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Curcumin inhibits TLR2/4-NF-κB signaling pathway and attenuates brain damage in permanent focal cerebral ischemia in rats.
Inflammation. 2014 Oct; 37(5):1544-51.I

Abstract

Toll-like receptors 2 and 4 (TLR2/4) and the downstream nuclear factor-kappa B (NF-κB) signaling pathway, which mediate the inflammatory reaction in cerebral ischemia, were demonstrated to be involved in the extension of cerebral infarction and the aggravation of ischemic brain damage. Reports showed that curcumin provides neuroprotection against ischemic brain damage. In this study, we investigated whether curcumin inhibits the activation of TLR2/4-NF-κB signaling pathway in rats of permanent focal cerebral ischemia. Adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO). Curcumin was administered by intraperitoneal injection twice at 2 and 12 h after the onset of ischemia. Neurological deficit scores, cerebral infarct size, morphological characteristic, and cerebral water content were measured after 24 h of pMCAO. The enzymatic activity of myeloperoxidase (MPO) was assessed after 24 h of pMCAO. Expression of TLR2 and TLR4 in ischemic brain was determined by western blot. Expression of NF-κB p65 in ischemic brain was detected by immunohistochemistry and western blot. The release of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in blood was examined by ELISA. Curcumin significantly reduced neurological deficit scores, cerebral infarct size, neuronal damage, cerebral water content, and MPO activity. It also inhibited the expression of TLR2/4 and decreased the expression and activity of NF-κB p65 in rat brain. In addition, curcumin attenuated the release of TNF-α and IL-1β in blood. Our results suggest that curcumin reduces inflammatory reaction and brain damage in a rat model of permanent focal cerebral ischemia. The neuroprotective effect and anti-inflammatory property of curcumin in cerebral ischemia might be associated with the inhibition of TLR2/4-NF-κB signaling pathway.

Authors+Show Affiliations

Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, Fujian, 350001, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24723245

Citation

Tu, Xian-kun, et al. "Curcumin Inhibits TLR2/4-NF-κB Signaling Pathway and Attenuates Brain Damage in Permanent Focal Cerebral Ischemia in Rats." Inflammation, vol. 37, no. 5, 2014, pp. 1544-51.
Tu XK, Yang WZ, Chen JP, et al. Curcumin inhibits TLR2/4-NF-κB signaling pathway and attenuates brain damage in permanent focal cerebral ischemia in rats. Inflammation. 2014;37(5):1544-51.
Tu, X. K., Yang, W. Z., Chen, J. P., Chen, Y., Ouyang, L. Q., Xu, Y. C., & Shi, S. S. (2014). Curcumin inhibits TLR2/4-NF-κB signaling pathway and attenuates brain damage in permanent focal cerebral ischemia in rats. Inflammation, 37(5), 1544-51. https://doi.org/10.1007/s10753-014-9881-6
Tu XK, et al. Curcumin Inhibits TLR2/4-NF-κB Signaling Pathway and Attenuates Brain Damage in Permanent Focal Cerebral Ischemia in Rats. Inflammation. 2014;37(5):1544-51. PubMed PMID: 24723245.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Curcumin inhibits TLR2/4-NF-κB signaling pathway and attenuates brain damage in permanent focal cerebral ischemia in rats. AU - Tu,Xian-kun, AU - Yang,Wei-zhong, AU - Chen,Jian-ping, AU - Chen,Yan, AU - Ouyang,Long-qiang, AU - Xu,Yi-chao, AU - Shi,Song-sheng, PY - 2014/4/12/entrez PY - 2014/4/12/pubmed PY - 2015/6/24/medline SP - 1544 EP - 51 JF - Inflammation JO - Inflammation VL - 37 IS - 5 N2 - Toll-like receptors 2 and 4 (TLR2/4) and the downstream nuclear factor-kappa B (NF-κB) signaling pathway, which mediate the inflammatory reaction in cerebral ischemia, were demonstrated to be involved in the extension of cerebral infarction and the aggravation of ischemic brain damage. Reports showed that curcumin provides neuroprotection against ischemic brain damage. In this study, we investigated whether curcumin inhibits the activation of TLR2/4-NF-κB signaling pathway in rats of permanent focal cerebral ischemia. Adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO). Curcumin was administered by intraperitoneal injection twice at 2 and 12 h after the onset of ischemia. Neurological deficit scores, cerebral infarct size, morphological characteristic, and cerebral water content were measured after 24 h of pMCAO. The enzymatic activity of myeloperoxidase (MPO) was assessed after 24 h of pMCAO. Expression of TLR2 and TLR4 in ischemic brain was determined by western blot. Expression of NF-κB p65 in ischemic brain was detected by immunohistochemistry and western blot. The release of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in blood was examined by ELISA. Curcumin significantly reduced neurological deficit scores, cerebral infarct size, neuronal damage, cerebral water content, and MPO activity. It also inhibited the expression of TLR2/4 and decreased the expression and activity of NF-κB p65 in rat brain. In addition, curcumin attenuated the release of TNF-α and IL-1β in blood. Our results suggest that curcumin reduces inflammatory reaction and brain damage in a rat model of permanent focal cerebral ischemia. The neuroprotective effect and anti-inflammatory property of curcumin in cerebral ischemia might be associated with the inhibition of TLR2/4-NF-κB signaling pathway. SN - 1573-2576 UR - https://www.unboundmedicine.com/medline/citation/24723245/Curcumin_inhibits_TLR2/4_NF_κB_signaling_pathway_and_attenuates_brain_damage_in_permanent_focal_cerebral_ischemia_in_rats_ L2 - https://doi.org/10.1007/s10753-014-9881-6 DB - PRIME DP - Unbound Medicine ER -