Chemical composition and antifungal activity of Capsicum pepper aqueous extracts against plant pathogens and food spoilage fungi.

Capsicum pepper is a rich source of phytochemical compounds such as capsaicinoids, phenols, flavonoids, and so forth. Due to their antimicrobial and antioxidant potential all of these compounds have been assessed and used for both human and plant health benefits. Herein, three fresh varieties of Capsicum annuum (Cacho de Cabra, Bell pepper, and Hungarian Wax varieties) and one fresh and ripe variety of C. baccatum (Cristal) were evaluated. Capsaicin, dihydrocapsaicin, nordihydrocapsaicin and the phenolic content of Capsicum spp. extracts were characterised. The antifungal potential of capsaicinoids and antioxidant activities, and the ecotoxicity of each Capsicum spp. extract, using the model Galleria mellonella, were also evaluated. Phytochemical analyses showed that the Cristal and Hungarian Wax varieties presented the highest amount of capsaicin, dihydrocapsaicin, and nordihydrocapsaicin; while Bell Pepper had the highest phenol content and antioxidant activity. Capsaicinoids' standards and Capsicum spp. extracts showed fungistatic activity against the fungal strains assessed. For the fungal strains assessed, the fungistatic activities of capsaicinoids' standards were higher than those observed in Capsicum spp. extracts. The Hungarian Wax extracts inhibited slightly the growth of Aspergillus niger MUM05.11 and Fusarium oxysporum MUM16.143. Similarly, A. niger, F. oxysporum, Rhizopus arrhizus MUM16.05 and Alternaria sp. UFRO17.178 had their growth retarded by the use of Cacho de Cabra and Cristal extracts. Noticeable changes were observed in the fungal strains' morphologies, such as the presence of fragile fungal structures, pigmentation loss, variation in the reproductive structures size and the conidia number. Capsicum extracts weaken the growth of fungi, indicating their fungistatic potential. Considering the fungistatic potential and non-ecotoxicity of these extracts, it is possible to suggest their use as a tool for pest management in the agri-food sector, controlling the growth and reproduction of fungi without posing a risk to non-target biodiversity.

Unraveling TRPV1's Role in Cancer: Expression, Modulation, and Therapeutic Opportunities with Capsaicin.

Cancer is a global health challenge with rising incidence and mortality rates, posing significant concerns. The World Health Organization reports cancer as a leading cause of death worldwide, contributing to nearly one in six deaths. Cancer pathogenesis involves disruptions in cellular signaling pathways, resulting in uncontrolled cell growth and metastasis. Among emerging players in cancer biology, Transient Receptor Potential (TRP) channels, notably TRPV1, have garnered attention due to their altered expression in cancer cells and roles in tumorigenesis and progression. TRPV1, also known as the capsaicin receptor, is pivotal in cancer cell death and pain mediation, offering promise as a therapeutic target. Activation of TRPV1 triggers calcium influx and affects cell signaling linked to growth and death. Additionally, TRPV1 is implicated in cancer-induced pain and chemo-sensitivity, with upregulation observed in sensory neurons innervating oral cancers. Also, when capsaicin, a compound from chili peppers, interacts with TRPV1, it elicits a "hot" sensation and influences cancer processes through calcium influx. Understanding TRPV1's multifaceted roles in cancer may lead to novel therapeutic strategies for managing cancer-related symptoms and improving patient outcomes. The current review elucidates the comprehensive role of capsaicin in cancer therapy, particularly through the TRPV1 channel, highlighting its effects in various cells via different signaling pathways and discussing its limitations.

TRESK channel activation ameliorates migraine-like pain via modulation of CGRP release from the trigeminovascular system and meningeal mast cells in experimental migraine models.

