Effects of Sho-saiko-to extract on liver fibrosis in relation to the changes in hydroxyproline and retinoid levels of the liver in rats.
To examine the effects of Sho-saiko-to extract on liver fibrosis, the drug was administered to rats with dimethylnitrosamine-induced liver-injury at various doses. Hydroxyproline and retinoid levels in the liver were measured as indicators of liver function. In liver-injured rats, the hydroxyproline level in the liver (957+/- 154nmol g(-1)) was about 4.16-times that found in normal liver (230+/-11 nmol g(-1)), but administration of Sho-saiko-to extract (0.75%, 1.5% or 3%) reduced the hydroxyproline level significantly (554+/-58, 356+/-51, 374+/-66nmol g(-1), P<0.01). Single administration of the active constituents of Sho-saiko-to extract, glycyrrhizin, baicalin or baicalein, decreased the hydroxyproline level significantly compared with the ordinary food group (P < 0.05), but the decrease was smaller compared with the Sho-saiko-to extract group. The liver retinoid level was higher in the Sho-saiko-to extract group than the ordinary food group and the value increased dose-dependently. A significant negative correlation, r=-0.814 (P<0.001) was detected between the hydroxyproline level and retinoid level in the liver of liver-injured rats. Significant negative correlations, r =-0.728 (P < 0.001) and r= -0.873 (P < 0.001), were also detected between the liver hydroxyproline level and the liver concentrations of the active constituents (glycyrretic acid, baicalin and baicalein) in the liver-injured rats. From these findings, it was considered that the liver concentrations of hydroxyproline and retinoid as well as the active constituents were involved in the improvement of liver fibrosis in the liver-injured rats administered Sho-saiko-to extract. Administration of Sho-saiko-to extract inhibited collagen production while an increase in retinoid level inhibited activation of Ito cells leading to inhibition and prevention of liver fibrosis.
Ono
M
M
Department of Pharmacy, Kochi Medical School Hospital, Japan.
Miyamura
M
M
Kyotani
S
S
Saibara
T
T
Ohnishi
S
S
Nishioka
Y
Y
D000284:Administration, Oral; D000818:Animals; D004128:Dimethylnitrosamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000627:therapeutic use*; D006909:Hydroxyproline / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012176:Retinoids / Q000378:metabolism*
D004365:Drugs, Chinese Herbal; D000960:Hypolipidemic Agents; D012176:Retinoids; C018142:saiko-keishi-to; D004128:Dimethylnitrosamine; D006909:Hydroxyproline