Hydroxysafflor yellow A protects against ischemic stroke-associated Weber syndrome by inhibiting oxidative stress and alleviating DNA damage

Weber syndrome, characterized by ipsilateral oculomotor palsy and contralateral hemiplegia, frequently occurs in ischemic stroke cases and is difficult to recover from. Hydroxysafflor yellow A (HSYA), a bioactive component present in Carthamus tinctorius L. and the standardized preparation Danhong injection, has shown protective effects in animal models of various neurological diseases. This research was conducted to evaluate the therapeutic potential of HSYA in ischemic stroke-associated Weber syndrome, while elucidating its mechanistic basis. A rat MCAO model was induced to detect the effects of HSYA on motor dysfunction, ipsilateral ptosis and neuronal death in the right cerebral peduncle. By western blot, immunohistochemistry staining and immunofluorescence staining, we explored the involvement of oxidative stress and DNA damage in HSYA's neuroprotective action. HSYA treatment for consecutive 7 days significantly improved neurological function, grip strength, and asymmetry of bilateral eye clefts in CI/R-injured rats. HSYA also reduced cerebral infarction, preserved neuronal survival, and mitigated histopathological damage in the cerebral peduncle. Mechanistically, HSYA alleviated oxidative stress by preserving CAT, GSH, and SODM levels while inhibiting iNOS overexpression. Furthermore, CI/R injury triggered substantial DNA damage in the cerebral peduncle, as indicated by upregulated levels of 53BP1 and γ-H2A.X. Contents of PARP1, AIF, and MIF were also significantly elevated, accompanied by obvious upregulation of apoptotic cell death, while HSYA treatment effectively attenuated these deleterious effects. HSYA protects against CI/R injury and associated Weber syndrome, and the mechanism involves suppressing oxidative stress and limiting DNA injury. Schematic diagram of HSYA ameliorating ischemic stroke-associated Weber syndrome by mitigating oxidative stress and DNA injury. • Weber syndrome, characterized by ipsilateral oculomotor palsy and contralateral hemiplegia, is prevalent in large cerebral infarction of anterior circulation system. • Excessive oxidative stress and DNA injury in the cerebral peduncle are involved in the pathogenesis of Weber syndrome. • Hydroxysafflor yellow A alleviates Weber syndrome induced by cerebral ischemia/reperfusion by reducing oxidative stress, DNA damage and inhibiting apoptotic cell death.