AIMS: Accumulating evidence indicates the involvement of TRESK potassium channels in migraine, however, effects of TRESK activation on migraine-related mechanisms remain unclear. We explored effects of TRESK channel modulation on migraine-related behavioral and molecular markers in in-vivo and ex-vivo rat models of migraine. MAIN METHODS: The selective TRESK activator cloxyquin at different doses, the TRESK inhibitor A2764, and the migraine drug sumatriptan were tested alone or in different combinations in nitroglycerin (NTG)-induced in-vivo model, and in ex-vivo meningeal, trigeminal ganglion and brainstem preparations in which CGRP release was induced by capsaicin. Mechanical allodynia, CGRP and c-fos levels in trigeminovascular structures and meningeal mast cells were evaluated. KEY FINDINGS: Cloxyquin attenuated NTG-induced mechanical allodynia, brainstem c-fos and CGRP levels, trigeminal ganglion CGRP levels and meningeal mast cell degranulation and number, in-vivo. It also diminished capsaicin-induced CGRP release from ex-vivo meningeal, trigeminal ganglion and brainstem preparations. Specific TRESK inhibitor A2764 abolished all effects of cloxyquin in in-vivo and ex-vivo. Combining cloxyquin and sumatriptan exerted a synergistic effect ex-vivo, but not in-vivo. SIGNIFICANCE: Our findings provide the experimental evidence for the anti-migraine effect of TRESK activation in migraine-like conditions. The modulation of TRESK channels may therefore be an attractive alternative strategy to relieve migraine pain.

Temperature-Dependent Activation of Thermosensitive Transient Receptor Potential Channels.

Temperature detection is essential for the survival and perpetuation of any species. Thermoreceptors in the skin sense the body temperature and also the temperatures of the ambient air and the objects. In 1997, Dr. David Julius and his colleagues found that a receptor expressed in small-diameter primary sensory neurons was activated by capsaicin (the pungent chemical in hot pepper). This receptor was also activated by temperature above 42 °C. That was the first time that a thermal receptor in primary sensory neurons has been identified. This receptor is named transient receptor potential vanilloid 1 (TRPV1). Now, 11 thermosensitive TRP channels are known. In this chapter, we summarize the reports and analyze thermosensitive TRP channels in a variety of ways to clarify the activation mechanisms by which temperature changes are sensed.

TRPV1 corneal neuralgia mutation: Enhanced pH response, bradykinin sensitization, and capsaicin desensitization.

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.

Capsaicin Improves Systemic Inflammation, Atherosclerosis, and Macrophage-Derived Foam Cells by Stimulating PPAR Gamma and TRPV1 Receptors.

BACKGROUND: Capsaicin, a bioactive compound found in peppers, is recognized for its anti-inflammatory, antioxidant, and anti-lipidemic properties. This study aimed to evaluate the effects of capsaicin on atherosclerosis progression. METHODS: Apolipoprotein E knockout mice and their C57BL/6 controls were utilized to assess blood lipid profile, inflammatory status, and atherosclerotic lesions. We also examined the influence of capsaicin on cholesterol influx and efflux, and the role of TRPV1 and PPARγ signaling pathways in bone marrow-derived macrophages. RESULTS: Capsaicin treatment reduced weight gain, visceral adiposity, blood triglycerides, and total and non-HDL cholesterol. These improvements were associated with a reduction in atherosclerotic lesions in the aorta and carotid. Capsaicin also improved hepatic oxidative and inflammatory status. Systemic inflammation was also reduced, as indicated by reduced leukocyte rolling and adhesion on the mesenteric plexus. Capsaicin decreased foam cell formation by reducing cholesterol influx through scavenger receptor A and increasing cholesterol efflux via ATP-binding cassette transporter A1, an effect primarily linked to TRPV1 activation. CONCLUSIONS: These findings underscore the potential of capsaicin as a promising agent for atherosclerosis prevention, highlighting its comprehensive role in modulating lipid metabolism, foam cell formation, and inflammatory responses.

The use of capsicum oleoresin microparticles to mitigate hepatic damage and metabolic disorders induced by obesity.

