3-4-di-o-caffeoylquinic-acid and Chemical-and-Drug-Induced-Liver-Injury

Although Laggera pterodonta as a folk medicine has been widely used for several centuries to ameliorate some inflammatory ailments as hepatitis in China, there have been no studies of the hepatoprotective and antioxidative effects of this plant. In this paper, the hepatoprotective effect of total phenolics from L. pterodonta (TPLP) against CCI4-, D-GalN-, TAA-, and t-BHP-induced injury was examined in primary cultured neonatal rat hepatocytes. TPLP inhibited the cellular leakage of two enzymes, hepatocyte ASAT and ALAT, caused by these chemicals and improved cell viability. Moreover, TPLP afforded much stronger protection than the reference drug silibinin. Meanwhile, DPPH and superoxide radicals scavenging activities of TPLP were also determined. The present investigation is the first to report chemical-induced injury model in primary cultured neonatal rat hepatocytes and provide evidence for the hepatoprotective and antioxidative effects of L. pterodonta. Neutralizing reactive oxygen species by nonenzymatic mechanisms may be one of main mechanisms of TPLP against chemical-induced hepatocyte injury. Furthermore, The total phenolic content of L. pterodonta and its main component type were quantified, and its principle components isochlorogenic acids were isolated and authenticated. These data support the folkloric uses of L. pterodonta in the treatment of hepatitis.

Topics: Alanine Transaminase; Animals; Animals, Newborn; Antioxidants; Aspartate Aminotransferases; Asteraceae; Cell Survival; Chemical and Drug Induced Liver Injury; Chlorogenic Acid; Drugs, Chinese Herbal; Free Radical Scavengers; Hepatocytes; Inhibitory Concentration 50; Monosaccharides; Quinic Acid; Rats; Rats, Sprague-Dawley; Superoxides; Xenobiotics

Pretreatment with a methanolic extract of Ligularia fischeri var. spiciformis (Compositae) herb inhibited hepatotoxicities caused by CCl4, D-galactosamine (GalN), alpha-naphthylisothiocyanate (ANIT), and DL-ethionine in rats. An ethyl acetate (EtOAc) extract fractionated from the methanolic extract showed a strong inhibitory effect. A major component, 3,4-dicaffeoylquinic acid (DCQA), isolated from the methanolic extract was examined for antihepatotoxicity. Pretreatment with DCQA (5 and 10 mg/kg, p.o.) significantly reduced serum aminotransferases (alanine and aspartate), sorbitol dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, and lactate dehydrogenase activities during CCl4- or GalN-induced hepatotoxicity, suggesting that DCQA is a major principle for the antihepatotoxic activity of L. fischeri var. spiciformis. DCQA also partially restored bile flow and reduced total bilirubin and cholic acid concentrations in rats with ANIT-induced cholestasis. Treatment with DCQA inhibited the increase in triglyceride, cholesterol, and total lipids in DL-ethionine-induced fatty liver. These results support the traditionally held belief that this plant can be used for the treatment of jaundice and hepatic failure.

Topics: 1-Naphthylisothiocyanate; Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Asteraceae; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Chlorogenic Acid; Ethionine; Fatty Liver; Galactosamine; gamma-Glutamyltransferase; L-Iditol 2-Dehydrogenase; L-Lactate Dehydrogenase; Lipids; Liver; Liver Diseases; Male; Plant Leaves; Rats; Rats, Sprague-Dawley