扶正化瘀方抗肝纤维化活性成分的配伍研究

Xin SUN; Ye TAN; Jing LYU; Hong-liang LIU; Zhi-min ZHAO; Cheng-hai LIU

doi:10.1007/s11655-021-3293-x

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扶正化瘀方抗肝纤维化活性成分的配伍研究

Original Article | Updated：2022-06-27

- 扶正化瘀方抗肝纤维化活性成分的配伍研究
- Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis
- Chinese Journal of Integrative Medicine 2022年28卷第6期页码：538-544
- Affiliations：
  
  1.Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai(201203), China
  2.Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai (201203), China
- Author bio：
  
  Prof. LIU Cheng-hai, E-mail: chenghailiu@hotmail.com
- Funds：
  
  Ministry of Science and Technology of the People's Republic of China(2014ZX10005001);the National Natural Science Foundation of China(81603467;81730109);the Third Batch of Open Projects of Shanghai Innovation Center of Traditional Chinese Medicine Health Service(ZYJKFW201811013)
- DOI：10.1007/s11655-021-3293-x
  中图分类号：
- 纸质出版日期：2022-06-01，
  
  网络出版日期：2021-09-28，
  
  录用日期：2020-08-03
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Xin SUN, Ye TAN, Jing LYU, 等. 扶正化瘀方抗肝纤维化活性成分的配伍研究[J]. Chinese Journal of Integrative Medicine, 2022,28(6):538-544.

Xin SUN, Ye TAN, Jing LYU, et al. Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis[J]. Chinese Journal of Integrative Medicine, 2022,28(6):538-544.
Xin SUN, Ye TAN, Jing LYU, 等. 扶正化瘀方抗肝纤维化活性成分的配伍研究[J]. Chinese Journal of Integrative Medicine, 2022,28(6):538-544. DOI： 10.1007/s11655-021-3293-x.

Xin SUN, Ye TAN, Jing LYU, et al. Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis[J]. Chinese Journal of Integrative Medicine, 2022,28(6):538-544. DOI： 10.1007/s11655-021-3293-x.

摘要

目的:

筛选扶正化瘀方的有效成分

重新设计有效成分组成的新配方

验证扶正化瘀方组分复方的抗肝纤维化作用.

方法:

体外分别采用6种细胞模型(肝细胞株L-02氧化应激模型、内皮细胞株SK-HEP-1缺氧损伤和增殖模型、肝窦内皮细胞HHSEC缺氧损伤和增殖模型、肝星状细胞株LX-2活化模型) 对扶正化瘀方中已知的32种成分进行活性评价. 根据扶正化瘀方中每味中药的作用和每种细胞在肝纤维化中的功能

对各成分进行抗肝纤维化的综合活性评分

筛选出7种活性成分

并按等比例组合形成一种新型的扶正化瘀方组分复方(Active Components Formulation

ACF). 继而通过体外LX-2细胞株活化模型、HHSEC细胞增殖模型及二甲亚硝胺诱导的肝纤维化小鼠模型进行抗肝纤维化药效验证. 采用随机数字表法将72只小鼠分为正常组、高剂量ACF对照组(20 μmol×7种成分/公斤体重)、模型组、低、中、高剂量ACF干预组(分别为5、10、20μmol×7种成分/公斤体重). 苏木精-伊红、天狼星红染色观察肝组织炎症和纤维化病理改变; 扫描电镜和透射电镜观察肝窦超微结构.

结果:

扶正化瘀方中有15种成分在抗肝纤维化活性综合计分中得分较高

将其中得分最高的丹参酮ⅡA、丹酚酸B、虫草素、扁桃苷、槲皮素、原人参三醇、五味子乙素7种成分以等比例重组形成扶正化瘀方ACF. 1、2、4μmol/L的ACF对HHSEC的增殖和LX-2的活化均有较强的抑制作用(

0.01); 与模型组比较

ACF可明显减轻肝组织胶原沉积

改善肝窦毛细血管化

且呈剂量依赖性改变 (

0.05) .

结论:

来源于扶正化瘀方的7种有效成分等比例配伍得到的ACF对实验性肝纤维化有较好的抑制作用

并可减轻肝窦毛细血管化

为今后抗肝纤维化中药活性成分的深入研究和挖掘提供借鉴意义.

Abstract

Objective:

To screen the active components from Fuzheng Huayu Recipe (FZHY) and redesign a new recipe composed of the active components

and validate the effect of active components formulation from FZHY against liver fibrosis.

Methods:

Thirty-two components from FZHY were evaluated for their activities against liver fibrosis respectively

with 6 kinds of cell models

in vitro

including oxidative stressed hepatocyte in L-02

hypoxia injured/proliferative hepatic sinusoidal endothelial cells in SK-HEP-1 and human hepatic sinusoidal endothelial cells (HHSEC)

and activated hepatic stellate cell in LX-2. The comprehensive activity of each component against liver fibrosis was scored according to the role of original herbs in FZHY and cell functions in fibrogenesis. Totally 7 active components were selected and combined with equal proportion to form a novel active components formulation (ACF). The efficacy of ACF on liver fibrosis were evaluated on activation of LX-2 and proliferation of HHSEC

in vitro

and in liver fibrosis model mice induced by dimethylnitrosamine (DMN). Totally 72 mice were divided into 6 groups using a random number table

including normal

high-dose ACF control (20 μmol/L×7 components/kg body weight)

model

low-

medium-

high-dose ACF groups (5

20 μmol/L×7 components/kg body weight

respectively). Hematoxylin eosin and Sirius red stainings were used to observe inflammation and fibrosis change of liver tissue; scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to observe the effect of ACF on ultrastructure of hepatic sinusoids.

