Multi-Response Optimization of Lantana camara, Chromolaena odorata, and Tithonia diversifolia Combination for & alfa-Glucosidase and & alfa-Amylase Inhibition using Response Surface Methodology and Molecular Docking
Cahya Bintang Salsabila1, Daniel Alfarado2, Ferlinahayati3

1. Undergraduate Program of Chemistry, Departement of Chemistry, Faculty of Mathematics and Natural Product, Sriwijaya University
2. Education Chemistry Laboratory, Faculty of Teaching and Education, Sriwijaya University
3. Departement of Chemistry, Faculty of Mathematics and Natural Product, Sriwijaya University

Abstract

Type 2 diabetes mellitus (T2DM) is a hyperglycemia disorder where the main therapeutic approach can be through with control postprandial hyperglycemia. Medicinal plants Lantana camara, Chromolaena odorata, and Tithonia diversifolia were known have ability treat diabetics, but their synergistic potential as enzyme inhibitors has not been systematically explored. This study aims to optimize the combination formula the three plants and evaluate their synergistic effects in inhibiting alfa-glucosidase and alfa-amylase using the Response Surface Methodology (RSM) approach validated by molecular docking studies. The optimization of the combination formula was conducted using RSM with Central Composite Design (CCD), where three independent variables extracts were optimized against two main responses, namely the percentage inhibition of alfa-glucosidase and alfa-amylase through 20 experimental runs. Data were analyzed using a polynomial quadratic model and validated with ANOVA, while molecular docking studies were conducted on the identified compounds in the database against the alfa-glucosidase enzyme (PDB ID: 3TOP) and alfa-amylase (PDB ID: 1B2Y) to analyze affinity and molecular interactions. The research results show that the quadratic polynomial model has a good fit with R square values above 0.900 for alfa-glucosidase and alfa-amylase inhibition, and the lack-of-fit value is not significant, indicating the models validity. The optimal formula was obtained from the dominant composition of the T. diversifolia plant, with alfa-glucosidase and alfa-amylase inhibition activities exceeding 90%, higher than single extracts, and demonstrating a synergistic effect. Molecular docking studies reveal that the dominant compounds of the three plants have a high binding affinity to both enzymes with a binding affinity value lower than acarbose. Based on the results, the combination of three extracts has a synergistic effect in inhibiting alfa-glucosidase and alfa-amylase.

Keywords: Lantana camara- Chromolaena odorata- Tithonia diversifolia- synergism- alfa-glucosidase- alfa-amylase- response surface methodology- molecular docking

Topic: Organics Chemistry