Abstract: | Reactive oxygen species (ROS)-induced oxidative stress is reportedly associated with progressive neuronal cell damage. Glechoma hederacea L. (Lamiaceae), belonging to the Labiatae family, has demonstrated several biologic activities including depigmentation, antimelanogenic, antitumor, antioxidative, hepatoprotective, and anti-inflammatory activities. Previously, we reported that rosmarinic acid, chlorogenic acid, caffeic acid, rutin, genistin, and ferulic acids were the most abundant phytochemicals detected in hot water extracts of G. hederacea L. (HWG). This study aimed to study the neuroprotective effects of phenolic acids and flavonoid-rich HWG against hydrogen peroxide (H2O2)-induced oxidative damage in PC12 cells and its inhibitory effect on acetylcholinesterase (AChE). The experiment analyzed cytotoxicity, ROS production, mitochondrial transmembrane potential (MMP) level, and caspase-3 activity and used comet assay and antioxidant enzyme activity to determine the redox status of PC12 cells. Results showed that the inhibitory effect of HWG on AChE was in a competitive pattern (IC50, 23.23 mg/ml). HWG antagonized H2O2-mediated cytotoxicity and DNA damage, reduced ROS production, stabilized MMP, and inhibited caspase-3 activity and apoptosis. Furthermore, HWG inhibited the release of cytochrome C and apoptosis-inducing factors (AIF) and decreased the malondialdehyde levels in PC12 cells. Collectively, HWG rich in antioxidant phenolic acids and flavonoids may have neuroprotective effects. Practical applications Polyphenolic compounds are one of the most important natural products, known to possess a range of health-promoting effects. In this study, it was found that HWG, which is rich in antioxidant phenolic acids and flavonoids, can protect PC12 cells from oxidative stress induced by H2O2 and may have neuroprotective effects. |