Abstract
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.
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