Baicalin inhibits TLR2/4 signaling pathway in rat brain following permanent cerebral ischemia.
Recent work from our laboratory demonstrated that baicalin attenuates inflammatory reaction and cerebral ischemia injury in rats. Toll-like receptor 2 and 4 (TLR2/4) and the downstream nuclear factor-kappa B (NF-κB) signaling pathway, which mediate the inflammatory reaction, are involved in the pathophysiological processes of cerebral ischemia. In this study, we investigated whether baicalin inhibits TLR2/4 signaling pathway in a rat model of permanent focal cerebral ischemia. Adult Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO). Baicalin was administered by intraperitoneally injected twice at 2 and 12 h after the onset of ischemia. Cerebral infarct area and infarct volume were measured 24 h after MCAO. Expression of TLR2/4, NF-κB, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were determined by RT-PCR or western blot. NO and PGE2 production in rat brain were measured 24 h after MCAO. Serum content of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were detected by ELISA. Baicalin reduced cerebral infarct area and infarct volume. Baicalin reduced the expression of TLR2/4 and NF-κB, decreased the expression and activity of iNOS and COX-2 in rat brain. Baicalin also attenuated the serum content of TNF-α and IL-1β. Our results suggest that baicalin inhibits the TLR2/4 signaling pathway in cerebral ischemia, which may be a mechanism underlying the baicalin's neuroprotection.
Tu
Xian-Kun
XK
Department of Neurosurgery, The Affiliated Union Hospital of Fujian Medical University, 29# Xinquan Road, Fuzhou, Fujian, 350001, China.
Yang
Wei-Zhong
WZ
Shi
Song-Sheng
SS
Chen
Ye
Y
Wang
Chun-Hua
CH
Chen
Chun-Mei
CM
Chen
Zhen
Z
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C498145:Rela protein, rat; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C038044:baicalin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat