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 µ mol/L × 7 components/kg body weight), model, low-, medium-, high-dose ACF groups (5, 10, 20 µ mol/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 II A, salvianolic acid B, cordycepin, amygdalin, quercetin, protopanaxatriol, and schizandrin B were recombined with equal proportions to form ACF. ACF at 1,2, 4 µ mol/L showed strong inhibitory effects on activation of LX-2 and proliferation of HHSEC in vitro (all P<0.01). Compared with the model group, ACF attenuated liver collagen deposition, improved sinusoidal capillarization in a dose-dependent manner (all P<0.05).
Conclusion
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.
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Liu CH designed the project; Tan Y, Sun X and Liu HL performed the experiments; Sun X, Lyu J and Zhao ZM analyzed the data; Sun X and Lyu J drafted the manuscript; Liu CH critically revised the manuscript. All the authors read and approved the manuscript for publication.
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Authors declare that they have no conflict of interest.
Supported by the Major Projects of the Ministry of Science and Technology of China (No. 2014ZX10005001), the National Natural Science Foundation of China (No. 81603467, 81730109) and the Third Batch of Open Projects of Shanghai Innovation Center of Traditional Chinese Medicine Health Service (No. ZYJKFW201811013)
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Sun, X., Tan, Y., Lyu, J. et al. Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis. Chin. J. Integr. Med. 28, 538–544 (2022). https://doi.org/10.1007/s11655-021-3293-x
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DOI: https://doi.org/10.1007/s11655-021-3293-x