title: Mechanism underlying mitochondrial protection of asiatic acid against hepatotoxicity in mice.
abstract: Asiatic acid (AA) is one of the triterpenoid components of Terminalia catappa L., which has antioxidative, anti-inflammatory and hepatoprotective activity. This research focused on the mitochondrial protection of AA against acute liver injury induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN) in mice. It was found that pretreatment with 25, 50 or 100 mg kg(-1) AA significantly blocked the LPS + D-GalN-induced increase in both serum aspartate aminotransferase (sAST) and serum alanine aminotransferase (sALT) levels, which was confirmed by ultrastructural observation under an electron microscope, showing improved nuclear condensation, ameliorated mitochondrion proliferation and less lipid deposition. Meanwhile, different doses of AA could decrease both the transcription and the translation level of voltage-dependent anion channels (VDACs), the most important mitochondrial PTP component protein, and block the translocation of cytochrome c from mitochondria to cytosol. On the other hand, pre-incubation with 25, 50 and 100 microg mL(-1) AA inhibited the Ca(2+)-induced mitochondrial permeability transition (MPT), including mitochondrial swelling, membrane potential dissipation and releasing of matrix Ca(2+) in liver mitochondria separated from normal mice, indicating the direct role of AA on mitochondria. Collectively, the above data suggest that AA could protect liver from damage and the mechanism might be related to up-regulating mitochondrial VDACs and inhibiting the process of MPT.
authors.affiliation: Institute of Materia Medica, School of Medicine, Nanjing University, 22 Hankou Road, Nanjing 210093, P. R. China. jinggao@nju.edu.cn
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Xinhui
authors.initials: X
authors.lastname: Tang
authors.forename: Liya
authors.initials: L
authors.lastname: Pan
authors.forename: Feng
authors.initials: F
authors.lastname: Fang
authors.forename: Lizhi
authors.initials: L
authors.lastname: Xu
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002118:Calcium / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D045304:Cytochromes c / Q000378:metabolism; D005688:Galactosamine / Q000633:toxicity; D007473:Ion Channels / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D053978:Pentacyclic Triterpenes; D012333:RNA, Messenger / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D050994:Voltage-Dependent Anion Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D007473:Ion Channels; D008070:Lipopolysaccharides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D053978:Pentacyclic Triterpenes; D012333:RNA, Messenger; D014315:Triterpenes; D050994:Voltage-Dependent Anion Channels; D005688:Galactosamine; D045304:Cytochromes c; C017032:asiatic acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002118:Calcium