Capsaicin is a bioactive compound found prominently in Capsicum annuum L. plants and takes on a pivotal role in their characteristic spiciness. Previous studies have delved into the potential analgesic effect of capsaicin in various oral conditions, such as oral neuropathic pain, trigeminal neuralgia, oral mucositis, temporomandibular joint disorders and burning mouth syndrome. Capsaicin has also demonstrated promise in inhibiting the proliferation of different oral cancer cell lines. Its antimicrobial properties have also been shown to inhibit the growth of oral pathogens associated with dental caries, periodontitis and oral candidiasis. However, to harness its benefits effectively, more studies are required to establish optimal dosages for pain relief while minimizing adverse effects. In addition, investigation of the effect of capsaicin on nonpathogenic oral bacteria and viruses is warranted. Human-based research is crucial for elucidating the biomolecular mechanisms underlying the properties of capsaicin, potentially leading to the development of more effective interventions for oral health problems.

The influence of extrinsic hand-feel touch cues on consumer experiences in food and beverage consumption is well established. However, their impact on trigeminal perception, particularly the oral irritation caused by capsaicin or spicy foods, is less understood. This study aimed to determine the existence of cross-modal associations between hand-feel touch and capsaicin-induced oral irritation. This study investigated whether these potential associations were driven by the sensory contributions of the hand-feel tactile materials (measured by instrumental physical parameters) or by affective responses (evaluated through hedonic scales and the self-reported emotion questionnaire, EsSense Profile®, by consumers). In our study, 96 participants tasted a capsaicin solution while engaging with nine hand-feel tactile materials, i.e., cardboard, linen, rattan, silicone, stainless steel, sandpaper (fine), sandpaper (rough), sponge, and towel. They subsequently rated their liking and emotional responses, perceived intensity of oral irritation, and the congruency between hand-feel tactile sensation and oral irritation. Instrumental measurements characterized the surface texture of the hand-feel tactile materials, which were correlated with the collected sensory data. The results revealed that unique cross-modal associations between hand-feel touch and capsaicin-induced oral irritation. Specifically, while sandpapers demonstrated high congruence with the sensation of oral irritation, stainless steel was found to be least congruent. These associations were influenced by both the common emotional responses (\"active,\" \"aggressive,\" \"daring,\" \"energetic,\" \"guilty,\" and \"worried\") evoked by the hand-feel tactile materials and the capsaicin, as well as by participants\' liking for the hand-feel tactile materials and the characteristics of the surface textures. This study provides empirical evidence of the cross-modality between hand-feel tactile sensations and capsaicin-induced oral irritation, opening new avenues for future research in this area.

The factors that contribute to pain after nerve injury remain incompletely understood. Laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) are common surgical techniques to correct refractive errors. After LASIK or PRK, a subset of patients suffers intense and persistent pain, of unknown origin, described by patients as feeling like shards of glass in their eye. Here, we evaluated a TRPV1 variant, p.V527M, found in a 49-y-old woman who developed corneal pain after LASIK and subsequent PRK enhancement, reporting an Ocular Surface Disease Index score of 100. Using patch-clamp and Ca2+ imaging, we found that the V527M mutation enhances the response to acidic pH. Increasing proton concentration induced a stronger leftward shift in the activation curve of V527M compared to WT, resulting in channel activity of the mutant in acidic pH at more physiological membrane potentials. Finally, comparing the responses to consecutive applications of different agonists, we found in V527M channels a reduced capsaicin-induced desensitization and increased sensitization by the arachidonic acid metabolite 12-hydroxyeicosatetraenoic acid (12-HETE). We hypothesize that the increased response in V527M channels to protons and enhanced sensitization by 12-HETE, two inflammatory mediators released in the cornea after tissue damage, may contribute to the pathogenesis of corneal neuralgia after refractive surgery.

Astringency, commonly described as a drying, roughening, and/or puckering sensation associated with polyphenol-rich foods affects their palatability. While the compounds eliciting astringency are known, its mechanism of action is debated. This study investigated the role of transient receptor potential (TRP) channels A1 and V1 in astringency perception. If TRP A1 or V1 have a functional role in astringency perception, then desensitizing these receptors should decrease perceived astringency. Thirty-seven panelists underwent unilateral lingual desensitization of TRP A1 and V1 channels using mustard oil and capsaicin, respectively. Panelists then evaluated four astringent stimuli: epicatechin (EC), epigallocatechin gallate (EGCG), tannic acid (TA) and potassium alum (Alum), via 2-AFC and intensity ratings. When TRPA1 receptors were desensitized on one half of the tongue via mustard oil, no significant differences were observed between the treated and untreated sides for both 2-AFC and intensity ratings. Similarly, when TRPV1 receptors were desensitized on one half of the tongue via capsaicin, no significant differences were observed between the treated and untreated sides for both 2-AFC and intensity ratings. These findings challenge the notion that TRP channels play a pivotal role in astringency perception.

