Effects of dahuangzhechong pills on cytokines and mitogen activated protein kinase activation in rats with hepatic fibrosis.
RELEVANCE TO ETHNOPHARMACOLOGY: Dahuangzhechong pill (DHZCP), a well-known and canonical Chinese medicine formula from "The Synopsis of Prescriptions of the Golden Chamber", is officially approved and recommended by Chinese association of integrative medicine for the prevention and treatment of hepatic fibrosis in China.


OBJECTIVE
To test the hypothesis that therapeutic effects of DHZCP on hepatic fibrosis are conferred by regulating cytokine profile through a mitogen activated protein kinase (MAPK) pathway.


METHODS
Hepatic fibrosis is inducted by carbon tetrachloride (CCl(4)) in rats which then were randomly divided into six groups: hepatic fibrosis model group, high dose DHZCP group, low dose DHZCP group, Fufang Biejia Ruangan Pian (FBRP) group, Colchicine group and control group. Pathological, immunohistochemical, multiplex immunoassay and protein expression studies (Western blotting) are performed.


RESULTS
DHZCP significantly decreases the levels of alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, laminin, type IV collagen and procollagen III, and reverses hepatic fibrosis in rat model. DHZCP also could reduce the expression of α-smooth muscle actin, and lower the serum level of tumor necrosis factor alpha (TNF-α) and interleukin 13 (IL-13). The expressions of phosphorylated p38 MAPK and extracellular signal-regulated kinase (ERK) are down-regulated, while no significant changes are found in phosphorylation of c-Jun N-terminal kinase (JNK).


CONCLUSIONS
DHZCP can alleviate hepatic fibrosis induced by CCl(4). The anti-fibrotic effects of DHZCP are conferred by decreasing the secretion of TNF-α and IL-13 through down-regulating p38 and ERK phosphorylation.
Cai
Hong Bing
HB
The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangdong, China.
Sun
Xue Gang
XG
Liu
Zhi Feng
ZF
Liu
Ya Wei
YW
Tang
Jing
J
Liu
Qiang
Q
Ji
Bao Min
BM
Song
Yu Hong
YH
Zhou
Ying Chun
YC
Yang
Ming Hui
MH
Lv
Zhi Ping
ZP
D000818:Animals; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D016207:Cytokines / Q000097:blood*; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007118:Immunoassay; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008111:Liver Function Tests; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
D015415:Biomarkers; D016207:Cytokines; C521634:Dahuang Zhechong pill; D004365:Drugs, Chinese Herbal; D020928:Mitogen-Activated Protein Kinases