title: Hepatoprotective effect of cryptotanshinone from Salvia miltiorrhiza in D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure.
abstract: Cryptotanshinone from Salvia miltiorrhiza Bunge was investigated for hepatoprotective effects in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Cryptotanshinone (20 or 40 mg/kg) was orally administered 12 and 1h prior to GalN (700 mg/kg)/LPS (10 μg/kg) injection. The increased mortality and TNF-α levels by GalN/LPS were declined by cryptotanshinone pretreatment. In addition, cryptotanshinone attenuated GalN/LPS-induced apoptosis, characterized by the blockade of caspase-3, -8, and -9 activation, as well as the release of cytochrome c from the mitochondria. In addition, cryptotanshinone significantly suppressed JNK, ERK and p38 phosphorylation induced by GalN/LPS, and phosphorylation of TAK1 as well. Furthermore, cryptotanshinone significantly inhibited the activation of NF-κB and suppressed the production of proinflammatory cytokines. These findings suggested that hepatoprotective effect of cryptotanshinone is likely associated with its anti-apoptotic activity and the down-regulation of MAPKs and NF-κB associated at least in part with suppressing TAK1 phosphorylation.
authors.affiliation: Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Bai
authors.affiliation: Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jin
authors.affiliation: Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China. Electronic address: lihualian@ymail.com.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Lian
authors.affiliation: Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China. Electronic address: jxnanybu@gmail.com.
authors.forename: Ji-Xing
authors.initials: JX
authors.lastname: Nan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D020169:Caspases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D045304:Cytochromes c / Q000378:metabolism; D005688:Galactosamine; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017114:Liver Failure, Acute / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000893:Anti-Inflammatory Agents; D001219:Aspartate Aminotransferases; D020169:Caspases; D045304:Cytochromes c; D005688:Galactosamine; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D010616:Phenanthrenes; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D000099151:MAP Kinase Kinase Kinase 7; C037886:cryptotanshinone
keywords: ALT; AST; Apoptosis; Cryptotanshinone; ERK; FHF; Fulminant hepatic failure; GAPDH; GalN; IL-1; JNK; LPS; MAPK; NF-κB; Salvia miltiorrhiza; TAK1; TGF-β-activated kinase 1; TNF-α; alanine aminotransferase; aspartate aminotransferase; c-Jun N-terminal kinase; d-galactosamine; extracellular signal regulated kinase; fulminant hepatic failure; glyceraldehydes-3-phosphate dehydrogenase; interleukin-1; lipopolysaccharide; mitogen-activated protein kinases; nuclear factor-κB; tumor necrosis factor-α