An herbal formula, CGX, exerts hepatotherapeutic effects on dimethylnitrosamine-induced chronic liver injury model in rats.
OBJECTIVE
To evaluate the therapeutic effect of Chunggan extract (CGX), a modified traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine (DMN)-induced chronic liver injury model in rats.


METHODS
Liver injuries were induced in Wistar rats by injection of DMN (ip, 10 mg/mL per kg) for 3 consecutive days per week for 4 wk. The rats were administered with CGX (po, 100 or 200 mg/kg per day) or distilled water as a control daily for 4 wk starting from the 15(th) d of the DMN treatment. Biochemical parameters (serum albumin, bilirubin, ALP, AST and ALT), lipid peroxides, hydroxyproline, as well as histological changes in liver tissues were analyzed. In addition, gene expression of TNF-alpha, TGF-beta, TIMP-1, TIMP-2, PDGF-beta, and MMP-2, all of which are known to be associated with liver fibrosis, were analyzed using real-time PCR.


RESULTS
CGX administration restored the spleen weight to normal after having been increased by DMN treatment. Biochemical analysis of the serum demonstrated that CGX significantly decreased the serum level of ALP (P < 0.05), ALT (P < 0.01), and AST (P < 0.01) that had been elevated by DMN treatment. CGX administration moderately lowered lipid peroxide production and markedly lowered hydroxyproline generation caused by DMN treatment in accordance with histopathological examination. DMN treatment induced a highly up-regulated expression of TNF-alpha, TGF-beta, TIMP-1, TIMP-2, PDGF-beta, and MMP-2. Of these, the gene expression encoding PDGF-beta and MMP-2 was still further enhanced 2 wk after secession of the 4-wk DMN treatment, and was remarkably ameliorated by CGX administration.


CONCLUSIONS
CGX exhibits hepatotherapeutic proper-ties against chronic hepatocellular destruction and consequential liver fibrosis.
Shin
Jang-Woo
JW
East-West Cancer Center, Dunsan Oriental Hospital of Oriental medical College of Daejeon University, 1136 Dunsan-dong, Seo-gu, Daejeon 302-122, South Korea.
Son
Jin-Young
JY
Oh
Se-Mi
SM
Han
Seung-Hyun
SH
Wang
Jing-Hua
JH
Cho
Jung-Hyo
JH
Cho
Chong-Kwan
CK
Yoo
Hwa-Seung
HS
Lee
Yeon-Weol
YW
Lee
Myong-Min
MM
Hu
Xiao-Ping
XP
Son
Chang-Gue
CG
D000818:Animals; D004128:Dimethylnitrosamine; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D015870:Gene Expression; D006909:Hydroxyproline / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008103:Liver Cirrhosis / Q000517:prevention & control*; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000473:pathology
D004365:Drugs, Chinese Herbal; C000589484:chunggan; D004128:Dimethylnitrosamine; D006909:Hydroxyproline