Anti-Inflammatory and Antidiabetic Metabolites From Mitragyna diversifolia: In Vitro, Phytochemical, and Computational Studies.

Mitragyna diversifolia is commonly used to cure diarrhoea in the Bandarban region. However, the impact of anti-inflammatory properties and underlying material basis remains unexplored. This study aimed to determine the anti-inflammatory and antidiabetic potential of metabolites from M. diversifolia. The results indicated that 2,4-di-tert-bylphenol (8), cryptotanshinone (9), and dihydrotanshinone I (10) not only effectively inhibited LPS-induced NO production but also demonstrated potential antidiabetic activities by promoting glucose uptake. Network pharmacological analysis, molecular docking, and molecular dynamics simulation revealed that AKT1 was a crucial target for the anti-inflammatory and antidiabetic effects of M. diversifolia. At the same time, molecular docking analysis showed that compounds 8, 9, and 10 possessed superior binding capacities with AKT1 (-7.3, -11.9, and -11.7 kcal/mol, respectively). Collectively, this study preliminarily clarified the possible material basis and mechanism of M. diversifolia to prevent inflammation and diabetes. Further research is needed to determine the in vivo conditions of compounds 8, 9, and 10, particularly with regard to their safety and efficacy.