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

作　　者：Xiuling Tang Tao Yan Saiying Wang Qingqing Liu Qi Yang Yongqiang Zhang Yujiao Li Yumei Wu Shuibing Liu Yulong Ma Le Yang 

机构地区：[1]Precision Pharmacy&Drug Development Center,Department of Pharmacy,Tangdu Hospital,Air Force Medical University,Xi’an,Shaanxi Province,China [2]Department of Clinical Pharmacy,Jinling Hospital,Medical School of Nanjing University,Nanjing,Jiangsu Province,China [3]Department of Pharmacology,School of Pharmacy,Air Force Medical University,Xi’an,Shaanxi Province,China [4]Department of Anesthesiology,The First Medical Center of Chinese PLA General Hospital,Beijing,China [5]Department of Anatomy,Histology and Embryology and K.K.Leung Brain Research Centre,Air Force Medical University,Xi’an,Shaanxi Province,China

出　　处：《Neural Regeneration Research》2024年第3期642-649,共8页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.82104158(to XT),31800887(to LY),31972902(to LY),82001422(to YL);China Postdoctoral Science Foundation,No.2020M683750(to LY);partially by Young Talent Fund of University Association for Science and Technology in Shaanxi Province of China,No.20200307(to LY).

摘　　要：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 whetherβ-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 ofβ-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.

关 键 词：APOPTOSIS blood-brain barrier Β-SITOSTEROL cerebral ischemia/reperfusion injury cholesterol overload cholesterol transport endoplasmic reticulum stress ischemic stroke molecular docking NPC1L1 

分 类 号：R743[医药卫生—神经病学与精神病学]