Capsicum oleoresin has potential health benefits, particularly against obesity markers. Due to its high pungency, few studies have been done to explore the intake of this ingredient. The objective of this study was to use the Capsicum oleoresin (CO) microencapsulated into a high-fat diet to evaluate its metabolic effect on mice. Two formulation containing 15 % solids were prepared: the first (F1) with 5% CO and 95% emulsifier, and the second (F2) with 2.5% corn oil, 2.5% CO, and 95% emulsifier. These formulation were atomized in a spray dryer. Ultra-Performance Liquid Chromatography determined the capsaicin content for both formulations. Mice were divided into two groups: lean control (normocaloric AIN diet, n = 10) and high fat (HF diet: hypercaloric, n = 30), which were subdivided into three subgroups: HF control diet (n = 10); diet F1: HF + 20 % CO oleoresin microparticles (n = 10); and diet F2: HF + 20 % CO microparticles containing corn oil (n = 10). The animals treated with the microparticles showed lower glucose levels than the HF control. Mice fed with HF-containing CO microparticles had cholesterol blood levels similar to that of the lean group and lower (<100 mg/dL) than that of the HF control group (150 mg/dL). Capsicum oleoresin microparticles added to high-fat diets promoted lower weight gain and protected the liver against hepatic steatosis. Leptin levels for mice fed with HF diet plus CO microparticles averaged between 2 and 5 ng/ml, whereas the fat control group developed leptin resistance. Capsicum microparticles evidenced a protective effect against dyslipidemia compared to the fat control group, which suggests their use as a potential ingredient for the control of obesity.

The role of TRPA1 and TRPV1 in the perception of astringency.

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.

Capsaicin mitigates ventilator-induced lung injury by suppressing ferroptosis and maintaining mitochondrial redox homeostasis through SIRT3-dependent mechanisms.

BACKGROUND: Ventilator-induced lung injury (VILI) is one of the severe complications in the clinic concerning mechanical ventilation (MV). Capsaicin (CAP) has anti-inflammatory and inhibitory effects on oxidative stress, which is a significant element causing cellular ferroptosis. Nevertheless, the specific role and potential mechanistic pathways through which CAP modulates ferroptosis in VILI remain elusive. METHODS: VILI was established in vivo, and the pulmonary epithelial cell injury model induced by circulation stretching (CS) was established in vitro. Both mice and cells were pretreated with CAP. Transmission electron microscopy, ELISA, Western blot, immunofluorescence, RT-PCR, fluorescent probes, and other experimental methods were used to clarify the relationship between iron death and VILI in alveolar epithelial cells, and whether capsaicin alleviates VILI by inhibiting iron death and its specific mechanism. RESULTS: Ferroptosis was involved in VILI by utilizing in vivo models. CAP inhibited ferroptosis and alleviated VILI's lung damage and inflammation, and this protective effect of CAP was dependent on maintaining mitochondrial redox system through SITR3 signaling. In the CS-caused lung epithelial cell injury models, CAP reduced pathological CS-caused ferroptosis and cell injury. Knockdown SIRT3 reversed the role of CAP on the maintaining mitochondria dysfunction under pathological CS and eliminated its subsequent advantageous impacts for ferroptosis against overstretching cells. CONCLUSION: The outcomes showed that CAP alleviated ferroptosis in VILI via improving the activity of SITR3 to suppressing mitochondrial oxidative damage and maintaining mitochondrial redox homeostasis, illustrating its possibility as a novel therapeutic goal for VILI.

Anti-cancer activity of capsaicin and its analogs in gynecological cancers.

Capsaicin is the hot and pungent ingredient of chili peppers. It is a potent pain-relieving agent and is often present in over-the-counter analgesic lotions and creams. Several convergent studies reveal that capsaicin displays growth-suppressive activity in human cancers in vitro and in vivo. Apart from its growth-suppressive activity (as a single agent), capsaicin has been found to sensitize human cancer cells to the pro-apoptotic effects of chemotherapy and radiation. The first part of this book chapter discusses the anti-cancer activity of capsaicin in gynecological cancers in cell culture experiments and mouse models. Out of all gynecological cancers, the anti-cancer activity of capsaicin (and its analogs) has only been investigated in cervical cancers and ovarian cancers. The clinical development of capsaicin as a viable anti-cancer drug has remained challenging due to its poor bioavailability and aqueous solubility properties. In addition, the administration of capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, irritation in the gut, nausea diarrhea and vomiting. Two strategies have been investigated to overcome these drawbacks of capsaicin. The first is to encapsulate capsaicin in sustained release drug delivery systems. The second strategy is to design non-pungent capsaicin analogs which will retain the anti-tumor activity of capsaicin. The second part of this chapter provides an overview of the anti-neoplastic (and chemosensitization activity) of capsaicin analogs and capsaicin-based sustained release formulations in cervical and ovarian cancers. The design of selective non-pungent capsaicin analogs and capsaicin-based polymeric drug delivery systems may foster the hope of novel strategies for the treatment and management of gynecological cancers.

