Mechanism of action of Xiayuxue decoction in inhibiting liver fibrosis by regulating glial cell line-derived neurotrophic factor

Wei ZHANG; Guangyue YANG; Dongxiao SHEN; Wenting MA; Le TAO; Liu WU; Ping YAN; Cheng LIU

doi:10.3969/j.issn.1001-5256.2021.03.015

Volume 37 Issue 3

Mar. 2021

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Article Navigation > Journal of Clinical Hepatology > 2021 > 37(3): 575-581

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Mechanism of action of Xiayuxue decoction in inhibiting liver fibrosis by regulating glial cell line-derived neurotrophic factor

DOI: 10.3969/j.issn.1001-5256.2021.03.015

a.
Laboratory of Liver Diseases of Experimental Center, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
b.
Department of Infectious Diseases, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China

Received Date: 2020-09-11
Accepted Date: 2020-11-05
Published Date: 2021-03-20

Abstract

Abstract

Objective To investigate whether Xiayuxue decoction exerts an anti-liver fibrosis effect by inhibiting glial cell line-derived neurotrophic factor (GDNF). Methods A total of 24 C57BL/6 mice were randomly divided into control group, model group, and Xiayuxue decoction group. The mice in the model group and the Xiayuxue decoction group were given intraperitoneal injection of 10% CCl₄, and those in the Xiayuxue decoction group were given 0.4678 g/kg Xiayuxue decoction by gavage since week 4. The liver function parameters alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and liver histopathology was observed. Immunohistochemistry was used to measure the protein expression of alpha-smooth muscle actin (α-SMA) and GDNF. GFP-Col-HSC and human primary hepatic stellate cells (HSCs) were treated with GDNF (10 ng/ml), and HSC activation was measured. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with the control group, the model group had significant increases in the levels of ALT and AST, and compared with the model group, the Xiayuxue decoction group had significant reductions in the levels of ALT and AST (all P < 0.01). Liver histopathology showed that the model group had marked inflammatory cell infiltration and formation of fibrous septa by proliferated collagen fibers, and the Xiayuxue decoction group had loose fibrous septa and alleviated inflammatory cell infiltration. Immunohistochemistry showed that compared with the control group, the model group had significant increases in the expression of α-SMA and GDNF (both P < 0.01), which were observed in fibrous septa, and compared with the model group, the Xiayuxue decoction group had significant reductions in the expression of α-SMA and GDNF (both P < 0.05). Western blotting showed that the control group had relatively low expression of GDNF in liver tissue, the formation of liver fibrosis at week 6 of CCl₄ modeling, and an around 10-fold increase in the expression of GDNF, and the Xiayuxue decoction group had significantly inhibited protein expression of GDNF (P < 0.01); there were significant increases in the expression of α-SMA and collagen type I α1 (Col1) in mice with liver fibrosis, with significant reductions in α-SMA and Col1 after treatment with Xiayuxue decoction (all P < 0.01). The in vitro experiment showed that GDNF induced the significant increases in the protein expression of α-SMA and Col1 in HSCs, which was significantly inhibited by Xiayuxue decoction (all P < 0.01). Conclusion The expression of GDNF is significantly upregulated in the formation of liver fibrosis. GDNF can induce HSC activation, and Xiayuxue decoction can exert an anti-liver fibrosis effect by inhibiting GDNF.
- Liver Cirrhosis,
- Xia-Yu-Xue Decoction,
- Glial Cell Line-Derived Neurotrophic Factor

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References

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Mechanism of action of Xiayuxue decoction in inhibiting liver fibrosis by regulating glial cell line-derived neurotrophic factor

DOI: 10.3969/j.issn.1001-5256.2021.03.015