Effect of baicalin on toll-like receptor 4-mediated ischemia/reperfusion inflammatory responses in alcoholic fatty liver condition.
Alcoholic fatty liver is susceptible to secondary stresses such as ischemia/reperfusion (I/R). Baicalin is an active component extracted from Scutellaria baicalensis, which is widely used in herbal preparations for treatment of hepatic diseases and inflammatory disorders. This study evaluated the potential beneficial effect of baicalin on I/R injury in alcoholic fatty liver. Rats were fed an alcohol liquid diet or a control isocaloric diet for 5 weeks, and then subjected to 60 min of hepatic ischemia and 5h of reperfusion. Baicalin (200mg/kg) was intraperitoneally administered 24 and 1h before ischemia. After reperfusion, baicalin attenuated the increases in serum alanine aminotransferase activity, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels in alcoholic fatty liver. The increased levels of TNF-α and IL-6 mRNA expression and inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expressions increased after reperfusion, which were higher in ethanol-fed animals, were attenuated by baicalin. In ethanol-fed animals, baicalin attenuated the increases in toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 protein expressions and the nuclear translocation of NF-κB after reperfusion. In conclusion, our findings suggest that baicalin ameliorates I/R-induced hepatocellular damage by suppressing TLR4-mediated inflammatory responses in alcoholic fatty liver.
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Seok-Joo
SJ
Kim
Sun-Mee
SM
Lee
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics; D005235:Fatty Liver, Alcoholic / Q000150:complications*; D005419:Flavonoids / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology*; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D015850:Interleukin-6; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C038044:baicalin; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000410:Alanine Transaminase