Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Discovery of cis-Gnetin H from peony seed coat as a potent antifibrotic agent modulating hepatic fibro-inflammatory pathways and gut microbiota homeostasis.
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Yuan Rong, Tian Zexi, Liu Yingbo, Yan Congjie, Liu Xinying, Yao Ming, Liu Zenggen, Wang Weidong
Аннотация
BACKGROUND: Liver fibrosis is a reversible stage of chronic liver disease lacking effective therapies. The peony seed coat, a major byproduct of peony oil production, is rich in bioactive stilbenes. However, its anti-fibrotic potential and underlying mechanisms remain systematically unexplored.
PURPOSE: This study aimed to isolate stilbenes from peony seed coat, identify the potent anti-fibrotic compounds, and evaluate their anti-fibrotic activity and mechanisms of action.
METHODS: A structure-oriented separation strategy, guided by spectroscopic analysis, enabled the isolation of stilbenes. Anti-fibrotic activity was screened in TGF-β1-induced hepatic stellate cells (HSCs). In vivo efficacy was evaluated in a CCl₄-induced mouse liver fibrosis model. Mechanisms were investigated using transcriptomics, Western blotting, and 16S rRNA gene sequencing.
RESULTS: Among seven isolated stilbenes, cis-Gnetin H exhibited the most potent inhibition of HSCs activation by downregulating α-SMA, Collagen I, and Smad3. In CCl₄-treated mice, cis-Gnetin H significantly ameliorated liver injury, inflammation, and fibrosis. Mechanistically, cis-Gnetin H activated the Nrf2/HO-1 antioxidant pathway while suppressing NF-κB and TGF-β1/Smad signaling. Furthermore, cis-Gnetin H remodeled the gut microbiota by enriching beneficial genera and reducing pathogenic Staphylococcus. This microbial modulation was accompanied by increased production of SCFAs, which correlated strongly with improved hepatic parameters.
CONCLUSION: cis-Gnetin H acts as an anti-fibrotic agent through modulating hepatic inflammatory and fibrotic signaling, and regulating the gut-liver axis via microbiota restoration and metabolite enhancement. These findings highlight cis-Gnetin H as a promising therapeutic candidate and support the high-value utilization of peony agricultural byproducts.
PURPOSE: This study aimed to isolate stilbenes from peony seed coat, identify the potent anti-fibrotic compounds, and evaluate their anti-fibrotic activity and mechanisms of action.
METHODS: A structure-oriented separation strategy, guided by spectroscopic analysis, enabled the isolation of stilbenes. Anti-fibrotic activity was screened in TGF-β1-induced hepatic stellate cells (HSCs). In vivo efficacy was evaluated in a CCl₄-induced mouse liver fibrosis model. Mechanisms were investigated using transcriptomics, Western blotting, and 16S rRNA gene sequencing.
RESULTS: Among seven isolated stilbenes, cis-Gnetin H exhibited the most potent inhibition of HSCs activation by downregulating α-SMA, Collagen I, and Smad3. In CCl₄-treated mice, cis-Gnetin H significantly ameliorated liver injury, inflammation, and fibrosis. Mechanistically, cis-Gnetin H activated the Nrf2/HO-1 antioxidant pathway while suppressing NF-κB and TGF-β1/Smad signaling. Furthermore, cis-Gnetin H remodeled the gut microbiota by enriching beneficial genera and reducing pathogenic Staphylococcus. This microbial modulation was accompanied by increased production of SCFAs, which correlated strongly with improved hepatic parameters.
CONCLUSION: cis-Gnetin H acts as an anti-fibrotic agent through modulating hepatic inflammatory and fibrotic signaling, and regulating the gut-liver axis via microbiota restoration and metabolite enhancement. These findings highlight cis-Gnetin H as a promising therapeutic candidate and support the high-value utilization of peony agricultural byproducts.