Phytocompounds Targeting Signaling Pathways in Stroke: Preclinical and Clinical Insights into Therapeutic Mechanisms...

Stroke, primarily due to ischemic injury and neurodegeneration, is a significant global cause of death and permanent neurological impairment in adults. Phytocompounds are promising candidates for stroke care because of their effects on key molecular signaling pathways that promote neuroprotection in stroke. This review highlights the therapeutic potential of phytocompounds, such as curcumin, resveratrol, quercetin, berberine, and epigallocatechin gallate, which target signaling pathways, including PI3K/Akt, Nrf2/ARE, MAPK, NF-κB, and JAK/STAT. These substances have neuroprotective properties by managing oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation, excitotoxicity, and blood-brain barrier integrity. Preclinical research has indicated that phytocompound therapy significantly decreases infarct volume, neuronal loss, and behavioral impairments. Despite strong experimental evidence, the clinical application of phytocompounds is limited by their low brain permeability, short half-life, poor bioavailability, and irregular dosages. Furthermore, demonstrating the neurotoxicity and safety profiles of phytocompounds is essential because of the potential risks, such as hepatotoxicity, genotoxicity, and brain transmission interference. Nanotechnology-based delivery methods, such as liposomes and phytocompound-loaded nanoparticles, have demonstrated the ability to overcome pharmacokinetic restrictions while reducing the toxicity. Phytocompounds that target various neuroprotective signaling pathways are potential supplements or alternative treatments for stroke. To ensure clinical efficacy and safety, it is essential to follow the recognized dosage guidelines, perform thorough neurotoxicity evaluations and conduct rigorous clinical studies. Future studies should explore the potential of phytocompounds in conjunction with traditional treatments and precision medicine techniques for personalized stroke care.