School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China.
School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China.
J Ethnopharmacol. 2022 Feb 10;284:114801. doi: 10.1016/j.jep.2021.114801. Epub 2021 Nov 5.
Fuzheng Xiaozheng prescription (FZXZP) is a traditional Chinese medicine (TCM) that was derived from Sanjiasan, a famous decoction documented in the book of Wenyilun in Ming dynasty. Based on our years' clinic application, FZXZP demonstrated satisfactory therapeutic effects in cirrhosis and hepatocellular carcinoma (HCC) treatments. However, the underlying mechanisms are still largely unknown.
In this study, we aim to systematically evaluate the intervention effects of FZXZP on rat HCC and deeply elucidate the underlying regulative mechanisms on rat HCC.
The HCC rats were induced by using diethylnitrosamine (DEN) and two doses of FZXZP were adopted to treat the HCC rats. Liver phenotype, blood chemistry and liver histopathology were used to evaluate the intervention effects. High performance liquid chromatography (HPLC) was conducted to analyze the components of FZXZP. Finally, miRNA-Seq and mRNA-Seq were performed to investigate the regulative mechanisms of FZXZP on rat HCC and qRT-PCR was carried out to verify the accuracies of the two RNA-Seqs.
Results of liver phenotypes, blood chemistry and liver histopathology demonstrated that FZXZP significantly alleviated the liver damage, inhibited the progresses of HCC. Nine potential components were identified from FZXZP, and anti-cancer prediction suggested that almost all of them were reported to show an anti-cancer effect. Mechanistically, FZXZP was found to promote the lipid related metabolisms, improve the anti-inflammation ability by activating PPAR signaling pathway, arachidonic acid metabolism, bile secretion, etc. CONCLUSION: our results suggested that FZXZP significantly alleviated the rat HCC, mechanistically by improving the anti-inflammation ability and promoting the lipid related metabolisms.
扶正消症方（FZXZP）是一种中药，源自明代文义论书中记载的著名方剂三芪散。基于我们多年的临床应用，FZXZP 在肝硬化和肝癌（HCC）治疗中显示出令人满意的治疗效果。然而，其潜在机制在很大程度上仍不清楚。
本研究旨在系统评价 FZXZP 对大鼠 HCC 的干预作用，并深入探讨其对大鼠 HCC 的潜在调节机制。
采用二乙基亚硝胺（DEN）诱导 HCC 大鼠，采用两种剂量的 FZXZP 治疗 HCC 大鼠。采用肝表型、血液化学和肝组织病理学评价干预效果。采用高效液相色谱法（HPLC）分析 FZXZP 的成分。最后，进行 miRNA-Seq 和 mRNA-Seq 以研究 FZXZP 对大鼠 HCC 的调节机制，并通过 qRT-PCR 验证两种 RNA-Seq 的准确性。
肝表型、血液化学和肝组织病理学结果表明，FZXZP 能显著减轻肝损伤，抑制 HCC 的进展。从 FZXZP 中鉴定出 9 种潜在成分，抗癌预测表明，几乎所有成分都被报道具有抗癌作用。机制上，FZXZP 被发现通过激活 PPAR 信号通路、花生四烯酸代谢、胆汁分泌等，促进脂质相关代谢，增强抗炎能力。
我们的结果表明，FZXZP 能显著缓解大鼠 HCC，其机制是通过增强抗炎能力和促进脂质相关代谢。
