Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders.

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.

Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation.

Background: Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Methods: Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalininduced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX- 2, PGE2, IL-1ß, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Results: Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenantriggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF- κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1ß, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Conclusions: Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.

UHPLC-qTOF-MS-Based Nontargeted Metabolomics to Characterize the Effects of Capsaicin on Plasma and Skin Metabolic Profiles of C57BL/6 Mice-An In vivo Experimental Study.

Background: Capsaicin is the main compound found in chili pepper and has complex pharmacologic effects. This study aimed to elucidate the mechanism of the effect of capsaicin on physiological processes by analyzing changes in metabolites and metabolic pathways. Methods: Female C57BL/6 mice were divided into two groups(n = 10/group) and fed with capsaicin-soybean oil solution(group T) or soybean oil(group C) for 6 weeks. Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) based metabolomics was undertaken to assess plasma and skin metabolic profile changes and identify differential metabolites through multivariate analysis. Results: According to the OPLS-DA score plots, the plasma and skin metabolic profiles in the group T and group C were significantly separated. In plasma, 38 significant differential metabolites were identified. KEGG pathway enrichment analysis revealed that the most significant plasma metabolic pathways included pyruvate metabolism and ABC transporters. In skin, seven significant differential metabolites were found. Four metabolic pathways with p values < 0.05 were detected, including sphingolipid metabolism, sphingolipid signaling pathway, apoptosis, and necroptosis. Conclusion: These findings will provide metabolomic insights to assess the physiological functions of capsaicin and contribute to a better understanding of the potential effects of a capsaicin-rich diet on health.

Therapeutic Potential of Capsaicin in Various Neurodegenerative Diseases with Special Focus on Nrf2 Signaling.

Neurodegenerative disease is mainly characterized by the accumulation of misfolded proteins, contributing to mitochondrial impairments, increased production of proinflammatory cytokines and reactive oxygen species, and neuroinflammation resulting in synaptic loss and neuronal loss. These pathophysiological factors are a serious concern in the treatment of neurodegenerative diseases. Based on the symptoms of various neurodegenerative diseases, different treatments are available, but they have serious side effects and fail in clinical trials, too. Therefore, treatments for neurodegenerative diseases are still a challenge at present. Thus, it is important to study an alternative option. Capsaicin is a naturally occurring alkaloid found in capsicum. Besides the TRPV1 receptor activator in nociception, capsaicin showed a protective effect in brain-related disorders. Capsaicin also reduces the aggregation of misfolded proteins, improves mitochondrial function, and decreases ROS generation. Its antioxidant role is due to increased expression of an nrf2-mediated signaling pathway. Nrf2 is a nuclear erythroid 2-related factor, a transcription factor, which has a crucial role in maintaining the normal function of mitochondria and the cellular defense system against oxidative stress. Intriguingly, Nrf2 mediated pathway improved the upregulation of antioxidant genes and inhibition of microglial-induced inflammation, improved mitochondrial resilience and functions, leading to decreased ROS in neurodegenerative conditions, suggesting that Nrf2 activation could be a better therapeutic approach to target pathophysiology of neurodegenerative disease. Therefore, the present review has evaluated the potential role of capsaicin as a pharmacological agent for the treatment and management of various neurodegenerative diseases via the Nrf2-mediated signaling pathway.

Capsaicin: A chili pepper bioactive phytocompound with a potential role in suppressing cancer development and progression.

