Investigation of the trans-anethole in diabetes induced cardiac fibrosis

Abstract

Diabetes is chronic metabolic disorder characterized by elevated blood glucose level. Globally, an expected 422 million adults are living with diabetes mellitus, according to World Health Organization. It also leads to serious complications like cardiovascular (CV), cerebrovascular, nephropathy; neuropathy, retinopathy, cataract and foot damage. Type II diabetes mellitus (T2DM) patients have two times higher risk of developing CV disorders, like coronary artery disease, sudden cardiac death, peripheral arterial disease, fibrosis as well as diabetic cardiomyopathy. Continuous damage of myocardium leads to cardiac fibrosis in which collagen deposition by fibroblast and abnormal production of matrix protein results into stiffness of heart walls. This cause decreased contractibility and relaxation. In hyperglycemic condition, high level of glucose enters in to cells by GLUT-1 and GLUT-4, which activates gene transcription resulting in to increased level of procollagen by activation of PKCβ and PKA. Increasing gene transcription also acts on aldose reductase (AR) which promotes the generation of reactive oxygen species (ROS). Along with this, intracellular glucose converts in to sorbitol which further converts in to 3-deoxyglucosone, an advanced glycated end product, causing elevation of procollagen. Another advanced glycated end product glyoxal is produced by intracellular glucose which increases the level of procollagen. These all processes end up into the cardiac fibrosis. Hyperinsulinemia also activates the signaling of cardiac fibrosis. Where high concentration of insulin binds with insulin like growth factor (IGF) and activates grb2 and SOS like docking protein. This activates RAS by converting GDP to GTP for activation of Ras-Raf-MEK-ERK pathway and ends up into ROS generation. This is responsible for collagen synthesis and fibroblast production finally resulting into cardiac fibrosis which promotes the risk associated with heart failure. Though development of modern medicine resulted in the advent of modern pharmacotherapeutics including insulin, biguanides, sulfonylureas and thiazolidinediones, there is still a need to look for new drugs as none of the (except strict glycemic control with insulin) has been shown to modify the course of diabetes. Traditional plant medicines or herbal formulations might offer a natural key to unlock diabetic complications. Trans-anethole is a volatile oil obtained from the various dietary sources like Foeniculum vulgare (81.63% to 87.85%), Pimpinella anisum (85-96%), Nigella sativa (38.3%),Illicium verum fruit(89.5%) and Croton zehntneri (85.7%). It has reported anti diabetic activity along with potent antioxidant activity.