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Effects of Capsaicin on Induction of Apoptosis and Inhibition of Adipogenesis in 3T3-L1 Cells

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Abstract

Currently, at the beginning of the 21st century, obesity has become the leading metabolic disease in the world. It is a serious health problem in industrialized countries. Previous research has suggested that decreased preadipocyte differentiation and proliferation and decreased lipogenesis are mechanisms to reduce obesity. In the present study, the effects of capsaicin on the induction of apoptosis and inhibition of lipid accumulation in 3T3-L1 preadipocytes and adipocytes were investigated. The results demonstrated that capsaicin decreased cell population growth of 3T3-L1 preadipocytes, assessed with the MTT assay. Flow cytometric analysis of 3T3-L1 preadipocytes exposed to capsaicin showed that apoptotic cells increased in a time- and dose-dependent manner. Treatment with capsaicin decreased the number of normal cells and increased the number of early apoptotic and late apoptotic cells in a dose-dependent manner. The treatment of cells with capsaicin caused the loss of mitochondria membrane potential (delta psi m). The induction of apoptosis in 3T3-L1 preadipocytes by capsaicin was mediated through the activation of caspase-3, Bax, and Bak, and then through the cleavage of PARP and the down-regulation of Bcl-2. Moreover, capsaicin significantly decreased the amount of intracellular triglycerides and glycerol-3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 adipocytes. Capsaicin also inhibited the expression of PPARgamma, C/EBPalpha, and leptin, but induced up-regulation of adiponectin at the protein level. These results demonstrate that capsaicin efficiently induces apoptosis and inhibits adipogenesis in 3T3-L1 preadipocytes and adipocytes.

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... Adipogenesis is an essential metabolic pathway for the storage of lipids in adipose tissue. Previous studies have suggested that the reduction of preadipocyte differentiation, proliferation, and lipogenesis could prevent obesity (9). Hsu et al. reported that capsaicin suppresses the expression of adipogenesis-related transcription factors such as peroxisome proliferator-activated receptor gamma (PPAR-γ) and CCAAT/enhancer binding protein alpha (C/EBP-α). ...
... Hsu et al. reported that capsaicin suppresses the expression of adipogenesis-related transcription factors such as peroxisome proliferator-activated receptor gamma (PPAR-γ) and CCAAT/enhancer binding protein alpha (C/EBP-α). It was also shown that capsaicin controls the protein expression of leptin and adiponectin, which are two hormones primarily produced by adipose tissue (6,9). Uncoupling protein 2 (UCP2), a protein situated in the inner mitochondrial membrane responsible for regulating lipid metabolism, was found to be diminished both in the omental and subcutaneous adipose tissues among obese individuals (10)(11)(12). ...
... Recent studies have shown that many natural food components have beneficial effects on weight loss and can prevent obesity (18,19). One of them, capsaicin, was reported to be effective in reducing body weight and fat storage in vivo and suppressing adipogenesis in vitro (9,(20)(21)(22). ...
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Objective: Adipose tissue stores lipids necessary for the maintenance of nutritional homeostasis. It is also an endocrine organ that reacts to changes in inflammation and energy status. Capsaicin, the principal bioactive compound in red pepper, has garnered significant attention for its reported anti-obesity, anti-diabetic, anti-oxidant, and anti-inflammatory properties. In this study, we aimed to elucidate the influence and most efficacious dose of capsaicin on the expression of lipid metabolism-related inflammatory proteins and the inhibition of adipocyte cell differentiation. Materials and Methods: Cell viability analysis was performed using CCK-8, cell differentiation was assessed using Oil Red O, and gene expression levels of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), adiponectin, leptin, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), nuclear factor kappa B1 (NF-κB1), tumor necrosis factor-alpha (TNF-α), sirtuin-1 (SIRT-1), transient receptor potential vanilloid receptor 1 (TRPV1), and uncoupling protein 2 (UCP2) were evaluated using quantitative real time polymerase chain reaction (qRT-PCR). Statistical analyses were conducted using GraphPad Prism 5. One-way ANOVA was performed to compare quantitative data between the groups. Results: Capsaicin suppressed preadipocyte-to-adipocyte differentiation and mitigated the release of pro-inflammatory cytokines, particularly at low concentrations. Capsaicin effectively suppressed adiponectin levels at all concentrations but decreased leptin levels at lower concentrations (0.5 µM and 1 µM). Capsaicin stimulated the expressions of SIRT1 and TRPV-1 in adipocytes. According to our findings, the most effective capsaicin dose for the regulation of SIRT1 and TRPV-1 expressions appears to be 20 μM. Conclusion: Capsaicin's effect on proteins regulating adipogenesis is not dose-related, but its inhibitory effect on adiposity-dependent inflammation was more pronounced at low concentrations.
... During insulin therapy, EGCG also promotes apoptosis in post-confluent premature preadipocytes, although the molecular pathways involved remain unclear. Induction of apoptosis in post-confluent differentiated cells leads to a decrease in the number of adipocytes, as preadipocytes undergo multiple rounds of replication during the first two days of differentiation [74,[95][96][97][98][99][100][101][102][103][104][105][106]. The effect of curcumin on the cell cycle was recently determined. ...
... EGCG-induced apoptosis is thought to be mediated by protein 1, nuclear factor kappa B (NF-kB), p53, and caspase-3 activity. Although the effects of conjugated linoleic acid (CLA) on body fat are not fully understood, the marked increase in TNF-α mRNA observed after treatment of adipocytes with uncoupling protein 2 (UCP2) suggests that CLA-induced suspected to be responsible for apoptosis [74,[102][103][104][105][106]. Genistein, ajoene, EGCG, and capsaicin exert apoptotic effects by stimulating the release of reactive oxygen species (ROS), thereby activating AMP-activated protein kinase (AMPK), an important target for antiobesity therapy. ...
... Genistein, ajoene, EGCG, and capsaicin exert apoptotic effects by stimulating the release of reactive oxygen species (ROS), thereby activating AMP-activated protein kinase (AMPK), an important target for antiobesity therapy. Ajoene also induces apoptosis in leukemia cells through the formation of ROS, and more recently, it was shown that ajoene also induces ROS-mediated apoptosis in adipocytes [74,[103][104][105][106][107][108][109][110]. ...
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Inflammation is a crucial factor in the development and progression of cardiovascular diseases (CVD). Cardiac remodeling in the presence of persistent inflammation leads to myocardial fibrosis and extracellular matrix changes, which reduce cardiac function, induce arrhythmias, and finally, cause heart failure. The majority of current CVD treatment plans concentrate on reducing risk factors such as hyperlipidemia, type 2 diabetes, and hypertension. One such strategy could be inflammation reduction. Numerous in vitro, animal, and clinical studies indicate that obesity is associated with low-grade inflammation. Recent studies have demonstrated the potential of medicinal plants and phytochemicals to cure and prevent obesity and inflammation. In comparison to conventional therapies, the synergistic effects of several phytochemicals boost their bioavailability and impact numerous cellular and molecular targets. Focusing on appetite, pancreatic lipase activity, thermogenesis, lipid metabolism, lipolysis and adipogenesis, apoptosis in adipocytes, and adipocyte life cycle by medicinal plants and phytochemicals represent an important goal in the development of new anti-obesity drugs. We conducted an extensive review of the literature and electronic databases, including Google Scholar, PubMed, Science Direct, and MedlinePlus, for collecting data on the therapeutic effects of medicinal plants/phytochemicals in curing obesity and its related inflammation and CVD diseases, including cellular and molecular mechanisms, cytokines, signal transduction cascades, and clinical trials.
... DAPI: diamido-2-phenylindole dihydrochloride. *P < 0.05 (black), **P < 0.05 (blue) and ***P < 0.0001 (red) and aid mass loss by preventing the development of hyperplasia in diabetes (Hsu and Yen 2007;Okuno et al. 1998). Proliferation and apoptosis are regulated together by many signaling pathways and transcription factors (Lee et al. 2019). ...
... Recent in-vivo and in-vitro studies have reported that 3T3-L1 adipocytes during differentiation develop resistance to apoptosis through modulating cell-survival genes (Muir et al. 2016;Hsu and Yen 2007). The induction of proapoptosis may contribute to the reduction of adipocyte number . ...
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It is crucial to investigate new anti-diabetic agents and therapeutic approaches targeting molecules in potential signaling pathways for the treatment of Type 2 diabetes mellitus (T2DM). The objective of the study was to investigate the total phenolic content, antioxidant capacity, α-glucosidase, and α-amylase inhibitory activities of Bolanthus turcicus (B. turcicus), as well as their cytotoxic, anti-adipogenic, anti-diabetic, apoptotic, and anti-migration potential on adipocytes. B. turcicus samples were extracted with methanol (MeOH), ethyl acetate (EA) and aqueous (Aq) solvents. The MeOH extract had the highest phenolic content (81.14 mg GAE/g), followed by EA (74.93 mg GAE/g) and Aq (51.09 mg GAE/g). All extracts exhibited dose-dependent increases in α-glycosidase and α-amylase inhibitory activity. B. turcicus extracts showed cytotoxic effect on adipocytes with IC50 values of MeOH (141.0 µg/mL) < Aq (155.3 µg/mL) < EA (199.5 µg/mL). Furthermore, B. turcicus extracts reduced lipid droplet formation and adipocyte diameter size. All extracts altered cell morphology to resemble fibroblasts. B. turcicus extracts exhibited anti-migratory effect delaying wound healing for up to 96 h. The B. turcicus extracts showed a pro-apoptotic effects on adipocytes by increasing Caspase-3 enzyme activity and the population of DAPI-positive cell with apoptotic nuclear-morphology. B. turcicus extracts upregulated the expression of the Glut-4 gene at the mRNA, protein and intracellular level in adipocytes. In conclusion, our findings indicate that B. turcicus not only exhibits strong antioxidant properties and enzyme inhibitory activities but also exerts significant anti-adipogenic and pro-apoptotic effects in adipocytes, thereby providing a comprehensive mechanism through which it may contribute to the management of T2DM. These effects highlight the potential of B. turcicus as a therapeutic agent for improving glucose homeostasis and insulin sensitivity.
... Nowadays it has been reported that during adipogenesis, the expression of the transcriptional factor PPAR-ɣ progressively increases meanwhile the expression of PREF-1 (Preadipocyte Factor 1) is inhibited (Montaigne et al., 2021) This expression is exacerbated in the development of adipose tissue. So, a potential mechanism to reduce adipogenesis is to PPAR-ɣ Capsaicin (8-methyl-N-vanillyl-6-nonenamide) (Leung, 2014), the pungent molecule of the red pepper (Capsicum annum L.), has been reported to increase thermogenesis (Diepvens et al., 2007), induction of apoptosis and inhibition of adipogenesis (Hsu & Yen, 2007), an increase in energy expenditure (Marlatt & Ravussin, 2017) and decreases the accumulation of body fat (Zheng et al., 2017). This molecule counters obesity by activating TRPV1 channel-dependent mechanisms (Baskaran et al., 2016). ...
