Multimodal therapeutic potential of Reinwardtia indica Dumort. in rodent model of cerebral ischemia: Attenuations of oxidative and neuroinflammatory stress, restoration of neurotransmitter and mitochondrial homeostasis, suppression of apoptotic signaling and preservation of blood-brain barrier integrity.

Ischemic stroke is a major cause of death and long-term neurological disability, driven by complex mechanisms including excitotoxicity, oxidative stress, neuroinflammation, mitochondrial dysfunction, blood–brain barrier (BBB) disruption, and neuronal apoptosis. The limited efficacy of current therapies necessitates the development of multi-target neuroprotective strategies. Reinwardtia indica Dumort., a traditional medicinal plant rich in bioactive phytoconstituents, represents a promising candidate. Thus, the present study aimed to elucidate the neuroprotective potential of R. indica hydroalcoholic extract against cerebral ischemia–reperfusion injury in rats and elucidated its underlying multi-target mechanisms. Cerebral ischemia was induced in Wistar rats via middle cerebral artery occlusion (MCAo), and rats received extract (250 and 500 mg/kg, p.o.) for seven days post-ischemia. Neurological, behavioural, biochemical, and histopathological assessments were performed on day 1 and day 7 post-ischemia, including evaluation of oxidative stress, inflammatory cytokines, mitochondrial enzyme activities, neurotransmitter levels, apoptotic markers, BBB integrity, and infarct size. R. indica significantly reduced infarct volume and improved neuronal survival. Treatment attenuated oxidative and neuroinflammatory stress, restored endogenous antioxidant defenses, suppressed apoptotic signaling, and preserved mitochondrial integrity through normalization of electron transport chain complex activities. Neurotransmitter homeostasis and BBB integrity were also markedly restored. Furthermore, these molecular effects translated into significant improvements in motor, sensorimotor, and cognitive performance. R. indica exerts sustained, multi-target neuroprotection, highlighting its potential as a promising plant-based therapeutic for the management of ischemic stroke. However, for clinical translation, more focus should be given on validating mechanisms and conducting comprehensive pharmacokinetic and safety assessments.