Vanilloid analogs, which can activate transient receptor potential vanilloid 1 (TRPV1), have been classified into two types based on susceptibility to forskolin (FSK). Treatment of cells expressing TRPV1 with FSK enhances TRPV1 responses to capsaicin-type ligands while diminishing the responses to eugenol-type ligands. In this study, we determined the effect of FSK on the activation of TRPV1 stimulated with vanilloid ligands, through the influx of Ca2+ in HEK293T cells expressing TRPV1. Our findings suggest that the effects of FSK can be attributed to the phosphorylation of TRPV1, as evidenced by using a protein kinase A (PKA) inhibitor and TRPV1 mutants at potential phosphorylation sites. Furthermore, we examined the structure-activity relationship of 13 vanilloid analogs. Our results indicated that vanilloid compounds could be classified into three types, i.e., the previously reported two types and a novel type of 10-shogaol, by which TRPV1 activation was insusceptible to the FSK treatment.

The objective of this work was to determine whether the addition of phytogenic compounds based on essential oils (carvacrol, eugenol, cinnamaldehyde) and resinous pepper oil (capsaicin) to the diet of Jersey cows at the beginning of lactation affects anti-inflammatory, antioxidant and immunomodulatory responses, as well as whether there are effects of EO on blood metabolites, ruminal fermentation, digestibility and milk production and composition. Six primiparous cows (370.00 ± 17 kg body weight (BW); 13.02 kg dry matter intake (DMI); 21 days of lactation and average milk production of 20 ± 2 L per day) were allocated to crossed experimental design (2 × 2) with two experimental periods of 28 days and two treatments. Blood, milk and rumen fluid were collected and, at the end of each period, feed and feces samples were collected to evaluate the apparent digestibility of nutrients. The groups were control (CLT) without supplementation and treated (BEO) with the addition of 150 mg/kg of dry matter of the phytogenic to the concentrated portion of the diet. Cows in the BEO group had lower numbers of leukocytes (P ≤ 0.05) and lymphocytes (P ≤ 0.02), but total protein and globulin levels were higher on days 21 and 28 (P ≤ 0.01). In the BEO group, the levels of immunoglobulin A, immunoglobulin heavy chain and transferrin were higher (P ≤ 0.05). The levels of ceruloplasmin, haptoglobin and C-reactive protein were lower in the BEO group (P ≤ 0.05). Lipid peroxidation levels and protein carbonyl content were lower in the BEO group. The total antioxidant capacity (P ≤ 0.09) and the activity of glutathione S-transferase (P ≤ 0.03) and glutathione peroxidase (P ≤ 0.05) were higher in the BEO group. Cows in the BEO group had lower pH (P ≤ 0.05), acetic acid concentrations (P ≤ 0.01) and higher protozoa counts (P ≤ 0.01). Our results suggest that phytogenic supplementation has positive effects on the health of Jersey cows in early lactation, characterized by immunostimulant, antioxidant and anti-inflammatory effects.

Chronic low-grade inflammation (CLGI) is associated with obesity and is one of its pathogenetic mechanisms. Lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, is the principal cause of CLGI. Studies have found that capsaicin significantly reduces the relative abundance of LPS-producing bacteria. In the present study, TRPV1-knockout (TRPV1-/-) C57BL/6J mice and the intestinal epithelial cell line Caco-2 (TRPV1-/-) were used as models to determine the effect of capsaicin on CLGI and elucidate the mechanism by which it mediates weight loss in vivo and in vitro. We found that the intragastric administration of capsaicin significantly blunted increases in body weight, food intake, blood lipid, and blood glucose in TRPV1-/- mice fed a high-fat diet, suggesting an anti-obesity effect of capsaicin. Capsaicin reduced LPS levels in the intestine by reducing the relative abundance of Proteobacteria such as Helicobacter, Desulfovibrio, and Sutterella. Toll-like receptor 4 (TLR4) levels decreased following decreases in LPS levels. Then, the local inflammation of the intestine was reduced by reducing the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mediated by TLR4. Attenuating local intestinal inflammation led to the increased expression of tight junction proteins zonula occludens 1 (ZO-1) and occludin and the restoration of the intestinal barrier function. Capsaicin increased the expression of ZO-1 and occludin at the transcriptional and translational levels, thereby increasing trans-endothelial electrical resistance and restoring intestinal barrier function. The restoration of intestinal barrier function decreases intestinal permeability, which reduces the concentration of LPS entering the circulation, and reduced endotoxemia leads to decreased serum concentrations of inflammatory cytokines such as TNF-α and IL-6, thereby attenuating CLGI. This study sheds light on the anti-obesity effect of capsaicin and its mechanism by reducing CLGI, increasing our understanding of the anti-obesity effects of capsaicin. It has been confirmed that capsaicin can stimulate the expression of intestinal transmembrane protein ZO-1 and cytoplasmic protein occludin, increase the trans-epithelial electrical resistance value, and repair intestinal barrier function.