Cancer profoundly influences morbidity and fatality rates worldwide. Patients often have dismal prognoses despite recent improvements in cancer therapy regimens. However, potent biomolecules derived from natural sources, including medicinal and dietary plants, contain biological and pharmacological properties to prevent and treat various human malignancies. Capsaicin is a bioactive phytocompound present in red hot chili peppers. Capsaicin has demonstrated many biological effects, including antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic capabilities. This review highlights the cellular and molecular pathways through which capsaicin exhibits antineoplastic activities. Our work also depicts the synergistic anticancer properties of capsaicin in conjunction with other natural bioactive components and approved anticancer drugs. Capsaicin inhibits proliferation in various cancerous cells, and its antineoplastic actions in numerous in vitro and in vivo carcinoma models impact oncogenesis, tumor-promoting and suppressor genes, and associated signaling pathways. Capsaicin alone or combined with other phytocompounds or approved antineoplastic drugs triggers cell cycle progression arrest, generating reactive oxygen species and disrupting mitochondrial membrane integrity, ultimately stimulating caspases and promoting death. Furthermore, capsaicin alone or in combination can promote apoptosis in carcinoma cells by enhancing the p53 and c-Myc gene expressions. In conclusion, capsaicin alone or in combination can have enormous potential for cancer prevention and intervention, but further high-quality studies are needed to firmly establish the clinical efficacy of this phytocompound.

Alterations of rumen and fecal microbiome in growing beef and dairy steers fed rumen-protected Capsicum oleoresin.

The microbiome has been linked to animal health and productivity, and thus, modulating animal microbiomes is becoming of increasing interest. Antimicrobial growth promoters (AGP) were once a common technology used to modulate the microbiome, but regulation and consumer pressure have decreased AGP use in food animals. One alternative to antimicrobial growth promoters are phytotherapeutics, compounds derived from plants. Capsaicin is a compound from the Capsicum genus, which includes chili peppers. Capsaicin has antimicrobial properties and could be used to manipulate the gastrointestinal microbiome of cattle. Both the rumen and fecal microbiomes are essential to cattle health and production, and modulation of either microbiome can affect both cattle health and productivity. We hypothesized that the addition of rumen-protected capsaicin to the diet of cattle would alter the composition of the fecal microbiome, but not the rumen microbiome. To determine the impact of rumen-protected capsaicin in cattle, four Holstein and four Angus steers were fed rumen-protected Capsicum oleoresin at 0 (Control), 5, 10, or 15 mg kg-1 diet dry matter. Cattle were fed in treatment groups in a 4 × 4 Latin Square design with a 21-d adaptation phase and a 7-d sample collection phase. Rumen samples were collected on day 22 at 0-, 2-, 6-, 12-, and 18-h post-feeding, and fecal swabs were collected on the last day of sample collection, day 28, within 1 h of feeding. Sequencing data of the 16s rRNA gene was analyzed using the dada2 pipeline and taxa were assigned using the SILVA database. No differences were observed in alpha diversity among fecal or rumen samples for either breed (P > 0.08) and no difference between groups was detected for either breed in rumen samples or for Angus steers in fecal samples (P > 0.42). There was a difference in beta diversity between treatments in fecal samples of Holstein steers (P < 0.01), however, a pairwise comparison of the treatment groups suggests no difference between treatments after adjusting for multiple comparisons. Therefore, we were unable to observe substantial overall variation in the rumen or fecal microbiomes of steers due to increasing concentrations of rumen-protected capsaicin. We do, however, see a trend toward increased concentrations of capsaicin influencing the fecal microbiome structure of Holstein steers despite this lack of significance.

The microbiome is the collection of microbes present in an animal's body and has been discovered to be directly connected to animal health and productivity. In production animals, such as feedlot cattle, the microbiome can be modulated by antimicrobials to promote growth, but increasing consumer pressure to reduce antimicrobial use has producers seeking alternatives. Capsaicin is a phytotherapeutic derived from chili peppers that can be used to modulate the microbiome due to its antimicrobial properties. Eight steers were fed rumen-protected Capsicum oleoresin to determine its effect on average daily gain. In addition, rumen and fecal samples were collected for microbiome testing. No differences were detected in the rumen microbiomes between cattle fed capsaicin (treatment) or those that received no capsaicin (control). While no overall effect was observed on the fecal microbiome of cattle fed different doses of capsaicin or control, we did observe changes in fecal beta diversity due to capsaicin treatment in Holstein steers fed greater doses. The fecal microbiome structure of Holsteins fed greater dosages of capsaicin differed from those fed control or low doses, as observed by the presence of two distinct clusters. This observation suggests an impact of greater doses of capsaicin treatment on microbiome structure.

