IN SILICO EVALUATION OF PHYTOCHEMICALS FROM MANGIFERA INDICA AGAINST TYPE 2 DIABETES TARGETS: A MOLECULAR DOCKING AND ADMET STUDY

Abstract

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance, impaired glucose regulation, and chronic hyperglycemia, which remains a major global health challenge.Unlike type 1 diabetes, which results from autoimmune-mediated β-cell destruction, T2DM is primarily associated with insulin resistance in peripheral tissues such as skeletal muscle, adipose tissue, and liver. This progressive condition involves multiple metabolic defects, including impaired incretin response, enhanced hepatic gluconeogenesis, and pancreatic β-cell exhaustion, which together lead to chronic hyperglycemia. On a global scale, the prevalence of T2DM has reached alarming proportions. Synthetic pharmacotherapies such as metformin, sulfonylureas, and thiazolidinediones have improved clinical outcomes but are often associated with limitations including side effects, high cost, and lack of multitarget efficacy. As a result, increasing attention has been directed toward natural phytochemicals with broad pharmacological activities. Mangifera indica (mango) is widely used in ethnomedicine for the management of diabetes, and its phytochemicals—including mangiferin, quercetin, catechins, and phenolic glycosides—have demonstrated promising antidiabetic effects. This systematic review, conducted in accordance with PRISMA guidelines, evaluated 114 eligible studies published between 2000 and 2022, integrating findings from molecular docking, ADMET profiling, in vitro assays, and in vivo experimental models. Docking studies consistently revealed strong inhibitory interactions of mango-derived phytochemicals with diabetes-related targets such as α-amylase, α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), and dipeptidyl peptidase-4 (DPP-4), while ADMET analyses indicated favorable safety margins despite challenges of solubility and oral bioavailability. Experimental investigations further confirmed improvements in glycemic indices, insulin sensitivity, lipid regulation, and oxidative stress modulation, reinforcing the computational predictions. Compared with conventional synthetic drugs, M. indica phytochemicals demonstrated the advantage of multitarget actions with fewer reported adverse effects. Collectively, the synthesis of 114 studies consolidates evidence that mango phytochemicals represent a validated and culturally significant resource with broad international relevance for T2DM management, bridging traditional ethnopharmacological practices with modern computational and pharmacological evaluation.