases liking in individuals with smell loss. Thirty-three participants 18–65 years old with confirmed smell loss for at least 12 weeks completed two sets of replicate test sessions (four total). In two sessions participants rated overall flavor intensity, taste qualities' intensities, spicy intensity, and liking for model tomato soups with low or regular sodium content and three levels of capsaicin (none, low, or moderate). In the other two sessions, participants rated the same sensory attributes for model food samples with three levels of added spice (none, low, or moderate). 24-hour urine samples were collected to determine sodium intake. Results indicate that although sodium intake is higher than recommended (<2300 mg/day) in those with smell loss (2893 ± 258 mg/day), they do not consume more sodium than population averages (3039 ± 100 mg/day; p = 0.3). Adding low and moderate amounts of capsaicin to a model tomato soup increased the intensity of overall flavor (p < 0.001) and saltiness (p = 0.004) compared to a model tomato soup without capsaicin. However, capsaicin's effect on liking differed by food type. Thus, capsaicin can improve flavor, salt taste intensity, and eating enjoyment in people with smell loss.

Neuropharmacological Study on Capsaicin in Scopolamine-injected Mice.

To evaluate the potential beneficial role of Capsaicin in cognitive dysfunction, mitochondrial impairment, and oxidative damage induced by scopolamine in mice. Capsaicin is the chief phenolic component present in red chili and is responsible for its pungent and spicy flavor. It affects TRPV1 channels in nociceptive sensory neurons and is present in the hippocampus, and hypothalamus of the brains of rodents and humans. The main objective is to investigate the effective role of capsaicin in attenuating cognitive dysfunction, mitochondrial impairment, and oxidative damage induced by scopolamine in mice and examine the feasible mechanisms. Various doses of capsaicin (5, 10, and 20 mg/kg) were given orally to mice daily for 7 consecutive days after the administration of scopolamine. Various behavioral tests (motor coordination, locomotor counts, hole board test) and biochemical assay (Pro-inflammatory cytokines, catalase, lipid peroxidation, nitrite, reduced glutathione, and superoxide dismutase), mitochondrial complex (I, II, III, and IV) enzyme activities, and mitochondrial permeability transition were evaluated in the distinct regions of the brain. Scopolamine-treated mice showed a considerable reduction in the entries and duration in the light zone as well as in open arms of the elevated plus maze. Interestingly, capsaicin at different doses reversed the anxiety, depressive-like behaviors, and learning and memory impairment effects of scopolamine. Scopolamine-administered mice demonstrated substantially increased pro-inflammatory cytokines levels, impaired mitochondrial enzyme complex activities, and increased oxidative damage compared to the normal control group. Capsaicin treatment reinstated the reduced lipid peroxidation, nitric oxide, catalase, superoxide dismutase, reduced glutathione activity, decreasing pro-inflammatory cytokines and restoring mitochondrial complex enzyme activities (I, II, III, and IV) as well as mitochondrial permeability. Moreover, the IL-1β level was restored at a dose of capsaicin (10 and 20 mg/kg) only. Capsaicin reduced the scopolamine-induced acetylcholinesterase activity, thereby raising the acetylcholine concentration in the hippocampal tissues of mice. Preservation of neuronal cell morphology was also confirmed by capsaicin in histological studies. From the above experimental results, capsaicin at a dose of 10 mg/kg, p.o. for seven consecutive days was found to be the most effective dose. The experiential neuroprotective effect of capsaicin through the restoration of mitochondrial functions, antioxidant effects, and modulation of pro-inflammatory cytokines makes it a promising candidate for further drug development through clinical setup.

Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro.

Acute kidney injury is a fatal disease characterized by a rapid deterioration of kidney function. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a natural product extracted from Capsicum. The aim of this study was to explore the protective effect of capsaicin on inflammation, apoptosis, and mitochondrial dysfunction in an in vitro model of acute kidney injury. Lipopolysaccharide (LPS)-induced acute kidney injury model was established in HK-2 cells to investigate the protective effect of capsaicin. Cell viability was assessed using CCK-8 assay, and protein expression was detected using western blot and immunofluorescence assay. Intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential were analyzed by flow cytometry. Cell apoptosis was detected by propidium iodide staining. The results showed that capsaicin ameliorated LPS-induced cytotoxicity in vitro and attenuated the release of interleukin (IL)-1β and IL-18. Intriguingly, genipin abolished the protective effect of capsaicin. Molecularly, capsaicin activated transient receptor potential cation channel subfamily V member 1 -mitochondrial uncoupling protein 2 axis and inhibited caspase-1-mediated pyroptosis. In addition, capsaicin alleviated LPS-induced ROS production and mitochondrial membrane potential disruption and inhibited apoptosis. These findings suggest that capsaicin shows a protective effect in in vitro acute kidney injury model.

Recent advances in analysis of capsaicin and its effects on metabolic pathways by mass spectrometry.

Capsaicin is the main food active component in Capsicum that has gained considerable attention due to its broad biological activities, including antioxidation, anti-inflammation, anti-tumor, weight regulation, cardiac protection, anti-calculi, and diurnal-circadian regulation. The potent biological effects of capsaicin are intimately related to metabolic pathways such as lipid metabolism, energy metabolism, and antioxidant stress. Mass spectrometry (MS) has emerged as an effective tool for deciphering the mechanisms underlying capsaicin metabolism and its biological impacts. However, it remains challenging to accurately identify and quantify capsaicin and its self-metabolites in complex food and biological samples, and to integrate multi-omics data generated from MS. In this work, we summarized recent advances in the detection of capsaicin and its self-metabolites using MS and discussed the relevant MS-based studies of metabolic pathways. Furthermore, we discussed current issues and future directions in this field. In-depth studies of capsaicin metabolism and its physiological functions based on MS is anticipated to yield new insights and methods for preventing and treating a wide range of diseases.

Synergistic Effects of Capsaicin and Quercetin Improved Induced Premature Ovarian Failure in Rat.

Premature ovarian failure (POF) is a heterogeneous disorder. POF is defined as hypergonadotropic hypoestrogenism in women under 40 years. There is no effective treatment to cure POF patients. Antioxidants prevent ovarian damage by reducing the lipid peroxidation cascades affecting folliculogenesis, meiosis and ovulation. Hence; the aim of present study was to investigate the effects of Capsaicin (CAP) and Quercetin (QUR) on cyclophosphamide (CYC)-induced POF in rat model. In this experimental study, POF was induced by intraperitoneal injection of 200 mg/kg CYC on first day and then 8 mg/kg/day for the following 3 days. After 4 days of CYC administration, rats were randomly divided into five groups (n=6/group) as follows: POF, dimethyl sulfoxide (DMSO), CAP (0.5 mg/kg/day), QUR (100 mg/kg/day) and CAP+QUR. Biochemical, hormonal, gene expression, and histological evaluations were performed on blood serum and tissue samples after 14 days of treatment with the CAP and QUR. CAP, QUR and CAP+QUR groups showed signs of restored ovarian function in the form of a significant increase in serum total antioxidant capacity (TAC), estrogen, progesterone and anti-mullerian hormone (AMH) levels versus POF and DMSO groups and a significant improvement in histological parameters and follicle numbers in treatment groups compared to POF and DMSO groups. Polymerase chain reaction (PCR) analysis demonstrated that CAP and QUR upregulate the expression of BAX gene and decreased the expression of apoptosis inducing genes (BCL-2 and P53). CAP and QUR treatment of CYC-induced POF rats showed a positive effect on reducing ovarian damage by improving TAC levels, expression of apoptotic genes, levels of ovarian reserve markers, and histological parameters. Our results suggest that treatment with CAP or QUR may be a conservative treatment approach for CYC -induced POF.

Cannflavins isolated from Cannabis sativa impede Caenorhabditis elegans response to noxious heat.