... The results of in vivo assays in mice, demonstrated a decrease in adipose tissue by the mice administered with olvanil, which correlates with the processes such as browning of adipocytes, and activation of metabolic modulators including AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 1 (UCP1), and glucagon-like peptide 1 (GLP-1) described in a previous work with capsaicin (Maréchal et al., 2018). AMPK regulates the adipogenic transcription factors, peroxisome proliferator-activated receptor-γ (PPAR-γ), and CCAAT enhancer binding protein-α (C/EBP-α), which are the central regulators of adipogenesis and lipid storage in adipocytes (Hsu & Yen, 2007;Bort et al., 2019). Therefore, the modulation of these pathways by olvanil can be a way to increase fat oxidation and decrease body fat. ...
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Aim: The present study is aimed to examine olvanil's effect in preadipocyte cell culture and on a murine model of diet-induced obesity. We hypothesized that olvanil by being a capsaicinoid will reduce the differentiation to mature adipocytes and reduce the weight of fat tissue in the studied mice. Methods: To determine the effect of olvanil on adipogenesis, 3T3-L1 cells were cultured. Oil red staining was performed to determine lipid accumulation, whereas triglycerides were measured by biochemical determination. Expression of PPAR-γ and PREF-1 were measured by RT-PCR. Therefore, male C57BL/6J mice (CICUAL:2018-020B) were fed with a high-fat diet for 12 weeks to develop a murine model of diet-induced obesity (DIO). Animals were separated into 6 experimental groups: control (standard diet), DIO (high-fat diet), DIO + orlistat (10 mg/kg), DIO + olvanil (10 mg/kg), DIO + olvanil (25 mg/kg) and DIO + olvanil (50 mg/kg), olvanil was administered for 4 weeks. Results: Olvanil inhibits adipogenesis, reduces lipid accumulation and triglycerides in 3T3-L1 adipocytes. PPAR-ɣ gene expression was suppressed while PREF-1 was increased in adipocytes treated with olvanil. Whereas protein expression of FABP4 and PPAR-ɣ decreases significantly with olvanil. The results suggest that olvanil can inhibit the differentiation of preadipocytes to adipocytes through the overexpression or maintenance of PREF-1 levels and the suppression of PPAR-ɣ, and FABP4. Therefore, in diet-induced obesity in mice, olvanil decreases fat accumulation in the body and improve lipid profile by decreasing LDL, VLDL and triglycerides in serum. Conclusion: Olvanil inhibits adipocyte differentiation in 3T3-L1 cells and reduces fat accumulation and ameliorate lipid profile in diet-induced obese mice.
... It was also reported to be effective in diabetic neuropathy and has anti-inflammatory and antidiabetic properties (Aryaeian et al., 2017) (Figure 5). Capsaicin was also found to decrease lipid accumulation by decreasing PPARγ, C/EBPα, and leptin protein expression, but increased adiponectin expression in 3T3-L1 adipocytes (Hsu and Yen, 2007). ...
... Ephedra sinica (Saper et al., 2004) -Metabolic stimulant -1.5 mg/kg/day of ephedrine Clinical trial (Carey et al., 2015) -Thermogenic agent (Stohs and Badmaev, 2016) Epigallocatechin gallate (EGCG) Camellia sinensis L. (Thitimuta et al., 2017) -Enhance fatty acid mobilization and oxidation (Jeukendrup and Randell, 2011) 0.45 mg/mL (Lipase Inhibition) (Jamous et al., 2018) 576 mg/day of catechins Clinical trial (Matsuyama et al., 2008) -Promote browning markers -Inhibit adipogenesis (Lin et al., 2005) Capsaicin Capsicum annuum L. (Barceloux, 2009) -Stimulates thermogenesis Reinbach et al. (2010) -1 g/day of red peppers containing 1995 µg capsaicin, 247 µg nordihydrocapsaicin and 1,350 µg dihydrocapsaicin Clinical trial Mattes, 2011) (Dömötör et al., 2006) -Enhance insulin sensitivity, and increase fat oxidation (Aryaeian et al., 2017) -400 µg/day of capsaicin -Decreases PPARγ, C/EBPα and leptin protein expression in 3T3-L1 adipocytes (Hsu and Yen, 2007) Korean pine nut-free fatty acids (FFA) ...
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Obesity affects more than 10% of the adult population globally. Despite the introduction of diverse medications aimed at combating fat accumulation and obesity, a significant number of these pharmaceutical interventions are linked to substantial occurrences of severe adverse events, occasionally leading to their withdrawal from the market. Natural products serve as attractive sources for anti-obesity agents as many of them can alter the host metabolic processes and maintain glucose homeostasis via metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancing, adipogenesis inhibition and adipocyte apoptosis induction. In this review, we shed light on the biological processes that control energy balance and thermogenesis as well as metabolic pathways in white adipose tissue browning, we also highlight the anti-obesity potential of natural products with their mechanism of action. Based on previous findings, the crucial proteins and molecular pathways involved in adipose tissue browning and lipolysis induction are uncoupling protein-1, PR domain containing 16, and peroxisome proliferator-activated receptor-γ in addition to Sirtuin-1 and AMP-activated protein kinase pathway. Given that some phytochemicals can also lower proinflammatory substances like TNF-α, IL-6, and IL-1 secreted from adipose tissue and change the production of adipokines like leptin and adiponectin, which are important regulators of body weight, natural products represent a treasure trove for anti-obesity agents. In conclusion, conducting comprehensive research on natural products holds the potential to accelerate the development of an improved obesity management strategy characterized by heightened efficacy and reduced incidence of side effects.
... In dairy cows, capsaicin ruminal escape was reportedly estimated between 15 and 33% depending on the dose provided (Oh et al., 2016). In humans and rats, capsaicin stimulates gastric emptying and decreases blood leptin levels, resulting in a greater food intake (McCann et al., 1988;Debreceni et al., 1999;Hsu and Yen, 2007). Feeding capsaicin to rats has also increased pancreatic secretion of digestive enzymes including lipase, amylase, trypsin, and chymotrypsin Srinivasan, 1996, 2000), which may improve degradation and absorption of nutrients in the small intestine. ...
... Cows fed CAP150 had greater DM and CP digestibility, especially in wk 3 and 6 of experiment, in comparison with other treatments. The reasons for greater digestibility when feeding CAP are unclear but can be associated with CAP effects on ruminal microbial population (Oh et al., 2015), pancreatic digestive enzymes secretion Srinivasan, 1996, 2000), gastric emptying (Debreceni et al., 1999), or blood leptin levels (Hsu and Yen, 2007). Contrasting with the current study, feeding different doses of CAP (0, 0.25, 0.5, or 1.0 g/d; containing 1.2% capsaicinoids) had no effect on DMI and digestibility of nutrients in dairy cows (Oh et al., 2015). ...
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Peppers (Capsicum spp.) contain capsaicin, an organic compound with a group of alkaloids that has shown thermoregulation properties in humans and mice, and may influence glucose and lipid metabolism in ruminants. An experiment was conducted to evaluate different doses of a feed additive containing encapsulated pepper on milk yield and composition, dry matter intake, feed sorting index, total-tract apparent digestibility of nutrients, purine derivatives excretion, and serum concentrations of urea-N and glucose, N excretion, respiration rate, rectal temperature, and skin temperature in different regions (forehead, face, and rumen). Thirty-six Holstein cows (150 ± 102.1 d in milk and 29.3 ± 5.81 kg/d milk yield) were used in a 9-wk randomized complete block (n = 12) design experiment. Following a 2-wk covariate period, cows were blocked according to parity, days in milk, and milk yield and were randomly assigned to the following treatments: 0 (CAP0), 0.75 (CAP75), or 1.5 (CAP150) g/d of a feed additive containing encapsulated pepper (1 g/kg, Capcin; NutriQuest) added to the concentrate along with minerals. Treatment differences were evaluated through orthogonal contrasts (CAP0 vs. CAP75 + CAP150 or CAP75 vs. CAP150). The average temperature-humidity index during the experiment was 72.0 ± 2.07. Dry matter intake was greater in cows fed a feed additive containing encapsulated pepper (CAP) treatments (CAP75 and CAP150) compared with CAP0. Cows fed CAP150 tended to have greater dry matter intake than those in CAP75 group. Feeding CAP decreased sorting for feed particles with size between 8 and 4 mm. An interaction effect between treatment and week was observed for crude protein digestibility whereas cows fed CAP150 had the greatest digestibility on the third week of experiment. Orthogonal contrasts did not detect differences in serum concentrations of glucose and urea-N, or purine derivatives excretion. Nitrogen excretion (as % of N intake) in milk, urine, and feces was not altered by treatments. Feeding CAP increased yields of 3.5% fat-corrected milk, fat, protein, and lactose. A tendency toward greater milk protein content was observed for cows fed CAP150 than CAP75. No differences were detected on respiration rate, rectal temperature, and skin temperature of cows. A feed additive containing encapsulated pepper fed at 0.75 or 1.5 g/d can improve yield of fat-corrected milk and milk solids by increasing feed intake without affecting nutrient digestibility and body temperature of lactating cows during the hot season.
... These compounds are known to alleviate and maintain human immune system [39]. Certain principal compounds especially 2-isobutyl-3-methoxypyrazine, linalool, hexanal, trans-2-hexenal, 3-carene and 2, 3-butanedione are known as the constituents of commercial fresh chilli (Capsicum annuum L.) at different maturity stages of the crop [40]. Confirmation on existence of such compounds in chilli was made confirmed by analytical techniques, such as gas chromatography, HPLC, gas chromatography and mass spectrophotometry [18]. ...
... In latest study by NHMS, one in every two adults in Malaysia was obese and females ranked in the highest category [10]. Recently a study by [40], C. annuum contributed to thermogenesis, on application of capsaicin on 3T3-L1 adipocytes lipid content at intracellular level was found to be decreased and thus involved in thermogenesis. In a study by Kang et al. [159], it was affirmed that capsaicin in dietary form could lessen the number of liposaccharides (LPS) content and high-fat diet provoked CLGI related anti-obesity factors. ...
