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This study aimed to investigate the neuroprotective capacity of PNS in a rat model of middle cerebral artery occlusion (MCAO)-induced cerebral IR injury, focusing specifically on understanding the involvement of the sirtuin 1 (SIRT1)\/nuclear factor erythroid 2-related factor 2 (Nrf2)\/heme oxygenase-1 (HO-1) pathway in mediating this protective effect. Male Sprague-Dawley rats (n=45, weighing 250\u2013280g and aged 12 weeks) were utilized in this experiment. Cerebral IR injury was induced by subjecting the rats to 30 minutes of MCAO followed by 24 hours of reperfusion. Prior to the surgery, PNS (120mg\/kg) was administered once daily via gavage for 14 days. The evaluation measures included assessing cerebral infarct volume, neurological function using the Longa method, conducting histopathological analysis, examining the expression of SIRT1, Nrf2, and HO-1 genes and proteins, as well as measuring the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA). Pretreatment with PNS markedly decreased infarct volume, enhanced neurological function, and mitigated histopathological alterations. Additionally, PNS intake resulted in the upregulation of SIRT1, Nrf2, and HO-1 genes and proteins, boosted enzymatic antioxidant activity, and lowered MDA levels, pointing towards a diminution in oxidative stress. The multifaceted antioxidant and neuroprotective properties of PNS underscore its promising role in preserving neuronal function, mitigating oxidative damage, and promoting tissue survival in ischemic conditions. These benefits were associated with the modulation of the SIRT1\/Nrf2\/HO-1 signaling pathway, emphasizing the therapeutic significance of PNS in addressing cerebral IR injury and related neurological complications.<\/jats:p>","DOI":"10.33549\/physiolres.935458","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:23:35Z","timestamp":1747722215000},"page":"313-326","source":"Crossref","is-referenced-by-count":8,"title":["Protective Effects of Panax notoginseng Saponins on Cerebral Ischemia\/Reperfusion Injury: Insights Into SIRT1\/NRF2\/HO-1 Pathway Activation"],"prefix":"10.33549","author":[{"given":"J","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SA","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Pu","sequence":"additional","affiliation":[{"name":"fengdaoyinmo007@sina.com"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Hospital of Kunming (Affiliated Calmette Hospital of Kunming Medical University), Kunming, China. 1978zhaonan@sina.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"19169","reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"Cowled P, Fitridge R. 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