Cannflavins, flavonoids abundantly present in Cannabis sativa, possess a distinct chemical structure comprising a vanillyl group. Notably, the capsaicin structure also contains a vanillyl group, which is considered essential for interacting with the vanilloid receptor. The vanilloid receptor plays a crucial role in the perception of pain, heat, and inflammation and mediates the analgesic effects of capsaicin. Therefore, we postulated that prolonged exposure to cannflavin A (Can A) and cannflavin B (Can B) would provoke vanilloid receptor desensitization and hinder nocifensive responses to noxious thermal stimuli. C. elegans wild-type (N2) and mutants were exposed to Can A and Can B solutions for 60min and then aliquoted on Petri dishes divided into quadrants for thermal stimulation. We then determined the thermal avoidance index for each C. elegans experimental group. Proteomics was performed to identify proteins and pathways associated with Can A or B treatment. Prolonged exposure to Can A and Can B hindered heat avoidance (32-35°C) in C. elegans. No antinociceptive effect was observed 6h post Can A or B exposure. Proteomics and Reactome pathway enrichment analyses identified hierarchical differences between Can A- and B-treated nematodes. However, both treatments were related to eukaryotic translation initiation (R-CEL-72613) and metabolic processes strongly associated with pain development. Our study aids in characterizing the pharmacological activity of cannflavins isolated from Cannabis sativa and outlines a possible application as pain therapy.

The Effect of Capsaicin on Growth Performance, Antioxidant Capacity, Immunity and Gut Micro-Organisms of Calves.

Capsaicin is the active ingredient of the red pepper plant of the genus Capsicum. The aim of this study was to investigate the effects of different doses of capsaicin on growth performance, antioxidant capacity, immunity, fecal fermentation parameters and gut microbial composition in nursing calves. Twenty-four newborn Holstein calves were randomly assigned to three treatment groups, which each consisted of eight calves. The milk replacer was supplemented with 0, 0.15 or 0.3 mL/d of capsaicin in each of the three treatment groups. During the 4-week experiment, intake was recorded daily, body weight and body size parameters were measured at the beginning and end of the trial and serum samples and rectal fecal samples were collected at the end of the trial to determine serum parameters, fecal fermentation parameters and fecal microbiome compartments. The results showed that both doses of capsaicin had no negative effect on the growth performance or the fecal fermentation parameters of calves, and the higher dose (0.3 mL/d) of capsaicin significantly improved the antioxidant capacity and immunity of calves. The calves in the high-dose capsaicin-treated group had lower fecal scores than those recorded in the control group. High doses of capsaicin increased glutathione antioxidant enzyme, superoxide dismutase, immunoglobulin A, immunoglobulin G, immunoglobulin M and interleukin-10 levels and decreased malondialdehyde and bound bead protein levels. In addition, capsaicin regulated the gut microbiota, reducing the abundance of diarrhea-associated bacteria, such as Eggerthella, Streptococcus, Enterococcus and Enterobacteriaceae, in the gut of calves in the treated group. Therefore, high doses of capsaicin can improve the antioxidant and immune capacity of calves without affecting growth performance, as well as improve the gut microbiological environment, which enables the healthy growth of calves.

Effects of Capsaicin on Glucose Uptake and Consumption in Hepatocytes.

Obesity represents a major health challenge because it substantially increases the risk of metabolic diseases. Capsaicin, the major active ingredient of Capsicum spp., has been reported to possess anti-obesity activity. Hereon, the effect of capsaicin on glucose uptake and consumption in hepatocytes was extensively studied. Capsaicin was shown to accelerate the glucose uptake/consumption and the ATP production of hepatocytes. The elevation of intracellular Ca2+ was thought to be a potential mechanism. By transcriptome analysis, 78, 146 and 507 differentially expressed genes (DEGs) were identified between capsaicin and the control group for 4 h, 12 h and 24 h treatments. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that most of the DEGs were involved in canonical pathways, like MAPK and PI3K-AKT signaling pathways. Clustering analysis showed that many DEGs were associated with glucose and amino acid metabolism. The variation trend in genes related to glucose and amino acid metabolism (like CTH, VEGFA, PCK2 and IGFBP3) in the quantitative PCR (q-PCR) assay was consistent with the transcriptome data. These results demonstrated that capsaicin efficiently accelerated the glucose uptake and consumption of hepatocytes.

