Targeting diabetes pathways: an in silico study of bioactive compounds from Mitragyna speciosa leaf extract

Background: The rapid expansion of urbanization has triggered significant lifestyle shifts, most notably an increase in sedentary lifestyles and the widespread consumption of processed, nutrient-poor foods. These factors have been strongly implicated in the rising prevalence of Diabetes Mellitus. Current treatment strategies for diabetes remain heavily reliant on conventional pharmacotherapy, which often carries risks of drug tolerance and adverse effects. In this context, Kratom (Mitragyna speciosa), a traditional medicinal plant native to Southeast Asia and historically used to manage various ailments, presents a promising avenue for the development of novel antidiabetic agents. Methods: In this study, kratom leaf extract was prepared using methanol-based maceration of kratom leaf powder to obtain a 100% methanolic extract (100%M). The extract was subsequently analyzed using Q-Tof-LCMS, leading to the putative identification of bioactive compounds. These compounds were further subjected to molecular docking against two key target proteins, namely PDB codes3A4A and 4N8D,to assess their binding affinities. Results: The results revealed several promising candidates including apigenin 7-(2''-E-p-coumaroylglucoside, kaempferol 3-(2''-(Z)-p-coumaryl-6''-(E)-p-coumarylglucoside, 5,6,7,3',4'-pentahydroxy-8-methoxyflavone 7-apioside, luteolin 7-rhamnosyl(1->6)galactoside and 6-hydroxyluteoin-7-(6'''-p-coumarylsophoroside), all of which demonstrated stronger binding affinities than both the standard and native ligands. Further evaluation of physicochemical and pharmacokinetic parameters revealed that 4-p-coumaroylquinic acid, scopolin, and emmotin A showed instant drug likeness, indicating their potential for direct drug development. Additionally, other compounds with high binding energies may be optimized through structural modifications to enhance their pharmacological profiles, thereby serving as lead candidates for the development of novel antidiabetic therapeutics. Conclusion: The current study has identified promising lead compounds for the development of novel antidiabetic agents, offering valuable guidance for future research on kratom‑based antidiabetic drug discovery.