Geraniin, a polyphenol isolated from Phyllanthus amarus, possesses extensive biological and pharmaceutical activities. In this study, we investigated the protective effect against cerebral ischemia/reperfusion (I/R) injury of geraniin and explored its potential mechanism. Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to simulate cerebral I/R injury in vivo, and oxygen-glucose deprivation/reoxygenation (OGD/R) was applied to establish an in vitro model of cerebral I/R injury. In this study, we performed TTC and HE staining and adopted a neurological score method to evaluate the neuroprotective effect of geraniin in vivo and used the CCK-8 assay to assess this effect in vitro. Indices of reactive oxidation capacity were measured in vivo and in vitro to verify the antioxidant capacity of geraniin. TUNEL staining and flow cytometry were applied to measure the apoptosis rate, and Western blotting was performed to assess the expression of apoptosis-related proteins. Finally, the expression of Nrf2 and HO-1 was evaluated in vivo and in vitro by Western blotting. Geraniin significantly reduced the infarct volume, decreased neurological deficit scores, alleviated pathological changes in neurons, and increased the cell survival rate. Geraniin increased the activity of superoxide dismutase (SOD) and decreased the activity of lactate dehydrogenase (LDH) and the contents of malondialdehyde (MDA), nitric oxide (NO), and neuronal nitric oxide synthase (nNOS) in vivo and in vitro. In addition, geraniin significantly reduced the apoptosis. Furthermore, geraniin also evidently increased Nrf2 (total and nuclear) and HO-1 protein expression in vivo and in vitro. Collectively, these results imply that geraniin may exert a protective effect against cerebral I/R injury by suppressing oxidative stress and neuronal apoptosis. The mechanism underlying the protective effect of geraniin is associated with activation of the Nrf2/HO-1 pathway. Our results indicate that geraniin may be a potential drug candidate for the treatment of ischemic stroke.
Ginsenosides are a class of active components extracted from ginseng plants (such as Panax ginseng, Panax quinquefolium, and Panax notoginseng). Ginsenosides have significant protective effects on the nervous system, cardiovascular system, and immune system, so they have been widely used in the treatment of related diseases. Entry of a variety of endogenous or exogenous harmful substances into the body can lead to an imbalance between the antioxidant defense system and reactive oxygen species, thus producing toxic effects on a variety of tissues and cells. In addition, oxidative stress can alter multiple signaling pathways, including the Keap1/Nrf2/ARE, PI3K/AKT, Wnt/β-catenin, and NF-κB pathways. With the deepening of research in this field, various ginsenoside monomers have been reported to exert antioxidant effects through multiple signaling pathways and thus have good application prospects. This article summarized the research advancements regarding the antioxidative effects and related mechanisms of ginsenosides, providing a theoretical basis for experimental research on and clinical treatment with ginsenosides.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.