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Worldwide, since ages and nowadays, traditional medicine is well known, owing to its biodiversity, which immensely contributed to the advancement and development of complementary and alternative medicines. There is a wide range of spices, herbs, and trees known for their medicinal uses. Chilli peppers, a vegetable cum spice crop, are bestowed with natural bioactive compounds, flavonoids, capsaicinoids, phytochemicals, phytonutrients, and pharmacologically active compounds with potential health benefits. Such compounds manifest their functionality over solo-treatment by operating in synergy and consortium. Co-action of these compounds and nutrients make them potentially effective against coagulation, obesity, diabetes, inflammation, dreadful diseases, such as cancer, and microbial diseases, alongside having good anti-oxidants with scavenging ability to free radicals and oxygen. In recent times, capsaicinoids especially capsaicin can ameliorate important viral diseases, such as SARS-CoV-2. In addition, capsaicin provides an ability to chilli peppers to ramify as topical agents in pain-relief and also benefitting man as a potential effective anesthetic agent. Such phytochemicals involved not only make them useful and a much economical substitute to wonder/artificial drugs but can be exploited as obscene drugs for the production of novel stuffs. The responsibility of the TRPV1 receptor in association with capsaicin in mitigating chronic diseases has also been justified in this study. Nonetheless, medicinal studies pertaining to consumption of chilli peppers are limited and demand confirmation of the findings from animal studies. In this artifact, an effort has been made to address in an accessible format the nutritional and biomedical perspectives of chilli pepper, which could precisely upgrade and enrich our pharmaceutical industries towards human well-being.
... It has been documented that the expression of the retinal PPARγ in diabetic rats significantly increased [16]. In addition, study has shown that capsaicin can inhibit the expression of PPARγ [17]. ...
... It has been documented that in bovine retinal vascular endothelial cells, hyperglycemia increases the expression of PPARγ1, PPARγ2 mRNA, and PPARγ protein, and that the expression of the retinal protein PPARγ in diabetic rats is significantly increased [16]. In addition, CAP efficiently suppresses adipogenesis in 3T3-L1 preadipocytes and adipocytes by downregulating PPARγ expression [17]. These results are consistent with our study's data. ...
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Background Oxidative stress and the resultant hyperpermeability play a vital role in the pathogenesis of diabetic retinopathy (DR). Poldip2 has been implicated in H2O2 production, but the effects of capsaicin on poldip2 have not been reported. Methods Diabetic Sprague-Dawley (SD) rats induced with STZ were treated with capsaicin or AAV9-poldip2-shRNA, and human retinal microvascular endothelial cells (HRMECs) were treated with capsaicin or poldip2 siRNA. Results Current data indicated that the expression of PPARγ, poldip2, Nox4, VCAM-1, HIF-1α, and VEGF increased in rat retinas with DR and in HRMECs treated with high glucose. The production of ROS or H2O2 in the tissues, serum, and cells increased, and the paracellular permeability of cultured HRMECs with high glucose significantly increased. In addition, overt hyperpermeability of retinal microvessels and increased retinal neovascularization in diabetic rats were observed. However, capsaicin treatment inhibited these increases and suppressed the expression of PPARγ by enhancing its phosphorylation and ubiquitination in the retinas of DR rats. Poldip2 knockdown in HRMECs or its silencing in the retina of DR rats concomitantly led to reduced levels of Nox4, VCAM-1, HIF-1α, VEGF, ROS, and H2O2, and the paracellular permeability of HRMECs or the hyperpermeability of retinal microvessels in diabetic rat retinas decreased. Similarly, after PPARγ knockdown in HRMECs, poldip2, Nox4, HIF-1α, VEGF, ROS, and H2O2 decreased, and the monolayer paracellular permeability was reduced accordingly. Conclusion Capsaicin may ameliorate diabetic retinopathy by activating TRPV1 and suppressing the PPARγ-poldip2-Nox4 pathway.
... The findings imply that dietary capsaicin consumption may contribute to weight control by decreasing energy intake and by triggering BAT activation [129]. Adipogenesis (differentiation of pre-adipocytes into adipocytes and the fat-storing cells) is the fundamental and distinctive mechanism of the accumulation of fatty adipose tissue [130,131]. ...
... Hsu and Yen 2007 [130] determined that capsaicin suppressed the expression of the proteins, namely, PPAR (peroxisome proliferatoractivated receptor), C/EBP (CCAAT/enhancer binding proteins), and leptin, whilst it elevated the adiponectin protein content, thus accelerating apoptosis and inhibiting fat accumulation in the 3T3-L1 cell-line concerned with preadipocytes and adipocytes. As a result of capsaicin administration, TRPV-1 expression was reduced in adipose tissue, adiponectin expression was increased in adipose tissue, and PPAR and PGC-1 expression were enhanced in the liver [132]. ...
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Plants are the source of numerous pharmaceutically important compounds that have been employed to cure various human ailments since ancient times. With the assistance of modern chemistry and materials science, such pharmaceutically important compounds have been identified and isolated to produce new drugs. Alkaloids are one of the most significant classes of naturally occurring secondary-metabolites, which are synthesized and widely distributed in various parts of plants. They regulate various metabolic activities and induce physiological responses in the human body. Capsaicin is a naturally occurring alkaloid found in many species of peppers and is attributed to their spicy nature and pungent flavor. This alkaloid is a member of the Capsaicinoids group, which includes capsaicin, homocapsaicin, homodihydrocapsaicin, dihydrocapsaicin, and nordihydrocapsaicin. Capsaicin has a wide range of therapeutic potential against various human ailments. In this article, we provide a comprehensive overview of the capsaicin molecule as well as an examination of its medicinal properties in a variety of human disorders, including pain, various types of cancer, ulcers, diabetes, obesity, inflammation, cardiovascular diseases, and neurodegenerative diseases.
... It has been documented that the expression of the retinal PPARγ in diabetic rats significantly increased [16]. In addition, study has shown that capsaicin can inhibit the expression of PPARγ [17]. ...
... It has been documented that in bovine retinal vascular endothelial cells, hyperglycemia increases the expression of PPARγ1, PPARγ2 mRNA, and PPARγ protein, and that the expression of the retinal protein PPARγ in diabetic rats is significantly increased [16]. In addition, CAP efficiently suppresses adipogenesis in 3T3-L1 preadipocytes and adipocytes by downregulating PPARγ expression [17]. These results are consistent with our study's data. ...
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Aims To primarily explore the mechanism of captopril in oxidative stress and investigate the link between captopril alleviated oxidative damage and diabetic retinopathy (DR). Main methods Human retinal microvascular endothelial cells (HRMECs) were used for in vitro experiments and cultured in a 5.5 mM or 30 mM glucose medium. Sprague-Dawley rats were used for in vivo experiments, and parts of the rats were established for diabetic groups by injected streptozotocin (n = 10, each group). Both experiments had a captopril-treated group. The levels of total cholesterol (TC), reactive oxygen species (ROS), nitric oxide (NO), and human 3-nitrotyrosine (3-NT) were detected in assay kits and ELISA. Western blotting was used to detect the expression of steroid regulatory element binding protein 2 (SREBP2), inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS). Hematoxylin-eosin staining and Evans blue were used to describe retinal histopathology. Key findings The levels of TC, ROS, NO, and 3-NT were increased in the higher glucose groups compared with the normal controls during in vivo and in vitro experiments. Western blotting showed a higher level of SREBP2, iNOS, and VEGF and a lower eNOS level in the higher glucose groups. These results were reversed by captopril. Captopril relieved diabetic retinal vascular leakage. Significance Our study suggested that captopril alleviates oxidative damage in DR due to creating lower peroxynitrite by decreasing ROS and NO, which may provide a visible direction for DR research.
... Few studies have focused on identifying a single bioactive compound that has beneficial effects on multiple targets for obesity treatment, even though this is a very economical and effective treatment strategy. Thus far, fucoidan, carsonic acid, capsaicin, and 6-shagol are well-known multi-targeting compounds derived from natural products [16][17][18][19][20]. Fucoidan, which is extracted from the sporophyll of Undaria pinnatifida, suppressed lipogenic targets, such as PPARγ, C/EBPα, Fas, and aP2, as well as downregulated the expression of inflammatory cytokines such as TNF-α, MCP-1, and PAI-1 [16]. ...
... In addition, carsonic acid, extracted from Rosmarinus officinalis, suppressed the adipogenic and inflammatory targets by regulating the NF-κB pathway [17]. Moreover, capsaicin, extracted from chili pepper, suppressed lipogenesis and lipolysis by upregulating lipases [18,19]. Finally, 6-shagaol suppressed lipogenesis by downregulating PPARγ and C/EBPα accelerating lipolysis and β-oxidation [20]. ...
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The efficacy of α-cubebenol isolated from Schisandra chinensis has been studied in several diseases, including cecal ligation, puncture challenge-induced sepsis, and degranulation of neutrophils. To identify the novel functions of α-cubebenol on lipid metabolism, alterations on the regulation of lipogenesis, lipolysis, and inflammatory response were observed in 3T3-L1 adipocytes treated with α-cubebenol. Most lipogenic targets, including lipid accumulation, level of lipogenic transcription factors, and expression of lipogenic regulators, were suppressed in MDI (3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-stimulated 3T3-L1 adipocytes treated with α-cubebenol without significant cytotoxicity. In addition, similar inhibition effects were observed in the iNOS-induced COX-2 mediated pathway and NLRP3 inflammasome pathway of MDI-stimulated 3T3-L1 cells treated with α-cubebenol. Lipolytic targets, such as cAMP concentration, expression of adenylyl cyclase and PDE4, and their downstream signaling pathway, in MDI-stimulated 3T3-L1 cells were stimulated by the α-cubebenol treatment. The levels of transcription factors and related proteins for β-oxidation were significantly higher in the MDI + α-cubebenol treated group than in the MDI + Vehicle treated group. These results show that α-cubebenol has a novel role as a lipogenesis inhibitor, lipolysis and β-oxidation stimulator, and inflammasome suppressor in MDI-stimulated 3T3-L1 adipocytes.
... Furthermore, Joo et al. [55] demonstrated that Cap exhibits anti-obesity effects by enhancing the mRNA expression of uncoupling protein 1 (UCP1) in WAT and upregulating proteins associated with thermogenesis, lipid metabolism, and energy transduction. Taken together, Cap suppresses adipocyte differentiation [56], promotes the browning of white adipocytes [57], enhances thermogenesis, and decreases intracellular lipid levels [58], highlighting its potential as a promising anti-obese agent. However, the clinical application of Cap is hindered by its poor solubility and low oral bioavailability, which may result in adverse effects, including gastric ulcers, stomatitis, vomiting, and diarrhea [59]. ...
