Phytoformulation with hydroxycitric acid and capsaicin protects against high-fat-diet-induced obesity cardiomyopathy by reducing cardiac lipid deposition and ameliorating inflammation and apoptosis in the heart.

Background and aim: Phytoformulation therapy is a pioneering strategy for the treatment of metabolic disorders and related diseases. The aim of the present study was to investigate the protective effect of a phytoformulation consisting of hydroxycitric acid and capsaicin against obesity-related cardiomyopathy. Experimental procedure: Sprague-Dawley rats were fed HFD for 21 weeks, and phytoformulation (100 mg/kg body weight) was administered orally for 45 days starting at week 16. Results and conclusion: We found that HFD supplementation resulted in significant hyperglycemia and caused an increase in cardiac lipid deposition, inflammation and apoptosis in the heart. Phytoformulation therapy not only significantly decreased blood levels of glucose, cholesterol, triglycerides, free fatty acids, and inflammatory cytokines in obese rats, but also protected cardiac tissue, as shown by histological analysis. Conversely, phytoformulation therapy decreased mRNA levels for sterol regulatory element-binding factor 1, fatty acid synthase, acetyl-CoA carboxylase, and fatty acid binding protein 1 genes involved in fatty acid synthesis and absorption in obese rats. It increased the levels of lysosomal acid lipase, hormone-sensitive lipase, and lipoprotein lipase genes involved in fatty acid degradation in the heart. In addition, the phytoformulation improved cardiac inflammation and apoptosis by downregulating the genes nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumour necrosis factor α, interleukin-6, toll-like receptor-4 (TLR-4), BCL2-associated X and caspase-3. In conclusion, our results show that the phytoformulation improved insulin sensitivity and attenuated myocardial lipid accumulation, inflammation, and apoptosis in the heart of HFD-induced obese rats by regulating fatty acid metabolism genes and downregulating NF-kB/TLR-4/caspase-3.

Hydroxycitric acid and capsaicin combination alleviates obesity-induced testicular apoptosis, oxidative stress and inflammation.

Recent research in rodents suggests that oxidative stress, inflammation, and apoptosis in the testes caused by high-fat diets (HFD) are a cause of male infertility. To investigate the therapeutic efficacy of the combination of hydroxycitric acid and capsaicin (HCC) against male reproductive disorders, we developed an HFD-induced obese rat model. Rats received HFD supplementation for 21 weeks, which induced obesity. From week 16, HCC (100 mg/kg body weight) was administered to investigate its potential to treat testicular toxicity. According to the results of the current study, treatment of obese rats with HCC improved their sperm quality, increased the production of testosterone, follicle-stimulating hormone, and luteinizing hormone and significantly increased the activities of steroidogenic enzymes and corresponding mRNA levels. In addition, HCC decreased lipid peroxidation and nitric oxide levels in both spermatozoa and testes while increasing the expression of mRNA for the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in the testes, which in turn reduced oxidative stress in the testes. Moreover, after HCC treatment, testicular tissues showed a remarkable decrease in mRNA levels responsible for inflammation (TNF-α, IL-6, NF-κB) and apoptosis (Bax and Bcl-2). Our results suggest that HCC may alleviate obesity-induced male reproductive dysfunction by attenuating oxidative stress, inflammation, and apoptosis in the testes of HFD-induced obese male rats.

Pathophysiology of obesity-related infertility and its prevention and treatment by potential phytotherapeutics.

