Affiliation:
1. Department of Neurosurgery Renmin Hospital of Wuhan University Wuhan China
2. Department of Pharmacy Renmin Hospital of Wuhan University Wuhan China
3. Central Laboratory Renmin Hospital of Wuhan University Wuhan China
4. Department of Neurosurgery, The Affiliated Huzhou Hospital Zhejiang University School of Medicine (Huzhou Central Hospital) Huzhou China
5. Department of Pathology Renmin Hospital of Wuhan University Wuhan China
Abstract
AbstractAimsThe 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.MethodsThe effects of NPGE were studied in a mouse model of ischemic stroke (IS) and in oxygen–glucose deprivation/reperfusion (OGD/R)‐induced HT22 cells.ResultsNPGE 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‐1β, IL‐6, TNF‐α, 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.ConclusionCollectively, our results demonstrate the protective effects of NPGE and highlight its therapeutic potential as a drug component for CIRI treatment.
Funder
National Natural Science Foundation of China
Subject
Pharmacology (medical),Physiology (medical),Psychiatry and Mental health,Pharmacology
Cited by
13 articles.
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