Chaihu Shugan San mitigates esophageal injury via AMPK-FUNDC1 mitochondrial homeostasis: Multi-omics insights

Chang X, Zhang Y, Xu W, Guo Z, Ong SB, Liu N, Li Y, Zhou H, Bai Y, Meng M · Phytomedicine · 2026 July

DOI 10.1016/j.phymed.2026.158208

Objective

To investigate whether Chaihu Shugan San (CHSG) ameliorates reflux esophagitis by regulating AMPK/FUNDC1-dependent mitophagy and mitochondrial metabolism.

Conclusions

CHSG mitigates reflux esophagitis through AMPK-driven activation of FUNDC1 mitophagy, restoration of mitochondrial function, and suppression of apoptosis.

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Insights

The Chinese medicine, Chaihu Shugan San, can alleviate reflux esophagitis by restoring mitochondrial function and reducing cell death through AMPK-enhanced, FUNDC1-dependent cell recycling.

This investigation employed a range of approaches, including live rat models with induced esophagitis, cellular tests in the lab, network pharmacology, molecular docking, and the use of AMPK genetic knockout models. Chaihu Shugan San (CHSG) was given to rats with esophagitis to assess the effects on esophageal damage, inflammation levels, and mitochondrial function. They also used network pharmacology and docking analyses to identify potential targets which they then validated in the lab using AMPK siRNA and knockout mice. The administration of CHSG significantly reduced inflammation in the esophageal area, boosted mitochondrial energy, and encouraged FUNDC1-mediated cellular recycling while also preventing excessive cell death. AMPK was identified as a key target and the withdrawal of its gene made the protective effects of CHSG ineffective. The study concludes that CHSG may be beneficial in treating reflux esophagitis through the activation of FUNDC1 cell recycling driven by AMPK, the restoration of mitochondrial function and inhibition of apoptosis.