BACKGROUND: Obesity is a complex multifactorial disease in which the accumulation of excess body fat has adverse health effects, as it can increase the risk of several problems, including infertility, in both men and women. Obesity and infertility have risen together in recent years. Against this background, the present review aims to highlight the impact of obesity on infertility and the underlying pathophysiology of obesity-related infertility (ORI) in men and women, and to provide readers with knowledge of current trends in the effective development of phytotherapeutics for its treatment. METHODS: We thoroughly searched in PubMed, MEDLINE, Scopus, EMBASE, and Google Scholar to find all relevant papers on ORI and the therapeutic effects of phytotherapeutics on ORI in men and women. RESULTS: The extensive search of the available literature revealed that obesity affects reproductive function through several complex mechanisms such as hyperlipidaemia, hyperinsulinaemia, hyperandrogenism, increased body mass index, disruption of the hormonal milieu, systemic inflammation, oxidative stress, alterations in epigenetics and dysbiosis. On the other hand, several studies reported that phytotherapeutics has a broad therapeutic spectrum of action by improving sex hormone homeostasis, ovarian dysfunction, menstrual cycle and inhibiting ovarian hyperplasia, as well as down-regulating ovarian apoptosis, inflammation and oxidative stress, and controlling metabolic dysfunction in obese women. Male infertility is also addressed by phytotherapeutics by suppressing lipogenesis, increasing testosterone, 3ß-HSD and 17ß-HSD levels, improving sperm parameters and attenuating testicular dyslipidaemia, oxidative stress, inflammation and germ cell apoptosis. CONCLUSIONS: In the present review, we discussed the effects of obesity on reproductive dysfunction in men and women and the underlying pathophysiology of ORI. In addition, the therapeutic effect of phytotherapeutics against ORI was highlighted.

Beta-glucan suppresses high-fat-diet-induced obesity by attenuating dyslipidemia and modulating obesogenic marker expressions in rats.

The current study was designed to evaluate the therapeutic potential of beta-glucan (BG), which is a key bioactive compound predominantly present in mushrooms and cereals against high-fat-diet (HFD)-induced obesity, and to understand its mechanism of action. Obesity was induced in rats by supplementing the diet with HFD and BG (40 mg/kg body weight) for a period of 6 weeks. At the end of the experimental period, the body weight, as well as hyperglycemic, dyslipidemia, and obesogenic marker expressions, was assessed in the control group and in the experimental obese rats. Administration of BG to obese rats significantly reduced body weight gain and attenuated hyperglycemia, which was confirmed by the decreased blood glucose and insulin resistance. At the same time, BG mitigated dyslipidemia by altering expressions of peroxisome proliferator-activated receptor-gamma (PPAR-γ), sterol regulatory element-binding protein 1 (SREBP-1c), fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, and fatty acid-binding protein-4 (Fab-4) in HFD-induced obese rats. In conclusion, this study revealed that BG is a potential candidate to ameliorate HFD-induced obesity by modulating obesogenic marker expressions, especially by regulating the master regulator PPAR-γ.

Effect of S-allylcysteine against diabetic nephropathy via inhibition of MEK1/2-ERK1/2-RSK2 signalling pathway in streptozotocin-nicotinamide-induced diabetic rats.

OBJECTIVE: In the current study, we evaluated the ameliorative effect of S-allylcysteine (SAC) against streptozotocin (STZ)-nicotinamide (NAD)-induced diabetic nephropathy (DN) in rats and also an attempt was made to establish the molecular mechanism of SAC. METHODS: DN rats were orally supplemented with SAC (150 mg/kg body weight) for a period of 45 days and the effect of SAC on urinary albumin excretion, metabolic parameters, and tubular injury biomarkers by ELISA, total levels and phosphorylation of MEK1/2, ERK1/2, and RSK2 by western blotting analysis in control and experimental rats were assessed. RESULTS: From this study, we observed that SAC considerably decreased polydipsia, poly urea, polyphagia, albuminuria and the levels of urinary N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, transforming growth factor-ß1 and SAC effectively altered the pathological changes in DN rats. SAC also reserved renal cortical phosphorylation of MEK1/2, ERK1/2 and RSK2. CONCLUSION: Hence this study recommended that SAC can successfully protect the DN through regulation of MEK1/2-ERK1/2-RSK2 signalling.

Biochanin A attenuates obesity cardiomyopathy in rats by inhibiting oxidative stress and inflammation through the Nrf-2 pathway.

