Therapeutic potential of <i>Chromolaena odorata</i> phyto-constituents against human pancreatic α-amylase

Abstract

Type II Diabetes Mellitus (DM) is caused by insulin resistance in peripheral tissue and impaired insulin secretion through a dysfunction of the pancreatic β-cell. Acarbose is an anti-DM drug, it is effective but its continuous use may lead to undesirable side effects. Hence, the development of novel drugs from natural source that have both anti-diabetic and anti-oxidant activities, with little or no side effect during long-term use is of great importance. To investigate the anti-DM and anti-oxidant phyto-constituents of <i>Chromoleana odorata</i>, e-pharmacophore model was generated using human pancreatic α-amylase (HPA) standard inhibitor, Acarbose to map important pharmacophoric features of HPA, and used to screen several phyto-constituents of <i>C. odorata</i> to match at least 4 sites of the generated hypothesis. Glide and Induced Fit Docking followed by Prime MM-GBSA calculation, drug-likeness and ADME studies were employed for high fitness (>1.0) compounds retrieved from e-pharmacophore screening process. The drug-likeness properties of the lead compounds, Quercetin and Ombuin were analyzed taking into account the Lipinski's and Veber's rules. Further, machine-learning approach was used to generate QSAR model. The computed model, kpls_desc_19 was used to predict the bioactivity (pIC50) of Quercetin and Ombuin. Phyto-constituents of <i>C. odorata</i>; Quercetin and Ombuin have shown better and promising results when compared to that of the standard, acarbose. Based on the present study, orally delivered Quercetin and Ombuin from <i>C. odorata</i> are relatively better inhibitor of HPA, thus they can be a useful therapeutic candidate in the management/treatment of DM when compared to acarbose.Communicated by Ramaswamy H. Sarma.