Therapeutic effects of SMND-309, a new metabolite of salvianolic acid B, on experimental liver fibrosis.
(2E)-2-{6-[(E)-2-carboxylvinyl]-2,3-dihydroxyphenyl}-3-(3,4-dihydroxyphenyl) propenoic acid, a novel compound designated SMND-309, is a new metabolite of salvianolic acid B. The present study was carried out to investigate the effects of SMND-309 on experimental liver fibrosis in rats induced by subcutaneous injection of carbon tetrachloride and explore its possible mechanisms on the basis of biochemical, histopathologic and immunohistochemical studies. The results showed that intragastrical treatment with SMND-309 ameliorated liver function and decreased the elevation of serum hyaluronic acid, laminin, procollagen type III levels and hydroxyproline content in liver tissue. It also decreased the elevation in the malondialdehyde level and restored the decrease in superoxide dismutase and glutathione peroxidase activities. Upon histopathologic examination, the SMND-309-treated rats reduced the liver damage and the liver fibrosis grade. Moreover, the results of immunohistochemical examination showed that SMND-309 powerfully down-regulated the expression of connective tissue growth factor (CTGF) rather than transforming growth factor-beta1 (TGF-β1) in serum and liver. Meanwhile, SMND-309 exhibits significantly higher potency compared with salvianolic acid B (Sal B) at the same dose. The antifibrotic mechanisms of SMND-309 might be associated with its ability to suppress the expression of CTGF as well as scavenge lipid peroxidation products and increase endogenous antioxidant enzyme activity.
Hou
Jian
J
School of Pharmacy, Yantai University, Yantai, Shandong 264005, PR China.
Tian
Jingwei
J
Jiang
Wanglin
W
Gao
Yubai
Y
Fu
Fenghua
F
D000818:Animals; D001572:Benzofurans / Q000378:metabolism*; D002109:Caffeic Acids / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D024061:Collagen Type III / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism; D053630:Depsides
D001572:Benzofurans; D002109:Caffeic Acids; D024061:Collagen Type III; D055513:Connective Tissue Growth Factor; D005979:Glutathione Peroxidase; D006820:Hyaluronic Acid; D006909:Hydroxyproline; D007797:Laminin; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D053773:Transforming Growth Factor beta1; C539487:2-(6-(2-carboxyvinyl)-2,3-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)acrylic acid; C526316:CCN2 protein, rat; C076944:salvianolic acid B; D053630:Depsides