Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2014, 6(12):860-865 Research Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 860 In silico binding and interaction studies of aldose reductase with the active components of triphala, a traditional herbal formulation B. Udhaya Lavinya, M. Sherry Joseph, S. Prathap, Uberewe Rutera Aline, Wimethune and E. P. Sabina* School of Biosciences and Technology, VIT University, Vellore, Tamilnadu, India _____________________________________________________________________________________________ ABSTRACT Aldose reductase is the key regulatory enzyme of the aldose reductase (AR)/polyol pathway which plays a major role in the development of diabetic retinopathy. Present study was an attempt to analyze the binding and interaction patterns of AR against 15 chosen active components of the herbal formulation Triphala in order to find a potent inhibitor of the enzyme. Molecular docking experiments were carried out using PatchDock online server. The protein ligand complexes thus obtained were analyzed on PyMol viewer. Phytochemicals such as ellagic acid, sennoside, ellagitannin, chebulinic acid, vitamin C and casuarinin showed significant interactions with AR. Of these ellagitannin was identified as a potent inhibitor of AR showing 18 hydrogen bond interactions.Therefore, this potential flavonoid could be used to prevent diabetic retinopathy and used as a potential therapeutic approach to diabetic retinopathy targeting AR. Keywords: Diabetes, Aldose reductase, Triphala, active compounds, docking _____________________________________________________________________________________________ INTRODUCTION Diabetes is a complex metabolic disorder where the affected individual is prone to both acute and chronic diabetic complications. The long term diabetic complications are mainly responsible for the morbidity and mortality in most cases of diabetes. These include vascular and non-vascular complications. Different molecular mechanisms have been proposed to be involved in the pathogenesis and progression of long-term diabetic complications. These include enhanced glucose flux through the polyol pathway, generation of reactive oxygen species (ROS), activation of protein kinase C (PKC) and formation of advanced glycation end products (AGEs) [1]. The polyol pathway plays a significant role in the development of microvascular complications [2]. Aldose reductase (AR) is the key regulatory enzyme of polyol pathway. AR catalyzes the reduction of glucose to sorbitol which is then acted upon by the enzyme sorbitol dehydrogenase (SDH) to yield fructose [3]. Several studies have demonstrated the increased activity of polyol pathway products which drive the utilization of NADPH and NAD + respectively. This affects the pyridine nucleotide flux and metabolism of glucose. Also, there is increased osmotic caused due to the accumulation of sorbitol leading to electrolyte imbalance causing swelling-up of cells and membrane damage [4]. Diabetic retinopathy is a complication of chronic hyperglycemia characterized by damaged blood vessels of the retina ultimately causing loss of vision. The pathogenesis of diabetic retinopathy involves increased activity of AR thereby causing derangement of the cellular membrane in ocular lens. This induces cataract formation. Furthermore,