Analysis of changes in nutritional compounds of dried yellow chili after different processing treatments.

Dried yellow chili is highly appreciated by consumers due to its excellent quality and flavor. The quality of products is determined by the drying and storage methods. In this study, dried yellow chilis were processed by natural air drying and hot air drying methods and then stored under three conditions: ambient temperature, ambient temperature with light avoidance, and at 10 °C with light avoidance for 12 months. The changes in the bioactive compounds during this period were analyzed attempting to reveal correlations between the different treatments and these compounds, with the aim of providing references for maintaining the bioactive compounds of pepper products. The results showed that samples treated with hot air had higher levels of fatty acids, resulting in a more pronounced flavor. During storage, samples stored at 10 °C with light avoidance were more effective in preserving soluble solids, total protein content, total phenols, capsaicinoids and most fatty acids.

"Spicy Touch": Cross-modal associations between hand-feel touch and capsaicin-induced oral irritation.

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.

Lactational performance and hematological effects of capsaicin supplementation in dairy cows: A meta-analysis.

A meta-analysis was performed to investigate the effects of capsaicin (CAP) on lactational performance and blood chemistry and cell counts in dairy cattle. The database comprised 11 peer-reviewed studies published between 2011 and 2024. The overall effect of CAP, challenge (e.g., ketosis, glucose tolerance, LPS), and dose were considered explanatory variables in the analysis. Lactation performance response variables included DMI, milk yield (MY), ECM yield, feed efficiency (FE), milk components, and BW. Hematological response variables included red and white blood cell counts and blood BHB, total fatty acids, insulin, and glucose concentrations. Data were analyzed using random- and mixed-effect models in the "robumeta" package in RStudio. Milk yield was increased by 2.9% by CAP when compared with control. Capsaicin supplementation increased FE by 3.4% compared with control. Milk fat concentration and yield were also increased by CAP compared with control by 2.6% and 4.0%, respectively. Blood glucose concentrations were decreased 2.5% by CAP supplementation, whereas insulin levels were unaffected. Cows fed CAP during a challenge had higher MY and FE and tended to have lower blood glucose than their control counterparts. Overall, this analysis suggests that CAP supplementation may be directly affecting host physiology by altering glucose metabolism, but further research to define the mechanism is warranted.

Cell-free adipose tissue extracts as a novel treatment for rosacea by downregulating TRPV1.

Rosacea is a chronic inflammatory skin disease that typically affects the central facial area. Its main clinical symptoms include paroxysmal flushing, telangiectasia, and non-temporary erythema. Cell-free adipose tissue extracts (ATEs) are liquid components extracted from human adipose tissue that contain large amounts of growth factors. Despite the scar-reducing, anti-aging, and wound-healing effects of ATEs, the efficacy of ATEs in rosacea remains unknown. Therefore, the anti-rosacea effects of ATEs were investigated in human cathelicidin peptide (LL-37) induced rosacea mice and capsaicin (CAP)-stimulated HaCaT keratinocytes. In vitro, ATEs significantly reduced TRPV1 expression, intracellular calcium ions influx and the release of inflammatory factors (such as KLK5, IL-6, IL-8 and TNF-α) after intervening in CAP-stimulated cells. The in vivo results revealed that ATEs alleviated rosacea symptoms, such as erythema score, erythema area, transepidermal water loss, abnormal epidermal thickness, mast cell infiltration and telangiectasia upon downregulating TRPV1 and CD31 expression. Moreover, the up-regulated TRPV1 protein expression was also recovered by ATEs administration in vivo and in vitro. Meanwhile, ATEs demonstrated good biocompatibility. In summary, ATEs could be a potential therapeutic agent for rosacea by regulating inflammation and alleviating telangiectasia.

Role of phosphorylation and vanilloid ligand structure in ligand-dependent differential activations of transient receptor potential vanilloid 1.

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 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, that is the previously reported two types and a novel type of 10-shogaol, by which TRPV1 activation was insusceptible to the FSK treatment.

Topical capsaicin modulates the two-point discrimination threshold-Modulation depends on stimulation modality and intensity.

