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Phyllanthus urinaria ameliorates the severity of nutritional steatohepatitis both in vitro and in vivo
Author(s) -
Shen Bo,
Yu Jun,
Wang Shiyan,
Chu Eagle S.H.,
Wong V.W.S.,
Zhou Xin,
Lin Ge,
Sung Joseph J.Y.,
Chan Henry L.Y.
Publication year - 2008
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.22039
Subject(s) - steatohepatitis , in vivo , in vitro , medicine , phyllanthus , chemistry , traditional medicine , biology , fatty liver , biochemistry , microbiology and biotechnology , disease
Abstract Hepatic oxidative stress plays a critical role in metabolic forms of steatohepatitis. Phyllanthus urinaria, an herbal medicine, has been reported to have potential antioxidant properties. We tested the effects of P. urinaria on nutritional steatohepatitis both in vitro and in vivo . Immortalized normal hepatocytes (AML‐12) or primary hepatocytes were exposed to control, the methionine‐and‐choline‐deficient (MCD) culture medium, in the presence or absence of P. urinaria for 24 hours. Hepatocyte triglyceride, release of alanine aminotransferase, lipoperoxides, and reactive oxygen species production were determined. Age‐matched C57BL/6 and db/db mice were fed control or MCD diet for 10 days with or without P. urinaria . Hepatic steatosis, necroinflammation, triglycerides, and lipid peroxide levels were determined. Hepatic expression of inflammatory factors and lipid regulatory mediators were assayed. P. urinaria reduced steatosis and alanine aminotransferase (ALT) levels in culture of hepatocytes in a dose‐dependent manner. Phyllanthus prevented MCD‐induced hepatic fat accumulation and steatohepatitis in mice. This effect was associated with repressed levels of hepatic lipid peroxides, reduced expression of cytochrome P450‐2E1, pro‐inflammatory tumor necrosis factor alpha, interleukin‐6, dampened activation of inflammatory c‐Jun N‐terminal kinase (JNK) and nuclear factor kappa B (NF‐κB), increased expression of lipolytic cytochrome P450 (Cyp4a10), and suppressed transcriptional activity of lipogenic CCAAT/enhancer binding protein β (C/EBPβ). Hepatic acyl co‐enzyme A oxidase that regulated hepatic beta‐oxidation of fatty acid and other lipid regulators were not affected by P. urinaria . In conclusion, P. urinaria effectively alleviated the steatohepatitis induced by the MCD, probably through dampening oxidative stress, ameliorating inflammation, and decreasing lipid accumulation. (H EPATOLOGY 2008.)