Investigations of Free Anthraquinones from Rhubarb Against alpha-Naphthylisothiocyanate-induced Cholestatic Liver Injury in Rats

The protective effects of anthraquinones from Rhubarb, a Chinese herbal medicine, consisting of the root and rhizome of Rheum palmatum L., R. tanguticum Maxim. Ex Balf., or R. officinale Baill. (family Polygonaceae) were investigated and compared in rats with liver injury induced by alpha-naphthylisothiocyanate. alpha-Naphthylisothiocyanate was given intragastrically in rats, liver injury with cholestasis developed within 36 hrs, as indicated by characteristic serum levels of glutamate-pyruvate transaminase, glutamic oxaloacetic transaminase, total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyltransferase and total bile acid. The intragastrical administration of rhein, aloe-emodin and physione to alpha-naphthylisothiocyanate-treated rats reduced significantly the serum level of both glutamate-pyruvate transaminase, glutamic oxaloacetic transaminase and the serum total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyltransferase and total bile acid. For all hepatic biochemical markers and cholestasis index, rhein was most efficient. By comparison, the administration of emodin and chrysophanol did not reduce the serum levels of hepatic enzymes glutamate-pyruvate transaminase and glutamic oxaloacetic transaminase but decreased the levels of serum total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyltransferase, and total bile acid, showing their partial protective effects on cholestatic liver injury. The liver in alpha-naphthylisothiocyanate-treated rats showed cholangiolitic hepatitis characterized by intrahepatic cholestasis, necrosis of hepatocytes and biliary epithelial cells and bile obstruction. The concurrent intragastrical administration of rhein reduced the severity of all morphological alteration, especially the neutrophil infiltration and sinusoid congestion. Rhein, aloe-emodin, and physione all exhibited protective effects on hepatocytes and cholangiocytes against alpha-naphthylisothiocyanate-induced damage, whereas emodin and chrystophanol provided partial protection.