Targeting neuroinflammation in ischemic stroke: The promise of phytoconstituents

Ischemic stroke (IS) stands as a major global health burden, often resulting in death or lasting disability. Beyond the initial deprivation of blood flow, the subsequent cerebral ischemia-reperfusion injury significantly amplifies neural damage through complex inflammatory mechanisms. When blood supply is restored after vascular blockage, the sudden influx of oxygen and immune cells intensifies oxidative stress and triggers a cascade involving glial cell activation, blood-brain barrier (BBB) disruption, and infiltration of peripheral leukocytes. Although this immune response begins as a protective effort, it frequently becomes dysregulated, leading to neuronal degeneration, cerebral edema, and worsened clinical outcomes. In light of this, recent studies have turned toward modulating neuroinflammation as a therapeutic avenue, with plant-derived compounds gaining traction due to their broad-spectrum activity and favourable safety profiles. Bioactive phytochemicals such as flavonoids, polyphenols, and terpenoids have shown potential in preclinical models by attenuating pro-inflammatory cytokine production, inhibiting NF-κB and NLRP3 inflammasome signaling, promoting microglial transition to neuroprotective phenotypes, and reinforcing BBB stability. Enhancing stroke therapy choices requires the creation of natural medications that are highly effective, low in toxicity, and reasonably priced. This review covers 40 phytoconstituents studied between 1996 and 2024, along with their experimental models, tested doses, and observed outcomes. These natural compounds show promise in reducing injury after ischemic stroke. However, their clinical use still requires more research, including detailed pharmacokinetic studies, improved delivery methods, and well-designed human trials to confirm their effectiveness and safety.