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AbstarctDiabetic complications are among the largely exigent health problems currently. Cardiovascular complications, including diabetic cardiomyopathy (DCM), account for more than 80% of diabetic deaths. Investigators are exploring new therapeutic targets to slow or abate diabetes because of the growing occurrence and augmented risk of deaths due to its complications. Research on rodent models of type 1 and type 2 diabetes mellitus, and the use of genetic engineering techniques in mice and rats have significantly sophisticated for our understanding of the molecular mechanisms in human DCM. DCM is featured by pathophysiological mechanisms that are hyperglycemia, insulin resistance, oxidative stress, left ventricular hypertrophy, damaged left ventricular systolic and diastolic functions, myocardial fibrosis, endothelial dysfunction, myocyte cell death, autophagy, and endoplasmic reticulum stress. A number of molecular and cellular pathways, such as cardiac ubiquitin proteasome system, FoxO transcription factors, hexosamine biosynthetic pathway, polyol pathway, protein kinase C signaling, NF-κB signaling, peroxisome proliferator-activated receptor signaling, Nrf2 pathway, mitogen-activated protein kinase pathway, and micro RNAs, play a major role in DCM. Currently, there are a few drugs for the management of DCM and some of them have considerable adverse effects. So, researchers are focusing on the natural products to ameliorate it. Hence, in this review, we discuss the pathogical, molecular, and cellular mechanisms of DCM; the current diagnostic methods and treatments; adverse effects of conventional treatment; and beneficial effects of natural product-based therapeutics, which may pave the way to new treatment strategies.

AimIn the present study, we evaluated the therapeutic potentiality of S-allylcysteine (SAC) in streptozotocin (STZ)–nicotinamide (NAD)-induced diabetic nephropathy (DN) in experimental rats.MethodsSAC was orally administered for 45 days to rats with STZ–NAD-induced DN; a metformin-treated group was included for comparison. Effect of SAC on body weight, organ weight, blood glucose, levels of insulin, glycated haemoglobin, and renal biochemical markers was determined. Body composition by total body electrical conductivity (TOBEC) and dual-X ray absorptiometry (DXA), kidney antioxidant analysis, real-time polymerase chain reaction, and western blot analysis of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), nuclear factor kappa B (NF-κB), interleukin (IL)-6, and tumor necrosis factor (TNF)-α; histopathological and scanning electron microscope (SEM) analysis of the kidneys were performed in both control and experimental rats.ResultsSAC treatment showed significantly decreased levels of blood glucose, glycated haemoglobin, creatinine, albumin, AST, ALT, creatinine kinase, lactate dehydrogenase, and expressions of NF-κB, IL-6, and TNF-α compared with DN control rats. Furthermore, SAC administration to DN rats significantly improved body composition and antioxidant defense mechanism which was confirmed by the upregulation of mRNA and protein expressions of antioxidant genes.ConclusionsThus, SAC showed adequate therapeutic effect against DN by downregulation of inflammatory factors and attenuation of oxidative stress. Histological and SEM observations also indicated that SAC treatment notably reverses renal damage and protects the kidneys from hyperglycemia-mediated oxidative damage.

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.

Background Black pepper or Piper nigrum is a well-known spice, rich in a variety of bioactive compounds, and widely used in many cuisines across the world. In the Indian traditional systems of medicine, it is used to treat gastric and respiratory ailments. The purpose of this investigation is to study the antihyperlipidemic and antiobesity effects of piperonal in high-fat diet (HFD)-induced obese rats. Methods Piperonal, an active constituent of Piper nigrum seeds, was isolated and confirmed by HPLC, 1 H and 13 C NMR spectroscopy. Male SD rats were fed on HFD for 22 weeks; Piperonal was supplemented from the 16th week as mentioned in the experimental design. Changes in body weight and body composition were measured by TOBEC, bone mineral composition and density were measured by DXA, and adipose tissue distribution was measured by 7 T–MRI. Plasma levels of glucose, insulin, insulin resistance and lipid profiles of plasma, liver and kidney, adipocyte hormones and liver antioxidants were evaluated using standard kit methods. Expression levels of adipogenic and lipogenic genes, such as PPAR-γ, FAS, Fab-4, UCP-2, SREBP-1c, ACC, HMG-COA and TNF-α were measured by RT-PCR. Histopathological examination of adipose and liver tissues was also carried out in experimental rats. Results HFD substantially induced body weight, fat%, adipocyte size, circulatory and tissue lipid profiles. It elevated the plasma levels of insulin, insulin resistance and leptin but decreased the levels of adiponectin, BMC and BMD. Increased expression of PPAR-γ, FAS, Fab-4, UCP-2, SREBP-1c, ACC, and TNF-α was noticed in HFD-fed rats. However, supplementation of piperonal (20, 30 and 40 mg/kg b.wt) for 42 days considerably and dose-dependently attenuated the HFD-induced alterations, with the maximum therapeutic activity being noticed at 40 mg/kg b.wt. Conclusions Piperonal significantly attenuated HFD-induced body weight and biochemical changes through modulation of key lipid metabolizing and obesogenic genes. Our findings demonstrate the efficacy of piperonal as a potent antiobesity agent, provide scientific evidence for its traditional use and suggest the possible mechanism of action.

