Mechanism of Ginsenosides in the Treatment of Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

TL;DR

This study explores how ginsenosides, compounds from ginseng, may treat diabetes by targeting multiple biological pathways and validating a new ginsenoside derivative in mice.

Contribution

The study introduces a novel ginsenoside derivative, AD-1, and validates its therapeutic effects in diabetic mice using network pharmacology and molecular simulations.

Findings

Ginsenosides bind stably to 25 core targets like NFKB1 and HDAC1, identified through network pharmacology and molecular docking.

The ginsenoside derivative AD-1 showed therapeutic efficacy in diabetic mice by downregulating key diabetic markers.

Molecular dynamics simulations confirmed the dynamic stability of ginsenoside-target interactions.

Abstract

Diabetes mellitus (DM) is a multifactorial metabolic disorder characterized by chronic hyperglycemia and systemic metabolic dysregulation. Although ginsenosides, the primary bioactive components of Panax ginseng Meyer, exhibit regulatory effects on glucose and lipid metabolism, their precise mechanisms and key targets in DM remain incompletely understood. Unlike previous studies focusing solely on crude extracts or individual ginsenosides, this study integrates network pharmacology, molecular docking, and molecular dynamics (MD) simulations to systematically elucidate the multi-target mechanisms of ginsenosides, with experimental validation using the ginsenoside derivative AD-1. Network pharmacology identified 134 potential targets, with protein–protein interaction (PPI) analysis revealing 25 core targets (such as NFKB1, HDAC1, ESR1, and EP300). Molecular docking and MD simulations showed that ginsenosides have stable binding conformations with these targets and exhibit excellent dynamic stability. Notably, in vivo experiments using AD-1 in streptozotocin-induced type 1 diabetic mice confirmed its therapeutic efficacy, significantly downregulating key diabetic markers (e.g., NFKB1 and HDAC1) in pancreatic tissues—a finding unreported in prior studies. This study not only revealed the multitarget pharmacological mechanism of ginsenosides but also highlighted the therapeutic potential of AD-1. These findings provide a foundation for further mechanistic studies and suggest new strategies for the application of novel ginsenoside derivatives in diabetes therapy.

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