title: Liv.52 regulates ethanol induced PPARgamma and TNF alpha expression in HepG2 cells.
abstract: Liver is a prime target of alcohol-induced damage by inducing inflammatory cytokines especially tumor necrosis factor alpha (TNFalpha). Activator of peroxisome proliferator activator receptor gamma (PPARgamma) is protective against alcohol-induced liver injury in animals. Liv.52, one of the major herbal hepatoprotective drugs, is shown to protect the liver from toxicity and is considered to be an effective hepatoprotective agent. However, the signal pathway involved in the Liv.52-induced hepatoprotection is not understood well especially in the case of cultured liver cells treated with ethanol. Hence, the study was aimed at determining whether ethanol and Liv.52 could modulate PPARgamma and TNFalpha induction in human hepatoma cells, HepG2. The present study with RT-PCR and confocal microscopy experiments showed that ethanol (100 mM) induced suppression of PPARgamma expression in HepG2 cells. The ethanol-induced PPARgamma suppression was abrogated by Liv.52. Moreover, Liv.52 also induced upregulation of PPARgamma mRNA in liver cells as compared to the untreated cells. Further, 100 mM ethanol has also induced TNFalpha gene expression in HepG2 cells and interestingly Liv.52 abolished ethanol-induced TNFalpha. The study also shows that Liv.52 alone downregulated TNFalpha expression in HepG2 cells. Taken together, these findings suggest that Liv.52 is capable of attenuating ethanol-induced expression of TNFalpha and abrogating ethanol-induced suppression of PPARgamma in liver cells. These results indicate that Liv.52-induced PPARgamma expression and concomitant suppression of ethanol-induced elevation of TNFalpha in HepG2 cells suggest the immunomodulatory and hepatoprotective nature of Liv.52.
authors.affiliation: Research and Development, Himalaya Drug Company, Makali, Bangalore, India.
authors.forename: Shankar K
authors.initials: SK
authors.lastname: Mitra
authors.forename: Sandeep Ravi
authors.initials: SR
authors.lastname: Varma
authors.forename: Ashok
authors.initials: A
authors.lastname: Godavarthi
authors.forename: Krishna S
authors.initials: KS
authors.lastname: Nandakumar
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004338:Drug Combinations; D000431:Ethanol / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018613:Microscopy, Confocal; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D047495:PPAR gamma; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; C002614:Liv 52