Abstract

Background & Aims: San huang yin chi decoction(SHYCD) is derived from the yin chen hao decoction, a well-known and canonical Chinese medicine formula from the “Treatise on Febrile Diseases”. Over the past decade, SHYCD has been used to treat and prevent the liver cirrhosis and liver failure. In the present study, we investigated the effects of SHYCD for acute on chronic liver failure(ACLF) and explored its potential mechanism. an ACLF rat model, which induced by carbon tetrachloride (CCl4) combined with D-galactosamine (D-GalN) and lipopolysaccharide(LPS), was used and confirmed by B-ultrasound analysis. Rats were randomly divided into control group, model group, SHYCD-H group, SHYCD-M group, SHYCD-L group, AGNHW group. Compared with the ACLF model group, High, medium, and low doses of SHYCD reduced ALT, AST, TBIL, NH3, IL-1β, IL-6, and TNFα expression levels in the serum, Shorten PT and INR time,and increased Fbg content in the whole blood, increased survival rate of the rats, improved liver pathological changes. APE1 / Ref-1 was mainly expressed in the nucleus, but the nucleus and cytoplasm were co-expressed after hepatocyte injury. SHYCD significantly downregulated APE1/Ref-1 expression in the cytoplasm. Increased APE1/Ref-1, Bcl-2, reduced p53, caspase-3, Bax, and Cyt-c in the total protein. Base on the results, we conclused that High, medium, and low doses of SHYCD could be applied in prevention and treatment of ACLF, and dose-dependent. The possible mechanism is to promote the APE1 / Ref-1 from the cytoplasm to the nuclear transfer, regulation of p53 apoptosis signal pathway prevention and treatment of ACLF.

Highlights

  • The pathogenesis of acute on chronic liver failure(ACLF) is complicated and the mortality is high [1].In recent years, many domestic studies have shown that the death rate of drug-induced hepatic failure has increased to 63.82% [2]

  • Our preliminary study demonstrated that Sanhuangyinchi decoction (SHYCD) reduced Aspartate transaminase (AST), ALT, and total bilirubin (TBIL) levels and cleaved caspase-3 protein expression [15]

  • Livers from the ACLF model group were enlarged with obvious ascites, lobular structural damage, and nodular liver morphology

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Summary

Introduction

The pathogenesis of acute on chronic liver failure(ACLF) is complicated and the mortality is high [1].In recent years, many domestic studies have shown that the death rate of drug-induced hepatic failure has increased to 63.82% [2]. The Chinese herbal medicine, QingganHuoxue, significantly improved liver function and increased survival rates in rats with www.impactjournals.com/oncotarget acute liver failure [6]. Traditional Chinese medicine has certain curatives effect on the prevention and treatment of severe hepatitis and ACLF. Compared with the ACLF model group, High, medium, and low doses of SHYCD reduced ALT, AST, TBIL, NH3, IL-1β, IL-6, and TNFα expression levels in the serum, Shorten PT and INR time,and increased Fbg content in the whole blood, increased survival rate of the rats, improved liver pathological changes. The possible mechanism is to promote the APE1 / Ref-1 from the cytoplasm to the nuclear transfer, regulation of p53 apoptosis signal pathway prevention and treatment of ACLF

Methods
Results
Conclusion

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