Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

• Published in: Neural regeneration research Vol. 19; no. 3; pp. 642 - 649
• Main Authors: Tang, Xiuling, Yan, Tao, Wang, Saiying, Liu, Qingqing, Yang, Qi, Zhang, Yongqiang, Li, Yujiao, Wu, Yumei, Liu, Shuibing, Ma, Yulong, Yang, Le
• Format: Journal Article
• Language: English
• Published: Mumbai Wolters Kluwer India Pvt. Ltd 01.03.2024; Medknow Publications & Media Pvt. Ltd; Precision Pharmacy & Drug Development Center,Department of Pharmacy,Tangdu Hospital,Air Force Medical University,Xi'an,Shaanxi Province,China%Department of Clinical Pharmacy,Jin ling Hospital,Medical School of Nanjing University,Nanjing,Jiangsu Province,China%Department of Pharmacology,School of Pharmacy,Air Force Medical University,Xi'an,Shaanxi Province,China%Department of Anesthesiology,The First Medical Center of Chinese PLA General Hospital,Beijing,China%Precision Pharmacy & Drug Development Center,Department of Pharmacy,Tangdu Hospital,Air Force Medical University,Xi'an,Shaanxi Province,China; Department of Anatomy,Histology and Embryology and K.K.Leung Brain Research Centre,Air Force Medical University,Xi'an,Shaanxi Province,China; Wolters Kluwer - Medknow; Wolters Kluwer Medknow Publications
• Subjects: Apoptosis; apoptosis; blood-brain barrier; β-sitosterol; cerebral ischemia/reperfusion injury; cholesterol overload; cholesterol transport; endoplasmic reticulum stress; ischemic stroke; molecular docking; npc1l1; Cholesterol; Endoplasmic reticulum; Ischemia; blood-brain barrier; cerebral ischemia/reperfusion injury; cholesterol transport; molecular docking; β-sitosterol; cholesterol overload; NPC1L1; apoptosis; endoplasmic reticulum stress; ischemic stroke
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.380904

[INLINE:1] β-Sitosterol is a type of phytosterol that occurs naturally in plants. Previous studies have shown that it has anti-oxidant, anti-hyperlipidemic, anti-inflammatory, immunomodulatory, and anti-tumor effects, but it is unknown whether β-sitosterol treatment reduces the effects of ischemic stroke. Here we found that, in a mouse model of ischemic stroke induced by middle cerebral artery occlusion, β-sitosterol reduced the volume of cerebral infarction and brain edema, reduced neuronal apoptosis in brain tissue, and alleviated neurological dysfunction; moreover, β-sitosterol increased the activity of oxygen- and glucose-deprived cerebral cortex neurons and reduced apoptosis. Further investigation showed that the neuroprotective effects of β-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke. In addition, β-sitosterol showed high affinity for NPC1L1, a key transporter of cholesterol, and antagonized its activity. In conclusion, β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.