Multi-Component Synergy in Hepatic Trauma Repair: Network Pharmacology and Molecular Docking Decipher Panax Notoginseng’s PI3K-Akt Pathway Activation
Yilong Zhao, Bohao Liu, Chenrong Zhang, Kaixiang Ren, Hongyi Wang, Yixing Li, Zhe Chen, Jinteng Feng, Guangjian Zhang, Rui GaoBackground:
A rising trend in the incidence of hepatic trauma has been noted annually over recent years. Panax Notoginseng (PN) is renowned for its hemostatic and wound-healing properties, but its multicomponent mechanism against hepatic trauma remains unclear.
Objective:
This study aimed to decipher the multi-component, multi-target mechanisms of PN in treating hepatic trauma by integrating network pharmacology, molecular docking, and in vivo experimental validation.
Methods:
The bioactive constituents of PN and their corresponding protein targets were acquired from the TCMSP database. Hepatic trauma-associated genes were sourced from the GeneCards and OMIM databases. A comprehensive drug-component-target network and a protein-protein interaction (PPI) network were constructed to identify core compounds and hub targets. Functional enrichment analyses (GO and KEGG) were performed to delineate involved biological processes and signaling pathways. Molecular docking and Molecular Dynamics Simulations assessed the binding affinities between pivotal components and targets. Finally, the anti-inflammatory effect of PN was experimentally verified in a rat model of mechanical hepatic trauma.
Results:
Our analysis identified seven primary bioactive compounds in PN. Among these, quercetin, β-sitosterol, and stigmasterol were discerned as the most influential based on network topology. PPI network analysis revealed AKT1, IL-6, and TNF as central hub targets. Enrichment analysis implicated several key pathways, most notably the PI3K-Akt, TNF, and IL-17 signaling pathways. Molecular docking and Molecular Dynamics Simulations confirmed stable binding conformations between the top compounds and the core targets, with favorable binding energies. Crucially, in vivo experimentation on mechanical hepatic trauma demonstrated that PN administration significantly suppressed the mRNA expression levels of pivotal proinflammatory cytokines (TNF-α, IL-6, and IL-1β) in injured liver tissue, thereby providing direct experimental corroboration for our computational predictions.
Discussion:
This study fills the critical gap in understanding the multi-component mechanism of PN against hepatic trauma, which remains unclear despite its long-standing clinical use for hemostasis and wound healing. Unlike previous research focusing on single saponin components, our work reveals the synergistic hepato- protective effects of PN’s core bioactive compounds via coordinated modulation of inflammatory cascades and pro-survival signaling pathways. Our integrated in silico and in vivo validation provides robust mechanistic support for PN’s clinical repurposing and offers promising leads for developing novel adjuvant therapies for hepatic trauma.
Conclusion:
This study reveals that PN alleviates hepatic trauma through a multi-component synergy mechanism, primarily by targeting the PI3K-Akt pathway and inhibiting inflammation. Our findings provide a solid foundation for its future experimental confirmation and clinical application.