Triblock Copolymer Nanomicelles Loaded with Curcumin Attenuates Inflammation via Inhibiting the NF-κB Pathway in the Rat Model of Cerebral Ischemia

Abstract

Fengguang Li,1,* Yan Xu,2,* Xing Li,1 Xinghua Wang,1 Zhigang Yang,1 Wanli Li,1 Wei Cheng,1 Gangli Yan1 1Department of Neurology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, 430081, People’s Republic of China; 2Department of Pharmacy, General Hospital of Central Theater Command, Wuhan, 430010, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gangli Yan No. 1 Benxi Street, Qingshan District, Wuhan, 430081, Hubei Province, People’s Republic of ChinaEmail [email protected]: Cerebral ischemic injury is one of the debilitating diseases showing that inflammation plays an important role in worsening ischemic damage. Therefore, studying the effects of some potential anti-inflammatory compounds can be very important in the treatment of cerebral ischemic injury.Methods: This study investigated anti-inflammatory effects of triblock copolymer nanomicelles loaded with curcumin (abbreviated as NC) in the brain of rats following transient cerebral ischemia/reperfusion (I/R) injury in stroke. After preparation of NC, their protective effects against bilateral common carotid artery occlusion (BCCAO) were explored by different techniques. Concentrations of free curcumin (C) and NC in liver, kidney, brain, and heart organs, as well as in plasma, were measured using a spectrofluorometer. Western blot analysis was then used to measure NF-κB-p65 protein expression levels. Also, ELISA assay was used to examine the level of cytokines IL-1β, IL-6, and TNF-α. Lipid peroxidation levels were assessed using MDA assay and H&E staining was used for histopathological examination of the hippocampus tissue sections.Results: The results showed a higher level of NC compared to C in plasma and organs including the brain, heart, and kidneys. Significant upregulation of NF-κB, IL-1β, IL-6, and TNF-α expressions compared to control was observed in rats after induction of I/R, which leads to an increase in inflammation. However, NC was able to downregulate significantly the level of these inflammatory cytokines compared to C. Also, the level of lipid peroxidation in pre-treated rats with 80mg/kg NC was significantly reduced.Conclusion: Our findings in the current study demonstrate a therapeutic effect of NC in an animal model of cerebral ischemia/reperfusion (I/R) injury in stroke through the downregulation of NF-κB-p65 protein and inflammatory cytokines.Keywords: ischemia-reperfusion injury, stroke, NF-ĸB, inflammation, curcumin, nanomicelle, rat

Keywords

• ischemia-reperfusion injury
• stroke
• nf-ĸb
• inflammation
• curcumin
• nanomicelle
• rat