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Obesity has become a major public health threat, as it can cause various complications such as diabetes, cardiovascular disease, sleep apnea, cancer, and osteoarthritis. The primary anti-obesity therapies include dietary control, physical exercise, surgical interventions, and drug therapy; however, these treatments often have poor therapeutic efficacy, significant side effects, and unavoidable weight rebound. As a revolutionized transdermal drug delivery system, microneedles (MNs) have been increasingly used to deliver anti-obesity therapeutics to subcutaneous adipose tissue or targeted absorption sites, significantly enhancing anti-obese effects. Nevertheless, there is still a lack of a review to comprehensively summarize the latest progress of MN-mediated treatment of obesity. This review provides an overview of the application of MN technology in obesity, focusing on the delivery of various therapeutics to promote the browning of white adipose tissue (WAT), suppress adipogenesis, and improve metabolic function. In addition, this review presents detailed examples of the integration of MN technology with iontophoresis (INT) or photothermal therapy (PTT) to promote drug penetration into deeper dermis and exert synergistic anti-obese effects. Furthermore, the challenges and prospects of MN technology used for obesity treatment are also discussed, which helps to guide the design and optimization of MNs. Overall, this review provides insight into the development and clinical translation of MN technology for the treatment of obesity.
... [33] These key proteins associated with apoptosis, such as Bax and Bcl-2, in mitochondria induce the subsequent activation of caspase-3 and poly (ADP-ribose) polymerase (PARP). [34,35] Our findings revealed that compound 5 g increased the expression of Bax while simultaneously decreasing the expression of Bcl-2 in A549 cells, suggesting a shift towards apoptosis. This dual modulation suggests a shift towards apoptosis. ...
Article
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Quinoxaline and its derivatives exhibit a broad spectrum of biological activity, making them valuable for various therapeutic applications. However, most quinoxalines are synthetically produced due to their scarcity in nature. In this article, a series of unsymmetric benzils were synthesized and subsequently condensed with 1,2‐diaminobenzene to produce unsymmetric quinoxalines. The novel synthetic benzils and quinoxalines were evaluated for their anticancer activities against human non‐small‐cell lung cancer (NSCLC) cells harboring different gene mutations, to explore their potential as anticancer agents. Among these synthesized molecules, compound 5 g demonstrated inhibitory effects comparable to those of cisplatin.
... Further, the administration of capsaicin for eight weeks increased brown adipose tissue (BAT) activity and thermogenesis in healthy individuals [18]. Also, capsaicin has been demonstrated to inhibit adipogenesis in 3T31 preadipocytes by alleviating the expression of PPARγ, and leptin [19]. However, their inhibitory potential against pancreatic lipase using computational studies is scanty. ...
Article
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Introduction Obesity is a complex multifaceted disease, characterized by excessive body fat accumulation. It is a major public health concern globally, affecting individuals of all ages, genders, and socioeconomic backgrounds. Lipase, a key enzyme involved in lipid metabolism, plays a crucial role in the hydrolysis of dietary fats. Pancreatic lipase performs hydrolysis of nearly 50%-70% of total dietary fats. Thus, inhibition of pancreatic lipase is recognized as one of the strategies for managing obesity. Aim To predict the effect of phytocompounds from pepper as pancreatic lipase inhibitors using computational approaches. Methodology The drug-likeness and pharmacokinetic properties of compounds were evaluated using Lipinski rule of five and absorption, distribution, metabolism, and excretion (ADME) analysis, respectively. The drug score value was computed using Molinspiration, while the lipase inhibitor potential of ligands was evaluated using prediction of activity spectra for substances. Molecular docking was carried out to evaluate the stability and ligand binding affinity. Results Computational approaches identified both piperine and capsaicin as potential candidates, exhibiting favorable affinities with binding energy values of -9.9 and -7.7 kcal/mol, respectively. Both piperine and capsaicin interacted with Ser-152 and His-263, demonstrating their binding at the substrate binding site. Conclusions Findings provide insights into the underlying anti-obesity potential of these bioactive compounds from pepper and support further experimental investigations for obesity treatment.
... This activation is believed to enhance energy expenditure and reduce body fat by promoting catabolic processes in adipose tissues (59). It also activates metabolic modulators such as AMPK and PPARα (60). Additionally, capsaicin has been found to decrease lipid accumulation by reducing the expression of PPARγ, C/EBPα, and leptin proteins, while increasing adiponectin expression in 3T3-L1 adipocytes (61). ...
Article
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Treating overweight and obesity with medications generally offers initial advantages but can result in weight regain after stopping the drugs, as well as in medication-related side effects, and the potential for substance misuse. The allure of herbal products lies in their natural origin, thus leading individuals towards these products in search of a healthier and more sustainable approach to weight loss. Understanding how herbal products interact with biological systems is crucial for assessing their therapeutic potential. Anti-obesity herbal products and their compounds can act through different mechanisms, such as: appetite suppression, digestion and absorption blocking, stimulation of thermogenesis, inhibition of adipogenesis, and modulation of these processes through gene expression. The physiological effects and therapeutic properties exhibited by herbal products are ascribed to the presence and activity of their active components, such as polyphenols, tannins, flavonoids, anthocyanins, stanols, sterols and alkaloids. Furthermore, the synergistic effects of various phytochemicals have been explored to enhance their anti-obesity properties.
... To detect early apoptosis, late apoptosis, and necrosis induced by the compound, MDA-MB-231 (1 × 10 6 cells/dish) was added to a 6 cm dish and treated for 48 h at 37 °C in 3 mL of culture medium containing test compounds at final concentrations of 0, 5 and 15 μM. The MDA-MB-231 (1 × 10 5 ) were then stained for 10 min at room temperature with FITC-conjugated Annexin V-FITC and PI in a Ca 2+ -enriched binding buffer (Annexin V-FITC kit) and analyzed by a FACScan flow cytometer 58 . Annexin V-FITC and PI emissions were detected in the FL 1 and FL 2 channels of a FACScan flow cytometer, using emission filters of 525 and 575 nm, respectively. ...
Article
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Sirtuin 3 (SIRT3) belongs to the Sirtuin protein family, which consists of NAD⁺-dependent lysine deacylase, involved in the regulation of various cellular activities. Dysregulation of SIRT3 activity has been linked to several types of cancer, including breast cancer. Because of its ability to stimulate adaptive metabolic pathways, it can aid in the survival and proliferation of breast cancer cells. Finding new chemical compounds targeted towards SIRT3 was the primary goal of the current investigation. Virtual screening of ~ 800 compounds using molecular docking techniques yielded 8 active hits with favorable binding affinities and poses. Docking studies verified that the final eight compounds formed stable contacts with the catalytic domain of SIRT3. Those compounds have good pharmacokinetic/dynamic properties and gastrointestinal absorption. Based on excellent pharmacokinetic and pharmacodynamic properties, two compounds (MI-44 and MI-217) were subjected to MD simulation. Upon drug interaction, molecular dynamics simulations demonstrate mild alterations in the structure of proteins and stability. Binding free energy calculations revealed that compounds MI-44 (− 45.61 ± 0.064 kcal/mol) and MI-217 (− 41.65 ± 0.089 kcal/mol) showed the maximum energy, suggesting an intense preference for the SIRT3 catalytic site for attachment. The in-vitro MTT assay on breast cancer cell line (MDA-MB-231) and an apoptotic assay for these potential compounds (MI-44/MI-217) was also performed, with flow cytometry to determine the compound’s ability to cause apoptosis in breast cancer cells. The percentage of apoptotic cells (including early and late apoptotic cells) increased from 1.94% in control to 79.37% for MI-44 and 85.37% for MI-217 at 15 μM. Apoptotic cell death was effectively induced by these two compounds in a flow cytometry assay indicating them as a good inhibitor of human SIRT3. Based on our findings, MI-44 and MI-217 merit additional investigation as possible breast cancer therapeutics.
... Apoptosis can be induced by activating two distinct signaling pathways. The chemical-induced mitochondria-related apoptotic pathway is controlled by important apoptotic proteins (e.g., cytochrome c, Bax, and Bcl-2) and subsequently by the activation of poly(ADP-ribose) polymerase (PARP) and caspase-3 [30,31]. Because natural compounds may affect apoptotic pathways that are typically inhibited in human malignancies, they may provide new opportunities for cancer therapy development. ...
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Introduction Pancreatic cancer (PC) has a poor prognosis and limited response to therapies. Combinatorial approaches, such as natural product-based therapies, can enhance anticancer efficacy while minimizing side effects. This study evaluated M. sativa’s anticancer properties and its potential as adjunctive therapy with GEM to sensitize PANC-1 cells to chemotherapy. Methods The antioxidant activity (AA) and total phenolic content (TPC) of M. sativa extracts (MeOH, EtOAc, and water) were assessed using the DPPH radical scavenging assay. Cytotoxic effects on PANC1 and HUVEC cells were also evaluated by utilizing the MTT assay. Then, apoptosis detection was performed by Annexin V/PI-flow cytometry (FC). Besides, the DNA fragmentation analysis was conducted utilizing agarose gel electrophoresis (AGE). BCL-2, BAX, and CASP3 expression levels in PANC-1 cells using western blot analysis and qRT-PCR. Results Herein, DPPH IC50 values for M. sativa extracts (water, MeOH, EtOH) were 76.21, 110.32, and 65.39 µg/ml, respectively. The water extract of M. sativa exhibited the highest TPC (4612.15 ± 119.4 mgGAE/g). The cytotoxicity IC50 values for EtOH M. sativa extract, GEM, and combined GEM with EtOH M. sativa on PANC1 cells were 68.74, 43.53, and 41.22 µg/ml M. sativa + 25 µg/ml GEM, respectively, with no toxicity observed in HUVEC cells. FC analysis revealed that Combining GEM and EtOH M. sativa yielded the highest apoptosis rate (25.6%). Expression changes in BCL-2, BAX, and CASP3, as well as morphological alterations and DNA fragmentation, indicated apoptotic cell death. Conclusion Our findings suggested that combining M.sativa EtOH extracts with GEM may represent a promising strategy for treating PC.
... (47) Capsaicin successfully reduced adipokine production and modulated macrophage behavior in the adipose tissue of mice with obesity by activating TRPV1 channels to induce Ca 2+ influx and inhibiting the downregulation of TRPV1 expression. (48,49) Population studies have shown that capsaicin controls obesity by increasing energy expenditure, promoting fat oxidation, reducing fat formation, suppressing appetite, and enhancing satiety. (50) A nationwide prospective study involving 12,970 Chinese adults revealed a negative association between chili intake and the risk of overweight/obesity. ...