OBJECTIVE: In the present study, we evaluated the effect of biochanin A (BCA) on high-fat diet (HFD)-induced obesity cardiomyopathy. METHODS: BCA (10 mg/kg body weight) was administered to HFD-induced obese rats for 30 days, and its effect on anthropometrical, morphological, plasma cardiac, and inflammatory biomarkers, along with cardiac lipid profiles was assessed. RESULTS: Supplementation of HFD to rats significantly increased body mass index, obesity index parameters, and cardiac lipid profile along with notable oxidative stress and inflammation. Additionally, BCA treatment in obese rats demonstrated a superior therapeutic action by restoring the altered parameters to almost normal levels. Simultaneously, BCA increased the activities and mRNA expressions of enzymatic antioxidants by upregulating the Nrf-2 pathway and inhibiting the NF-κB cascade. CONCLUSION: BCA may attenuate obesity and its associated cardiomyopathy by suppressing oxidative stress and inflammation through activation of the Nrf-2 pathway and inhibition of NF-κB activation.

Polyherbal Formulation Ameliorates Diabetic Cardiomyopathy Through Attenuation of Cardiac Inflammation and Oxidative Stress Via NF-κB/Nrf-2/HO-1 Pathway in Diabetic Rats.

ABSTRACT: The present study was intended to evaluate the effect of polyherbal formulation (PHF) made with 3 nutraceuticals, such as Piper nigrum, Terminalia paniculata, and Bauhinia purpurea on inflammation and oxidative stress in diabetic cardiomyopathy (DCM), which is induced by streptozotocin and nicotinamide administration in rats. We supplemented DCM rats with PHF (250 and 500 mg/kg/BW) for 45 days and evaluated their effects on oxidative stress markers, proinflammatory cytokines, and messenger RNA expressions of the nuclear factor erythroid 2-related factor-2 (Nrf-2) and its linked genes [heme oxygenase-1 (HO-1), superoxide dismutase, catalase] along with inflammatory genes [tumour necrosis factor α and nuclear factor kappa B (NF-κB)]. Our study demonstrated that PHF successfully attenuated inflammation and oxidative stress via messenger RNA upregulation of Nrf-2, HO-1, superoxide dismutase, and catalase and concomitantly with downregulation of tumour necrosis factor α and NF-κB. Conversely, PHF also protected hyperglycemia-mediated cardiac damage, which was confirmed with histopathological and scanning electron microscopy analysis. In conclusion, our results suggested that PHF successfully ameliorated hyperglycemia-mediated inflammation and oxidative stress via regulation of NF-κB/Nrf-2/HO-1 pathway. Therefore, these results recommend that PHF may be a prospective therapeutic agent for DCM.

Evaluation of the Antioxidant and Antidiabetic Potential of the Poly Herbal Formulation: Identification of Bioactive Factors.

BACKGROUND AND OBJECTIVES: The present investigation is intended to prepare a Poly Herbal Formulation (PHF) with Piper nigrum (fruits), Terminalia paniculata (bark) and Bauhinia purpurea (bark) and assess their antioxidant and glucose-lowering effects utilizing in vitro models. METHODS: The individual plant methanolic extracts and PHF are exposed to phytochemical examination and to distinguish the bioactive factors by GC-MS. We assessed the antioxidant properties of individual plant extracts and the PHF by using the DPPH scavenging method, H2O2 scavenging assay, TBARS assay and total antioxidant estimation. Likewise, the anti-diabetic activity was assessed by ɑ-amylase and α-glucosidase enzyme inhibition and glucose diffusion inhibitory techniques. RESULTS: We found that PHF contains a high measure of total phenolics, total flavonoids and tannin compared to individual plant extracts. The GC-MS identified the bioactive components. We also found that PHF had significantly higher antioxidant and glucose-lowering effects than the individual plant concentrates. CONCLUSION: In conclusion, it could be reasoned that due to the nearness of antioxidant components, the PHF has good potential in the administration of hyperglycemia, diabetes and the related state of oxidative stress. This study shows that PHF is superior to individual plant extracts, supporting the conventional PHF concept.

Antiobesity efficacy of asiatic acid: down-regulation of adipogenic and inflammatory processes in high fat diet induced obese rats.