Ten weeks of Capsicum annuum L. extract supplementation did not change adipose tissue-derived hormones, appetite, body composition, and muscle strength when combined with resistance training in healthy untrained men: A clinical trial study.

Capsiate (CAP) is a nonpungent capsaicin analog (Capsicum annuum L. extract) that has been studied as a potential antiobesity agent. However, the interaction between chronic CAP supplementation and resistance training is not clear. The purpose of this study was to examine the changes in adipose tissue-derived hormones, body composition, appetite, and muscle strength after 10 weeks of resistance training, combined with chronic CAP supplementation in healthy untrained men. We hypothesized that CAP could induce higher benefits when combined with resistance training after 10 weeks of intervention compared to resistance training alone. Twenty-four young men (age, 22.0 ± 2.9) were randomized to either capsiate supplementation (CAP = 12 mg/day) or placebo (PL), and both groups were assigned to resistance training. Body composition, leptin and adiponectin concentrations, subjective ratings of appetite, energy intake, and exercise performance were assessed at before and after 10 weeks of progressive resistance training. There was a significant increase in body mass (P < .001), fat-free mass (CAP: 58.0 ± 7.1 vs. post, 59.7 ± 7.1 kg; PL: pre, 58.4 ± 7.3 vs. post, 59.8 ± 7.1 kg; P < .001), resting metabolic rate (CAP: pre, 1782.9 ± 160.6 vs. post, 1796.3 ± 162.0 kcal; PL: pre, 1733.0 ± 148.9 vs. post, 1750.5 ± 149.8 kcal; P < .001), maximal strength at 45 leg press (P < .001) and bench press (P < .001) in both groups, but no significant (P > .05) supplementation by training period interaction nor fat mass was observed. For subjective ratings of appetite, energy intake, leptin, and adiponectin, no significant effect of supplementation by training period interaction was observed (P > .05). In conclusion, 10 weeks of resistance training increased total body weight, muscle mass, and maximum strength in healthy untrained men; however, CAP supplementation (12 mg, 7 days per week) failed to change adipose tissue-derived hormones, appetite, body composition and muscle strength in this population. Registered under Brazilian Registry of Clinical Trials (RBR-8cz9kfq).

Phenolic Compounds and Capsaicinoids in Three Capsicum annuum Varieties: From Analytical Characterization to In Silico Hypotheses on Biological Activity.

The affinity of specific phenolic compounds (PCs) and capsaicinoids (CAPs) present in three Capsicum annuum varieties (Friariello, Cayenne and Dzuljunska Sipka) to the transient receptor potential vanilloid member 1 (TRPV1) was investigated by integrating an analytic approach for the simultaneous extraction and analysis through high-performance liquid chromatography coupled with ion trap mass spectrometry (HPLC/ITMS) and UV detection (HPLC-UV) of PCs and CAPs and structural bioinformatics based on the protein modelling and molecular simulations of protein-ligand docking. Overall, a total of 35 compounds were identified in the different samples and CAPs were quantified. The highest content of total polyphenols was recorded in the pungent Dzuljunska Sipka variety (8.91 ± 0.05 gGAE/Kg DW) while the lowest was found in the non-pungent variety Friariello (3.58 ± 0.02 gGAE/Kg DW). Protein modelling generated for the first time a complete model of the homotetrameric human TRPV1, and it was used for docking simulations with the compounds detected via the analytic approach, as well as with other compounds, as an inhibitor reference. The simulations indicate that different capsaicinoids can interact with the receptor, providing details on the molecular interaction, with similar predicted binding energy values. These results offer new insights into the interaction of capsaicinoids with TRPV1 and their possible actions.

Targeting TRPV1 and TRPA1: A feasible strategy for natural herbal medicines to combat postoperative ileus.

