Protective effect of naringenin in experimental ischemic stroke: down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.
Inflammatory damage plays a pivotal, mainly detrimental role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Naringenin (NG) has gained growing appreciation for its beneficial biological effects through its anti-inflammatory property. Whether this protective effect applies to cerebral ischemic injury, we therefore investigate the potential neuroprotective role of NG and the underlying mechanisms. Focal cerebral ischemia in male Sprague-Dawley rats was induced by permanent middle cerebral artery occlusion (pMCAO) and NG was pre-administered intragastrically once daily for four consecutive days before surgery. Neurological deficit, brain water content and infarct volume were measured at 24 h after stroke. Immunohistochemistry, Western blot and RT-qPCR were used to explore the anti-inflammatory potential of NG in the regulation of NOD2, RIP2 and NF-κB in ischemic cerebral cortex. Additionally, the activities of MMP-9 and claudin-5 were analyzed to detect NG's influence on blood-brain barrier. Compared with pMCAO and Vehicle groups, NG noticeably improved neurological deficit, decreased infarct volume and edema at 24 h after ischemic insult. Consistent with these results, our data also indicated that NG significantly downregulated the expression of NOD2, RIP2, NF-κB and MMP-9, and upregulated the expression of claudin-5 (P < 0.05). The results provided a neuroprotective profile of NG in cerebral ischemia, this effect was likely exerted by down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.
Department of Neurology, Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, Hebei, People's Republic of China.
Xue
X
Bai
Xiangjian
X
Zhang
Linyu
L
Chen
Jian
J
Zhang
Lan
L
Zhang
Xumeng
X
Zhao
Ting
T
Zhao
Yuan
Y
Zhao
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D062507:Claudin-5 / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000378:metabolism; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D062507:Claudin-5; C491510:Cldn5 protein, rat; D044950:Flavanones; D016328:NF-kappa B; C512493:NOD2 protein, rat; D018696:Neuroprotective Agents; D053473:Nod2 Signaling Adaptor Protein; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; C005273:naringenin