vv International Journal of Clinical Endocrinology and Metabolism CC By 018 Citation: Mohanty IR, Kumar S, Rajesh Suman (2017) Dipeptidyl Peptidase IV Inhibitory Activity of Berberine and Mangiferin: An In Silico Approach. Int J Clin Endocrinol Metab 3(1): 018-022. Clinical Group DOI: http://dx.doi.org/10.17352/ijcem ISSN: 2640-7582 Abstract Background: Dipeptidyl peptidase-IV (DDP-IV) Inhibitors may represent single anti-diabetic drugs, the multiple actions of which may translate into demonstrable therapeutic benefits in diabetes. The marketed synthetic DPP-IV Inhibitors are expensive drugs and have been reported to cause unacceptable adverse effects such as pancreatitis, angioedema, thyroid and pancreatic cancers. In this scenario, research to identify DPP-IV Inhibitors from alternative sources is desirable. Aims and Objective: The study was designed to elucidate the DPP-IV Inhibitory activity of Berberine and Mangiferin, determine the binding sites and affinity of Berberine and Mangiferin for DPP- IV enzyme using in silico studies and compare it to synthetic DPP-IV Inhibitor: Vildagliptin. Material and Methods: The crystal structure of human DPP IV (PDB Id: 2QT9) was downloaded from Protein Databank. Berberine and Mangiferin were computationally designed and screened through in silico docking studies against crystal structure of DPP-IV. Computational in silico studies were used to identify the sites as well as amino acid residues on DPP-IV enzyme to which these natural DPP-IV Inhibitors binds. Results: The DPP-IV Inhibitory activity of Mangiferin was found to be comparable to synthetic marketed DPP-IV Inhibitors; Vildagliptin and Sitagliptin. Like Vildagliptin, Berberine and Mangiferin bind within the active site pocket (the 1st largest pocket) of DPP-IV enzyme whereas, Sitagliptin prefers to bind in the second largest pocket of DPP-IV enzyme. Berberine prefers to bind to the active site pocket of DPP- IV enzyme. Berberine binds very close to Glu205 and Glu206. As delineated using in silico binding energy results, Mangiferin, possess superior DPP-IV inhibitory activity as compared to Sitagliptin and Vildagliptin. Conclusion: In silico studies demonstrates that Berberine and Mangiferin possess significant DPP-IV Inhibitory activity comparable to marketed synthetic DPP-IV Inhibitors. Research Article Dipeptidyl Peptidase IV Inhibitory Activity of Berberine and Mangiferin: An In Silico Approach Ipseeta Ray Mohanty 1 *,Selvaa Kumar 2 and Rajesh Suman 1 1 Department of Pharmacology, MGM Medical College, Navi Mumbai, India 2 School of Biotechnology and Bioinformatics, DY Patil University, Navi Mumbai, India Dates: Received: 29 May, 2017; Accepted: 07 July, 2017; Published: 08 July, 2017 *Corresponding author: Ipseeta Ray Mohanty, Department of Pharmacology, MGM Medical College Kamothe, Navi Mumbai, Maharasthra, 410209, India, Tel: 91-9819908498; E-mail: Keywords: Berberine, Mangiferin; Sitagliptin; Vilda- gliptin; in silico and DPP-IV https://www.peertechz.com Introduction Recently, one of the additions to this anti-diabetic armament of drugs is dipeptidyl peptidase-IV Inhibitors (DPP- IV) [1], DPP-IV Inhibitors increase incretin levels: Glucagon- like peptide-1 (GLP-1) and Glucagon inhibitory peptide (GIP), which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels [2,3]. A recent study has shown beneficial effects of DPP-IV Inhibitor on metabolic parameters in type 2 diabetic patients [4], DPP-IV Inhibitors have a large number of beneficial effects in the subgroup of metabolic syndrome with diabetes. Apart from glycemic control, they are known to lower blood pressure, are weight neutral, improve dyslipidemia, reduce inflammatory markers, diminish oxidative stress, improve endothelial function and reduce platelet aggregation in patients with type II diabetes [5], Therefore, it is plausible to explore the therapeutic potential of DPP-IV Inhibitors in experimental diabetes with metabolic syndrome. As a drug class, DPP-IV Inhibitors are widely used clinically because of their low risk of hypoglycemia, once daily dosing, pharmacological effects such as weight neutral and preservation of beta cell mass [6], However, in spite of their beneficial effects, they have limitations: high cost of therapy and unacceptable adverse effects such as pancreatitis, pancreatic cancer, angioedema and thyroid cancer. In this scenario, it would be desirable to identify novel DPP-IV Inhibitors from alternative sources, that share the beneficial effects of the available synthetic DPP-IV Inhibitors and at the same time are cost effective. In this light, the DPP-IV Inhibitors obtained