Affiliation:
1. Department of Geriatrics, Xijing Hospital, Airforce Military Medical University, Xi’an, Shaanxi 710032, China
Abstract
Oxidative stress acts as an essential culprit factor in the development of stroke and Alzheimer’s disease. Norcepharadione B possesses various pharmacologic features as an extract obtained from Houttuynia cordata. Nevertheless, the anti-apoptotic and neuroprotective characteristics of norcepharadione B remain unclear. In this study, the neuronal protection effect provided by norcepharadione B against injury caused by hydrogen peroxide (H2O2) in HT22 cell as well as the fundamental mechanism was systematically explored. The neurotoxicity assays of hippocampal cells, which were co-cultured with H2O2, showed that norcepharadione B had the ability to insulate the toxicity induced by H2O2 with significant reduced cell apoptosis. Besides, norcepharadione B potentiated the activity of superoxide dismutase (SOD), increased the level of glutathione (GSH), and decreased malondialdehyde content. The H2O2-induced apoptotic protein Bax was suppressed, and the anti-apoptotic protein Bcl-2 was boosted by norcepharadione B. Norcepharadione B promoted Akt phosphorylation and further upregulated heme oxygenase (HO-1) in cells exposed to oxidative stress. However, the inductive effect of HO-1 by norcepharadione B was shut off via the PI3K/Akt inhibitor LY294002. Furthermore, 2-h incubation with H2O2 substantially increased cell volume in HT22 cells, while norcepharadione B effectively alleviated such effect by interrupting the activation of VSOR Cl− channel. Collectively, our data revealed protective properties of norcepharadione B in resisting oxidative stress induced by H2O2 through elevation of HO-1 in the dependence of PI3K/Akt and in inhibiting H2O2-induced cell swelling by VSOR Cl− channel obstruction in HT22 cells. Impact statement Norcepharadione B is an aporphine alkaloid compound extracted from Chinese herb Houttuynia cordata. It was well known for its anti-inflammatory, anti-cancer, and anti-platelet aggregation outcomes. Our study demonstrated that Norcepharadione B protected hippocampal neurons against oxidative stress and the resultant cell apoptosis upon H2O2 exposure. Meanwhile, Norcepharadione B also substantially reduced cell swelling induced by H2O2 via inhibiting VSOR Cl− channel in neurons. These findings uncovered the potential mechanisms of Norcepharadione B in protecting neuron apoptosis under oxidative stress and propose that Norcepharadione B may serve as a favorable herb medicine for restoring neuronal injury in the pathogenesis of stroke together with other neurodegenerative diseases.
Funder
National Natural Science Foundation of China
Major Basic Research Projects in Natural Science Foundation of Shaanxi Province
Subject
General Biochemistry, Genetics and Molecular Biology