Effects of tanshinone IIA on the hepatotoxicity and gene expression involved in alcoholic liver disease.
Tanshinone IIA is one of the most abundant constituents of the root of Salvia miltiorrhiza BUNGE which exerts antioxidant and anti-inflammatory actions in many experimental disease models. In the present study, we demonstrated that the standardized fraction of S. miltiorrhiza (Sm-SF) was able to protect RAW 264.7 cells from ethanol-and lipopolysaccharide (LPS)-induced production of superoxide radical, activation of NADPH oxidase and subsequently death of the cells. Among four main components of Sm-SF, tanshinone IIA was the most potent in protecting cells from LPS-and ethanol-induced cytotoxicity. LPS or ethanol induced the expression of CD14, iNOS, and SCD1 and decreased RXR-alpha, which was completely reversed by tanshinone IIA. In H4IIEC3 cells, 10 microM tanshinone IIA effectively blocked ethanol-induced fat accumulation as evidenced by Nile Red binding assay. These results indicate that tanshinone IIA may have potential to inhibit alcoholic liver disease by reducing LPS-and ethanol-induced Kupffer cell sensitization, inhibiting synthesis of reactive oxygen/nitrogen species, inhibiting fatty acid synthesis and stimulating fatty acid oxidation.
Yin
Hu-Quan
HQ
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Kim
Youn-Su
YS
Choi
You-Jin
YJ
Kim
Youn-Chul
YC
Sohn
Dong-Hwan
DH
Ryu
Shi-Yong
SY
Lee
Byung-Hoon
BH
D045784:Abietanes; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019610:Cytoprotection; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008108:Liver Diseases, Alcoholic / Q000378:metabolism; D051379:Mice; D010616:Phenanthrenes / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza
D045784:Abietanes; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D010616:Phenanthrenes; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C021751:tanshinone; D000431:Ethanol