Article
Previous studies revealed that consuming spicy food reduced mortality from cardiovascular disease and lowered stroke risk. However, no studies reported the relationship between spicy food consumption, stroke types, and dose-response. This study aimed to further explore the association between the frequency of spicy food intake and the risk of stroke in a large prospective cohort study. In this study, 50,174 participants aged 30-79 years were recruited. Spicy food consumption data were collected via a baseline survey questionnaire. Outcomes were incidence of any stroke, ischemic stroke (IS), and hemorrhagic stroke (HS). Multivariable-adjusted Cox proportional hazard models estimated the association between consumption of spicy food and incident stroke. Restricted cubic spline analysis was used to examine the dose-response relationship. During the median 10.7-year follow-up, 3,967 strokes were recorded, including 3,494 IS and 516 HS. Compared to those who never/rarely consumed spicy food, those who consumed spicy food monthly, 1-2 days/week, and 3-5 days/week had HRs (95% CIs) of 0.914 (0.841,0.995), 0.869 (0.758,0.995), and 0.826 (0.714,0.956) for overall stroke, respectively. For IS, the corresponding HRs (95%CIs) were 0.909(0.832,0.994),0.831(0.718,0.962), and 0.813(0.696,0.951), respectively. This protective effect showed a U-shaped dose-response relationship. For obese participants, consuming spicy food ≥3 days/week was negatively associated with the risk of ischemic stroke. We found consumption of spicy food was negatively associated with the risk of ischemic stroke and had a U-shaped dose-response relationship with risk of ischemic stroke. Individuals who consumed spicy food 3-5 days/week had a significantly lowest risk of ischemic stroke.
... Research have demonstrated that capsaicin contributed to increased appetite and food intake by promoting gastric emptying and decreasing leptin levels in humans and rats (McCann et al., 1988;Debreceni et al., 1999;Hsu and Yen, 2007). Conversely, more recent research has demonstrated the potential of red pepper to suppress energy intake through appetite and satiety regulation, contributing to prevention and treatment of obesity in humans (Zheng et al., 2017). ...
Article
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The objective of this study was to evaluate lacta-tional performance, enteric gas emissions, ruminal fermentation, nutrient use efficiency, milk fatty acid profile, and energy and inflammatory markers in blood of peak-lactation dairy cows fed diets supplemented with Capsicum oleoresin or a combination of Capsicum oleoresin and clove oil. A 10-wk randomized complete block design experiment was conducted with 18 pri-miparous and 30 multiparous Holstein cows. Cows were blocked based on parity, days in milk, and milk yield (MY), and randomly assigned to 1 of 3 treatments (16 cows/treatment): (1) basal diet (CON); (2) basal diet supplemented with 300 mg/cow per day of Capsicum oleoresin (CAP); and (3) basal diet supplemented with 300 mg/cow per day of a combination of Capsicum oleoresin and clove oil (CAPCO). Premixes containing ground corn (CON), CAP, or CAPCO were mixed daily with the basal diet at 0.8% of dry matter intake (DMI). Supplementation of the diet with CAP or CAPCO did not affect DMI, MY, milk components, and feed efficiency of the cows. Body weight (BW) was increased during the last 2 wk of the experiment by CAP and CAPCO, compared with CON. The botani-cals improved BW gain (0.85 and 0.66 kg/d for CAP and CAPCO, respectively, compared with −0.01 kg/d for CON) and CAP enhanced the efficiency of energy utilization, compared with CON (94.5% vs. 78.4%, respectively). Daily CH 4 emission was not affected by treatments, but CH 4 emission yield (per kg of DMI) and intensity (per kg of MY) were decreased by up to 11% by CAPCO supplementation, compared with CON and CAP. A treatment × parity interaction indicated that the CH 4 mitigation effect was pronounced in pri-miparous but not in multiparous cows. Ruminal molar proportion of propionate was decreased by botanicals, compared with CON. Concentrations of trans-10 C18:1 and total trans fatty acids in milk fat were decreased by CAP and tended to be decreased by CAPCO, compared with CON. Total-tract apparent digestibility of nutrients was not affected by treatments, except for a tendency for decreased starch digestibility in cows supplemented with botanicals. Blood concentrations of β-hydroxybutyrate, total fatty acids, and insulin were not affected by botanicals. Blood haptoglobin concentration was increased by CAP in multiparous but not in primiparous cows. Lactational performance of peak-lactation dairy cows was not affected by the botanicals in this study, but they appeared to improve efficiency of energy utilization and partitioned energy toward BW gain. In addition, CH 4 yield and intensity were decreased in primiparous cows fed CAPCO, suggesting a potential positive environmental effect of the combination of Capsicum oleoresin and clove oil supple-mentation.
... Several studies have demonstrated that capsaicin inhibits the expression of leptin, PPARγ, and C/EBP-α while up-regulating adiponectin at the protein level, and in this manner efficiently induces apoptosis and adipogenesis to inhibit 3T3-L1 preadipocytes in vitro [181,182]. ...
Article
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Obesity is the most prevalent health problem in the Western world, with pathological body weight gain associated with numerous co-morbidities that can be the main cause of death. There are several factors that can contribute to the development of obesity, such as diet, sedentary lifestyle, and genetic make-up. Genetic predispositions play an important role in obesity, but genetic variations alone cannot fully explain the explosion of obesity, which is why studies have turned to epigenetics. The latest scientific evidence suggests that both genetics and environmental factors contribute to the rise in obesity. Certain variables, such as diet and exercise, have the ability to alter gene expression without affecting the DNA sequence, a phenomenon known as epigenetics. Epigenetic changes are reversible, and reversibility makes these changes attractive targets for therapeutic interventions. While anti-obesity drugs have been proposed to this end in recent decades, their numerous side effects make them not very attractive. On the other hand, the use of nutraceuticals for weight loss is increasing, and studies have shown that some of these products, such as resveratrol, curcumin, epigallocatechin-3-gallate, ginger, capsaicin, and caffeine, can alter gene expression, restoring the normal epigenetic profile and aiding weight loss.
... The growth of adipose tissue involves an increase in adipocyte size and differentiation of adipocytes from preadipocyte precursor cells [2]. Under conditions of excess body fat and obesity, the body accumulates excessive amounts of triglycerides in adipocytes, which increases the triglyceride content of the liver, muscle, adipose tissue, and plasma, leading to pathological dysfunctions, such as metabolic syndrome, coronary heart disease, hypertension, type 2 diabetes, cancer, and osteoarthritis [3,4]. ...
Article
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Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA repair and redox regulation. The redox activity of APE1/Ref-1 is involved in inflammatory responses and regulation of DNA binding of transcription factors related to cell survival pathways. However, the effect of APE1/Ref-1 on adipogenic transcription factor regulation remains unknown. In this study, we investigated the effect of APE1/Ref-1 on the regulation of adipocyte differentiation in 3T3-L1 cells. During adipocyte differentiation, APE1/Ref-1 expression significantly decreased with the increased expression of adipogenic transcription factors such as CCAAT/enhancer binding protein (C/EBP)-α and peroxisome proliferator-activated receptor (PPAR)-γ, and the adipocyte differentiation marker adipocyte protein 2 (aP2) in a time-dependent manner. However, APE1/Ref-1 overexpression inhibited C/EBP-α, PPAR-γ, and aP2 expression, which was upregulated during adipocyte differentiation. In contrast, silencing APE1/Ref-1 or redox inhibition of APE1/Ref-1 using E3330 increased the mRNA and protein levels of C/EBP-α, PPAR-γ, and aP2 during adipocyte differentiation. These results suggest that APE1/Ref-1 inhibits adipocyte differentiation by regulating adipogenic transcription factors, suggesting that APE1/Ref-1 is a potential therapeutic target for regulating adipocyte differentiation.
... ; W.Sun et al. 2017) : l'activation de TRPV1 par la CAP inhibe la différenciation des adipocytes via l'activation de l'AMPK et réduit la quantité de triglycérides intracellulaires en favorisant la lipolyse (L. L.Zhang et al. 2007;Hsu et Yen 2007). De plus, la CAP induit le brunissement des pré-adipocytes 3T3-L1(Baboota et al. 2014). ...
Thesis
Le rôle de la mitochondrie dans la production d’énergie cellulaire est universellement connu, mais son implication dans la thermogenèse cellulaire reste peu considérée et étudiée. Néanmoins, de récentes données indiquent que la température mitochondriale serait largement supérieure à celle de son environnement cellulaire et qu’elle pourrait atteindre 50°C. Dans l’optique de caractériser un thermostat mitochondrial, nous avons identifié un acteur moléculaire qui pourrait être impliqué dans la régulation de la thermogenèse mitochondriale: le canal TRPV1. En effet, TRPV1 est sensible à des températures élevées (>43°C) et son activité permet de générer des flux d’ions Ca2+, connu pour être un régulateur important de la fonction mitochondriale. Dans ce sens, nous avons identifié TRPV1mito, un variant du canal TRPV1humain présentant une séquence d’adressage mitochondriale. Après avoir validé son adressage à la mitochondrie, nous avons montré que TRPV1mito est impliqué dans la régulation de l’homéostasie calcique cellulaire et mitochondriale. Nos résultats suggèrent également que TRPV1mito est responsable d’une augmentation de la fuite de protons à travers la membrane interne mitochondriale et d’une diminution de son potentiel de membrane. De fait, l’identification et la caractérisation de TRPV1mito renforcent notre hypothèse d’un rôle dans la régulation de la thermogenèse mitochondriale, même si cela reste à démontrer. De plus, nos prédictions in silico indiquent que TRPV1mito serait présent uniquement chez les mammifères placentaires homéothermes, et constituerait un élément clé dans la compréhension des mécanismes évolutifs ayant abouti à l’homéothermie. Ces données permettent d’envisager une meilleure compréhension des mécanismes défaillants du contrôle de la thermogenèse cellulaire, responsables de l’hyperthermie maligne et du coup de chaleur à l’exercice.
... The lack of response to CAP treatment in most parameters evaluated in this study raises the question whether CAP may have had altered postabsorptive metabolism in cows which will be later discussed in this section. Because capsaicin may increase pancreatic digestive secretion Srinivasan, 2000, 1996), stimulate gastric emptying (Debreceni et al., 1999), or decrease blood leptin levels (Hsu and Yen, 2007) in humans and mice, authors have investigated the capsaicin effects on feed intake and digestibility. Aligning with the current study, feeding different levels of capsaicinoids (unprotected from rumen as Capsicum oleoresin in a granular form with 1.2% capsaicinoids) did not influence DM intake and nutrient digestibility (Oh et al., 2015). ...
