Therapeutic effect of Taohong Siwu decoction on a mouse model of carbon tetrachloride-induced liver fibrosis and its mechanism

Xuling LIU; Guangyue YANG; Wei ZHANG; Tiantian SUN; Wenting MA; Liu WU; Dongying XUE; Cheng LIU; Le TAO

doi:10.3969/j.issn.1001-5256.2021.11.016

Volume 37 Issue 11

Nov. 2021

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Article Navigation > Journal of Clinical Hepatology > 2021 > 37(11): 2563-2568

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Therapeutic effect of Taohong Siwu decoction on a mouse model of carbon tetrachloride-induced liver fibrosis and its mechanism

DOI: 10.3969/j.issn.1001-5256.2021.11.016

Xuling LIU^{a, b},
Guangyue YANG^c,
Wei ZHANG^c,
Tiantian SUN^c,
Wenting MA^{a, b},
Liu WU^{a, b},
Dongying XUE^{a, b},
Cheng LIU^{a, c},
Le TAO^{a, b
,
,}

a.
Laboratory of Liver Diseases, 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
c.
Central Laboratory, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China

Research funding:

National Natural Science Foundation of China (81673788);

National Natural Science Foundation of China (81873136);

National Natural Science Foundation of China (81803898);

National Natural Science Foundation of China (81803232);

National Natural Science Foundation of China (82004106);

Shanghai National Natural Science Foundation (20ZR1450300);

Shanghai Municipal Health Commission (202040149);

Indenpdent Innovation Project of Shanghai Puotuo District Project (ptkwws201817);

Indenpdent Innovation Project of Shanghai Puotuo District Project (ptkwws201904)

Received Date: 2021-03-09
Accepted Date: 2021-04-21
Published Date: 2021-11-20

Abstract

Abstract

Objective To investigate the therapeutic effect of Taohong Siwu decoction on a mouse model of carbon tetrachloride (CCl₄)-induced liver fibrosis and its mechanism of action. Methods A total of 24 male C57BL/6 mice were randomly divided into normal group, model group, and Taohong Siwu decoction group, with 8 mice in each group. The mice in the model group and the Taohong Siwu decoction group were given intraperitoneal injection of 10% CCl₄, and Taohong Siwu decoction was given by gavage since week 3 for 4 consecutive weeks. Liver function [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] was measured, and liver pathomorphology was observed. Real-time PCR was used to measure the mRNA expression of α-smooth muscle actin (α-SMA), hyaluronic acid synthase-2 (HAS-2), and collagen type Ⅰ(Col1), and Western blotting was used to measure the protein expression of α-SMA, Col1, and HAS-2. Primary hepatic stellate cells (HSCs) were isolated, and HAS-2 was silenced by siRNA to observe its influence on HSC activation. The t-test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the SNK or least significant difference t-test was used for further comparison between two groups. Results Compared with the normal group, the model group had significant increases in serum liver function parameters (ALT, AST) and the Taohong Siwu decoction group had significant reductions in the serum levels of ALT and AST (all P < 0.01). Pathological staining showed that the model group had marked inflammatory cell infiltration and formation of fibrous septa by proliferated collagen fibers, and the Taohong Siwu decoction group had loose fibrous septa and alleviated inflammatory cell infiltration. Compared with the model group, the Taohong Siwu decoction group had significant reductions in the mRNA and protein expression of α-SMA and Col1(all P < 0.001). Compared with the normal group, the model group had a significant increase in the mRNA expression level of HAS-2 in liver tissue (t=6.14, P < 0.05), and compared with the model group, the Taohong Siwu decoction group had a significant reduction in the protein expression level of HAS-2 (0.29±0.10 vs 1.00±0.12, t=70.73, P < 0.001). After HAS-2 was silenced by siRNA, the Si HAS-2+transforming growth factor β (TGFβ) group (treated with TGFβ) had significant reductions in the mRNA expression levels of α-SMA and Col-Ⅰ compared with the NC+TGFβ group (P < 0.01). Conclusion Taohong Siwu decoction exerts a marked therapeutic effect on CCl₄-induced liver fibrosis in mice by inhibiting HAS-2.
- Liver Cirrhosis,
- Taohong Siwu Decoction,
- Hyaluronic Acid Synthase-2,
- Mice, Inbred C57BL

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References

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Therapeutic effect of Taohong Siwu decoction on a mouse model of carbon tetrachloride-induced liver fibrosis and its mechanism

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Therapeutic effect of Taohong Siwu decoction on a mouse model of carbon tetrachloride-induced liver fibrosis and its mechanism

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