Results:

Fifteen components from FZHY showed higher scores for their activity on against liver fibrosis. Among them

7 components including tanshinone ⅡA

salvianolic acid B

cordycepin

amygdalin

quercetin

protopanaxatriol

and schizandrin B were recombined with equal proportions to form ACF. ACF at 1

4 μmol/L showed strong inhibitory effects on activation of LX-2 and proliferation of HHSEC

in vitro

(all

0.01). Compared with the model group

ACF attenuated liver collagen deposition

improved sinusoidal capillarization in a dose-dependent manner (all

0.05).

Conclusions:

ACF exerts a satisfactory effect against experimental liver fibrosis and attenuates sinusoidal capillarization

which warrant a further research and development for herbal components formulation on liver fibrosis.

关键词

Keywords

active components formulationFuzheng Huayu RecipeChinese medicineliver fibrosishepatic stellate cellshepatic sinusoidal capillarization

references

Mercedes F, David S, Jordi B, Isabelle C, Massimo P, Jaume B. Angiogenesis in liver disease. J Hepatol 2009;50:604-620.

DeLeve LD. Liver sinusoidal endothelial cells in hepatic fibrosis. Hepatology 2015;61:1740-1746.

Thabut D, Shah V. Intrahepatic angiogenesis and sinusoidal remodeling in chronic liver disease: new targets for the treatment of portal hypertension? J Hepatol 2010;53:976-980.

Friedman Scott L. Hepatic fibrosis: emerging therapies. Dig Dis 2015;33:504-507.

Lee Youngmin A, Wallace Michael C, Friedman Scott L.Pathobiology of liver fibrosis: a translational success story.Gut 2015;64:830-841.

Liu P, Hu YY, Liu C, Xu LM, Liu CH, Sun KW, et al.Multicenter clinical study on Fuzhenghuayu Capsule against liver fibrosis due to chronic hepatitis B. World J Gastroenterol 2005;11:2892-2899.

Hassanein T, Box TD, Tong MJ, Pozza R, Rossaro L, Glenn JS, et al. A phase Ⅱ, randomized, placebo-controlled,double-blind, multicenter study to assess the antifibrotic activity of Fuzheng Huayu in chronic hepatitis C patients with hepatic fibrosis. Hepatol Int 2014;8:S308-S309.

Liu CH, Hu YY, Xu LM, Liu C, Liu P. Effect of Fuzheng Huayu Formula and its actions against liver fibrosis. Chin Med 2009;4:38-53.

Liu HL, Lv J, Zhao ZM, Xiong AM, Tan Y, Glenn Jeffrey S,et al. Fuzhenghuayu Decoction ameliorates hepatic fibrosis by attenuating experimental sinusoidal capillarization and liver angiogenesis. Sci Rep 2019;9:18719.

Zhao ZM, Liu HL, Sun X, Guo T, Shen L, Tao YY, et al.Levistilide A inhibits angiogenesis in liver fibrosis via vascular endothelial growth factor signaling pathway. Exp Bio Med 2017;242:974-985.

Lv J, Tan Y, Zhao ZM, Huang K, Shen L, Tao YY, et al.Fuzheng Huayu components formula exerted anti-liver fibrosis through inhibiting angiogenesis. World Chin Med(Chin) 2015;10:186-191.

Jamall IS, Finelli VN, Que Hee SS. A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues. Anal Biochem 1981;112:70-75.

Friedman Scott L. Evolving challenges in hepatic fibrosis.Nat Rev Gastroenterol Hepatol 2010;7:425-436.

Liu CH, Zhao ZM, Lv J. Advances in the understanding and treatment of liver fibrosis in traditional Chinese medicine. J Clin Hepatol (Chin) 2019;35:728-733.

Cui XW, Zhang GJ. Component Chinese medicine and Chinese medicine modernization. Lishizhen Med Mater Med Res (Chin) 2009;20:1290-1291.

Zhang BL, Wang YY. Basic research on key scientific issues of TCM prescription-modern Chinese medicine was developed by the combination of components. Chin J Nat Med (Chin) 2005;3:258-261.

Huang K, Zhao ZM, Liu HL, Sun X, Lv J, Tao YY, et al.Evaluation of cryptotanshinone inhibition of angiogenesis in human hepatic sinusoidal endothelial cells. Acta Pharmaceut Sin (Chin) 2016;51:1257-1262.

Zhu CW, Lv J, Zhao ZM, Tao YY, Liu CH. Effect of schisantherin A inhibit liver sinusoid endothelial cell function and action against liver fibrosis relating to angiogenesis.China J Tradit Chin Med Pharm (Chin) 2016;41:279-284.

Guo T, Liu ZL, Zhao Q, Zhao ZM, Liu CH. A combination of astragaloside Ⅰ, levistilide A and calycosin exerts anti-liver fibrosis effects in vitro and in vivo. Acta Pharmacol Sin 2018;39:1483-1492.

Xu MM, Wang XH, Zou Y, Zhong XS. Key role of liver sinusoidal endothelial cells in liver fibrosis. Biosci Trends 2017;11:163-168.

Greuter T, Shah VH. Hepatic sinusoids in liver injury,inflammation, and fibrosis: new pathophysiological insights.J Gastroenterol 2016;51:511-519.

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