Salidroside Reduces Inflammation and Brain Injury After Permanent Middle Cerebral Artery Occlusion in Rats by Regulating
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ORIGINAL ARTICLE
Salidroside Reduces Inflammation and Brain Injury After Permanent Middle Cerebral Artery Occlusion in Rats by Regulating PI3K/PKB/Nrf2/NFκB Signaling Rather than Complement C3 Activity X. Zhang,1 W. Lai,1 X. Ying,1 L. Xu,1 K. Chu,1 J. Brown,1 L. Chen,1 and G. Hong
1,2
Salidroside, an active constituent of Rhodiola rosea, is neuroprotective after transient middle cerebral artery occlusion (tMCAO). However, its effects in other experimental stroke models are less understood. Here, we investigated the effect of daily intraperitoneal injections of salidroside in rats after permanent MCAO (pMCAO). Cerebral infarct volumes at 1 day after pMCAO were significantly reduced by treatment with 100 mg/kg/day salidroside, but not by 25 or 50 mg/kg/day, and this benefit of salidroside increased significantly over at least 7 days of treatment, when it was also accompanied by decreased neurological deficit scores. These observations led us to investigate the underlying mechanism of action of salidroside. 100 mg/kg salidroside for 1 day increased NeuN, Nrf2, and its downstream mediator HO-1, while it reduced nuclear NFκB p50, IL-6, and TNFα. Brusatol, a Nrf2 inhibitor, blocked the actions of salidroside on Nrf2, NFκB p50, IL-6, and TNFα. Salidroside also increased the ratio of p-PKB/PKB at 1 day after pMCAO even in the presence of brusatol. LY294002, a PI3K inhibitor, prevented all these effects of salidroside, including those on NeuN, p-PKB/PKB, Nrf2, HO-1, and pro-inflammatory mediators. In contrast, salidroside had no significant effect on the level of cerebral complement C3 after pMCAO, or on the activity of C3 as measured by the expression of cerebral Egr1. Our findings therefore suggest that salidroside reduces neuroinflammation and neural damage by regulating the PI3K/PKB/Nrf2/NFκB signaling pathway after pMCAO, and that this neuroprotective effect does not involve modulation of complement C3 activity.
Abstract—
KEY WORDS: Complement C3; Inflammation; Ischemic stroke; Neuroprotection; Nrf2; Salidroside.
X. Zhang and W. Lai contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10753-019-01045-7) contains supplementary material, which is available to authorized users. 1
Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, No. 1 Huatou Road, Minhou Shangjie, Fuzhou, China 2 To whom correspondence should be addressed at Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, No. 1 Huatou Road, Minhou Shangjie, Fuzhou, China. Email: [email protected]
0360-3997/19/0000-0001/0 # 2019 Springer Science+Business Media, LLC, part of Springer Nature
Zhang, Lai, Ying, Xu, Chu, Brown, Chen, and Hong INTRODUCTION Salidroside is a key bioactive component of the medicinal plant Rhodiola rosea, which is thought to be neuroprotective and to improve cognitive functions [1]. Treatment with salidroside can reduce cerebral infarct volume and neurological defici
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