In the current study, we evaluated the effects of Asiatic acid (AA) on lipid metabolic markers in HFD-induced obese Sprague-Dawley rat model. AA (20 mg/kg BW) was administered orally to HFD-fed rats for 42 days. Changes in body composition, glucose, insulin resistance (IR) and lipid profiles of tissues, plasma and the pattern of gene expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and its target genes fatty-acid synthase (FAS), adipocyte protein-2 (aP2) and uncoupling protein-2 (UCP-2) and pro-inflammatory factor tumor necrosis factor (TNF)-α were observed in experimental rats. Oral administration of AA exerts therapeutic effects similar to orlistat in attenuating body weight gain, glucose, IR, plasma and tissue lipids and mRNA levels of PPAR-γ, FAS, aP2 and inflammatory factor TNF-α and increasing UCP-2 expression in HFD-fed rats. Hence, these findings concluded that AA attenuate HFD-induced obesity by modulating PPAR-γ and its target genes and regulate lipid metabolism, suggesting their possible antiobesity effects.

Asthma-Alleviating Potential of 6-Gingerol: Effect on Cytokines, Related mRNA and c-Myc, and NFAT1 Expression in Ovalbumin-Sensitized Asthma in Rats.

In this study, we aimed at assessing the therapeutical potential of 6-gingerol ([5S]-5-hydroxy-1-[4-hydroxy- 3-methoxyphenyl]-3-decanone) against ovalbumin-sensitized asthma in rats. The rats were treated intraperitoneally with 6-gingerol (75 mg/kg body weight) for 30 days and a theophylline (200 mg/kg body weight)-treated group as a control. Changes in the levels of T-cell-linked cytokines (interleukin-4 [IL-4], IL-5, IL-13, and interferon-gamma [IFN-?]), total immunoglobulin E (IgE), gene expressions of bitter taste-sensing type 2-receptor 10 (T2R10), inositol 1,4,5-triphosphate receptor 1 (IP3R1), Orai1 and protein expressions of nuclear factor of activated T cells 1 (NFAT1), c-Myc and histopathological changes were observed in rats. 6-Gingerol exerts its beneficial impacts like theophylline in lessening IL-4, IL-5, and IL-13, and IgE and increasing the level of IFN-?. Significant down-regulation of T2R10 gene expression and up-regulation of IP3R1 and Orai1 gene expression were observed in experimental rats and these alterations were normalized after treatment with 6-gingerol or theophylline. The histopathological study revealed that the accumulation of glycoprotein and thickness of alveolar epithelium in asthmatic rats and supplementation with 6-gingerol or theophylline in asthmatic rats restored these changes to normal. In conclusion, 6-gingerol has a protective effect on lungs in ovalbumin-sensitized asthma in rats.

Reversal of high fat diet-induced obesity through modulating lipid metabolic enzymes and inflammatory markers expressions in rats.

In this study, we evaluated the ameliorative potential of Cucurbita maxima seeds oil (CSO (100 mg/kg body weight)) supplementation to high fat diet (HFD)-induced obese rats for 30 days on the changes in body weight, markers of lipid metabolism such as LDL, HDL, triglycerides, total cholesterol, adiponectin, leptin, amylase, and lipase. We also investigated the effects of CSO on the changes of lipid metabolic enzymes such as fatty-acid synthase, acetyl CoA carboxylase, carnitine palmitoyl transferase-1, HMG CoA reductase, and inflammatory markers (TNF-α and IL-6). Administration of CSO revealed significant diminution in body weight gain, altered the activity, expressions of lipid marker enzymes and inflammatory markers. It demonstrated that CSO had considerably altered these parameters when evaluated with HFD control rats. In conclusion, this study suggested that CSO might ameliorate the HFD-induced obesity by altering the enzymes and mRNA expressions important to lipid metabolism.

Obesity-alleviating potential of asiatic acid and its effects on ACC1, UCP2, and CPT1 mRNA expression in high fat diet-induced obese Sprague-Dawley rats.