We aimed to investigate the role of capsaicin (CAP) in modulating lipopolysaccharide (LPS)-induced hepatic and intestinal inflammation, oxidative stress, and its colonic microflora in mice. Thirty healthy male Kunming mice with similar body weights were randomly assigned to three groups: the control group (CON), the LPS group, and the CAP group, with ten mice in each group. The CON and the LPS groups received a daily dose of normal saline, respectively, while the CAP group received an equivalent dose of CAP. On the 28th day of the experiment, the LPS and the CAP groups were intraperitoneally injected with LPS, while the CON group was injected with an equal volume of normal saline. The results lead to the following conclusions. Compared to the LPS group, CAP improved the loss of hepatic lobular structure and significantly increased the duodenal villus length and ratio of villus length to crypt depth. CAP increased hepatic and colon interleukin-10 (IL-10) and decreased IL-6, IL-1β, and tumor necrosis factor (TNF-α) levels. CAP also increased hepatic catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) expression, and decreased malondialdehyde (MDA) levels. CAP significantly increased the relative abundances of Mucispirillum, Helicobacter, Prevotellaceae-UCG-001, Colidextribacter, unclassified-f-Oscillospiraceae, and Odoribacter, some of which were closely related to hepatic and colonic immune and oxidative markers. CAP also decreased the overall content of short-chain fatty acids, except for propionic acid. Overall, CAP can regulate the colon microbiota and exert anti-inflammatory and antioxidant effects. Whether CAP exerts its anti-inflammatory and antioxidant effects by modulating the colonic microflora, mainly Mucispirillum spp. and Helicobacter spp., requires further investigation.

Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors among oral cancers, and its treatment is based on radio-chemotherapy and surgery, which always produces more serious side effects and sequelae. Traditional medicine can compensate for the shortcomings of modern medical treatments and play a better therapeutic role. Currently, active ingredients derived from plants are attracting the attention of researchers and clinical professionals. We examined capsaicin (CAP), an active ingredient isolated from Capsicum annuum (family Solanaceae), and explored the effect of CAP combined with cisplatin (DDP) on epithelial-mesenchymal transition (EMT) and TSCC cells migration. Our results demonstrated that Transforming growth factor-β1(TGF-β1) induced EMT and promoted cell migration in TSCC cells. CAP combined with DDP inhibits non-TGF-β1-induced or TGF-β1-induced EMT and migration. Mechanistically, the inhibition of non-TGF-β1-induced EMT and migration by CAP combined with DDP was mediated by the AMPK/mTOR pathway, whereas TGF-β1-induced EMT and migration were regulated by the Claudin-1/PI3K/AKT/mTOR pathway. A nude lung metastasis mouse model was established for in vivo validation. These results support our hypothesis that the combination of CAP and DDP inhibits TSCC metastasis. These data set the stage for further studies aimed at validating CAP as an effective active ingredient for enhancing chemotherapy efficacy and reducing the dosage and toxicity of chemotherapeutic drugs, ultimately paving the way for translational research and clinical trials for TSCC eradication.

Capsaicin, the most prominent pungent compound of chilli peppers, has been used in traditional medicine systems for centuries; it already has a number of established clinical and industrial applications. Capsaicin is known to act through the TRPV1 receptor, which exists in various tissues; capsaicin is hepatically metabolised, having a half-life correlated with the method of application. Research on various applications of capsaicin in different formulations is still ongoing. Thus, local capsaicin applications have a pronounced anti-inflammatory effect, while systemic applications have a multitude of different effects because their increased lipophilic character ensures their augmented bioavailability. Furthermore, various teams have documented capsaicin\'s anti-cancer effects, proven both in vivo and in vitro designs. A notable constraint in the therapeutic effects of capsaicin is its increased toxicity, especially in sensitive tissues. Regarding the traditional applications of capsaicin, apart from all the effects recorded as medicinal effects, the application of capsaicin in acupuncture points has been demonstrated to be effective and the combination of acupuncture and capsaicin warrants further research. Finally, capsaicin has demonstrated antimicrobial effects, which can supplement its anti-inflammatory and anti-carcinogenic actions.