Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Huaganjian decoction attenuates liver fibrosis via purine metabolic-inflammatory synergistic crosstalk: network pharmacology combined with multi-omics analyses.
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Zhang Yunqiang, Su Wenjie, Chen Wei, Yao Shen, Chen Shibin, Wang Siming, Zhao Daqing, Liu Huihui, Liu Meichen
Аннотация
BACKGROUND AND PURPOSE: Liver fibrosis (LF) is a precursor to cirrhosis. Approved therapies remain limited and are restricted to specific etiologies, necessitating effective anti-LF interventions. Huaganjian decoction (HGJD) has long been used for chronic liver diseases. However, the mechanism of action and active components remain unclear. This study aimed to characterize anti-LF efficacy of HGJD and clarify its mechanism through a phenotype-component-target-pathway evidence chain.
METHODS AND RESULTS: The anti-LF efficacy of HGJD was first evaluated in CCl4-induced mouse LF and TGF-β1-stimulated hepatic stellate cell (HSC) activation models. HGJD alleviated hepatic injury and fibrotic remodeling, reduced collagen deposition, extracellular matrix accumulation, inflammatory mediators, and fibrogenic markers. It also suppressed HSC proliferation and migration while promoting apoptosis and cell-cycle arrest. The chemical composition of HGJD was profiled using UPLC-Q-Exactive MS/MS, and network pharmacology identified inflammation as a key hub, linking HGJD active compounds to fibrosis-related targets. Integrated metabolomics and transcriptomics converged on the reversal of a metabolism-inflammation imbalance. HGJD exerts multi-component synergistic effects to modulate pathological networks through a dual mechanism: by reducing adenosine levels, thereby removing a critical upstream metabolic trigger, and by directly inhibiting the signaling pathway. The dual mechanism, supported by loss-of-function, gain-of-function, and adenosine rescue experiments, allowed HGJD to inhibit HSC activation, reduce extracellular matrix accumulation-related protein expression and deposition, and promote fibrosis regression.
CONCLUSION: HGJD mitigates LF by reprogramming the metabolism-inflammation-fibrosis axis, centered on blockade of the NF-κB/NLRP3/IL-18 feed-forward circuit, providing a mechanistic rationale for its multi-component anti-LF potential.
METHODS AND RESULTS: The anti-LF efficacy of HGJD was first evaluated in CCl4-induced mouse LF and TGF-β1-stimulated hepatic stellate cell (HSC) activation models. HGJD alleviated hepatic injury and fibrotic remodeling, reduced collagen deposition, extracellular matrix accumulation, inflammatory mediators, and fibrogenic markers. It also suppressed HSC proliferation and migration while promoting apoptosis and cell-cycle arrest. The chemical composition of HGJD was profiled using UPLC-Q-Exactive MS/MS, and network pharmacology identified inflammation as a key hub, linking HGJD active compounds to fibrosis-related targets. Integrated metabolomics and transcriptomics converged on the reversal of a metabolism-inflammation imbalance. HGJD exerts multi-component synergistic effects to modulate pathological networks through a dual mechanism: by reducing adenosine levels, thereby removing a critical upstream metabolic trigger, and by directly inhibiting the signaling pathway. The dual mechanism, supported by loss-of-function, gain-of-function, and adenosine rescue experiments, allowed HGJD to inhibit HSC activation, reduce extracellular matrix accumulation-related protein expression and deposition, and promote fibrosis regression.
CONCLUSION: HGJD mitigates LF by reprogramming the metabolism-inflammation-fibrosis axis, centered on blockade of the NF-κB/NLRP3/IL-18 feed-forward circuit, providing a mechanistic rationale for its multi-component anti-LF potential.