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

[1]	PAROLA M, PINZANI M. Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues[J]. Mol Aspects Med, 2019, 65: 37-55. DOI: 10.1016/j.mam.2018.09.002.
[2]	LIU FW. The curative effect of Taohong Siwu Decoction in the treatment of decompensated cirrhosis and its effect on coagulation function[J]. Mod J Integr Tradit Chin West Med, 2016, 25(15): 1662-1664. DOI: 10.3969/j.issn.1008-8849.2016.15.023. 刘发文. 桃红四物汤加减治疗失代偿期肝硬化的疗效及对凝血功能的影响[J]. 现代中西医结合杂志, 2016, 25(15): 1662-1664. DOI: 10.3969/j.issn.1008-8849.2016.15.023.
[3]	WANG WQ, WANG BX, SHAO WW. The effect of Angelica on the content of liver collagen protein of hepatic fibrosis rats induced by CCl₄[J]. Heilongjiang Med Pharm, 2003, 26(3): 25. DOI: 10.3969/j.issn.1008-0104.2003.03.011. 王伟群, 王柏欣, 邵文武. 当归对CCl₄致大鼠肝纤维化胶原蛋白含量的影响[J]. 黑龙江医药科学, 2003, 26(3): 25. DOI: 10.3969/j.issn.1008-0104.2003.03.011.
[4]	WANG YQ. Anti hepatic fibrosis effect of peach kernel extract and its molecular mechanism[J]. J Med Theor & Pract, 2014, 27(15): 2015-2016. DOI:10.3969/j.issn.1008- 0104.2003.03.011. 王玉清. 桃仁提取物抗肝纤维化作用及其分子机制研究[J]. 医学理论与实践, 2014, 27(15): 2015-2016. DOI:10.3969/j.issn.1008- 0104.2003.03.011.
[5]	MCQUITTY CE, WILLIAMS R, CHOKSHI S, et al. Immunomodulatory role of the extracellular matrix within the liver disease microenvironment[J]. Front Immunol, 2020, 11: 574276. DOI: 10.3389/fimmu.2020.574276.
[6]	WANG F, CHANG HM, YI Y, et al. TGF-β1 promotes hyaluronan synthesis by upregulating hyaluronan synthase 2 expression in human granulosa-lutein cells[J]. Cell Signal, 2019, 63: 109392. DOI: 10.1016/j.cellsig.2019.109392.
[7]	LIU C, YUAN X, TAO L, et al. Xia-yu-xue decoction (XYXD) reduces carbon tetrachloride (CCl₄)-induced liver fibrosis through inhibition hepatic stellate cell activation by targeting NF-κB and TGF-β1 signaling pathways[J]. BMC Complement Altern Med, 2015, 15: 201. DOI: 10.1186/s12906-015-0733-1.
[8]	SHI K, LIU Y, WANG X, et al. Adjuvant Fuzheng Huayu Capsule reduces the incidence of hepatocellular carcinoma in patients with hepatitis B-caused cirrhosis[J]. Evid Based Complement Alternat Med, 2020, 2020: 8826091. DOI: 10.1155/2020/8826091.
[9]	ZHANG W, YANG GY, SHEN DX, et al. Mechanism of action of Xiayuxue decoction in inhibiting liver fibrosis by regulating glial cell line-derived neurotro phic factor[J]. J Clin Hepatol, 2021, 37(3): 575-581. DOI: 10.3969/j.issn.1001-5256.2021.03.015. 张玮, 杨广越, 沈东晓, 等. 下瘀血汤抑制胶质细胞源性神经营养因子抗肝纤维化的作用机制[J]. 临床肝胆病杂志, 2021, 37 (3): 575-581. DOI: 10.3969/j.issn.1001-5256.2021.03.015.
[10]	LI ZY, TIAN YZ. Treatment of liver fibrosis by the Tibetan medicine Lang Qing A Ta according to stasis and heat[J]. J Changchun Univ Chin Med, 2019, 35(6): 1223-1225. DOI: 10.13463/j.cnki.cczyy.2019.06.061. 李忠意, 田耀洲. 藏药郎庆阿塔从瘀热论治肝纤维化[J]. 长春中医药大学学报, 2019, 35(6): 1223-1225. DOI: 10.13463/j.cnki.cczyy.2019.06.061.
[11]	CHEN FY, TU CT. The role and molecular mechanism of Notch signaling transduction pathway on liver fibrogenesis[J/CD]. Chin J Liver Dis(Electronic Edition), 2020, 12(4): 23-28. DOI: 10.3969/j.issn.1674-7380.2020.04.004. 陈方园, 涂传涛. Notch信号转导通路在肝纤维化形成中的作用与分子机制[J/CD]. 中国肝脏病杂志(电子版), 2020, 12(4): 23-28. DOI: 10.3969/j.issn.1674-7380.2020.04.004.
[12]	KISSELEVA T, BRENNER D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(3): 151-166. DOI: 10.1038/s41575-020-00372-7.
[13]	YUAN H, ZHAO C, BAO X, et al. Anti-liver fibrosis effect of total flavonoids from Scabiosa comosa Fisch. ex Roem. et Schult. on liver fibrosis in rat models and its proteomics analysis[J]. Ann Palliat Med, 2020, 9(2): 272-285. DOI: 10.21037/apm.2020.02.29.
[14]	PASSI A, VIGETTI D, BURASCHI S, et al. Dissecting the role of hyaluronan synthases in the tumor microenvironment[J]. FEBS J, 2019, 286(15): 2937-2949. DOI: 10.1111/febs.14847.
[15]	YANG YM, NOUREDDIN M, LIU C, et al. Hyaluronan synthase 2-mediated hyaluronan production mediates Notch1 activation and liver fibrosis[J]. Sci Transl Med, 2019, 11(496): eaatg284. DOI: 10.1126/scitranslmed.aat9284.

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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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