195 Effect of Phyllanthus amarus Schum. & Thonn. and Its Protective Mechanism on Paracetamol Hepatotoxicity in Rats Malinee Wongnawa, Peerarat Thaina and Nisita Bumrungwong Department of Pharmacology Faculty of Science Prince of Songkla University Hat-Yai, 90112 Thailand Anupong Nitiruangjarat and Apichat Muso Department of Pathology Faculty of Medicine Prince of Songkla University Hat-Yai, 90112 Thailand Vipavadee Prasartthong Department of Biomedical Science Faculty of Medicine Prince of Songkla University Hat-Yai, 90112 Thailand Keywords: antioxidant activity, cytochrome P450, Luk-tai-bai, paracetamol metabolism, medicinal plant, glutathione Abstract The hepatoprotective effect of Phyllanthus amarus Schum. & Thonn. was studied on paracetamol hepatotoxicity in rats by monitoring serum transaminase (SGOT and SGPT), alkaline phosphatase (ALP) and bilirubin as well as by histopathological examination of liver. Furthermore, the hepatoprotective mechanisms were investigated by determining the amount of paracetamol and its metabolites (glucuronide, sulfate, cysteine and mercapturic acid conjugates) in urine and pentobarbital-induced sleeping time to indicate the inhibition on cytochrome P450. The involvement of glutathione was evaluated by determining hepatic reduced glutathione. Its antioxidant activity was estimated by DPPH (1,1-diphenyl-2- picrylhydrazyl) assay. Hot water extracts of P. amarus (0.8, 1.6 or 3.2 g/kg) were orally administered b.i.d. for 7 d prior, 2 d after, or 7 d prior and 2 d after single oral dose of paracetamol (3 g/kg). The results showed that the extract at 1.6 and 3.2 g/kg decreased the paracetamol-induced hepatotoxicity as indicated by the decrease in SGOT and SGPT, bilirubin and histopathological score while the ALP did not change. It is evident that the hepatoprotective mechanism of this plant was neither related to inhibition on cytochrome P450, nor induction on sulfate and glucuronide conjugation pathways of paracetamol, but partly due to the antioxidant activity and the protective effect on the decrease of hepatic reduced glutathione. These results support the value of P. amarus, which has been used in folk medicine for the treatment of toxic liver diseases. INTRODUCTION Luk-tai-bai is the Thai common name for Phyllanthus amarus Schum. & Thonn. (Euphorbiaceae). It is a small herb used in Thai folk medicine for treatment of fever, jaundice, ascites, hemorrhoid and diabetes (Pongboonrod, 1979). Apart from these medicinal uses, there are reports showing anti-hepatitis B virus effect (Thyagarajan et al., 1988), hypoglycemic effect (Moshi et al., 1997), antinociceptive effect (Santos et al., 2000) and the increase in life span of rats with hepatocellular carcinoma (Rajeshkumar and Kuttan, 2000). Paracetamol is a popular analgesic and antipyretic agent. Its antipyretic and analgesic properties have been widely abused. Indiscriminate ingestion can lead to accidental poisoning and potentially lethal hepatotoxicity (Prescott et al., 1971). Lignans from luk-tai-bai (phyllanthin and hypophyllanthin) showed protective Proc. WOCMAP III, Vol.6: Traditional Medicine & Nutraceuticals Eds. U.R. Palaniswamy, L.E. Craker and Z.E. Gardner Acta Hort. 680, ISHS 2005