PMID- 18420187 OWN - NLM STAT- MEDLINE DCOM- 20080825 LR - 20161124 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 587 IP - 1-3 DP - 2008 Jun 10 TI - Protective effect of baicalin against lipopolysaccharide/D-galactosamine-induced liver injury in mice by up-regulation of heme oxygenase-1. PG - 302-8 LID - 10.1016/j.ejphar.2008.02.081 [doi] AB - Baicalin, a traditional anti-inflammatory drug, has been found to protect against liver injury in several experimental animal hepatitis models; however, the mechanisms underlying the hepatoprotective properties of baicalin are poorly understood. In the present study,we investigated the effects of baicalin on the acute liver injury in mice induced by Lipopolysaccharide/D-galactosamine (LPS/D-GalN). Baicalin (50, 150, and 300 mg/kg) was pretreated intraperitoneally (i.p.) at 2, 24, and 48 h respectively before LPS/D-GalN injected in mice. The mortality, hepatic tissue histology, hepatic tissue Tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO), plasma levels of TNF-alpha and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Besides, western blotting analyses of nuclear factor kappa B (NF-kappaB) translocation and Heme oxygenase-1(HO-1) protein expression, as well as HO-1 activity were determined. The results showed that baicalin protected against LPS/D-GalN-induced liver injury, including dose-dependent alleviation of mortality and hepatic pathological damage, decrease of ALT/AST release and the rise of MPO. Baicalin reduced nuclear translocation of NF-kappa B, TNF-alpha mRNA and protein levels in hepatic tissues and plasma levels of TNF-alpha induced by LPS/D-GalN. Moreover, baicalin dose-dependently increased HO-1 protein expression and activity. Further, inhibition of HO-1 activity significantly reversed the protective effect of baicalin against LPS/D-GalN-induced liver injury. These results suggest that baicalin can effectively prevent LPS/D-GalN-induced liver injury by inhibition of NF-kappa B activity to reduce TNF-alpha production and the underlying mechanism may be related to up-regulation of HO-1 protein and activity. FAU - Wan, Jing-Yuan AU - Wan JY AD - Department of Pharmacology, Chongqing Medical University, Chongqing 400016, PR China. jywan@cqmu.edu.cn FAU - Gong, Xia AU - Gong X FAU - Zhang, Li AU - Zhang L FAU - Li, Hong-Zhong AU - Li HZ FAU - Zhou, Yu-Fan AU - Zhou YF FAU - Zhou, Qi-Xin AU - Zhou QX LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080307 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Flavonoids) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 347Q89U4M5 (baicalin) RN - 7535-00-4 (Galactosamine) RN - EC 1.11.1.7 (Peroxidase) RN - EC 1.14.14.18 (Heme Oxygenase-1) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology MH - Blotting, Western MH - Chemical and Drug Induced Liver Injury/enzymology/pathology/*prevention & control MH - Flavonoids/*pharmacology MH - Galactosamine/*antagonists & inhibitors/toxicity MH - Heme Oxygenase-1/*metabolism MH - Lipopolysaccharides/*antagonists & inhibitors/toxicity MH - Liver/enzymology/pathology MH - Mice MH - Mice, Inbred BALB C MH - Peroxidase/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/metabolism MH - Up-Regulation/drug effects EDAT- 2008/04/19 09:00 MHDA- 2008/08/30 09:00 CRDT- 2008/04/19 09:00 PHST- 2007/07/30 00:00 [received] PHST- 2008/01/26 00:00 [revised] PHST- 2008/02/28 00:00 [accepted] PHST- 2008/04/19 09:00 [pubmed] PHST- 2008/08/30 09:00 [medline] PHST- 2008/04/19 09:00 [entrez] AID - S0014-2999(08)00268-9 [pii] AID - 10.1016/j.ejphar.2008.02.081 [doi] PST - ppublish SO - Eur J Pharmacol. 2008 Jun 10;587(1-3):302-8. doi: 10.1016/j.ejphar.2008.02.081. Epub 2008 Mar 7.