Abstract
Yinchenhao decoction (YCHD), comprising Yinchenhao (Artemisiae Scopariae Herba), Zhizi (Gardeniae Fructus) and Dahuang (Radix Rhei et Rhizoma), is widely used for treating various diseases. We aimed to investigate the bile acid metabolic mechanism of YCHD in dimethylnitrosamine (DMN)-induced liver fibrosis model. Rats received DMN (10 mg/kg, intraperitoneally) for four successive weeks for liver fibrosis induction and were treated with YCHD for the last 2 weeks. Histopathological analysis showed that YCHD prevented DMN-induced histopathological changes in liver tissues. Serum liver function in YCHD group improved. Ultraperformance liquid chromatography-mass spectrometry analysis showed that YCHD significantly restored both free and conjugated bile acid levels increased by DMN, to normal levels. RT-qPCR results showed that YCHD treatment upregulated the expression of genes related to bile acid synthesis, reabsorption, and excretion. Western blotting analysis showed that YCHD downregulated α-SMA, TGF-β1, p-Smad3, and p-ERK1/2 expression in chenodeoxycholic acid (CDCA)-activated hepatic stellate cells (HSCs). The viability of CDCA-activated HSCs significantly increased after treatment with YCHD and PD98059 (an ERK inhibitor) compared to YCHD treatment alone. Our findings suggest that YCHD alleviated DMN-induced liver fibrosis by regulating enzymes responsible for bile acid metabolism. Additionally, it inhibits CDCA-induced HSC proliferation and activation via TGF-β1/Smad/ERK signalling pathway.
Highlights
Traditional Chinese medicine (TCM) has been used from ancient times for the treatment of various diseases[9,10,11,12]
Higher fibrosis scores were observed in DMN-treated rats than in normal control rats; Yinchenhao decoction (YCHD) significantly improved these scores compared with DMN (Table 1)
Increasing evidence has shown that liver fibrosis can regress in many cases in the past decades[36], there is a lack of clinically effective drugs for the treatment of cirrhosis
Summary
Traditional Chinese medicine (TCM) has been used from ancient times for the treatment of various diseases[9,10,11,12]. As a classic traditional Chinese formula widely used for treating various liver diseases, Yinchenhao decoction (YCHD) was first described in the Treatise on Febrile Diseases (Shanghan Lun). The components of YCHD, Yinchenhao, Zhizi and Dahuang, have been widely used for treating diseases such a liver and kidney diseases[13,14,15,16,17]. YCHD improves biochemical and histological statuses in nonalcoholic fatty liver disease[18] and protects against dimethylnitrosamine (DMN)-induced inflammatory injury in hepatic parenchymal cells in rats[19]. The mechanisms underlying the hepatoprotective effects of YCHD remain to be elucidated. We used a DMN-induced chronic liver injury rat model to investigate the mechanisms of YCHD against liver fibrosis and the underlying metabolic profiles of bile acids. We investigated whether YCHD inhibits CDCA-induced HSC activation through TGF-β1/Smad/ERK signalling pathway
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