Article
The aim of this study was to evaluate the effects of a feed additive containing encapsulated pepper on total-tract apparent nutrient digestibility, sorting index, ruminal fermentation, milk yield and composition, serum concentrations of urea-N and glucose, purine derivative excretion, and N utilization efficiency in dairy cows. Twenty-two Holstein cows (182 ± 86.3 days in milk, 35.4 ± 4.85 kg/d milk yield), of which 4 were rumen cannulated, were used in a crossover design experiment with 21-d periods (14 days allowed to treatment adaptation and 7 days for sampling). Cows were blocked according to parity, days in milk, and milk yield and randomly assigned to the following treatments: Control (CON), or 1.5 g/d (CAP) of a feed additive containing encapsulated pepper (Capcin; NutriQuest, Campinas, Brazil) added to the concentrate along with minerals. Data were analyzed using the mixed procedure of SAS modelling the fixed effects of treatment, period, and the random effect of animal. Ruminal fermentation data were analyzed as repeated measurements adding the fixed effect of time and its interaction with treatments to the previous model. No differences in intake of dry matter or nutrients were detected. Sorting for feed particles between 19-8 mm size was greater in cows fed CAP compared to CON (1.000 and 0.992 kg/kg, respectively). Feeding CAP had no effects on digestibility of dry matter, crude protein, ether extract, or neutral detergent fiber. Nor treatment or interaction effect between treatment and time were observed for ruminal pH, NH3-N concentration, or short-chain fatty acids concentration. Yields of milk (35.3 vs 34.3 kg/d) and fat-corrected milk (37.4 vs 36.0 kg/d) were greater for cows under CAP treatment compared to CON. Yield of milk solids (fat, protein, and lactose) was increased when feeding CAP. Milk fat concentration tended to be greater in cows fed CAP than those in CON group (39.5 vs 38.3 g/kg, respectively). Feed efficiency (fat-corrected milk ÷ dry matter intake) tended to be greater in cows fed CAP than CON-cows (1.45 vs 1.40, respectively). Serum concentrations of urea-N and glucose were similar between treatment groups. Feeding CAP did not alter purine derivative excretion (allantoin in urine and milk, and uric acid in urine), as well as the nitrogen excreted (g/g N intake) through feces, milk, or urine. In conclusion, feeding CAP at 1.5 g/d improved performance without altering nutrient digestibility, ruminal fermentation, excretion of purine derivatives, or efficiency of nitrogen utilization in dairy cows.
... Red peppers (Capsicum annuum L.) have been used as traditional food pigments, spices, and medicines since ancient times [14][15][16][17]. Several studies suggest that capsaicin predominantly accounts for the beneficial effect of peppers [18][19][20][21][22]; however, capsaicin is predominantly present in the placenta of red pepper fruit [15]. Pepper seeds, the major waste products of pepper processing, rarely contain capsaicin [15]. ...
Article
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Although the red pepper and its seeds have been studied for metabolic diseases, the effects and potential mechanisms of red pepper seed extract (RPS) on hepatic lipid accumulation are not yet completely understood. This study aimed to evaluate the inhibitory effect of RPS on hepatic lipid accumulation via autophagy. C57BL/6 mice were fed a high-fat diet (HFD) or a HFD supplemented with RPS. RPS treatment inhibited hepatic lipid accumulation by suppressing lipogenesis, inducing hepatic autophagic flux, and activating AMPK in HFD-fed mice. To investigate the effect of RPS on an oleic acid (OA)-induced hepatic steatosis cell model, HepG2 cells were incubated in a high-glucose medium and OA, followed by RPS treatment. RPS treatment decreased OA-induced lipid accumulation and reduced the expression of lipogenesis-associated proteins. Autophagic flux dramatically increased in the RPS-treated group. RPS phosphorylated AMPK in a dose-dependent manner, thereby dephosphorylated mTOR. Autophagy inhibition with 3-methyladenine (3-MA) antagonized RPS-induced suppression of lipogenesis-related protein expressions. Moreover, the knockdown of endogenous AMPK also antagonized the RPS-induced regulation of lipid accumulation and autophagy. Our findings provide new insights into the beneficial effects of RPS on hepatic lipid accumulation through the AMPK-dependent autophagy-mediated downregulation of lipogenesis.
... In the meantime, it promoted anti-adipogenic genes and apoptosis and inhibited adipogenesis. Meanwhile, a high dosage of Capsaicin stimulated adipogenesis with a low expression of anti-adipogenic genes [77,78]. In Caco-2 cells, without the activation of TRPV1, Capsaicin reduced the absorption of fatty acids and increased the stimulation of acetyl-coenzyme A synthetase [79]. ...
Article
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Capsaicin is a chili peppers extract, genus Capsicum, commonly used as a food spice. Since ancient times, Capsaicin has been used as a “homeopathic remedy” for treating a wild range of pathological conditions but without any scientific knowledge about its action. Several studies have demonstrated its potentiality in cardiovascular, nephrological, nutritional, and other medical fields. Capsaicin exerts its actions thanks to the bond with transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is a nociceptive receptor, and its activation starts with a neurosensitive impulse, responsible for a burning pain sensation. However, constant local application of Capsaicin desensitized neuronal cells and leads to relief from neuropathic pain. In this review, we analyze the potential adjuvant role of Capsaicin in the treatment of different pathological conditions either in internal medicine or dentistry. Moreover, we present our experience in five patients affected by oro-facial pain consequent to post-traumatic trigeminal neuropathy, not responsive to any remedy, and successfully treated with topical application of Capsaicin. The topical application of Capsaicin is safe, effective, and quite tolerated by patients. For these reasons, in addition to the already-proven beneficial actions in the internal field, it represents a promising method for the treatment of neuropathic oral diseases.
... In contrast, a limited number of studies have shown direct effects of Capsaicin in metabolic tissues such as liver, kidney, pancreas, gastrointestinal tract, WAT, and BAT, where TRPV1 is expressed 26,27 . For example, treatment with Capsaicin in murine 3T3-L1 adipocytes suppressed adipogenesis and decreased triglyceride accumulation 28,29 , although the high-dose regimen increased lipid accumulation 30 . In HB2 immortalised mouse brown preadipocytes, TRPV1 expression was induced during adipocyte differentiation 31 . ...
Article
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Human brown fat is a potential therapeutic target for preventing obesity and related metabolic diseases by dissipating energy as heat through uncoupling protein 1 (UCP1). We have previously reported a method to obtain chemical compound-induced brown adipocytes (ciBAs) converted from human dermal fibroblasts under serum-free conditions. However, pharmacological responses to bioactive molecules have been poorly characterised in ciBAs. This study showed that the treatment with Capsaicin, an agonist of transient receptor potential vanilloid 1, directly activated adipocyte browning such as UCP1 expression, mitochondrial biogenesis, energy consumption rates, and glycerol recycling in ciBAs. Furthermore, genome-wide transcriptome analysis indicated that Capsaicin activated a broad range of metabolic genes including glycerol kinase and glycerol 3-phosphate dehydrogenase 1, which could be associated with the activation of glycerol recycling and triglyceride synthesis. Capsaicin also activated UCP1 expression in immortalised human brown adipocytes but inhibited its expression in mesenchymal stem cell-derived adipocytes. Altogether, ciBAs successfully reflected the direct effects of Capsaicin on adipocyte browning. These findings suggested that ciBAs could serve as a promising cell model for screening of small molecules and dietary bioactive compounds targeting human brown adipocytes.
... Capsaicin (trans-8-methyl-N-vanillyl-6-noneneamide) is the source of spicy-aromatic compounds in the capsicum genus and the active ingredients in Capsicum oleoresin. Dietary capsaicin can increase food intake by directly acting on the neurons [13] and stimulate the secretion of digestive juices [14] in the digestive tract. The dietary intake of capsaicin reportedly improved feed efficiency in chickens [15], pigs [16,17], goats [18], sheep [19], beef [20], and dairy cows [21][22][23]. ...
Article
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The present study investigates the effect of Capsicum oleoresin (CAP) supplementation on the dry matter intake, milk performance, plasma metabolites, and nutrient digestibility of dairy cows during the summer. Thirty-two lactating Holstein dairy cows (n = 32) were randomly divided into four groups. The CAP was dissolved in water and added to the total mixed ration with graded levels of CAP (0, 20, 40, and 80 mg/kg of dry matter). The trial period consisted of seven days for adaptation and thirty days for sampling. Data were analyzed using the MIXED and GLM procedure SAS. The linear and quadratic effects were tested. The milk yield, milk fat, and milk urea nitrogen increased linearly with the dietary addition of CAP (p < 0.05). The dry matter intake increased linearly in the 20CAP group (p < 0.05). Additionally, the 4% fat-corrected milk, energy-corrected milk, milk fat yield, and milk fat to milk protein ratio increased quadratically (p < 0.05), while the rectal temperature decreased quadratically (p < 0.05). Serum total cholesterol and non-esterified fatty acids increased linearly (p < 0.05); glucose and β-hydroxybutyrate tended to increase quadratically with the dietary addition of CAP (p = 0.05). Meanwhile, CAP supplementation did not affect the milk protein yield, blood concentration of triglyceride, insulin, lipopolysaccharide, immunoglobulin G, or heat shock protein 70 expression level (p > 0.05). In addition, nutrient digestibility was comparable among groups (p > 0.05). These findings indicated that CAP supplementation could enhance the lactation performance of dairy cows during the summer.
... In addition, CAP inhibits the expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT-enhancer-binding protein-α (C/EBP-α) and leptin; but induces up-regulation of adiponectin at the protein level. Therefore, it can effectively induce apoptosis of 3T3-L1 pre-adipocytes and adipocytes; and inhibit adipogenesis in vitro (46). ...
Article
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Background Patients with metabolic syndrome (MetS) have increased cardiovascular risk. Capsaicin (CAP) has been shown to reduce lipids, but efficacy for patients with MetS is unknown. Methods A systematic review was performed according to PRISMA guidelines, to compare the effects of CAP against a placebo. Differences in the weight mean difference (WMD) with 95% confidence intervals (95% CI) were then pooled using a random effects model. Results Nine randomized controlled trials including 461 patients were identified in the overall analysis. CAP significantly decreased total cholesterol (TC) (WMD = −0.48, 95% CI: −0.63 to −0.34, I²= 0.00%) and low-density lipoprotein cholesterol (LDL-C) (WMD = −0.23, 95% CI: −0.45 to −0.02, I² = 68.27%) among patients with MetS. No significant effects of CAP were found on triglycerides (TG) or high-density lipoprotein cholesterol (HDL-C) (WMD = −0.40, 95% CI: −1.50 to 0.71, I² = 98.32%; WMD = −0.08, 95% CI: −0.21 to 0.04, I² = 86.06%). Subgroup analyses indicated that sex and intervention period were sources of heterogeneity. The results revealed that CAP decreased TG levels in women (WMD = −0.59, 95% CI: −1.07 to −0.10) and intervention period <12 weeks (WMD = −0.65; 95% CI: −1.10 to −0.20). And there was no potential publication bias according to funnel plot, Begg' test and Egger regression test. Conclusions CAP supplementation is a promising approach to decreasing TC and LCL-C levels in patients with MetS. However, short-term (<12 weeks) use of CAP in women may also reduce TG levels. Systematic Review Registration Identifier: CRD42021228032.
... Chili pepper is also used in a therapeutic diet due to the activities of unique components, capsaicin and capsaicinoids, that contribute to the pungent scent of hot chili pepper. Recent studies on chili peppers have focused on their beneficial functions as potential anti-tumor, anti-cancer, antioxidant, anti-obesity agents [8][9][10]. ...
