title: Curcumin attenuates ischemia-like injury induced IL-1β elevation in brain microvascular endothelial cells via inhibiting MAPK pathways and nuclear factor-κB activation.
abstract: Inflammatory reactions play a key role in the cerebral injury after stroke or other ischemic brain diseases. Curcumin, which is extracted from herb turmeric, has been reported to have anti-inflammatory effects. The present study was aimed to investigate the anti-inflammatory effects of curcumin on oxygen-glucose deprivation (OGD) injured brain microvascular endothelial cells (BMECs). Rat BMECs were used and the results showed that OGD induced a significant elevation of the leakage of lactate dehydrogenase and the secretion of the proinflammation cytokine, IL-1β. Activation of p38, JNK MAPKs, and NF-κB in BMECs was also observed after OGD. The treatment of curcumin (20 μM) inhibited the increased production of IL-1β both at the protein and mRNA levels. The increased phosphorylation of p38 and JNK induced by OGD was decreased under the treatment of curcumin, whereas the p38 inhibitor, SB203580, significantly inhibited OGD-induced IL-1β production, but the JNK inhibitor, SP600125, failed to do so. These results suggest that the inhibition of IL-1β by curcumin may dependent on the p38 signaling pathway. The OGD-induced IL-1β production was also inhibited by the NF-κB inhibitor, and curcumin suppressed OGD-induced NF-κB activation. Furthermore, the NF-κB activation was attenuated by the SB203580, indicating that NF-κB activation was dependent on p38 signaling pathway. The present study suggests that curcumin displays an anti-inflammatory effect on OGD-injured BMECs via down-regulating of MAPK and NF-κB signaling pathways and might have therapeutic potential for the ischemic brain diseases.
authors.affiliation: Department of Human Anatomy, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Hua-Jiang
authors.initials: HJ
authors.lastname: Dong
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Shang
authors.forename: Ding-Wei
authors.initials: DW
authors.lastname: Peng
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Peng-Xiao
authors.initials: PX
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Zhan
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D055806:Microvessels / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007093:Imidazoles; D053583:Interleukin-1beta; D016328:NF-kappa B; D011725:Pyridines; D007770:L-Lactate Dehydrogenase; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin; D005947:Glucose; C093642:SB 203580