Morroniside in Ischemic Stroke: Preclinical Evidence and a Proposed Stage-Dependent Framework for Neurovascular Repair

Ischemic stroke remains a leading cause of death and long-term disability. Although thrombolysis and mechanical thrombectomy have improved reperfusion, secondary neurovascular injury and incomplete tissue repair remain important challenges. Morroniside (MOR), an iridoid glycoside from Cornus officinalis, has shown neuroprotective and repair-associated effects in experimental stroke models. This narrative review synthesizes preclinical evidence from 11 eligible in vivo cerebral ischemia or post-stroke recovery studies identified through searches of PubMed, Web of Science, and Scopus. Reported findings associate MOR treatment with changes in neuroinflammation, pyroptosis, oxidative stress, apoptosis, blood–brain barrier (BBB) integrity, angiogenesis, and neural progenitor responses. On this basis, we propose a hypothesis-generating, stage-dependent framework that organizes injury-associated and repair-associated outcomes according to their reported post-ischemic timing. These outcomes may represent complementary aspects of MOR activity, but because the findings derive from separate experiments, they do not establish a validated temporal sequence or stage-specific treatment regimen. Inconsistent methodological reporting and unresolved questions about brain exposure, target engagement, treatment timing, and safety also limit translational interpretation. MOR therefore merits further investigation as a potential adjunct to reperfusion and rehabilitation, although its efficacy and therapeutic window require rigorous validation before clinical application.