In the present study, we investigated the effects of oil products from two Allium species: Allium sativum (garlic) and Allium hookeri (Chinese chives) on cell proliferation and neuroblast differentiation in the mouse dentate gyrus. Using corn oil as a vehicle, the essential oil from garlic (10 ml/kg), or Chinese chives (10 ml/kg) was administered orally to 9-week-old mice once a day for 3 weeks. One hour following the last treatment, a novel object recognition test was conducted and the animals were killed 2 h after the test. In comparison to the vehicle-treated group, garlic essential oil (GO) treatment resulted in significantly increased exploration time and discrimination index during the novel object recognition test, while Chinese chives essential oil (CO) reduced the exploration time and discrimination index in the same test. In addition, the number of Ki67-immunoreactive proliferating cells and doublecortin-immunoreactive neuroblasts significantly increased in the dentate gyrus of GO-treated animals. However, administration of CO significantly decreased cell proliferation and neuroblast differentiation. Administration of GO significantly increased brain-derived neurotrophic factor (BDNF) levels and decreased acetylcholinesterase (AChE) activity in the hippocampal homogenates. In contrast, administration of CO decreased BDNF protein levels and had no significant effect on AChE activity, compared to that in the vehicle-treated group. These results suggest that GO significantly improves novel object recognition as well as increases cell proliferation and neuroblast differentiation, by modulating hippocampal BDNF protein levels and AChE activity, while CO impairs novel object recognition and decreases cell proliferation and neuroblast differentiation, by reducing BDNF protein levels in the hippocampus.

In traditional herbal medicine, the Polyscias fruticosa has been frequently used for the treatment of ischemia and inflammation. Oxidative stress mediated by elevated glutamate levels cause neuronal cell death in ischemia and various neurodegenerative diseases. However, so far, the neuroprotective effects of this plant extract against glutamate-mediated cell death have not been investigated in cell models. The current study investigates the neuroprotective effects of ethanol extracts of Polyscias fruticosa (EEPF) and elucidates the underlying molecular mechanisms of EEPFs relevant to neuroprotection against glutamate-mediated cell death. The oxidative stress-mediated cell death was induced by 5 mM glutamate treatment in HT22 cells. The cell viability was measured by a tetrazolium-based EZ-Cytox reagent and Calcein-AM fluorescent dye. Intracellular Ca²⁺ and ROS levels were measured by fluorescent dyes, fluo-3 AM and 2′,7′-dichlorodihydrofluorescein diacetate (DCF-DA), respectively. Protein expressions of p-AKT, BDNF, p-CREB, Bax, Bcl-2, and apoptosis-inducing factor (AIF) were determined by western blot analysis. The apoptotic cell death was measured by flow cytometry. The in vivo efficacy of EEPF was evaluated using the Mongolian gerbil mouse by surgery-induced brain ischemia. EEPF treatment showed a neuroprotective effect against glutamate-induced cell death. The EEPF co-treatment reduced the intracellular Ca²⁺ and ROS and apoptotic cell death. Furthermore, it recovered the p-AKT, p-CREB, BDNF, and Bcl-2 levels decreased by glutamate. The EEPF co-treatment suppressed the activation of apoptotic Bax, the nuclear translocation of AIF, and mitogen-activated protein kinase (MAPK) pathway proteins (ERK1/2, p38, JNK). Further, EEPF treatment significantly rescued the degenerative neurons in the ischemia-induced Mongolian gerbil in vivo model. EEPF exhibited neuroprotective properties that suppress glutamate-mediated neurotoxicity. The underlying mechanism of EEPF is increasing the level of p-AKT, p-CREB, BDNF, and Bcl-2 associated with cell survival. It has therapeutic potential for the treatment of glutamate-mediated neuropathology.

Brain ischemia-reperfusion (I/R) injury, commonly occurring in ischemic stroke and post-cardiac arrest scenarios, results in complex secondary damage involving oxidative stress, inflammation, apoptosis, and blood-brain barrier (BBB) breakdown. Despite decades of research, no pharmacological agent has yet been clinically approved for post-I/R neuroprotection. Natural compounds have recently gained attention for their multimodal therapeutic potential, including antioxidant, anti-inflammatory, anti-apoptotic, and neuroregenerative effects. This review highlights nine promising candidates—resveratrol, curcumin, quercetin, berberine, ginkgolide B, baicalin, naringin, fucoidan, and astaxanthin—that exhibit efficacy in experimental models of I/R injury when administered after the insult. Their chemical structures, pharmacokinetics, and mechanisms of action are described in detail, focusing on key signaling pathways such as nuclear factor erythroid 2-related (Nrf2), nuclear factor kappa B (NF-κB), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and brain-derived neurotrophic factor (BDNF). Importantly, we outline the selection criteria for these compounds, including demonstrated neuroprotective efficacy, mechanistic clarity, and translational feasibility. While several challenges remain—such as limited bioavailability, BBB penetration, and species-specific metabolism—emerging strategies like nanoparticle delivery, synthetic analogs, and drug combinations offer potential solutions. By emphasizing the therapeutic versatility and mechanistic diversity of these natural agents, this review supports their clinical potential and encourages further preclinical optimization and biomarker-guided human trials.