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Fruits and vegetables are important components of a healthy diet. They are rich sources of vitamins and minerals, dietary fibre and a host of beneficial non-nutrient substances including plant sterols, flavonoids and other antioxidants. It has been reported that reduced intake of fruits and vegetables may increase the risk of non-communicable diseases (NCDs). Chili pepper, is a common and important spice used to enhance taste and nutrition. Over the years, reports have shown its potential as antioxidant and an anti-obesity agent. Obesity is a serious health concern as it may initiate other common chronic diseases. Due to the side effects of synthetic antioxidants and anti-obesity drugs, scientists are now focusing on natural products which produce similar effects to synthetic chemicals. This up-to-date review addresses this research gap and presents, in an accessible format, the nutritional, antioxidant and anti-obesity properties of different chili peppers. This review article serves as a reference guide for use of chili peppers as anti-obesity agents.
... Exposure to CAP triggers a potent neuronal calcium influx, often followed by a reflex down-regulation of the TRPV 1 activity [1][2][3]. For this reason, CAP is a promising clinical tool to modulate TRPV 1 -related pathways, from pain perception [1][2][3][4], inflammation [5], and immunity [6], to most severe pathologies like schizophrenia [7], anxiety, depression [8], obesity [9] and chronic fatigue [10]. Ingestion of CAP increases thermogenesis by stimulating catecholamine secretion from the adrenal medulla, decreasing adipogenesis, and enhancing energy metabolism [11][12][13][14][15], improving mitochondrial biogenesis and adenosine triphosphate (ATP) synthesis, and is even suggested to improve markers of cardiovascular health [16][17][18][19][20]. ...
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Capsaicin (CAP) activates the transient receptor potential vanilloid 1 (TRPV1) channel on sensory neurons, improving ATP production, vascular function, fatigue resistance, and thus exercise performance. However, the underlying mechanisms of CAP-induced ergogenic effects and fatigue-resistance, remain elusive. To evaluate the potential anti-fatigue effects of CAP, 10 young healthy males performed constant-load cycling exercise time to exhaustion (TTE) trials (85% maximal work rate) after ingestion of placebo (PL; fiber) or CAP capsules in a blinded, counterbalanced, crossover design, while cardiorespiratory responses were monitored. Fatigue was assessed with the interpolated twitch technique, pre-post exercise, during isometric maximal voluntary contractions (MVC). No significant differences (p > 0.05) were detected in cardiorespiratory responses and self-reported fatigue (RPE scale) during the time trial or in TTE (375 ± 26 and 327 ± 36 s, respectively). CAP attenuated the reduction in potentiated twitch (PL: −52 ± 6 vs. CAP: −42 ± 11%, p = 0.037), and tended to attenuate the decline in maximal relaxation rate (PL: −47 ± 33 vs. CAP: −29 ± 68%, p = 0.057), but not maximal rate of force development, MVC, or voluntary muscle activation. Thus, CAP might attenuate neuromuscular fatigue through alterations in afferent signaling or neuromuscular relaxation kinetics, perhaps mediated via the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps, thereby increasing the rate of Ca2+ reuptake and relaxation.
... Capsaicin, which is found in pepper and causes a bitter taste, has recently been shown to be an anti-obese agent in animal studies, with few studies conducted in humans, and data on obese and morbidly obese patients are limited [12]. Transient receptor potential vanilloid-1 (TRPV1), a nonselective cation channel, is mainly found in neuronal tissue and has also been shown to be present in adipose tissue and skeletal muscles and mediates the effect of capsaicin on adipose tissue [13][14][15][16]. ...
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Background: Transient receptor potential vanilloid-1 (TRPV1), a nonselective cation channel, is activated by capsaicin, a pungent ingredient of hot pepper. Previous studies have suggested a link between obesity and capsaicin-associated pathways, and activation of TRPV1 may provide an alternative approach for obesity treatment. However, data on the TRPV1 distribution in human gastric mucosa are limited, and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown. Aim: To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals. Methods: Forty-six patients with a body mass index (BMI) of > 40 kg/m2 and 20 patients with a BMI between 18-25 kg/m2 were included. Simultaneous biopsies from the fundus, antrum, and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy. Age, sex, history of alcohol and cigarette consumption, and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly. Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus, antrum, and duodenum tissues using an immunoreactivity score. Data were analyzed using SPSS 17.0. Results: TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum. Unlike foveolar cells in the antrum, TRPV1 was relatively low in foveolar cells in the fundus (4.92 ± 0.49 vs 0.48 ± 0.16, P < 0.01, Mann-Whitney U test). Additionally, the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum (1.33 ± 0.31 vs 2.95 ± 0.46, P < 0.01, Mann-Whitney U test). TRPV1 expression levels of different cell types in the fundus, antrum, and duodenum tissues of the morbidly obese group were similar to those of the control group. Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged ≥ 45 years than in patients < 45 years (3.03 ± 0.42, 4.37 ± 0.76, 2.28 ± 0.55 vs 1.9 ± 0.46, 1.58 ± 0.44, 0.37 ± 0.18, P = 0.03, P < 0.01, P < 0.01, respectively, Mann-Whitney U test). The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension (diabetes: 2.11 ± 0.67 vs 1.02 ± 0.34, P = 0.04; hypertension: 2.42 ± 0.75 vs 1.02 ± 0.33, P < 0.01 Mann-Whitney U test). Conclusion: The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.
... Consistently, in 3T3-L1 white adipocytes, a combination treatment of CAP (25 µM) and capsiate (25 µM) could induce browning through activation of peroxisome proliferator-activated receptor γ and β 3 -adrenergic receptor (PPARγ/β 3 -AR) signaling pathway (147). Moreover, CAP time-and dose-dependently inhibited lipid accumulation in 3T3-L1 adipocytes via inducing apoptosis and suppressing adipogenesis (148). Likewise, an in vitro study also showed that palmitic acid-treated HepG2 cells exhibited an improvement in lipid metabolism upon CAP treatment (100 µM), as evidenced by decreased lipid accumulation and concentrations of TG and TC as well as increased HDL-C levels (149). ...
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Obesity has become one of the most serious chronic diseases threatening human health. Its occurrence and development are closely associated with gut microbiota since the disorders of gut microbiota can promote endotoxin production and induce inflammatory response. Recently, numerous plant extracts have been proven to mitigate lipid dysmetabolism and obesity syndrome by regulating the abundance and composition of gut microbiota. In this review, we summarize the potential roles of different plant extracts including mulberry leaf extract, policosanol, cortex moutan, green tea, honokiol, and capsaicin in regulating obesity via gut microbiota. Based on the current findings, plant extracts may be promising agents for the prevention and treatment of obesity and its related metabolic diseases, and the mechanisms might be associated with gut microbiota.
... This agrees with the assertion that there is a correlation between antioxidative action and apoptosis induction. [60,61] DCFH-DA is a non-fluorescent probe that enters the cells and detects easily intracellular ROS release. [62] DCFH-DA is hydrolysed into DCFH with the aid of an intracellular enzyme, esterase. ...
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Chapter
The spicy flavour of chilli pepper fruit comes from chemicals, called capsaicinoids. Capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, and homocapsaicin are the most important capsaicinoids in chilli pepper. Over 92% of the capsaicinoids in chilli pepper fruit are capsaicin and dihydrocapsaicin. These are the most powerful capsaicinoids, and the only difference between them is the saturation of the acyl group. Amides of vanillyl-amine plus long-chain fatty acids yield capsaicin and all other capsaicinoid derivatives. Analogues of capsaicin that keep the homovanillyl group safe are good options for blocking TRPV1 (a membrane channel). Because vanilloids function on sensory nerve fibres, they are anti-inflammatory and painkilling. Non-spicy capsaicin analogues synthesised from n-3 polyunsaturated fatty acid were studied for antioxidant and carbohydrate-hydrolyzing enzyme-blocking activities. Both two capsaicin analogues, N-eicosapentaenoyl vanillylamine and N-docosahexaenoyl vanillylamine, non-spicy forms of capsaicin can inhibit amylase and glucosidase. Capsaicinoids and capsaicin have antioxidant, anticarcinogenic, energy metabolism, lipid profile, and inflammation-reducing properties, according to study. Still, these molecules’ fragrance can make people irritated, limiting their utilisation. ‘CH-19-Sweet pepper’, a mild red pepper, contains capsinoids similar to capsaicin. Capsiate, dihydrocapsiate, and nordihydrocapsiate are capsinoids. Capsinoids offer consistent biopotency to capsaicin devoid of pungency or spiciness. The anti-cancer effect of capsaicin epoxide is the same as capsaicin. Resiniferatoxin is a thousand times stronger than capsaicin as an agonist of TRPV1. Zucapsaicin, the cis-isomer of capsaicin, treats cluster migraines, episodic collection headaches, and neuropathic pain. The first antagonist was capsazepine, a synthetic form of capsaicin produced by modifying its molecules. Despite its negative consequences, capsaicin is employed in many treatments to treat human ailments. Several capsaicin equivalents from nature or the laboratory were employed to create novel medications with fewer or no lethal side effects. This chapter emphasises the necessity for Structure Activity Relationships (SAR) investigations to develop novel capsaicin analogues with minimal or no harmful effects, as well as bioisostere analogues as a prospective scaffold.
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Abstract : This study was conducted to evaluate the effect of commercial and nanocapsaicin on the level of fat and liver and kidney function in rats. In this experiment, 40 female rats were used at the age of 4-5 months divided into 8 groups according to the following: The control group was left untreated, and the second, third and fourth groups were dosed with cholesterol at a concentration of 20 mg/kg of body weight in addition to the nanocapsaicin in concentrations of 1,2.3 mg/kg respectively. The fifth, sixth and seventh group was dosed with cholesterol at a concentration of 20 mg/kg body weight, in addition to commercial capsaicin at a concentration of 8.4.2 mg/kg body weight respectively. Finally, the eighth group was dosed with cholesterol and a concentration of 20 mg/kg body weight. The results showed a significant decrease in the level of cholesterol, trigly fats, low-density protein fats, very low-density protein fats, and a high level of high-density fats, good when using commercial and nanocapsin. The effect of nanomaterial was more by the low level of fat images compared to commercial capsaicin. The results also showed that there are no negative effects of nanocapsaicin on liver function, which included measuring the effectiveness of the enzyme amine-conducting enzyme amine-conducting spartite, as well as kidney function, which included the level of blood urea and creatinine. Keywords; Lipid profile, Rats, Blood urea, AST and AL
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Inflammation is a crucial factor in the development and progression of cardiovascular diseases (CVD). Cardiac remodeling in the presence of persistent inflammation leads to myocardial fibrosis and extracellular matrix changes, which reduce cardiac function, induce arrhythmias, and finally, cause heart failure. Medicinal plants and phytochemicals can cure and prevent obesity and inflammation. In comparison to conventional therapies, the synergistic effects of several phytochemicals boost their bioavailability and impact numerous cellular and molecular targets.