Sex dependent attenuating effects of capsaicin administration on the mechanoreflex in healthy rats.

Stimulation of mechanically sensitive channels on the sensory endings of group III and IV thin fiber muscle afferents activates the mechanoreflex which contributes to reflex increases in sympathetic nerve activity (SNA) and blood pressure during exercise. Accumulating evidence suggests that activation of the non-selective cation channel transient receptor potential vanilloid-1 (TRPV1) on the sensory endings of thin fiber afferents with capsaicin may attenuate mechanosensation. However, no study has investigated the effect of capsaicin on the mechanoreflex. We tested the hypothesis that in male and female decerebrate, unanesthetized rats, the injection of capsaicin (0.05 µg) into the arterial supply of the hindlimb reduces the pressor and renal SNA (RSNA) response to 30s of 1 Hz rhythmic hindlimb muscle stretch (a model of isolated mechanoreflex activation). In male rats (n=8), capsaicin injection significantly reduced the integrated blood pressure (blood pressure index or BPI; pre: 363±78, post: 211±88 mmHg×s; P=0.023) and RSNA (∫ΔRSNA; pre: 687±206, post: 216±80 a.u., P=0.049) response to hindlimb muscle stretch. In female rats (n=8), capsaicin injection had no significant effect on the pressor (BPI; pre: 277±67; post: 207±77 mmHg×s; P=0.343) or RSNA (∫ΔRSNA pre: 697±123; post: 440±183 a.u.; P=0.307) response to hindlimb muscle stretch. The data suggest that the injection of capsaicin into the hindlimb arterial supply to stimulate TRPV1 on the sensory endings of thin fiber muscle afferents attenuates the mechanoreflex in healthy male, but not female, rats. The findings may carry important implications for chronic conditions in which an exaggerated mechanoreflex contributes to aberrant sympathoexcitation during exercise.

Capsaicin functions as a selective degrader of STAT3 to enhance host resistance to viral infection.

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.

Uncovering Novel Capsaicin Inhibitory Activity towards Human Carbonic Anhydrase Isoforms IX and XII by Combining In Silico and In Vitro Studies.

Hot pepper (Capsicum annuum) represents one of the most widespread functional foods of the Mediterranean diet, and is associated with a reduced risk of developing cardiovascular disease, cancer, and mental disorders. In particular, its bioactive spicy molecules, named Capsaicinoids, exhibit polypharmacological properties. Among them, Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the most studied and reported in variegated scientific contributions for its beneficial effects, often linked to mechanisms of action unrelated to the activation of Transient Receptor Potential Vanilloid 1 (TRPV1). In this study, we present the application of in silico methods to Capsaicin for evaluating its inhibitory activity against the tumor-associated human (h) expressed CA IX and XII. In vitro assays confirmed Capsaicin inhibitory activity towards the most relevant tumor-related hCA isoforms. In particular, the hCAs IX and XII showed an experimental KI value of 0.28 μM and 0.064 μM, respectively. Then, an A549 model of non-small cell lung cancer, typically characterized by an elevated expression of hCA IX and XII, was employed to test the inhibitory effects of Capsaicin in vitro under both normoxic and hypoxic conditions. Finally, the migration assay revealed that Capsaicin [10 µM] inhibits cells from moving in the A549 cells model.

Cryopreservation of Ram Semen Using Capsaicin Supplemented Tris Extender

In this study, it was designed to reveal the effects of capsaicin on oxidative stress and freezability of ram semen. Ejaculates were taken from Sönmez rams and divided into five specimens and diluted with extender at different rates (4 mM, 2 mM, 1 mM, 500 µM) with and without capsaicin (control; C). At the end of the study, sperm motility and kinetic parameters, plasma membrane acrosome integrity (PMAI), mitochondrial membrane potential (MMP), DNA damage, oxidant and antioxidant parameters were analyzed. A decrease was observed in the groups containing capsaicin compared to the C in terms of progressive, total motility and kinetic parameters (p

Neuroprotective effect of transient receptor potential Vanilloid 1 agonist capsaicin in Alzheimer's disease model induced with okadaic acid.

