Dipeptidyl Peptidase IV Inhibitory Activity of Berberine and Mangiferin: An In Silico Approach

• Main Authors: Ipseeta Ray Mohanty (Author), Selvaa Kumar (Author), Rajesh Suman (Author)
• Format: Book
• Published: International Journal of Clinical Endocrinology and Metabolism - Peertechz Publications, 2017-07-08.
• Subjects: Research Article
• Online Access: Connect to this object online.

<p><strong>Background:</strong> 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. <br></p><p><strong>Aims and Objective: </strong>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. <br></p><p><strong>Material and Methods:</strong> 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 DP-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. <br></p><p><strong>Results:</strong> 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. </p><p><strong>Conclusion:</strong> In silico studies demonstrates that Berberine and Mangiferin possess significant DPP-IV Inhibitory activity comparable to marketed synthetic DPP-IV Inhibitors.</p>