Prospects for treatment of cerebral ischemic stroke with Hydroxysafflower Yellow A

Cerebral ischemic stroke (CIS) is characterized by high morbidity, disability, and mortality, representing a major global public health challenge and imposing a substantial social and economic burden worldwide. Cerebral ischemia/reperfusion (I/R) triggers complex pathological cascades, resulting in secondary brain injury, thereby limiting the therapeutic efficacy of single-target interventions. Therefore, the development of novel neuroprotective strategies with multitarget pharmacological properties remains an important research focus. Hydroxysafflower yellow A (HSYA), the major bioactive component of safflower (Carthamus tinctorius L.), has demonstrated protective effects in multiple experimental models of CIS. Accumulating preclinical evidence indicates that HSYA mitigates ischemic brain injury through multiple pathways, including maintaining mitochondrial homeostasis, suppressing excitotoxicity and calcium overload, attenuating oxidative stress, inhibiting inflammatory responses, and promoting angiogenesis. However, current mechanistic evidence is predominantly derived from cellular and animal studies. Limited clinical investigations have explored the effects of HSYA-containing preparations or HSYA injection in ischemic stroke; however, current evidence remains insufficient to establish definitive clinical efficacy. The clinical efficacy, optimal dosing strategies, and long-term benefits of HSYA remain to be fully established. In addition, limited brain distribution and unfavorable pharmacokinetic properties represent important challenges for its further clinical translation. This review summarizes the current understanding of the pharmacological effects of HSYA during different phases of CIS. Furthermore, from the perspective of the stroke-heart syndrome, the potential therapeutic value of HSYA in brain-heart comorbidity is discussed. Collectively, this review provides a new perspective on the therapeutic potential and translational challenges of HSYA in CIS management.