The presence of Transient Receptor Potential Vanilloid 1 (TRPV1) channels was detected in many regions of the human and rat brain, including the cortex and hippocampus. TRPV1 channels have functions such as the modulation of synaptic transmission and plasticity and the regulation of cognitive functions. Previous studies conducted with TRPV1 agonists and antagonists show that this channel is associated with the neurodegenerative process. In the present study, the purpose was to investigate the effects of capsaicin, which is a TRPV1 agonist, and capsazepine, a TRPV1 antagonist, in the Alzheimer's Disease (AD) model that was induced by intracerebroventricular (ICV) administration of okadaic acid (OKA). The AD-like experimental model was created with bilateral ICV OKA injection. Intraperitoneal capsaicin and capsazepine injections were administered to the treatment groups for 13 days and histological and immunohistochemical examinations were performed from the cortex and hippocampal CA3 regions of the brain. The Morris Water Maze Test was used for spatial memory measurement. ICV OKA administration increased the levels of caspase-3, phosphorylated-tau-(ser396), Aβ, TNF-α, and IL1-β, from the cortex and hippocampal CA3 regions of the brain and decreased the phosphorylated-Glycogen synthase kinase-3 beta-(ser9) levels. In addition, the OKA administration corrupted the spatial memory. The TRPV1 agonist capsaicin reversed the pathological changes induced by ICV OKA administration, but not the TRPV1 antagonist capsazepine. It was found in the study that the administration of the TRPV1 agonist capsaicin reduced neurodegeneration, neuroinflammation, and deterioration in spatial memory in the AD model induced by OKA.

Capsaicin inhibits aortic valvular interstitial cell calcification via the redox-sensitive NFκB/AKT/ERK1/2 pathway

Calcific aortic valve stenosis (CAVS), the third most prevalent cardiovascular disorder is known to impose a huge social and economic burden on patients. However, no pharmacotherapy has yet been established. Aortic valve replacement is the only treatment option, although its lifelong efficacy is not guaranteed and involves inevitable complications. So, there is a crucial need to find novel pharmacological targets to delay or prevent CAVS progression. Capsaicin is well known for its anti-inflammatory and antioxidant properties and has recently been revealed to inhibit arterial calcification. We thus investigated the effect of capsaicin in attenuating aortic valve interstitial cells (VICs) calcification induced by pro-calcifying medium (PCM). Capsaicin reduced the level of calcium deposition in calcified VICs, along with reductions in gene and protein expression of the calcification markers Runx2, osteopontin, and BMP2. Based on Gene Ontology biological process and Kyoto Encyclopedia of Genes and Genomes pathway analysis oxidative stress, AKT and AGE–RAGE signaling pathways were selected. The AGE–RAGE signaling pathway activates oxidative stress and inflammation-mediated pathways including ERK and NFκB signaling pathways. Capsaicin successfully inhibited oxidative stress- and reactive oxygen species-related markers NOX2 and p22phox. The markers of the AKT, ERK1/2, and NFκB signaling pathways, namely, phosphorylated AKT, ERK1/2, NFκB, and IκBα were upregulated in calcified cells, while being significantly downregulated upon capsaicin treatment. Capsaicin attenuates VICs calcification in vitro by inhibition of redox-sensitive NFκB/AKT/ERK1/2 signaling pathway, indicating its potential as a candidate to alleviate CAVS.

Effect of Capsaicin on Pharmacokinetics and Pharmacodynamics of Nateglinide in normal and diabetic rats

The Cytochrome P-450 (CYP) enzymes present in the human body are responsible for the metabolism of most antidiabetic drugs. These CYP enzymes may metabolize the drugs either to active metabolites or to inactive metabolites. Some phytoconstituents which are present in vegetables, fruits and ayurvedic products will alter the activity of CYP enzymes. In the present research, the alterations in pharmacokinetics and pharmacodynamics of Nateglinide in the presence of a phytochemical like Capsaicin were studied. The study was conducted both in normal and diabetic rats. Rats were divided into different groups. Drug was administered as alone in one group and administered in combination with Capsaicin to other groups. After 8 days of treatment, the blood samples were collected and analysed. The Pharmacokinetic parameters like Cmax, tmax, AUC, MRT, Vd and ClT were estimated for all groups and compared. The mean blood glucose levels before and after treatments were recorded and compared among the groups. From the results, it could be concluded that the Capsaicin has inhibited the activity of CYP 2C9 and CYP 3A4 enzymes, thereby decreased the metabolism of drug which ultimately resulted in the increase of Cmax and AUC. The Capsaicin could raise the antidiabetic effect of drug.

