Abstract
The present study investigated the neuroprotective properties of whole plants of Grewia bilamellata Gagnep. extract (GBEE) against cerebral ischemia by harnessing both In vivo studies in a rat model and In silico studies focusing on nitric oxide synthase (NOS) inhibition. High-resolution liquid chromatography‒mass spectrometry (HR LC‒MS) analysis identified 32 phytochemicals in the GBEE, 15 of which adhered to Lipinski's rule of five. These compounds exhibited diverse physicochemical properties and high binding affinity to NOS, with cleomiscosin D showing the greatest potential. In vivo, GBEE had significant neuroprotective effects on bilateral common carotid artery occlusion/reperfusion (BCCAO/R) in rats, especially at doses of 200 mg/kg and 400 mg/kg body weight. GBEE treatment improved brain function, as evidenced by EEG normalization, substantial reductions in cerebral infarction size, mitigated neuronal loss, and the restoration of regular histological arrangement in the CA1 hippocampal area of the brain. Furthermore, GBEE enhanced antioxidant defenses by augmenting the activity of catalase (CAT) and superoxide dismutase (SOD), reducing malondialdehyde (MDA) levels, and restoring reduced glutathione (GSH) levels. These effects were accompanied by a decrease in nitric oxide (NO) levels, indicative of attenuated oxidative and nitrosative stress. Collectively, our findings suggest that GBEE is a promising natural therapeutic agent that may prevent or alleviate ischemic brain injury through a multifaceted mechanism involving NOS inhibition and attenuation of the oxidative stress response. This study highlights the therapeutic potential of GBEE and warrants further research into its mechanism of action and possible clinical applications.