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Oncotarget. 2017 Aug 4;8(49):84782-84797. doi: 10.18632/oncotarget.19891. eCollection 2017 Oct 17.

SHYCD induces APE1/Ref-1 subcellular localization to regulate the p53-apoptosis signaling pathway in the prevention and treatment of acute on chronic liver failure.

Author information

1
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
2
Gao Ming People's Hospital, Foshan, Guangdong, China.
3
Nanfang Hospital, Southern Medical University, Guangdong,Guangzhou, China.
4
Zhujiang Hospital of Southern Medical University, Guangdong, Guangzhou, China.

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.

KEYWORDS:

APE1/Ref-1; Pathology Section; San huang yin chi decoction; acute on chronic liver failure; apoptosis; p53

Conflict of interest statement

CONFLICTS OF INTEREST The authors are solely responsible for the statements made herein.The authors declare that they have no competing interests.

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