期刊
CNS NEUROSCIENCE & THERAPEUTICS
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.1111/cns.14456
关键词
ferroptosis; ischemic stroke; neuroinflammation; neutral polysaccharide from Gastrodia elata; NRF2/HO-1 signaling pathway
This study investigated the potential effects of Neutral polysaccharide from Gastrodia elata (NPGE) on cerebral ischemia-reperfusion injury (CIRI) neuropathology. The results showed that NPGE treatment could alleviate neurological deficits, reduce infarct volume, and promote cell survival. Mechanistically, NPGE could regulate the expression of various signaling molecules, alleviating neuroinflammation and ferroptosis.
Aims The crosstalk between ferroptosis and neuroinflammation considerably impacts the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Neutral polysaccharide from Gastrodia elata (NPGE) has shown significant effects against oxidative stress and inflammation. This study investigated the potential effects of NPGE on CIRI neuropathology.Methods The effects of NPGE were studied in a mouse model of ischemic stroke (IS) and in oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cells.Results NPGE treatment decreased neurological deficits, reduced infarct volume, and alleviated cerebral edema in IS mice, and promoted the survival of OGD/R-induced HT22 cells. Mechanistically, NPGE treatment alleviated neuronal ferroptosis by upregulating GPX4 levels, lowering reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2+ excessive hoarding, and meliorating GSH levels and SOD activity. Additionally, it inhibited neuroinflammation by down-regulating the level of IL-1 beta, IL-6, TNF-alpha, NLRP3, and HMGB1. Meanwhile, NPGE treatment alleviated ferroptosis and inflammation in erastin-stimulated HT22 cells. Furthermore, NPGE up-regulated the expression of NRF2 and HO-1 and promoted the translocation of NRF2 into the nucleus. Using the NRF2 inhibitor brusatol, we verified that NRF2/HO-1 signaling mediated the anti-ferroptotic and anti-inflammatory properties of NPGE.Conclusion Collectively, our results demonstrate the protective effects of NPGE and highlight its therapeutic potential as a drug component for CIRI treatment.
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