Therapeutic effect of emodin on cholestatic liver injury in mice based on CYP7A1 / FXR / SHP pathway

doi:10.12092/j.issn.1009-2501.2026.02.008

Abstract

Abstract:

AIM: To investigate the therapeutic effect of emodin on cholestatic liver injury in mice. METHODS: C57BL/6J mice were subcutaneously injected with ethinyl estradiol (EE) for 7 consecutive days to establish a cholestasis model. The changes of body weight and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GT) and total bilirubin (TBIL) were detected. HE (hematoxylin-eosin) staining and MASSON staining were used to evaluate the effects on liver and other organs. After the efficacy was determined by animal model administration experiment, the human normal liver cell L02 was induced by lithocholic acid (LCA) to construct a cholestatic cell model. The CCK-8 method was used to detect the median lethal dose (IC₅₀) by LCA intervention for 24 hours to determine the modeling concentration. Through emodin intervention for 24 h, the survival rate of each group was detected to determine the concentration of emodin. The survival rate of emodin on liver cells after LCA modeling was detected and evaluated. By detecting the changes of liver injury index related enzymes ALT, AST levels and oxidative stress related enzymes glutathione (GSH), serum superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species(ROS) levels in each group of L02 cells, the mechanism of emodin in anti-cholestasis by improving oxidative stress was evaluated. Western blot was used to detect the protein expression of Cholesterol 7α-hydroxylase (CYP7A1), Farnesol X receptor (FXR) and small heterodimer partner (SHP) in the liver of mice. RESULTS: Emodin significantly improved the body weight change and liver index of mice, reduced the levels of ALT, AST, γ-GT and TBIL in serum, improved the trend of liver lesions, and inhibited liver damage. Improving the survival rate of L02 cells improved the survival state of cells, reduced the changes of ALT and AST levels and improved cell damage. It also changed the level of oxidative stress by increasing GSH and SOD levels and reducing MDA and ROS levels. In addition, emodin significantly increased FXR and SHP in the liver of mice and decreased the protein expression level of CYP7A1. CONCLUSION: Emodin can play a protective role in cholestatic liver injury, and its mechanism may be through inhibiting oxidative stress injury and regulating bile acid synthesis and metabolism through FXR / CYP7A1 / SHP pathway.

Key words: emodin, cholestasis, liver injury, oxidative stress

CLC Number:

R965.2

Weichen WANG, Yaping MA, Meng WANG, Qinglin LI, Hui CHENG. Therapeutic effect of emodin on cholestatic liver injury in mice based on CYP7A1 / FXR / SHP pathway[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(2): 204-212.

Figures/Tables 7

Fig.1 Effect of emodin on physiological and biochemical indexes of EE model mice ($ \overline{x} $±s, n=6) A-B: effect of body weight and liver index on C57BL/6J mice. C-F: effect of ALT, AST, γ-GT and TBIL levels in C57BL/6J mice. cP<0.01, compared with control group. eP<0.05, fP<0.01, compared with model group.

Fig.2 Pathological effects of HE staining sections of liver, heart, kidney, spleen and ileum in C57BL/6J mice The black arrow indicates severe inflammatory cell infiltration, liver, heart, kidney, spleen (×100), ileum(×200).

Fig.3 Pathological effects of MASSON staining sections of C57BL/6J mouse liver ($ \overline{x} $±s, n=6) The black arrow indicates severe inflammatory cell infiltration (×100).

Fig.4 Effect of emodin on LCA-induced L02 cell viability ($ \overline{x} $±s, n=6) A: effect of LCA on cytotoxicity. B: effect of emodin on cytotoxicity. C: effect of emodin on LCA-induced cell viability. bP<0.05, cP<0.01, compared with control group; eP<0.05,fP<0.01, compared with model group.

Fig.5 Effect of emodin on ALT and AST in LCA-induced L02 cells ($ \overline{x} $±s, n=3) cP<0.01, compared with control group; eP<0.05, fP<0.01, compared with model group.

Fig.6 Effect of emodin on GSH, SOD, MDA and ROS in LCA-induced L02 cells ($ \overline{x} $±s, n=3) cP<0.01, compared with control group; eP<0.05, fP<0.01, compared with model group.

Fig.7 Effect of emodin on protein expression of FXR, CYP7A1and SHP induced by LCA in CLD mouse ($ \overline{x} $±s, n=3) cP<0.01, compared with control group.

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