Inflammation and oxidative stress play an important part in the pathogenesis of focal cerebral ischemia/reperfusion (I/R) injury, resulting in neuronal death. The signaling pathways involved and the underlying mechanisms of these events are not fully understood. Chrysin, which is a naturally occurring flavonoid, exhibits various biological activities. In this study, we investigated the neuroprotective properties of chrysin in a mouse model of middle cerebral artery occlusion (MCAO). To this end, male C57/BL6 mice were pretreated with chrysin once a day for seven days and were then subjected to 1 h of middle cerebral artery occlusion followed by reperfusion for 24 h. Our data show that chrysin successfully decreased neurological deficit scores and infarct volumes, compared with the vehicle group. The increases in glial cell numbers and proinflammatory cytokine secretion usually caused by ischemia/reperfusion were significantly ameliorated by chrysin pretreatment. Moreover, chrysin also inhibited the MCAO-induced up-regulation of nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), compared with the vehicle. These results suggest that chrysin could be a potential prophylactic agent for cerebral ischemia/reperfusion (I/R) injury mediated by its anti-inflammatory and anti-oxidative effects.

Centella asiatica (L.) Urb., a traditional medicinal plant widely distributed in Southeast Asia, has been demonstrated to possess significant neuroprotective effect. However, the pharmacological and molecular mechanisms of C. asiatica (CA) in treating neurological diseases remain to be further explored. This review synthesizes evidence on CA's pharmacokinetics, antioxidant/anti-inflammatory mechanisms, and therapeutic potential in various neurological disorders. Evidence shows CA can mitigate oxidative stress, inflammation, mitochondrial dysfunction, and neuronal apoptosis-key mechanisms underlying these conditions. In epilepsy models, asiatic acid suppresses glutamate release, improves synaptic and mitochondrial function, and reduces neuronal damage. In neurodegenerative diseases, CA extracts enhance memory and cognitive functions by activating antioxidant response pathways and protecting hippocampal mitochondria from oxidative stress. CA extracts also display anticonvulsant effects without major toxicity. Against Bisphenol A-induced neurotoxicity, CA alleviates oxidative stress and inflammation while restoring mitochondrial function. For radiation-induced brain injury, CA improves cognition and memory via antioxidant pathways and anti-inflammatory effects. In cerebral ischemia-reperfusion injury, asiaticoside reduces oxidative stress and neuroinflammation through NOD2/MAPK/NF-κB pathway modulation and microglial regulation. Recent research suggests that CA also plays a significant role in alleviating symptoms of anxiety and depression. The plant's active components have been found to regulate neurotransmitter activity, reduce oxidative stress, and modulate the hypothalamic-pituitary-adrenal (HPA) axis. CA demonstrates broad neuroprotective potential, offering multi-target benefits with relatively low toxicity. These findings support its development as a novel therapeutic agent for neurological disorders. Further clinical research is warranted to confirm safety, optimize dosing, and translate preclinical results into effective human treatments.

Background Endovascular therapy within 24 hours of stroke onset is effective and safe, but successful recanalization does not always give favorable outcomes. Ischemic postconditioning (IPostC), a reperfusion strategy with potential neuroprotective effects, has been extensively studied in preclinical models, but its impact in humans remains unclear. Building on a previous dose escalation study, we aimed to investigate the effect of in situ IPostC on infarct volume in patients with acute ischemic stroke following mechanical thrombectomy. Methods This prospective, externally controlled, non-randomized trial compared in situ IPostC (four cycles of 2 min of occlusion/2 min of release) plus thrombectomy with contemporaneous external controls receiving thrombectomy alone. Propensity score matching (PSM) minimized selection bias. The primary outcome was infarct volume at 72 hours post-thrombectomy. Deep infarct volume was also compared in post hoc analyses. Peripheral blood was collected 24 hours post-procedure to assess leukocyte populations, with mononuclear cell subsets characterized by flow cytometry. Serum inflammatory biomarkers were also measured in both groups. Results After 1:1 PSM, 19 patients per group were analyzed. The IPostC group showed significantly less deep infarct volume progression (median 2.3 vs 4.7 mL; P=0.045), lower interleukin 6 levels (median 26.4 vs 32.6 pg/mL; P=0.032), higher Th/CTL ratios (median 2.04 vs 1.65; P<0.01), and reduced natural killer cell proportions (median 1.10% vs 1.68%; P=0.047). Conclusions In situ IPostC following thrombectomy for large vessel occlusion stroke may be associated with reduced deep infarct volume progression and favorable immunomodulatory effects, warranting further validation in phase II trials. Trial registration ClinicalTrials.gov NCT05909982.