Blood coagulation and cancer are intricately related. Hypercoagulation associated with cancer leads to aberrant thrombin generation, which contributes to thrombosis. Thrombin also activates anticoagulant protein C and the activated protein C (aPC), in addition to regulating the coagulation pathway, it also elicits cell signaling by binding to endothelial cell protein C receptor (EPCR) and activating protease-activated receptor 1 (PAR1)-mediated cell signaling. Earlier studies showed that aPC promotes lung adenocarcinoma survival and metastasis. However, the underlying mechanism remains largely unknown. Our present study provides mechanistic insight into how aPC promotes lung adenocarcinoma survival, metastasis, and drug resistance. Our study shows that aPC, through EPCR-PAR1-driven activation of RhoA-ROCKII-JNK1/2-MLC2 signaling, triggers extracellular vesicle (EV) release from lung adenocarcinoma cells. aPC-EVs, via the transfer of microRNA (miR)-200a, promote proliferation, migration, and invasion of normal lung epithelial cells. They also confer resistance to lung cancer against chemotherapeutic agents. Inhibition of miR-200a functions through the incorporation of anti-miR-200a abrogates aPC-EVs-mediated tumorigenic effects. Furthermore, loading miR-200a mimic into control EVs showed similar phenotypic responses to that of aPC-EVs. miR-200a is shown to target SOX17 in the recipient cells, leading to tumorigenesis. miR-200a upregulation and SOX17 downregulation are consistently observed in lung cancer tissues in the UALCAN portal database of clinical specimens. Consistent with these findings, our in vivo studies in BALB/c nude mice showed that aPC-EVs from lung cancer cells promote tumor growth, metastasis, and drug resistance through miR-200a transfer. Targeting EV biogenesis, EV’s miR-200a, and/or EV uptake mechanisms may offer novel therapeutic strategies in limiting lung tumorigenesis, thereby increasing patients’ survival.

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. Graphical Abstract

Correction Following publication of the original article [1], the authors requested a correction to the name of one of the co-authors. The correct name and spelling is V.V. Sathibabu Uddandrao. The original article has been updated.

The current study is designed to evaluate the cardiorenal protective efficacy of the Biochanin-A (BCA) against high-fat-diet (HFD) and streptozotocin (STZ)-induced diabetes in rats. BCA (10mg/kg body weight) was administered to the diabetic rats for a period of 30 days and evaluated its effect on hyperglycemic markers, formation of lipid peroxidation, nitric oxide production and antioxidant enzymes such as superoxide dismutase, catalase and glutathione mediated enzymes. Further, we assessed the impact of BCA on nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) along with antioxidant enzymes mRNA expressions by RT-PCR. BCA administration to diabetic rats resulted in attenuation of hyperglycemia and oxidative stress in both the kidney and heart. Further, BCA enhanced the endogenous antioxidant activities in the kidney and heart and up-regulated their corresponding mRNA expressions. In addition, BCA treatment produced notable up-regulation of Nrf-2 and HO-1 mRNA expressions in the cardiac and renal tissue of diabetic rats. In conclusion, the current study revealed that BCA could protect from diabetes-induced complications such as cardiomyopathy and nephropathy by activating the Nrf-2/HO-1 pathway and enhancing the endogenous antioxidant state in the kidney and heart.

Lentinula edodes (L. edodes) is the globally second most widely consumed mushroom that is well-known for its therapeutic potential and is a commonly used experimental fungus model. This review was focused on the benefits, efficacy, and potential mechanism of action of the extracts from L. edodes as described in the previous studies. With limited information on the health-related benefits of L. edodes, several investigators have now diverted their attention towards this macrofungus. Several studies have now revealed its antitumor, immune-modulating, antitumor, antiviral, antimicrobial, cholesterol-regulating, anti-atherosclerotic, antidiabetic, antioxidant, and homocysteinemia activities.

The present study was aimed to evaluate the restorative efficacy of asiatic acid (AA), an active constituent in Centella asiatica (L.) in streptozotocin (STZ)-nicotinamide (NAD)-induced diabetic rats. Male Wistar albino rats were made diabetic with STZ-NAD administration and assessed the effect of AA (20, 30, and 40 mg/kg body weight per day, for 45 days) on body weight, glucose, insulin, insulin resistance, lipid metabolic parameters in plasma and tissue (liver and kidney), and histopathology of liver in control and experimental diabetic rats. A significant ( p  < 0.05) increase in the concentrations of plasma and tissue lipids cholesterol, triglycerides, free fatty acids, and phospholipids and low-density and very low-density lipoproteins, and a decrease in the concentration of high-density lipoproteins were observed in diabetic rats. A significant elevation in the activity and expression of 3-hydroxy 3-methylglutaryl coenzyme A reductase in plasma and tissue and a concomitant decline in the activity of plasma lipoprotein lipase and lecithin cholesterol acyl transferase were observed in diabetic rats. The pathological abnormalities in plasma and tissues of diabetic rats were significantly ameliorated by AA supplementation for a period of 45 days and offered great support to the biochemical findings. AA also reduced the fat accumulation in the liver and protected from the hepatic steatosis. In conclusion, AA exhibited antidiabetic potential through extenuating hyperglycemic status, changing insulin resistance by alleviating metabolic dysregulation of lipid profile in both plasma and tissues.