Zhongfeng Xingnao Liquid ameliorates post-stroke cognitive impairment through SIRT1/Nrf2/HO-1 pathway

Oxidative stress-induced apoptosis and mitochondrial damage can be avoided by activating the SIRT1/Nrf2/HO-1 pathway, which lowers ROS level. Zhongfeng Xingnao Liquid (ZFXN) has been demonstrated to mitigate post-stroke cognitive impairment (PSCI) in clinical trials. However, it is unclear if this occurs via protecting mitochondria and inhibiting apoptosis through promoting SIRT1/Nrf2/HO-1 pathway. In the current study, an oxygen-glucose deprivation (OGD) cell model was established in SH-SY5Y cells, and PSCI was induced in rats by the modified bilateral carotid artery ligation (2VO). In vivo and in vitro, the effects of ZFXN on the learning and memory, neuroprotective activity, mitochondrial function, oxidative stress, and the SIRT1/Nrf2/HO-1 pathway were assessed. The results showed that ZFXN considerably raised the Bcl2/Bax ratio and decreased TUNEL⁺ cells, while also significantly improved cognition, synaptic plasticity and neuron function in hippocampus and cortex. Moreover, ZFXN showed strong antioxidant activity, as seen by a drop in ROS and MDA content and a rise in SOD, CAT and GSH level. ZFXN also shown a considerable increase of the mitochondrial membrane potential (MMP), the fluorescence intensity of Tom20, the amount of ATP and EC, and the activity of mitochondrial complex I and III to inhibit mitochondrial damage. Additionally, ZFXN significantly increased SIRT1 activity as well as SIRT1, nuclear Nrf2 and HO-1 level. It’s interesting to note that these effects of ZFXN were markedly counteracted when a SIRT1 inhibitor, EX-527, suppressed SIRT1 in vitro. In conclusion, this study suggested that ZFXN alleviated PSCI via stimulating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.