Investigating Palmatine’s inhibitory mechanism on type 2 diabetes via molecular docking

Abstract

Type 2 diabetes mellitus (T2DM) is the most common form, accounting for more than 90% of all individuals with diabetes worldwide. Currently, T2DM is on the rise and is increasingly affecting younger individuals, becoming a serious public health issue. Palmatine is a natural isoquinoline alkaloid belonging to the protoberberine group. The purpose of this study was to evaluate the anti-diabetic properties of Palmatine through molecular docking with several protein targets related to T2DM, such as α-amylase, pyruvate dehydrogenase kinase 4 (PDK4), α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), aldose reductase (AKR1B1), and 11β-hydroxysteroid dehydrogenase (11β-HSD1). Lipinski’s rule of five was employed to assess the drug-like characteristics of Palmatine. The pharmacokinetic properties of Palmatine were evaluated using the pkCSM tool, which aids in predicting its absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile. The oral bioavailability of Palmatine was assessed using the SwissADME tool. The results indicated that Palmatine inhibits 11β-HSD1 with the lowest binding energy (-8.4 kcal/mol). According to Lipinski’s analysis, Palmatine exhibits properties consistent with druglike behaviour. The predicted pharmacokinetic parameters suggest that this compound possesses excellent intestinal absorption. Furthermore, Palmatine demonstrated favourable oral bioavailability. Consequently, additional in vitro and in vivo research is necessary to further explore the potential of this compound as a future treatment for diabetes.