Mechanism of Inhibitory Effects of Phellodendrine on Diabetes Mellitus Using Molecular Docking Method

Abstract

Diabetes mellitus is a common non-communicable disease globally, one of the leading causes of cardiovascular mortality compared to other causes. Phellodendrine is an isoquinoline alkaloid derived from the cortex of the Phellodendron chinense Schneid or Phellodendron amurense Rupr, which has therapeutic potential in diabetes mellitus. This study evaluates the inhibitory effect of phellodendrine on 10 receptors and enzymes that play an important role in the mechanism of diabetes mellitus using the molecular docking method. The 3D structures of the receptors and enzymes were obtained from the RCSB Protein Data Bank. The phellodendrine structure was obtained from the PubChem database (https://PubChem.ncbi.nlm.nih.gov/). The molecular docking screening was conducted using Autodock Vina software (https://vina.scripps.edu/). Lipinski's rule of five was used to evaluate the drug-like properties of phellodendrine. Pharmacokinetic parameters of phellodendrine were evaluated using the pkCSM tool. The oral bioavailability of phellodendrine was assessed using the SwissADME tool. The results showed that phellodendrine with PTP1B, aldose reductase, and 11β-HSD had significantly low binding energies (∆G = -8.7 kcal/mol, -8.5 kcal/mol, and -8.4 kcal/mol, respectively). Lipinski analysis showed that phellodendrine had drug-like properties. Prediction results of pharmacokinetic parameters showed that this compound had good intestinal absorption and toxicity. In addition, phellodendrine showed an oral bioavailability response, thus phellodendrine is a potential compound that can become an antidiabetic drug.