BACKGROUND: Spatial acuity concerns the ability to localize and discriminate sensory input and is often tested using the two-point discrimination threshold (2PDT). Sensitization of the pain system can affect the spatial acuity, but it is unclear how 2PDTs of different testing modalities are affected. The aim was to investigate if the 2PDTs for mechanical and heat stimulation at different intensities were modulated by topical capsaicin sensitization. METHODS: 30 healthy subjects were divided into either a capsaicin or a placebo group. The 2PDT was tested using two different modalities, mechanical and thermal (laser) delivered at innocuous and noxious intensities. The 2PDT were determined at baseline and re-assessed 48 h later. In the follow-up session, the subjects either had a capsaicin patch (8%) or placebo patch placed in the testing area for 30 min before re-testing the 2PDT. RESULTS: The 2PDT was highly dependent on stimulation modality and intensity. The lowest 2PDT was found for innocuous mechanical stimuli (40.0 mm, 95% CI 38.1-41.9 mm), and the highest 2PDT was found for innocuous thermal stimuli (81.7 mm, 95% CI 73.9-89.5 mm). Topical capsaicin generally increased the 2PDT, but this was only significant for innocuous mechanical stimuli. The perceived intensity of the stimuli was increased following capsaicin and was generally higher for noxious stimuli than for innocuous stimuli (ANOVA, p < 0.001). CONCLUSIONS: This study showed that capsaicin provoked pain sensitization increased the 2PDT. The 2PDT tested using innocuous mechanical stimuli showed less variable results indicating that this test is most suitable to detect this aspect of spatial acuity. SIGNIFICANCE STATEMENT: This study investigated how the two-point discrimination threshold (2PDT) can be modulated by topical capsaicin. The 2PDT was assessed for two different modalities (thermal and mechanical) and for two different intensities (innocuous and noxious) before and after capsaicin. The results showed that the 2PDT was generally impaired following capsaicin, but this was only significant for mechanical innocuous stimuli. Furthermore, it was shown that mechanical innocuous stimuli assessed the 2PDT with lower variability than other combinations.

Dietary capsaicin attenuates cardiac injury after myocardial infarction in type 2 diabetic mice by inhibiting ferroptosis through activation of TRPV1 and Nrf2/HMOX1 pathway.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major 21st-century epidemic. T2DM elevates the risk of myocardial infarction and heart failure while also reducinges survival rates. Recently Ferroptosis has been found to be involved in the development of various cardiovascular diseases. TRPV1 is also a potential therapeutic target for cardioprotection. This study explores whether capsaicin, a transient receptor potential vanilloid receptor 1 (TRPV1) agonist, can prevent diabetic myocardial infarction-induced injury by inhibiting ferroptosis. METHODS: T2DM model was induced by high-fat diet (HFD) feeding combined with streptozocin (STZ) injections, and the diabetic mice were treated with capsaicin(0.015 %) in their food. Myocardial infarction model was established as well. Mouse' general characteristics, cardiac function, and morphological histology were observed and analyzed. RNA-seq was used to investigate the possible mechanism of injury in AC16 cardiomyocytes cultured with high glucose and hypoxia. In addition, the potential mechanism of capsaicin against injury was further investigated in AC16 cardiomyocytes cultured with high glucose and hypoxia. RESULTS: The RNA-seq analysis revealed that ferroptosis was associated with cell death induced by high-glucose in combination with hypoxia, and CAP treatment could effectively inhibit ferroptosis to enhance cell survival. In vivo studies demonstrated that CAP treatment significantly improved post-MI cardiac function, attenuated myocardial inflammation and fibrosis. Furthermore, it was observed that CAP reduced ferroptosis levels by activating TRPV1 in the heart, upregulating Nrf2 expression, promoting Nrf2 nuclear translocation and increasing the expression of the Nrf2 downstream molecule Heme oxygenase-1 (HMOX1). CONCLUSIONS: Dietary capsaicin may inhibit cardiomyocyte ferroptosis through activation of myocardial TRPV1 and Nrf2/HMOX1 signaling pathway, which in turn exerts a protective effect on the myocardium after myocardial infarction in type 2 diabetic mice.

Electroacupuncture Alleviates Streptozotocin-Induced Diabetic Neuropathic Pain via the TRPV1-Mediated CaMKII/CREB Pathway in Rats.