Under physiological or pathological conditions, transient receptor potential (TRP) channel vanilloid type 1 (TRPV1) and TRP ankyrin 1 (TRPA1) possess the ability to detect a vast array of stimuli and execute diverse functions. Interestingly, increasing works have reported that activation of TRPV1 and TRPA1 could also be beneficial for ameliorating postoperative ileus (POI). Increasing research has revealed that the gastrointestinal (GI) tract is rich in TRPV1/TRPA1, which can be stimulated by capsaicin, allicin and other compounds. This activation stimulates a variety of neurotransmitters, leading to increased intestinal motility and providing protective effects against GI injury. POI is the most common emergent complication following abdominal and pelvic surgery, and is characterized by postoperative bowel dysfunction, pain, and inflammatory responses. It is noteworthy that natural herbs are gradually gaining recognition as a potential therapeutic option for POI due to the lack of effective pharmacological interventions. Therefore, the focus of this paper is on the TRPV1/TRPA1 channel, and an analysis and summary of the processes and mechanism by which natural herbs activate TRPV1/TRPA1 to enhance GI motility and relieve pain are provided, which will lay the foundation for the development of natural herb treatments for this disease.

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

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

Peppers and their constituents against obesity.

Phytotherapy can be an efficient tool for prevention and treatment of disorders including obesity. The purpose of this narrative review is to summarize the available knowledge concerning the positive effects of peppers (Capsicum spp.) and their alkaloid capsaicin on human health, in particular on fat and obesity. Search for literature was performed in Medline/Pubmed, Web of Science and SCOPUS databases between the year 2000 and 2023. Words used to search were pepper, Capsicum, capsaicin, review, obesity, fat, weight loss and mechanisms. The available data demonstrate that both pepper extract and capsaicin can positively influence human health and treat several disorders. Moreover, they can reduce fat storage affecting brain centres responsible for the sensation of hunger, nutrient uptake by gastrointestinal tract, state of adipocytes, increase in carbohydrate and fat oxidation, metabolism and thermogenesis and other mechanisms. Therefore, despite some possible limitations, these substances could be useful for treatment of obesity.

A Little Pepper-Upper? Systematic Review of Randomized Controlled Studies on Capsaicinoids, Capsinoids, and Exercise Performance.

Capsaicinoids and capsinoids are bioactive compounds mostly found in peppers. Although preclinical studies have reported that these compounds can improve exercise performance due to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated thermogenesis, sympathetic modulation, and releasing calcium, it is still unclear how they affect exercise performance in humans as ergogenic supplements. Conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guide 2020, this systematic review examined the ergogenic effect of capsaicinoids and capsinoids on exercise performance in healthy adults. A total of 19 randomized placebo-controlled trials were included in the study. Studies were accessed by searching five databases (PubMed, Scopus, SPORTDiscus, Web of Science, and Cochrane Library). The quality of the studies was evaluated using the Cochrane risk-of-bias assessment tool. According to the study results, 10 studies examining the effect of capsaicinoid and capsinoid supplements on exercise performance reported positive effects. Also, the effect of capsaicinoids and capsinoids on exercise performance is more pronounced in resistance training. This difference, which varies according to the type of exercise, may be due to the correlation between capsaicin transient receptor potential vanilloid subtype 1 and insulin-like growth factor-1.

Capsaicin derived from endemic chili landraces combats Shigella pathogen: Insights on intracellular inhibition mechanism.

Ethnic tribals in northeast India have been growing and maintaining local chili landraces for ages. These chilies are known for their characteristic pungency and immense therapeutic properties. Capsaicin, a significant chili metabolite, is recognized as a natural drug for pain relief, diabetic neuropathy, psoriasis, arthritis, etc. In this study, we tried to observe the influence of locality factors on the pungency and bioactive features of Capsicum annuum L. landraces. We also checked the gastro-protective ability of these chilies, especially in the cure of shigellosis. Phytometabolite characterization and estimation were done through spectrophotometric methods. Preparative and analytical HPLC techniques were employed for extracting and purifying capsaicin-enriched fractions. Shigella flexneri growth retardation was determined through the broth dilution method. Gentamicin protection assay and ELISA were done to assess the intracellular invasion and IL-1ß inflammasome production by S.flexneri. The correlation analyses postulated that phenols, flavonoids, chlorophylls, ß-carotene, and capsaicin synthase upregulation strongly influenced capsaicin biosynthesis in chili cultivars. Correspondingly, the inhibitory efficacy of the HPLC-purified Balijuri-derived capsaicin was more effective than the Raja-derived capsaicin in inhibiting intracellular Shigella growth. Reduced levels of pro-inflammatory cytokine (IL1ß) in capsaicin-treated Shigella-infected cells probably reduced inflammation-mediated intestinal damage, limiting bacterial spread. This investigation advocates the unique potential of local chilies in curing deadly 'shigellosis' with mechanistic evidence. Our observation justifies the traditional healing practices of the ethnic people of NE India.

