A number of recent research studies have been done on different species of the plants of the genus Phyllanthus. The plants are widely distributed in most tropical and subtropical countries and have long been used for the treatment of liver diseases in China and India. / Hepatitis B virus (HBV) is a major pathogen of human viral hepatitis. It has been estimated that 350 million people are chronic carriers of HBV throughout the world. Increasing evidence indicates that persistent viral infection of the liver is associated with cirrhosis and hepatocellular carcinoma. Hepatitis B virus belongs to a family of DNA viruses called hepadnaviruses. The current treatments of HBV infection with interferon or lamivudine have several disadvantages, and there appears to be much room for improvement in terms of medical treatment. / My project research focuses on two poorly characterized Indian Phyllanthus species called Phyllanthus nanus ("PN") and Phyllanthus niruri ("PI"). In my studies, random amplified polymorphic DNA ("RAPD") technique and high performance liquid chromatography ("HPLC") fingerprinting were used to authenticate different species of Phyllanthus. Both aqueous and ethanolic extracts of PN and PI were prepared to study their cytotoxicity in hepatoma cell lines. The effect of these extracts on hepatitis B virus was also examined in the HBV-genome integrated cell lines - PLC/PRF/5 (Alexander) and HepG2 2.2.15. Microparticle enzyme immunoassay ("MEIA") and enzyme-linked immunosorbent assay were used to measure the amount of hepatitis B surface antigen ("HBsAg") and hepatitis B e antigen ("HBeAg") secretion from the cell lines. RT-PCR was used to detect the change in HBsAg mRNA's expression level in the drug-treated cell lines. Real-time PCR was also employed to examine the effect of drug treatment on the level of HBV DNA replication and the amount of virions secreted into the medium. The experimental results showed that both the aqueous and ethanolic extracts of PN and PI exerted suppressive effect on HBsAg secretion and HBsAg mRNA level. The PN and PI ethanolic extracts also showed mild suppression of viral replication in vitro. The ethanolic extract of PN seemed to be more potent in suppressing HBV than the other extracts tested. (Abstract shortened by UMI.) / Lam Wai Yip. / "June 2005." / Advisers: Mary Waye; Vincent Ooi. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3594. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 217-234). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

Immortalized normal hepatocytes AML-12 or primary hepatocytes were cultured in control, and the methionine and choline deficient (MCD) culture medium in the presence or absence of Phyllanthus urinaria for 24 hours. Hepatocyte triglyceride contents, release of alanine aminotransferase, lipoperoxides and reactive oxygen species production were determined in the cell culture study. Age-matched wild-type C57BL/6 and diabetes db/db mice were fed control or MCD diet for 10 days with or without Phyllanthus urinaria. The levels of Hepatic steatosis, necroinflammation, triglycerides and oxidative stress were investigated. Hepatic expression of inflammatory factors and lipid regulatory mediators were assayed. The results demonstrated that Phyllanthus urinaria reduced steatosis and alanine aminotransferase (ALT) levels in culture of hepatocytes in a dose-dependent manner. Phyllanthus urinaria protected the livers against MCD-induced hepatic fat accumulation and steatohepatitis in mice. This effect was associated with repressed levels of hepatic lipid peroxides, reduced expression of cytochrome P450 (CYP) 2e1, pro-inflammatory tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), dampened activation of inflammatory C-jun N-teuninal kinase (JNK) and nuclear factor kappaB (NF-kappaB), increased expression of lipolytic Cyp4a10 and suppressed transcriptional activity of lipogenic CCAAT/enhancer binding protein beta (C/EBPbeta). Hepatic acyl co-enzyme A oxidase (ACO) that regulated hepatic beta-oxidation of fatty acid and other lipid regulators were not affected by Phyllanthus urinaria. / Non-alcoholic steatohepatitis (NASH) results from excessive accumulation of hepatic fat (steatosis) and oxidative stress. Therefore, inhibition of fatty acid cytotoxicity and liver inflammtary change is an important goal in the treatment of NASH. Phyllanthus urinaria, a herbal medicine, has been reported to have potential anti-oxidant property. We tested the effects of Phyllanthus urinaria on nutritional steatohepatitis both in vitro and in vivo, and determined the mechanism of its action. / Our study indicated that Phyllanthus urinaria effectively prevented MCD-induced steatohepatitis. This effect were probably mediated through dampening oxidative stress, ameliorating inflammation and decreasing lipid accumulation. Phyllanthus urinaria deserves further evaluation for its potential therapeutic effect on NASH in humans. / Shen, Bo. / Adviser: Henry Ly Chan. / Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: . / Thesis submitted in: November 2008. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 128-142). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.