Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis

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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Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis

Original Article | Updated：2022-06-27

- Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis
- Chinese Journal of Integrative Medicine Vol. 28, Issue 6, Pages: 538-544(2022)
- 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：
- DOI：10.1007/s11655-021-3293-x
  CLC：
- Published：01 June 2022，
  
  Published Online：28 September 2021，
  
  Accepted：03 August 2020
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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 28(6):538-544(2022)
DOI：

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 28(6):538-544(2022) 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

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College of Integrated Traditional Chinese and Western Medicine, Jining Medical University

School of Traditional Chinese Medicine, Southern Medical University

Department of Traditional Chinese Medicine, Affiliated Hospital of Jining Medical University

Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University

Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University

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