[Inhibiting effects of denshensu, baicalin, astragalus and Panax notoginseng saponins on hepatic fibrosis and their possible mechanisms].
OBJECTIVE
To study the anti-fibrotic effects of danshensu, baicalin, astragalus and Panax notoginseng saponins (PNS) and their possible mechanisms.


METHODS
The four Chinese herb products mentioned above were given intraperitoneally to experimental rats with hepatic fibrosis. Colchicine was administered to a control group. Comparisons were made in four aspects: (1) Degrees of liver fibrosis; (2) Serum levels of hyaluronic acid (HA) and type IV collagen (CIV), using radioimmunoassay; (3) Densities of malondialdehyde (MDA), superoxide dismutase (SOD) and hydroxyproline (Hyp), using chromatometry, to detect the expression of tissue inhibitors of matrix metalloproteinase-1 (TIMP-1), matrix metalloproteinase-1(MMP-1) and transforming growth factor beta 1 (TGF beta 1) in liver tissues, using immunohistochemical techniques; and (4) For hepatic stellate cells (HSCs): proliferation using MMT calorimetric assay, the cell cycles using flow cytometry, apoptosis using AO/EB fluorescence staining and type I and type III collagens using immunocytochemical stainings.


RESULTS
(1) Compared with the model group, the serum levels of HA and CIV decreased significantly in all four drug-treated groups, especially in the danshensu-treated group. Astragalus and baicalin had better effects over PNS (P<0.05 or 0.01). (2) In contrast to the model group, all four drugs dramatically reduced the amount of Hyp and MDA, increased SOD activity and reduced the degrees of liver fibrosis and the expressions of TIMP-1 and TGFbeta1 in liver tissues (P<0.05 or 0.01). Danshensu had the best effect, astragalus and baicalin had similar effects which were stronger than PNS. (3) All four drugs inhibited HSCs proliferation, induced HSCs apoptosis and decreased type I, III collagen synthesis of HSC.


CONCLUSIONS
The four drugs could minimize the hepatic fibrosis of rats in different degrees. Danshensu had the best effect, astragalus and baicalin had similar effects. The possible mechanisms of these effects might be related to inhibiting actions on activation and proliferation, promoting apoptosis and lowering the expression of type I and type III collagen of HSCs by down-regulating the expression of TGFbeta1; the decrease in the amount of MDA and the increase of SOD activity; and the reduction of extracellular matrix by down-regulation of TIMP-1/MMP-1.
Li
Xin
X
Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Peng
Xiao-dong
XD
Zhang
Wen-li
WL
Dai
Li-li
LL
D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry; D027885:Astragalus propinquus; D024061:Collagen Type III / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D005419:Flavonoids / Q000494:pharmacology*; D036145:Ginsenosides / Q000494:pharmacology*; D055166:Hepatic Stellate Cells; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy*; D008297:Male; D053723:Panax notoginseng / Q000737:chemistry; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D024061:Collagen Type III; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D036145:Ginsenosides; D010936:Plant Extracts; C038044:baicalin