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Pubmed ID: 31950587
Publication Date: 2020/01/17

Effects and therapeutic mechanism of YinZhiHuang on high-fat high-cholesterol diet induced steatohepatitis in rats.


Due to the complex pathophysiologic processes of nonalcoholic steatohepatitis (NASH), effective treatments should target several key regulators of cellular and molecular events. YinZhiHuang (YZH) oral liquid, a traditional Chinese medicine, is mainly composed of extracts of four components. Our hypothesis is that the complex multicomponent natures of YZH oral liquid may be an appropriate drug for NASH due to synergistic effects. We aimed to investigate the therapeutic mechanism of YZH oral liquid on high-fat high-cholesterol diet (HFHCD)-induced NASH in rats.

Thirty Sprague-Dawley rats were randomized in three groups: the control group was given a normal diet; the model group was given a HFHCD and saline once daily at the same time beginning at the end of the eighth week; and the treatment group was given a HFHCD and YZH oral liquid once daily beginning at the end of the eighth week. Liver histological features and serum biochemical parameters were assessed at the end of the sixteenth week. Four rats in each group were randomized in selecting for RNA sequencing and protein mass spectrometry detection. The genes and proteins expressed differentially were subjected to KEGG pathway enrichment analysis and included into a network-based regulatory model.

All rats in the HFHCD+saline group developed NASH. Compared with those in the HFHCD+saline group, the rats in the HFHCD+YZH group showed lower weights, liver indices and fat indices (P<0.01) and decreased serum ALT, AST, and TC levels (P<0.05). Hepatic steatosis, ballooning and lobular inflammation were relieved and 64 hepatic genes and 73 hepatic proteins could be also reversed in their expression patterns after YZH treatment (P<0.05). The network-based regulatory model showed that these deregulated genes and proteins were mainly involved in oxidative phosphorylation, Toll-like receptor, nucleotide-binding oligomerization domain (NOD)-like receptor, peroxisome proliferator-activated receptor (PPAR) signaling, nuclear factor-kappa B (NF-kB), tumor necrosis factor (TNF) signaling pathways and fatty acid metabolism.

Our study identified that YZH oral liquid could alleviate NASH in HFHCD-fed rats by inhibiting lipogenesis, accelerating lipid β-oxidation, alleviating oxidative stress, and relieving necroinflammation in the liver. This article is protected by copyright. All rights reserved.
Authors: Zeng Jing , Liu Xiao-Lin , Xin Feng-Zhi , Zhao Ze-Hua , Shao You-Lin , Yang Rui-Xu , Pan Qin , Fan Jian-Gao ,

Reference:

  1. ncbi.nlm.nih.gov. [Last access 2020/01/17].

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