Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Bibenzyls from Dendrobium huoshanense attenuate alcohol-associated liver disease via AMPK/ATGL, CYP2E1/ALDH2, and gut microbiota modulation.
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Yan Congjie, Tian Zexi, Yuan Rong, Liu Yingbo, Wang Weidong, Liu Zenggen
Аннотация
BACKGROUND: Dendrobium huoshanense, a renowned traditional Chinese medicine, is widely used for liver disease prevention and treatment, exhibiting potential therapeutic effects against alcohol-associated liver disease (ALD). However, its specific active components and mechanisms of action remain unclear.
PURPOSE: This study aimed to isolate bibenzyl compounds from D. huoshanense via structure-guided separation, identify the core active component for ALD treatment, and elucidate its underlying mechanism.
METHODS: Bibenzyl compounds were isolated using preparative HPLC. An in vitro HepG2 cell injury model induced by ethanol/palmitic acid was employed for bioactivity screening. The anti-ALD effects of the active component were comprehensively evaluated in an ALD mouse model and cellular experiments. Integrated multi-omics strategies (liver proteomics, gut microbiota 16S rRNA sequencing) combined with molecular biology techniques (Western blotting, immunofluorescence) were utilized to decipher the core molecular mechanisms.
RESULTS: Five bibenzyl compounds were isolated and identified from D. huoshanense. Among them, 4-hydroxy-3,4',5, α-tetramethoxybibenzyl (HT) exhibited the most potent activity. HT exerted hepatoprotective effects through remodeled gut microbiota by increasing beneficial bacteria and restoring short-chain fatty acid production; activated the AMPK/PPAR-γ/ATGL pathway to promote lipolysis and reduce lipid droplet accumulation; and suppressed oxidative stress by inhibiting CYP2E1 overexpression while enhancing ALDH2 activity, thereby alleviating ethanol-induced oxidative damage.
CONCLUSION: Bibenzyl compounds are the primary active constituents of D. huoshanense for ALD treatment. HT, as the core component, exerts multi-target effects by synergistically modulating the gut-liver axis, lipid metabolism, and oxidative stress pathways, demonstrating significant potential as a novel therapeutic candidate for ALD.
PURPOSE: This study aimed to isolate bibenzyl compounds from D. huoshanense via structure-guided separation, identify the core active component for ALD treatment, and elucidate its underlying mechanism.
METHODS: Bibenzyl compounds were isolated using preparative HPLC. An in vitro HepG2 cell injury model induced by ethanol/palmitic acid was employed for bioactivity screening. The anti-ALD effects of the active component were comprehensively evaluated in an ALD mouse model and cellular experiments. Integrated multi-omics strategies (liver proteomics, gut microbiota 16S rRNA sequencing) combined with molecular biology techniques (Western blotting, immunofluorescence) were utilized to decipher the core molecular mechanisms.
RESULTS: Five bibenzyl compounds were isolated and identified from D. huoshanense. Among them, 4-hydroxy-3,4',5, α-tetramethoxybibenzyl (HT) exhibited the most potent activity. HT exerted hepatoprotective effects through remodeled gut microbiota by increasing beneficial bacteria and restoring short-chain fatty acid production; activated the AMPK/PPAR-γ/ATGL pathway to promote lipolysis and reduce lipid droplet accumulation; and suppressed oxidative stress by inhibiting CYP2E1 overexpression while enhancing ALDH2 activity, thereby alleviating ethanol-induced oxidative damage.
CONCLUSION: Bibenzyl compounds are the primary active constituents of D. huoshanense for ALD treatment. HT, as the core component, exerts multi-target effects by synergistically modulating the gut-liver axis, lipid metabolism, and oxidative stress pathways, demonstrating significant potential as a novel therapeutic candidate for ALD.