{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:38:18Z","timestamp":1792179498576,"version":"4.4.0"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,14]],"date-time":"2024-04-14T00:00:00Z","timestamp":1713052800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174167"],"award-info":[{"award-number":["82174167"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p><jats:italic>Astragaloside IV<\/jats:italic> (AST IV) and <jats:italic>ligustrazine<\/jats:italic> (Lig), the main ingredients of <jats:italic>Astragali Radix<\/jats:italic> and <jats:italic>Chuanxiong Rhizoma<\/jats:italic> respectively, have demonstrated significant benefits in treatment of cerebral ischemia \u2010reperfusion injury (CIRI); however, the mechanisms underlying its benificial effects remain unclear. SUMO\u20101ylation and deSUMO\u20102\/3ylation of dynamin\u2010related protein 1 (Drp1) results in mitochondrial homeostasis imbalance following CIRI, which subsequently aggravates cell damage. This study investigates the mechanisms by which AST IV combined with Lig protects against CIRI, focusing on the involvement of SUMOylation in mitochondrial dynamics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rats were administrated AST IV and Lig for 7\u2009days, and middle cerebral artery occlusion was established to mimic CIRI. Neural function, cerebral infarction volume, cerebral blood flow, cognitive function, cortical pathological lesions, and mitochondrial morphology were measured. SH\u2010SY5Y cells were subjected to oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) injury. Mitochondrial membrane potential and lactic dehydrogenase (LDH), reactive oxygen species (ROS), and adenosine triphosphate (ATP) levels were assessed with commercial kits. Moreover, co\u2010immunoprecipitation (Co\u2010IP) was used to detect the binding of SUMO1 and SUMO2\/3 to Drp1. The protein expressions of Drp1, Fis1, MFF, OPA1, Mfn1, Mfn2, SUMO1, SUMO2\/3, SENP1, SENP2, SENP3, SENP5, and SENP6 were measured using western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In rats with CIRI, AST IV and Lig improved neurological and cognitive functions, restored CBF, reduced brain infarct volume, and alleviated cortical neuron and mitochondrial damage. Moreover, in SH\u2010SY5Y cells, the combination of AST IV and Lig enhanced cellular viability, decreased release of LDH and ROS, increased ATP content, and improved mitochondrial membrane potential. Furthermore, AST IV combined with Lig reduced the binding of Drp1 with SUMO1, increased the binding of Drp1 with SUMO2\/3, suppressed the expressions of Drp1, Fis1, MFF, and SENP3, and increased the expressions of OPA1, Mfn1, Mfn2, SENP1, SENP2, and SENP5. SUMO1 overexpression promoted mitochondrial fission and inhibited mitochondrial fusion, whereas SUMO2\/3 overexpression suppressed mitochondrial fission. AST IV combined with Lig could reverse the effects of SUMO1 overexpression while enhancing those of SUMO2\/3 overexpression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study posits that the combination of AST IV and Lig has the potential to reduce the SUMO\u20101ylation of Drp1, augment the SUMO\u20102\/3ylation of Drp1, and thereby exert a protective effect against CIRI.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14725","type":"journal-article","created":{"date-parts":[[2024,4,14]],"date-time":"2024-04-14T21:14:20Z","timestamp":1713129260000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["<i>Astragaloside IV<\/i> combined with <i>ligustrazine<\/i> ameliorates abnormal mitochondrial dynamics via Drp1 <scp>SUMO<\/scp>\/<scp>deSUMOylation<\/scp> in cerebral ischemia\u2013reperfusion 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