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Updated: Apr 20, 2026
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
Single-cell transcriptomics reveals the ameliorative effect of gastrodin on cholestatic liver fibrosis
Di Pan1, Tian Zheng1, Canping Chen2
1The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province (The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability) / The State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China; Key Laboratory of Novel Anti-Cancer Drug Targets Discovery and Application, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China.
Background:
Cholestatic liver diseases, such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and biliary atresia (BA), are characterized by bile accumulation and frequently progress to liver fibrosis, cirrhosis, and organ failure.
Objective:
Given its well-documented hepatoprotective and anti-inflammatory properties, this study aimed to investigate the therapeutic potential and underlying mechanisms of gastrodin (4-(hydroxymethyl) phenyl β-D-glucopyranoside, C13H18O7), a primary bioactive compound from Gastrodia elata, for the treatment of cholestatic liver fibrosis.
Methods:
Two established mouse models of cholestatic fibrosis were used: the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet model and the bile duct ligation (BDL) model. An integrated analysis of single-nucleus RNA sequencing (snRNA-seq) data was performed, combining an in-house dataset from the DDC model with a public dataset.
Results:
Gastrodin treatment significantly alleviated liver injury, reduced serum levels of total bilirubin (TBIL) and total bile acids (TBA), decreased collagen deposition, and prolonged survival in mouse models. snRNA-seq analysis revealed that gastrodin promoted hepatocyte repair by regulating key sulfotransferases (Sult2a1 and Sult1e1), enhanced detoxification, reduced the proportion of Kupffer cells, and suppressed their production of inflammatory mediators (e.g., TNF-α, IL-6), potentially via upregulation of immunomodulatory genes (Pilrb1, Ifi27l2a, Rtp4). Furthermore, gastrodin modulated hepatic stellate cell (HSC) heterogeneity by expanding a novel HSC subgroup characterized by Serpina expression and associated with anti-fibrotic traits.
Conclusion:
Gastrodin alleviates cholestatic liver fibrosis through coordinated multi-cellular mechanisms involving hepatocytes, Kupffer cells, and HSCs. It represents a promising natural therapeutic candidate, with Sult2a1, Sult1e1, and Serpina1a identified as potential targets.
