In-silico ADMET profile of Ellagic Acid from Syzygium cumini: A Natural Biaryl Polyphenol with Therapeutic Potential to Overcome Diabetic Associated Vascular Complications

Abstract

Plant Based Natural Products (PBNPs) are the primary source of natural antioxidants capable of neutralizing or eliminating harmful Reactive Oxygen Species (ROS). Oxidative stress contributes not only to the pathogenesis of type 2 diabetes (T2DM) but also to diabetic related vascular complications by lipid peroxidation. Oxidation induced DNA and protein damage leads to development of vascular complications like coronary heart disease, CVD, stroke, neuropathy, retinopathy, nephropathy, CKD, and other long term complications associated with diabetics. Likewise Multidrug resistance (MDR) is one of the major clinical challenges in cancer treatment and compromises the effectiveness of conventional anticancer chemotherapeutics. P-glycoprotein (P-gp) has been characterized as a major mechanism of MDR. Ellagic acid (EA) is a bioactive secondary metabolite widely distributed in vegetables and fruits (Strawberry, Grapes, Blackberry, Raspberry, Plums etc.) Chemically, EA is 2,3,7,8-tetrahydroxychromeno [5,4, -cde] chromene-5, 10-dione, a heterotetracyclic dimer of Gallic Acid (GA) molecules formed by oxidative aromatic coupling involving intramolecular lactonization. EA is associated with pharmacological activities such as anti-inflammatory, neuroprotective, cardio-protective, antioxidant, anti-mutagenic, multidrug resistance etc. EA has been marketed as a dietary supplement with claimed benefits against cancer, CVD, CKD and other metabolic disorders. However, pharmacological limitation of EA is attributed to its low solubility in water and reduced bioavailability. In the present study, bimolecular potential of EA has been bioprospected in the revised framework of ADMET pharmacoinformatics to further widen its biomedical applications. Keywords: ADMET; Pharmacoinformatics; Ellagic Acid; Gallic Acid; Syzygium cumini; Alagarkovil Reserve Forest (ARF); Reactive Oxygen Species (ROS)