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Yinchenzhufu decoction (YCZFD) is a classic formula for treating Yin Huang syndrome, which can improve liver injury caused by cholestasis. However, the mechanism of action of YCZFD still remains unclear. This article used network pharmacology, molecular docking, animal experiments, and molecular biology methods to explore the mechanism of YCZFD in treating liver injury caused by cholestasis. A mouse model of acute cholestasis induced by lithocholic acid was used to investigate the effects of YCZFD on liver injury. The experimental procedures described in this paper were reviewed and approved by the Ethical Committee at the Shanghai University of Traditional Chinese Medicine (approval NO. PZSHUTCM190823002). The results showed that YCZFD could reduce the levels of blood biochemical indicators and improve hepatocyte damage of cholestatic mice. Then, multiple databases were used to predict the corresponding targets of YCZFD active components on cholestatic liver injury. An intersection target protein-protein interaction (PPI) networks based on String database and Cytoscape software was used to demonstrate the possible core targets of YCZFD against cholestatic liver injury. The results indicated that core targets of YCZFD include tumor necrosis factor, interleukin-1β, non-receptor tyrosine kinase Src, interleukin-6, etc. GO (gene ontology) and KEGG (kyoto encyclopedia of genes and genomes) enrichment analysis indicated that YCZFD may regulate the tumor necrosis factor signaling pathway, nuclear factor-κB signaling pathway, bile secretion, and other related factors to ameliorate the cholestatic liver injury. AutoDockTools software was used to perform molecular docking verification on the core targets and components of YCZFD. To verify the results of network pharmacology, UPLC-MS/MS method was used to determine the effect of YCZFD on levels of bile acid profiles in mouse liver tissues. It was found that treatment with YCZFD significantly reduced the content of free bile acids, taurine bound bile acids, and total bile acids in the liver tissues of cholestatic mice. Then, results from real time PCR and Western blot also found that YCZFD can upregulate the expression of hepatic nuclear receptor farnesoid X receptor, metabolizing enzyme (UDP glucuronidase transferase 1a1), and efflux transporters (bile salt export pump, multidrug resistance-associated protein 2, multidrug resistance-associated protein 3, etc) in cholestasis mice, promote bile acid metabolism and excretion, and improve bile acid homeostasis. Moreover, YCZFD can also inhibit pyroptosis and inflammation by regulating NOD-like receptors 3 pathway, thereby inhibiting cholestatic liver injury.
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AIM: To investigate the hepatoprotective effects of Yinchenzhufu decoction (YCZFD) via TLR4/NF-κB pathway on the hepatic injury in alpha-naphthyisothiocyanate (ANIT)-induced intrahepatic cholestasis mice. METHODS: Male C57BL/6 mice were administered with YCZFD for consecutive 10 days, and intrahepatic cholestasis mice model was induced by orally given ANIT at dose of 75 g/kg on the seventh day. On the last day, the blood samples and liver samples were collected 2 hours after oral administration of YCZFD. The serum biochemical index, liver histopathology, the change of bile acid contents in mice liver, and the expression of relative proteins in TLR4/NF-κB pathway were determined. RESULTS: Compared with the model group, YCZFD treatment group significantly improved the hepatic necrosis and reduced the inflammatory cell infiltration. The plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid (TBA), and total bilirubin (TBIL) levels were significantly decreased, and the free and conjugated bile acids were both reduced. The expression of TLR4, IL-1β, IL-6, TNF-α, and MCP-1 were significantly decreased. CONCLUSION: YCZFD presents hepatoprotective effects on the hepatic injury in ANIT-induced intrahepatic cholestasis mice, which may be related to inhibiting the TLR4/NF-κB pathway, reducing the intrahepatic bile acids, and suppressing the inflammatory reaction.
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Objective To investigate the clinical effects of Yinchenzhufu decoction combined routine treatment in treatment of chronic cholestatic hepatitis. Methods 100 patients with chronic cholestatic hepatitis were selected from Pingyang Hospital of traditional Chinese medicine from February 2011 to November 2016. They were randomly divided into the study group (n=50) and the control group (n=50). The control group was given routine treatment, the study group on the basis of routine therapy was given modified Yinchenzhufu decoction. The clinical efficacy and adverse reactions (drug related) during the 8 weeks of continuous treatment were recorded in two groups of patients with chronic cholestatic hepatitis. Results After treatment, the total efficiency in the study group of patients with chronic cholestatic hepatitis was 90.00% and the control group was 72.00%, and there was significant difference between two group (P<0.05); there was no statistical significance in adverse reactions of treatment in the study group, compared with the control group. Conclusion The application of the basic method of treatment for chronic cholestatic hepatitis plus modified Yinchenzhufu decoction could significantly improve the clinical efficacy.
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Objective To investigate the clinical effects of Yinchenzhufu decoction combined routine treatment in treatment of chronic cholestatic hepatitis. Methods 100 patients with chronic cholestatic hepatitis were selected from Pingyang Hospital of traditional Chinese medicine from February 2011 to November 2016. They were randomly divided into the study group (n=50) and the control group (n=50). The control group was given routine treatment, the study group on the basis of routine therapy was given modified Yinchenzhufu decoction. The clinical efficacy and adverse reactions (drug related) during the 8 weeks of continuous treatment were recorded in two groups of patients with chronic cholestatic hepatitis. Results After treatment, the total efficiency in the study group of patients with chronic cholestatic hepatitis was 90.00% and the control group was 72.00%, and there was significant difference between two group (P<0.05); there was no statistical significance in adverse reactions of treatment in the study group, compared with the control group. Conclusion The application of the basic method of treatment for chronic cholestatic hepatitis plus modified Yinchenzhufu decoction could significantly improve the clinical efficacy.