The present study evaluated the effects of asiatic acid (AA), a pentacyclic triterpenoid from Centella asiatica on lipid metabolism parameters in a rat model of obesity induced using a high fat diet (HFD) for 42 days. AA (20 mg/kg body weight [BW]) was administered orally once daily for 42 days, and an orlistat-treated group of rats (10 mg/kg BW) was included for comparison. Changes in BW, blood glucose levels, insulin resistance and leptin, adiponectin, amylase, and lipase levels in the blood; lipid profiles of plasma; liver antioxidants levels; and acetyl CoA carboxylase(ACC), uncoupling protein-2 (UCP2), and carnitine palmitoyltransferase-1 (CPT1) mRNA expression were observed in the experimental rats. Our results revealed that AA (20 mg/kg BW), similar to orlistat, reduced the increase in BW; increased bone mineral contents and bone mineral densities; reduced blood glucose levels, insulin resistance, leptin, plasma lipid levels; increased adiponectin, amylase, lipase levels in the blood; showed antioxidant activity; and altered mRNA expression of lipid metabolism-related genes, including ACC, UCP 2, and CPT 1, in the HFD-fed rats. From these results, we concluded that AA possesses significant anti-obesity potential through the suppression of BW gain, lipid lowering action, development of insulin and leptin sensitivity, antioxidant activity, and increased mRNA expression of lipid metabolism-related genes.

Reversal of endothelial dysfunction in aorta of streptozotocin-nicotinamide-induced type-2 diabetic rats by S-Allylcysteine.

Dietary measures and plant-based therapies as prescribed by native systems of medicine have gained attraction among diabetics with claims of efficacy. The present study investigated the effects of S-Allylcysteine (SAC) on body weight gain, glucose, insulin, insulin resistance, and nitric oxide synthase in plasma and argininosuccinate synthase (AS) and argininosuccinate lyase (ASL), lipid peroxides and antioxidant enzymes in aorta of control and streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. Changes in body weight, glucose, insulin, insulin resistance, and antioxidant profiles of aorta and mRNA expressions of nitric oxide synthase, AS, and ASL were observed in experimental rats. SAC (150 mg/kg b.w) showed its therapeutic effects similar to gliclazide in decreasing glucose, insulin resistance, lipid peroxidation, and increasing body weight; insulin, antioxidant enzymes, and mRNA levels of nitric oxide synthase, argininosuccinate synthase, and argininosuccinate lyase genes in STZ-NA rats. Histopathologic studies also revealed the protective nature of SAC on aorta. In conclusion, garlic and its constituents mediate the anti-diabetic potential through mitigating hyperglycemic status, changing insulin resistance by alleviating endothelial dysregulation in both plasma and tissues.

Ameliorative potential of gingerol: Promising modulation of inflammatory factors and lipid marker enzymes expressions in HFD induced obesity in rats.

Obesity, generally linked to hyperlipidemia, has been occurring of late with distressing alarm and has now become a global phenomenon casting a huge economic burden on the health care system of countries around the world. The present study investigated the effects of gingerol over 30 days on the changes in HFD-induced obese rats in marker enzymes of lipid metabolism such as fatty-acid synthase (FAS), Acetyl CoA Carboxylase (ACC), Carnitine Palmitoyl Transferase-1(CPT-1), HMG co-A Reductase (HMGR), Lecithin Choline Acyl Transferase (LCAT) and Lipoprotein Lipase (LPL) and inflammatory markers (TNF-α and IL-6). The rats were treated orally with gingerol (75 mg kg(-1)) once daily for 30 days with a lorcaserin-treated group (10 mg kg(-1)) included for comparison. Changes in body weight, glucose, insulin resistance and expressions of lipid marker enzymes and inflammatory markers in tissues were observed in experimental rats. The administration of gingerol resulted in a significant reduction in body weight gain, glucose and insulin levels, and insulin resistance, which altered the activity, expressions of lipid marker enzymes and inflammatory markers. It showed that gingerol had significantly altered these parameters when compared with HFD control rats. This study confirms that gingerol prevents HFD-induced hyperlipidemia by modulating the expression of enzymes important to cholesterol metabolism.