Capsaicin fails to produce changes in contractile tension in large gut of neonate rats

Objectives: Capsaicin, the most pungent constituent of chilli pepper (Capsicum annuum L.), is known to alter the physiological activity of the gut. Capsaicin mediates its action through a transient receptor potential vanilloid type 1 (TRPV1) channel. The action of capsaicin on gut smooth muscle varies from segment to segment in different species. The earlier studies were carried out in adult animals only, and its status in the neonate gut, which is in a development stage, is not known. Objective: Therefore, the present study was done to assess the effect of capsaicin on the large gut of neonates. Materials and Methods: In an organ bath preparation, isometric contractions were recorded from segments of dissected rat colon and rectum. The gut segments were exposed to cumulative concentrations of capsaicin (0.01 nM–3 µM) and a capsaicin-induced contractile response was observed. TRPV1 receptor antagonist capsazepine (1 µM) and a nitric oxide synthase inhibitor, L-NAME (100 µM), were used to assess their blocking effect on capsaicin-induced contractile response. Results: Capsaicin raised contractile tension in the colon and rectum of adult rats but not in neonate rats. In adult rats, capsazepine pre-treatment (1 µM) failed to block the capsaicin-induced response in the colon, but in the lower concentrations, it increased contractile tension in the rectum. Pre-application of L-NAME (100 µM) potentiated capsaicin-induced response in the adult rectum and neonate’s colon but had no effect in the neonate rectum and adult colon. Capsaicin with a low concentration (0.01 nM–0.01 µM) increased contractile frequency in both the colon and rectum of adult rats. However, the effect of capsaicin on frequency was abolished at higher concentrations (0.01 µM–3 µM). A capsaicin-evoked change in contractile frequency in adult rats was blocked by capsazepine and L-NAME. At lower concentrations (0.01 nM–0.01 µM), capsaicin did not show any change in frequency in the neonatal colon, while a decrease in contractile frequency was observed with the higher concentrations (0.1 µM–3 µM) of capsaicin. In neonates, capsazepine pre-treatment produced changes in frequency for both the colon and rectum. However, pre-application of L-NAME decreased frequency in the neonate rectum but not in the colon. Conclusion: Capsaicin-induced changes in contractile activity may or may not involve TRPV1 or the Nitric Oxide (NO) pathway, depending on the part of the large gut and developmental maturity.

Enhanced Hypoglycemic Bioactivity via RAS/Raf-1/MEK/ERK Signaling Pathway by Combining Capsaicin and QUERCETIN from Chili Peppers.

This research work is designed and conducted to explore the joint effect of capsaicin and quercetin and the potential mechanism for the regulation of hyperglycemia. Insulin-resistance HepG2 cell model and high-fat diet combined with streptozotocin-induced type 2 diabetes mouse model are applied for the investigation. The results illustrate that capsaicin and quercetin can exert hypoglycemic effects via reducing the concentrations of serum lipids of total cholesterol, triglyceride and low-density lipoprotein cholesterol, decreasing hepatic enzyme activities of phosphoenolpyruvate, carboxykinase, and glucose-6-phosphatase, as well as improving the histopathological morphology of liver and pancreas tissues. After administration with capsaicin and quercetin, the relative protein expression abundance of Ras, Raf-1, MEK1/2, and ERK1/2 is obviously attenuated compared to diabetic mice. Capsaicin and quercetin at a ratio of 3:1 are generally determined as the optimal combination. Capsaicin and quercetin present in the chili pepper fruit can act in a synergistic way to alleviate hyperglycemia. This study provides supporting data for the discovery of novel anti-diabetic components and for the valorization of chili pepper industry.