The Vanilloid (Capsaicin) Receptor TRPV1 in Blood Pressure Regulation: A Novel Therapeutic Target in Hypertension?

Today's sedentary lifestyle with excess food and little exercise increases the number of people with hypertension, a major risk factor for stroke. New knowledge of treatments in this field is of utmost importance. In animal experiments, the activation by capsaicin of TRPV1-expressing sensory afferents evokes a drop in blood pressure by triggering the Bezold-Jarisch reflex. In hypertensive rats, capsaicin reduces blood pressure. Conversely, genetic ablation of the TRPV1 receptor results in elevated nocturnal (but not diurnal) blood pressure. These observations imply a therapeutic potential for TRPV1 activation in hypertensive patients. Indeed, in a major epidemiological study involving 9273 volunteers, dietary capsaicin was found to lower the risk for hypertension. New research indicates that the mechanism of action of capsaicin on blood pressure regulation is far more complex than previously thought. In addition to the well-recognized role of capsaicin-sensitive afferents in blood pressure regulation, TRPV1 seems to be expressed both in endothelial cells and vascular smooth muscle. This review aims to evaluate the therapeutic potential of TRPV1-targeting drugs in hypertensive patients.

Therapeutic potential of phytochemicals for cystic fibrosis.

The aim of this review was to review and discuss various phytochemicals that exhibit beneficial effects on mutated membrane channels, and hence, improve transmembrane conductance. These therapeutic phytochemicals may have the potential to decrease mortality and morbidity of CF patients. Four databases were searched using keywords. Relevant studies were identified, and related articles were separated. Google Scholar, as well as gray literature (i.e., information that is not produced by commercial publishers), were also checked for related articles to locate/identify additional studies. The relevant databases were searched a second time to ensure that recent studies were included. In conclusion, while curcumin, genistein, and resveratrol have demonstrated effectiveness in this regard, it should be emphasized that coumarins, quercetin, and other herbal medicines also have beneficial effects on transporter function, transmembrane conductivity, and overall channel activity. Additional in vitro and in vivo studies should be conducted on mutant CFTR to unequivocally define the mechanism by which phytochemicals alter transmembrane channel function/activity, since the results of the studies evaluated in this review have a high degree of heterogenicity and discrepancy. Finally, continued research be undertaken to clearly define the mechanism(s) of action and the therapeutic effects that therapeutic phytochemicals have on the symptoms observed in CF patients in an effort to reduce mortality and morbidity.

The translational implications of the science behind the overactive bladder and the role of OnabotulinumtoxinA.

Urinary incontinence (UI) is a very common condition that can affect patients of all ages and the commonest cause is an overactive bladder (OAB). Most patients with OAB were treated with pharmacotherapy and major surgery. Over 25 years ago, Dasgupta, Fowler et al. studied the presence and role of C fibres in the human bladder which are highly sensitive to capsaicin, the active ingredient of chillies. When capsaicin was instilled into patients' bladders as a synthetic solution, it was found to be highly effective in some patients. Capsaicin was later replaced by Resiniferatoxin. Both toxins desensitised C-fibres through the capsaicin receptor, TRPV1, without any lasting damage to the bladder itself. The discovery of botulinum toxin and its use in the treatment of OAB represents a major breakthrough, in the treatment of OAB. Another key innovation was the development of technique to administer the drug under local anaesthesia which allowed numerous patients to benefit from treatment who would otherwise have been precluded because of the need for injection under general anaesthetic. After extensive trials over many years Botox (OnabotulinumtoxinA) is now licensed for use in OAB. Compared to other treatments for overactive bladder, OnabotulinumtoxinA is more cost-effective and less invasive. It is thought to have changed the quality of life of an estimated 5 million patients worldwide.