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Capsaicin (Cap) is a promising bioactive compound having many health-promoting benefits. However, it is difficult to be applied in food due to its poor aqueous solubility, low stability and bioavailability. Besides, its strong spicy taste and irritation to the gastrointestinal tract further limit the application of Cap in food. To solve this problem, Cap was loaded into a self-assembled nanocarrier formed by partial hydrolysis of α-lactalbumin (α-lac). The Cap was successfully loaded into the 21.2 nm micelles with a loading capacity of 123.4 ± 6.1 mg g-1. The aqueous solubility was greatly improved. Besides, nanomicelles also showed intestinal responsive release behavior. The in vivo bioavailability of Cap was improved by nanomicelles for 3.1 times. The Cap loaded nanomicelles in the milk system showed good colloidal stability compared to solely Cap in milk. Therefore, the Cap loaded nanocarriers were added into the de-fatted milk to prepare de-fatted cheese with an acceptable spicy flavor. The nanocarriers were clearly captured in the cheese casein network as confirmed by confocal microscopy. The sensory evaluation results showed the spicy taste of capsaicin was reduced in the nanomicelle system and further reduced in the nanomicelle-cheese systems. We postulated that it might be due to the nanomicelles reducing the contact of capsaicin with sensory neurons in the tongue thus masking the spicy taste. The cheese casein network structure further masked their contact. The above results indicated that Cap embedding via α-lac nanocarriers was feasible for masking their spicy taste and applying Cap to food systems such as milk and cheese.
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Hypothesis This review article represents a brief layout of the risk factors and pathophysiology responsible for obesity, customary treatment strategies, and nanotechnology-based nutraceutical for therapeutics of obesity. Experiments An exhaustive search of the literature was done for this purpose, using Google Scholar, PubMed, and ScienceDirect databases. A study of the literature was conducted using publications published in peer-reviewed journals between the years 2000 and 2022. Findings This was revealed that risk factors responsible for obesity were genetic abnormalities, environmental, and socio-economic factors. Number of research articles published between 2000 and 2022 were based on phytoconstituents based nanoformulation for obesity therapeutics and therefore, have been systematically compiled in this review. Various nutraceuticals like Garcinia cambogia, quercetin, resveratrol, capsaicin, Capsicum, Curcuma longa, Camella Sinensis, Zingiber officinalis, Citrus aurantium, Aegle marmelos, Coffea canephora, Asparagus officinalis, Gardenia jasminoides, Catha edulis, Clusia nemroisa, Rosmarinus officinalis, Cirsium setidens, Betula platyphylla, Tripterygium wilfordi possessing anti-obesity actions are discussed in this review along with their patents, clinical trials as well as their nanoformulation available. Conclusion This review illustrates that the nanotechnology have a great propensity to impart promising role in the delivery of phytochemicals and nutraceuticals in management of obesity conditions and other related disorders.
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To provide a brief overview of the chemical history, analysis, nomenclature, biology, pharmacology, and pharmacotherapy of capsaicin. Chemical Abstracts, Biological Abstracts, and a MEDLINE search were used to identify pertinent literature; selected literature was used in this review. Original articles, reviews, and abstracts of articles were used to select material pertinent to the objectives of the review. The volume of material available prohibits comprehensive data extraction. A history of the use of Capsicum spp. and the predominant active ingredient, capsaicin, the parent compound of a group of vanillyl fatty acid amides, is presented. Distinct structural differences are noted between this compound and the capsaicinoids, especially the synthetic analog nonivamide, which has appeared as an adulterant in capsaicin-labeled products. Analysis shows that although some of these synthetic analogs eventually may prove to be true natural products, conclusive evidence based on isolation and structure elucidation is still absent after decades of attempted isolation from several potential natural sources. Although the crude, dark oleoresin extract of capsicum contains over 100 distinct volatile compounds and therefore may function in many ways dissimilar to capsaicin, the oleoresin continues to be marketed in products with a high degree of variability in efficacy. Capsaicin as a pure white crystalline material, however, acts specifically by depleting stores of substance P from sensory neurons, and has been successful in the treatment of several painful conditions (e.g., rheumatoid arthritis, osteoarthritis, peripheral neuropathies.
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Apoptosis is a major form of cell death, characterized initially by a series of stereotypic morphological changes. In the nematode Caenorhabditis elegans, the gene ced-3 encodes a protein required for developmental cell death. Since the recognition that CED-3 has sequence identity with the mammalian cysteine protease interleukin-1 beta-converting enzyme (ICE), a family of at least 10 related cysteine proteases has been identified. These proteins are characterized by almost absolute specificity for aspartic acid in the P1 position. All the caspases (ICE-like proteases) contain a conserved QACXG (where X is R, Q or G) pentapeptide active-site motif. Capases are synthesized as inactive proenzymes comprising an N-terminal peptide (prodomain) together with one large and one small subunit. The crystal structures of both caspase-1 and caspase-3 show that the active enzyme is a heterotetramer, containing two small and two large subunits. Activation of caspases during apoptosis results in the cleavage of critical cellular substrates, including poly(ADP-ribose) polymerase and lamins, so precipitating the dramatic morphological changes of apoptosis. Apoptosis induced by CD95 (Fas/APO-1) and tumour necrosis factor activates caspase-8 (MACH/FLICE/Mch5), which contains an N-terminus with FADD (Fas-associating protein with death domain)-like death effector domains, so providing a direct link between cell death receptors and the caspases. The importance of caspase prodomains in the regulation of apoptosis is further highlighted by the recognition of adapter molecules, such as RAIDD [receptor-interacting protein (RIP)-associated ICH-1/CED-3-homologous protein with a death domain]/CRADD (caspase and RIP adapter with death domain), which binds to the prodomain of caspase-2 and recruits it to the signalling complex. Cells undergoing apoptosis following triggering of death receptors execute the death programme by activating a hierarchy of caspases, with caspase-8 and possibly caspase-10 being at or near the apex of this apoptotic cascade.
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We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. Apaf-3 was identified as a member of the caspase family, caspase-9. Caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation. Activated caspase-9 in turn cleaves and activates caspase-3. Depletion of caspase-9 from S-100 extracts diminished caspase-3 activation. Mutation of the active site of caspase-9 attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.
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Significant advances have been made recently toward understanding the molecular events that regulate adipocyte differentiation. In vitro models of adipogenesis, such as the 3T3-L1 and F-442A preadipocyte cell lines have proven to be an invaluable resource in elucidating mechanisms of adipocyte differentiation. Subject to modulation by hormonal, dietary, and genetic influences, the differentiation program now appears to be distinctly controlled through the coordinate regulation of transcription factors that predominantly include members of the C/EBP and PPAR families. Increased understanding of these critical factors and how they are regulated will provide insights into adipose tissue development as well as treatment of obesity.
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When prevention fails, medicinal treatment of obesity may become a necessity. Any strategic medicinal development must recognize that obesity is a chronic, stigmatized and costly disease that is increasing in prevalence. Because obesity can rarely be cured, treatment strategies are effective only as long as they are used, and combined therapy may be more effective than monotherapy. For a drug to have significant impact on body weight it must ultimately reduce energy intake, increase energy expenditure, or both. Currently approved drugs for long-term treatment of obesity include sibutramine, which inhibits food intake, and orlistat, which blocks fat digestion.
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A family of mitogen-activated protein (MAP) kinases comprising the extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and p38 MAP kinases are involved in proliferation and apoptosis. However, there are some arguments concerning the role of these kinases in Ag-induced B cell apoptosis. Two of the B lymphoma cell lines (CH31 and WEHI-231) susceptible to anti-IgM-induced apoptosis were used as a model. To address these issues, we examined the kinetics of anti-IgM-induced activation of MAP kinases and established cell lines overexpressing a dominant-negative (dn) mutant form of JNK1 (dnJNK1). Anti-IgM induced a sustained JNK1 activation with a peak at 8 h, with a marginal activation of ERK1/ERK2 in CH31 cells. The sustained JNK1 activation was not a secondary event through a caspase activation. The peak point of the JNK1 activation was just before the onset of a decline in mitochondrial membrane potential, which preceded anti-IgM-induced cell death. Following anti-IgM stimulation, dnJNK1 prevented a decline in mitochondrial membrane potential at 24 h, with a prolonged inhibition up to 72 h in WEHI-231, although it did so only partially during a later time period in CH31. The dnJNK1 cells also demonstrated diminished procaspase-3 activation and a decreased rate of apoptosis upon anti-IgM stimulation, with a concomitant increased arrest in G(1) phase, which could be explained by enhanced levels of cyclin-dependent kinase inhibitor p27(Kip1) protein. Thus, anti-IgM-induced JNK activation might be implicated in cell cycle progression as well as in apoptosis regulation, probably involving p27(Kip1) protein.
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Hepatocellular carcinoma is one of the most lethal malignancies and there is no effective preventive measure in this highly malignant disease to date. In the present study, we investigated the chemopreventive potential of capsaicin (8-methyl-N- vanillyl-6-nonenamide), the principal pungent ingredient found in hot red pepper, in SK-Hep-1 hepatocellular carcinoma cells. Treatment of capsaicin inhibited growth of SK-Hep-1 cells in a concentration-dependent manner while 4-methoxy capsaicin (Met-capsaicin) was less potent. This inhibitory effect of capsaicin on SK-Hep-1 cell growth was mainly due to the induction of apoptosis as evidenced by DNA fragmentation and nuclear condensation. Furthermore, capsaicin prominently reduced the ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax and consequently increased caspase-3 activity. These results demonstrate that capsaicin efficiently induced apoptosis in SK-Hep-1 cells through a caspase-3-dependent mechanism, which may contribute to its chemopreventive function.
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The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes.
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A wide variety of phenolic substances derived from spice possess potent antimutagenic and anticarcinogenic activities. Examples are curcumin, a yellow colouring agent, contained in turmeric (Curcuma longa L., Zingiberaceae), [6]-gingerol, a pungent ingredient present in ginger (Zingiber officinale Roscoe, Zingiberaceae) and capsaicin, a principal pungent principle of hot chili pepper (Capsicum annuum L, Solanaceae). The chemopreventive effects exerted by these phytochemicals are often associated with their antioxidative and anti-inflammatory activities. Cyclo-oxygenase-2 (COX-2) has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. Recent studies have shown that COX-2 is regulated by the eukaryotic transcription factor NF-kappaB. This short review summarizes the molecular mechanisms underlying chemopreventive effects of the aforementioned spice ingredients in terms of their effects on intracellular signaling cascades, particularly those involving NF-kappaB and mitogen-activated protein kinases.