Effects of endogenous capsaicin stress and fermentation time on the microbial succession and flavor compounds of chili paste (a Chinese fermented chili pepper)

Chili paste, is a popular traditional product derived from chili pepper, and its fermentation system is affected by the variable concentration of capsaicin, which originates from the peppers. In the present study, the effects of capsaicin and fermentation time on the microbial community and flavor compounds of chili paste were investigated. After capsaicin supplementation, the total acid was significantly decreased (p < 0.05) along with lower total bacteria, especially lactic acid bacteria. Lactiplantibacillus, Lactobacillus, Weissella, Issatchenkia, Trichoderma, and Pichia were the shared and predominant genera; whereas, the Bacteroides and Kazachstania abundance was significantly increased due to the selection effect of capsaicin over time. Additionally, alterations of the microbial interaction networks and their metabolic preferences led to less lactic acid content with greater accumulation of ethyl nonanoate, methyl nonanoate, etc. This study will provide a perspective for selecting chili pepper varieties and improving the quality of fermented chili paste.

Capsaicin: A Potential Treatment to Improve Cerebrovascular Function and Cognition in Obesity and Ageing.

Impaired cognition is the primary symptom of dementia, which can lead to functional disability and reduced quality of life among an increasingly ageing population. Ageing is associated with increased oxidative stress, chronic low-grade systemic inflammation, and endothelial dysfunction, which reduces cerebrovascular function leading to cognitive decline. Chronic low-grade systemic inflammatory conditions, such as obesity, exacerbate this decline beyond normal ageing and predispose individuals to neurodegenerative diseases, such as dementia. Capsaicin, the major pungent molecule of chilli, has recently demonstrated improvements in cognition in animal models via activation of the transient receptor potential vanilloid channel 1 (TRPV1). Capsaicin-induced TRPV1 activation reduces adiposity, chronic low-grade systemic inflammation, and oxidative stress, as well as improves endothelial function, all of which are associated with cerebrovascular function and cognition. This review examines the current literature on capsaicin and Capsimax, a capsaicin supplement associated with reduced gastrointestinal irritation compared to capsaicin. Acute and chronic capsaicin treatment can improve cognition in animals. However, studies adequately assessing the effects of capsaicin on cerebrovascular function, and cognition in humans do not exist. Capsimax may be a potentially safe therapeutic intervention for future clinical trials testing the effects of capsaicin on cerebrovascular function and cognition.

The effects of capsaicin intake on weight loss among overweight and obese subjects: A systematic review and meta-analysis of randomized controlled trials.

Animal studies have shown that capsaicin plays a positive role in weight management. However, the results in human research are controversial. Therefore, the present systematic review and meta-analysis aimed to evaluate the effect of capsaicin on weight loss in adults. We searched PubMed, Embase, China Biomedical Literature Database (CBM), Cochrane library and clinical registration center, identifying all randomized controlled trials (RCTs) published in English and Chinese to May 3, 2022. A random effect model was used to calculate the weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity between studies was assessed by the Cochran Q statistic and I-squared tests (I 2 ). Statistical analyses were performed using STATA version 15.1. P <0.05 were considered as statistically significant. From 2377 retrieved studies, 15 studies were finally included in the meta-analyses. Fifteen RCTs with 762 individuals were included in our meta-analysis. Compared with the control group, the supplementation of capsaicin resulted in significant reduction on body mass index (BMI) (WMD: -0.25 kg/m2, 95%CI=-0.35∼-0.15 kg/m2, P<0.05), body weight (BW) (WMD: -0.51 kg, 95%CI=-0.86∼-0.15 kg, P<0.05) and waist circumference (WC) (WMD: -1.12 cm, 95%CI=-2.00∼-0.24 cm, P<0.05). We found no detrimental effect of capsaicin on waist-to-hip ratio (WHR) (WMD: -0.05, 95%CI=-0.17∼0.06, P>0.05). The current meta-analysis suggests that capsaicin supplementation may have rather modest effects in reducing BMI, BW and WC for overweight or obese individuals.