Capsaicin Reduces Cancer Stemness and Inhibits Metastasis by Downregulating SOX2 and EZH2 in Osteosarcoma.

Metastasis of osteosarcoma is an important adverse factor affecting patients' survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100[Formula: see text][Formula: see text]M, 24[Formula: see text]h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment's inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin's dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or disease-free survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2. Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness.

Cough desensitization treatment for patients with refractory chronic cough: results of a second pilot randomized control trial.

OBJECTIVE: The purpose of this study was to collect pilot efficacy data on a novel treatment for refractory chronic cough (RCC), which we call cough desensitization treatment (CDT). DESIGN AND METHODS: In this parallel cohort, sham-controlled, randomized controlled trial, 21 adults with RCC were randomly assigned to 12 sessions of either CDT (progressive doses of aerosolized capsaicin while behaviorally suppressing cough; n = 11) or a sham treatment (repeated exposure to aerosolized saline; n = 9). The Leicester Cough Questionnaire (LCQ) was the primary outcome measure. Perceived cough severity with a visual analogue scale and cough challenge testing (for measuring cough-reflex sensitivity) were secondary outcome measures. Data were analyzed with mixed effects linear regression and follow-up contrasts. RESULTS: Results on all measures favored CDT. Excluding one sham participant, whose baseline LCQ scores were deemed unreliable, mean change in LCQ at 3-weeks post treatment was 6.35 and 2.17 in the CDT and sham groups, respectively. There was moderate to strong evidence of a greater improvement in the CDT group in total LCQ score (p = .058) and LCQ Psychological domain (p = .026) and Physical domain (p = .045) scores. Strong evidence was found for a greater reduction in urge-to-cough during CCT in the CDT group (p = .037) and marginal for a reduction in the capsaicin cough-reflex sensitivity (p = .094). There was weak evidence of a greater reduction in cough severity in the CDT group (p = .103). DISCUSSION: Although the study is limited due to the small sample size, the data provide additional evidence supporting further research on CDT. CDT resulted in a greater change in the primary efficacy measure (LCQ) than both pharmaceutical and behavioral treatments currently found in the literature. TRIAL REGISTRATION: This trial (NCT05226299) was registered on Clinicaltrials.gov on 07/02/2022.

Capsaicin encapsulated in W/O/W double emulsions fabricated via ethanol-induced pectin gelling: Improvement of bioaccessibility and reduction of irritation.

Capsaicin is a water-insoluble bioactive component with several beneficial physiological functions. However, the widespread application of this hydrophobic phytochemical is limited by its low water-solubility, intense irritation, and poor bioaccessibility. These challenges can be overcome by entrapping capsaicin within the internal water phase of water-in-oil-in-water (W/O/W) double emulsions via using ethanol to induce pectin gelling. In this study, ethanol was used both to dissolve capsaicin and to promote pectin gelation, thereby forming capsaicin-loaded pectin hydrogels that were used as the internal water phase of the double emulsions. Pectin addition improved the physical stability of the emulsions and led to a high encapsulation efficiency of capsaicin (>70 % after 7d storage). After simulated oral and gastric digestion, capsaicin-loaded double emulsions maintained their compartmentalized structure, avoiding capsaicin leakage in the month and stomach. The double emulsions were digested in the small intestine, thereby releasing the capsaicin. Capsaicin bioaccessibility was significantly enhanced after encapsulation, which was attributed to mixed micelle formation by the digested lipid phase. Furthermore, encapsulation of capsaicin within the double emulsions reduced the irritation in the gastrointestinal tissues of mice. This kind of double emulsion may have great potential for the development of more palatable capsaicin-loaded functional food products.