The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,re-mains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SH-SY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial func-tion,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bc12)/Bc12-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neur-onal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxid-ant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demon-strated considerable enhancement of mitochondrial membrane potential(MMP),Tom20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mi-tochondrial complex Ⅰ and Ⅲ activity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the in-hibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
Institute of Material Medica Integration and Transformation for Brain Disorders,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
Emergency Department,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,China
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