VIRTUAL SCREENING OF SAPONIN DERIVATIVES TARGETING ENZYMES ENDOTHELIAL NITRIC OXIDE SYNTHASE AND CYTOCHROME P450 2E1

Saponin derivatives from Vietnamese ginseng are proven for their efficacies in modulating oxidative stress, but there had been no reports about the interaction between them and two enzymes, endothelial nitric oxide synthase (eNOS) and cytochrome P450 2E1 (CYP2E1). eNOS and CYP2E1 are proposed to be attractive targets for the development of inhibitors against oxidative stress, a contributing factor in aging, cancer, cardiovascular diseases, diabetes mellitus type 2, and neurodegenerative diseases. Therefore, this study aimed to evaluate the binding abilities of the saponin derivatives on both enzymes eNOS and CYP2E1 using structure-based approaches. An in-house library of 50 saponin derivatives from Vietnamese ginseng was computationally analyzed for their binding affinities and interactions with eNOS and CYP2E1 using Autodock Vina 1.5.6. The results showed that ginsenoside Rc, ginsenoside R3, vina-ginsenoside R20, ginsenoside Re, notoginsenoside R1 and 20(R)-ginsenoside Rh1 established the favorable interactions and exhibited high binding affinities with eNOS and CYP2E1. These compounds are potential candidates for in-vitro and in-vivo assays to assess their promising application in inhibition of these enzymes. This study also contributed to the understanding of saponin derivatives interactions with eNOS and CYP2E1 in antioxidative stress process.