Liquiritigenin alleviates inflammation and mitochondrial dysfunction in acute pancreatitis via ERβ–VDAC1 signaling

作者：Yifan Miao, Ding Bai, Shu-han Fan, Hongying Li, Jia-qi Yao, Ji‐Hun Mo, Yong Chen, Wei Jin, Yun Lü · 发表于：Journal of Ethnopharmacology · 年份：2025 · DOI：10.1016/j.jep.2025.120526 · 被引用次数：7 · 研究领域：Pancreatitis Pathology and Treatment、Galectins and Cancer Biology、Pharmacological Effects of Natural Compounds

ETHNOPHARMACOLOGICAL RELEVANCE: Liquorice (Gancao), a classic Chinese herb, has been historically prescribed for inflammation and gastrointestinal disorders. Its bioactive flavonoid liquiritigenin (4',7-dihydroxyflavone) exhibits anti-inflammatory properties, yet its efficacy against acute pancreatitis (AP) remains unexplored. AIM: To systematically investigate the therapeutic potential of liquiritigenin against AP and decipher its estrogen receptor beta (ERβ)-mediated mitochondrial regulatory mechanisms. METHODS: Employing caerulein-induced murine AP and sodium taurocholate-treated pancreatic acinar cell models, we quantified pancreatic injury and cellular damage. Temporal profiling of ERβ/estrogen receptor alpha (ERα) was correlated with disease progression, complemented by analysis of publicly available transcriptomic datasets. Multimodal approaches including network pharmacology, molecular docking, and transcriptomics identified ERβ-voltage-dependent anion channel 1 (VDAC1) as the pivotal axis, validated by: (i) ethylene glycol bis(succinimidyl succinate) crosslinking/Western blot for VDAC1 oligomerization, (ii) comparative studies with VDAC1 inhibitor VBIT-12, and (iii) mitochondrial assessments. RESULTS: Liquiritigenin significantly attenuated AP severity, reducing pancreatic enzymes and histopathological damage while suppressing inflammation. ERβ expression showed a stronger inverse correlation with disease severity than ERα. Mechanistically, liquiritigenin selectively...