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.

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.

Phenolic fraction extracted from Kedrostis foetidissima leaves ameliorated isoproterenol-induced cardiotoxicity in rats through restoration of cardiac antioxidant status.

In this study, the cardioprotective effects of partially purified phenolic fraction of Kedrostis foetidissima leaves (PFK) were evaluated in isoproterenol (ISO)-induced myocardial infarction rat model. ISO induction to experimental rats for two consecutive days significantly increased the levels of triglycerides, cholesterol, phospholipids, free fatty acids, low-density lipoproteins, and cardiac biomarker enzymes, and decreased the levels of high-density lipoproteins and antioxidant enzyme activity. Pretreatment of experimental rats with PFK for 45 days led to a significant elevation in antioxidant enzyme activity. PFK-pretreated rats exhibited significantly reduced levels of circulating lipids and cardiac-specific biomarker enzymes compared to ISO-treated rats. Thus, the present study demonstrated that PFK ameliorated ISO-induced cardiotoxicity through the augmentation of the endogenous cardiac antioxidant system, thereby modulating the lipid peroxidation caused by ISO-induced free radicals, and prevented the myocardial damage, which was confirmed through histopathological analysis. PRACTICAL APPLICATIONS: Kedrostis foetidissima is edible medicinal plant and phenolic fraction extracted from the leaves of this plant may help the common man in the protection of heart. The phenolic fraction shows significant antioxidant activity, so this might be referred to as dietary supplement and also helps to develop new pharmaceutical formulations.

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.

Beneficial Role of Some Natural Products to Attenuate the Diabetic Cardiomyopathy Through Nrf2 Pathway in Cell Culture and Animal Models.

Diabetic cardiomyopathy, as one of the main cardiac complications in diabetic patients, is identified to connect with oxidative stress that is due to interruption in balance between reactive oxygen species or/and reactive nitrogen species generation and their clearance by antioxidant protection systems. Transcription factor the nuclear factor erythroid 2-related factor 2 (Nrf2) plays a significant role in maintaining the oxidative homeostasis by regulating multiple downstream antioxidants. The Nrf2 plays a significant role in ARE-mediated basal and inducible expression of more than 200 genes that can be grouped into numerous categories as well as antioxidant genes and phase II detoxifying enzymes. On the other hand, activation of Nrf2 by natural and synthetic therapeutics or antioxidants has been revealed effective for the prevention and treatment of toxicities and diseases connected with oxidative stress. Hence, recently focus has been shifted toward plants and plant-based medicines in curing such chronic diseases, as they are supposed to be less toxic. In this review, we focused on the role of some natural products on diabetic cardiomyopathy through Nrf2 pathway.

Cardioprotective activity of Amaranthus viridis Linn: effect on serum marker enzymes, cardiac troponin and antioxidant system in experimental myocardial infarcted rats.

BACKGROUND: Cardiovascular diseases (CVDs) have a high prevalence in developing and developed countries and myocardial infarction accounts for majority of deaths and disabilities. The current study dealt with the protective role of Amaranthus viridis Linn on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. METHODS: Subcutaneous injection of ISO (20 mg/kg body weight in 1 ml saline) to rats for two consecutive days offered significant alteration in cardiac marker enzymes (AST, ALT, LDH and CPK), cardiac troponin, lipid peroxidation products (TBARS and hydroperoxide) and antioxidant system (CAT, SOD, GPx, GST, GSH and GSSG). ISO-induced myocardial damage was indicated by increased activities of marker enzymes in serum and the levels of cardiac troponin in the serum. In addition to these diagnostic markers, the levels of lipid peroxidation products in the heart were significantly (p<0.05) increased and the activities of enzymic antioxidants and non-enzymic antioxidant such as glutathione in the heart was significantly (p<0.05) decreased and GSSG in the heart was increased in ISO-induced rats. RESULTS: Effect of Amaranthus viridis oral treatment (100, 200 and 300 mg/kg body weight) for 45 days elicited a significant cardio protective activity by lowering the levels of serum marker enzymes, cardiac troponin, GSSG and lipid peroxidation and elevated the levels of antioxidant enzymes and GSH. The effect at a dose of 300 mg/kg of A. viridis was more pronounced than that of the dose 100 mg/kg and 200mg/kg and brought back all the parameters to near normal. The effect produced by A. viridis was compared with α-tocopherol. CONCLUSIONS: The present findings have demonstrated that the cardioprotective effects of A. viridis in ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidants and inhibition of lipid peroxidation of membrane.