Biological activities of meroterpenoids isolated from different sources.

Meroterpenoids are natural products synthesized by unicellular organisms such as bacteria and multicellular organisms such as fungi, plants, and animals, including those of marine origin. Structurally, these compounds exhibit a wide diversity depending upon the origin and the biosynthetic pathway they emerge from. This diversity in structural features imparts a wide spectrum of biological activity to meroterpenoids. Based on the biosynthetic pathway of origin, these compounds are either polyketide-terpenoids or non-polyketide terpenoids. The recent surge of interest in meroterpenoids has led to a systematic screening of these compounds for many biological actions. Different meroterpenoids have been recorded for a broad range of operations, such as anti-cholinesterase, COX-2 inhibitory, anti-leishmanial, anti-diabetic, anti-oxidative, anti-inflammatory, anti-neoplastic, anti-bacterial, antimalarial, anti-viral, anti-obesity, and insecticidal activity. Meroterpenoids also possess inhibitory activity against the expression of nitric oxide, TNF- α, and other inflammatory mediators. These compounds also show renal protective, cardioprotective, and neuroprotective activities. The present review includes literature from 1999 to date and discusses 590 biologically active meroterpenoids, of which 231 are from fungal sources, 212 are from various species of plants, and 147 are from marine sources such as algae and sponges.

Biochanin A Attenuates Cardiomyopathy in Type 2 Diabetic Rats by Increasing SIRT1 Expression and Reducing Oxidative Stress.

Diabetic cardiomyopathy is one of the major complications in type 2 diabetes associated with myocardial structure abnormality and major cause of morbidity in type 2 diabetic patients. Biochanin A is a methylated isoflavone present in flowering tops of Trifolium pratense reported for anti-inflammatory, anti-oxidant, anti-infective, anti-cancer and anti-diabetic activity. The study was designed to assess the efficacy of Biochanin A in type 2 diabetic cardiomyopathy. Type 2 diabetes was induced in rats feeding high fat diet for two weeks and administration of single low dose of streptozotocin. Biochanin A was administered for 16 weeks orally once in a day (10, 20 and 40 mg/kg of body weight). Various parameters such as blood glucose, cardiac markers, oxidative stress and hemodynamic parameters, immunohistochemical, histopathological investigation and SIRT1 expression were measured at the end of the study. Biochanin A treatment resulted into reduction in plasma concentration of cardiac markers along with reduction in hyperglycemia, hyperlipidemia and oxidative stress in cardiac tissue. Biochanin A treated animals also demonstrated improvement in hemodynamic parameters. Diabetic animals treated with different doses of Biochanin A shown increased SIRT1 expression in cardiac tissue, and also confirmed reduced cardiac hypertrophy and cardiac protection in histopathological study. Outcome of the study indicates that Biochanin A is the potential candidate to control hyperglycemia, oxidative stress and improve SIRT1 expression in cardiac tissue. Biochanin A might be considered as potential candidate to control progression of cardiomyopathy in type 2 diabetes mellitus.

Formononetin attenuates kidney damage in type 2 diabetic rats.

AIM: Diabetic nephropathy is the commonly developed complication of vasculature in type 2 diabetic patients. Chronic hyperglycemia leads to nephropathy in diabetics because of the formation of excessive reactive oxygen species and advanced glycation end products which is reflected in the form of glomerulosclerosis, tubular atrophy and interstitial fibrosis. As per the various reports reduction in SIRT1 expression in kidney tissue is key factor in the development of nephropathy in diabetes because its reduction in tissue is linked with excessive formation of ROS. Formononetin is a polyphenolic compound reported for its effect on SIRT1 and ROS. MAIN METHODS: Type 2 diabetes was induced in rats by diet modification using high fat diet for fifteen days prior to streptozotocin regimen (35 mg/kg, i.p.). Treatment of formononetin was started after confirmation of diabetes and continued for 16 weeks. Formononetin was administered orally to the diabetic animals at the dose of 10. 20 and 40 mg/kg. KEY FINDINGS: Formononetin treatment for 16 week was able to control hyperglycemia and insulin resistance in diabetic animals. It has also been reduced triglyceride and cholesterol in blood. Formononetin treatment reduced blood concentration of creatinine, blood urea nitrogen and increased albumin concentration. Formononetin treatment also enhanced creatinine clearance in diabetic animals. Oxidative stress burden was also reduced significantly after formononetin treatment along with increased SIRT1 expression in kidney tissues of diabetic animals. SIGNIFICANCE: Formononetin is a potential molecule which increases the expression of SIRT1 in kidney tissue of diabetic. Thus formononetin is an effective molecule to control nephropathy in type 2 diabetes mellitus.

Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment.

Cancer is an uncontrolled and abnormal growth of cells in the body. Gene that guards the cell cycle and function as tumor suppressor is p53 (also called as the guardian of the genome) which is encoded by the TP53 gene. Various events like DNA damage, heat shock, hypoxia and oncogene over expression, results in activation of p53.Thus, it plays a major role as a regulatory protein which regulates various diverse biological responses, responsible for genetic stability by preventing genome mutation. More than 50% mutations in human cancers along with the increase in expression of murine double minute 2 gene (mdm2), has been found as one of the reason for cancer progression. Murine double minute 2 (MDM2) is the negative regulator of p53 gene forming an autoregulatory feedback loop controlling each other cellular levels. Murine double minute 2 is unique E3 ubiquitin ligase protein which is responsible for ubiquitination and degradation of p53 gene. Many drugs/compounds have been developed for reactivation of p53 gene by inhibiting MDM2 interaction with p53, using MDM2 antagonism, inhibiting E3 ubiquitination of p53. Many compounds have entered clinical trials in haematological malignancies. This review will throw some light on reactivation of p53 gene by MDM2 and its homologues.

Biochanin A improves insulin sensitivity and controls hyperglycemia in type 2 diabetes.

Biochanin A (5,7-Dihydroxy-4'-methoxyisoflavone) is an O-methylated isoflavone known for its anti-inflammatory, lipid lowering and anti-cancer activity. The current study was designed to find out antidiabetic efficacy of Biochanin A in type 2 diabetes in rats. Induction of type 2 diabetes mellitus in experimental animals was carried out by manipulation of diet using high fat diet for fourteen days and then administration of streptozotocin at low dose of 35 mg/kg, i.p. The diabetic animals were treated with 10, 20 and 40 mg/kg of Biochanin A for 28 days. The effect of Biochanin A treatment in diabetic animals was evaluated by measuring changes in body weight, biochemical parameters, insulin sensitivity index, Homeostatic model assessment-Insulin resistance (HOMA-IR), oral glucose tolerance test, glycohaemoglobin and hepatic glycogen level. Changes in histopathological characteristics of pancreatic tissue were also evaluated after treatment with Biochanin A. Immunohistochemical analysis of pancreatic tissue was carried out for the expression of SIRT1. The results showed that the selected doses of (10, 20 and 40 mg/kg) Biochanin A significantly decreased blood glucose (p < 0.001). The higher dose (40 mg/kg) of Biochanin A significantly reduced glucose tolerance (p < 0.001) in diabetic animals. Biochanin A treatment significantly reduced insulin resistance (p < 0.001) and improved inulin sensitivity (p < 0.01 for 10 mg/kg, 20 mg/kg, p < 0.001 for 40 mg/kg) at all selected dose levels. It also improved lipid profile significantly (p < 0.001) at lower, middle and higher dose level. Glycohaemoglobin formation was significantly decreased in diabetic animals (p < 0.001) after treatment with Biochanin A at all three dose levels. Liver glycogen level was also improved significantly after treatment with Biochanin A in diabetic animals at 20 mg/kg and 40 mg/kg dose level. Biochanin A at dose of 40 mg/kg increased SIRT1 expression in pancreatic tissue. In conclusion, Biochanin A has significant effect in type 2 diabetes mellitus which might be linked to its effects on SIRT1.