Diabetic neuropathic pain (DNP) is a diabetic complication that causes severe pain and deeply impacts the quality of the sufferer's daily life. Currently, contemporary clinical treatments for DNP generally exhibit a deficiency in effectiveness. Electroacupuncture (EA) is recognized as a highly effective and safe treatment for DNP with few side effects. Regrettably, the processes via which EA alleviates DNP are still poorly characterized. Transient receptor potential vanilloid 1 (TRPV1) and phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMKII) are overexpressed on spinal cord dorsal horn (SCDH) in DNP rats, and co-localization is observed between them. Capsazepine, a TRPV1 antagonist, effectively reduced nociceptive hypersensitivity and downregulated the overexpression of phosphorylated CaMKIIα in rats with DNP. Conversely, the CaMKII inhibitor KN-93 did not have any impact on TRPV1. EA alleviated heightened sensitivity to pain caused by nociceptive stimuli and downregulated the level of TRPV1, p-CaMKIIα, and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) in DNP rats. Intrathecal injection of capsaicin, on the other hand, reversed the above effects of EA. These findings indicated that the CaMKII/CREB pathway on SCDH is located downstream of TRPV1 and is affected by TRPV1. EA alleviates DNP through the TRPV1-mediated CaMKII/CREB pathway.

Influence of ultrasonic pretreatment on the quality attributes and pectin structure of chili peppers (Capsicum spp.).

Chili peppers (Capsicum spp.) exhibit a diverse range of quality characteristics and pectin structures, which are influenced by various factors. This study aimed to investigate the effects of ultrasound (US), ultrasonic combined hot blanching (US-BL), and ultrasonic combined freezing and thawing (US-FT) on the quality characteristics and pectin structure of vacuum pulsation-dried (VP) chili peppers. The results indicated that US-BL samples exhibited the highest L* and a* values, retained maximum capsorubin, and showed an increase in vitamin C, total phenols, and rehydration by 14.28 %, 40.87 %, and 8.66 %, respectively. In contrast, the US-FT samples exhibited the highest capsaicin and dihydrocapsaicin content, which increased by 54.97 % and 64.04 %, respectively. Pretreatment resulted in higher pectin linearity, a lower degree of branching, and a reduced molecular weight in the US-BL sample. Atomic force microscopy confirmed the degrading effect of pretreatment on the pectin structure. Pearson's correlation analysis revealed that capsorubin, capsaicin analogs, vitamin C, and total phenols were highly correlated with pectin linearity and molecular weight. This study found that US-BL was the most effective pretreatment method for improving the quality of pulsatile chili peppers and provides theoretical support for the application of VP chili peppers.

Orofacial antinociceptive activity of codeine-associated geraniol in mice: a controlled triple-blind study.

This is a nonclinical, controlled, and triple-blind study to investigate the effects of codeine-associated geraniol on the modulation of orofacial nociception and its potential central nervous system depressing effect in an animal model. The orofacial antinociceptive activity of geraniol in combination with codeine was assessed through the following tests: (i) formalin-induced pain, (ii) glutamate-induced pain, and (iii) capsaicin-induced pain. Six animals were equally distributed into six groups and received the following treatments, given intraperitoneally (i.p.) 30 minutes before the experiments: a) geraniol/codeine 50/30 mg/kg; b) geraniol/codeine 50/15 mg/kg; c) geraniol/codeine 50/7.5 mg/kg; d) geraniol 50 mg/kg; e) codeine 30 mg/kg (positive control); or f) 0.9% sodium chloride (negative control). We performed pain behavior analysis after the injection of formalin (20 µL, 20%), glutamate (20 µL, 25 µM), and capsaicin (20 µL, 2.5 µg) into the paranasal region. Rubbing time of the paranasal region by the hind or front paw was used as a parameter. In the neurogenic phase of the formalin test, the geraniol/codeine at 50/7.5 mg/kg was able to promote the maximum antinociceptive effect, reducing nociception by 71.9% (p < 0.0001). In the inflammatory phase of the formalin test, geraniol/codeine at 50/30 mg/kg significantly reduced orofacial nociception (p < 0.005). In the glutamate test, geraniol/codeine at 50/30 mg/kg reduced the rubbing time by 54.2% and reduced nociception in the capsaicin test by 66.7% (p < 0.005). Geraniol alone or in combination does not promote nonspecific depressing effects on the central nervous system. Based on our findings, we suggest the possible synergy between geraniol and codeine in the modulation of orofacial pain.