title: Ginsenoside Rg1 protects against hydrogen peroxide-induced cell death in PC12 cells via inhibiting NF-κB activation.
abstract: Oxidative stress is a major cause in neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and cerebral ischemia. Ginsenoside Rg1, a natural product extracted from Panax ginseng C.A. Meyer, has been reported to exert notable neuroprotective activities, which partly ascribed to its antioxidative activity. However, its molecular mechanism against oxidative stress induced by exogenous hydrogen peroxide (H(2)O(2)) remained unclear. In this study, we investigated its effect on H(2)O(2)-induced cell death and explored possible signaling pathway in PC12 cells. We proved that pretreatment with Rg1 at concentrations of 0.1-10 μM remarkably reduced the cytotoxicity induced by 400 μM of H(2)O(2) in PC12 cells by MTT and Hoechst and PI double staining assay. Of note, we demonstrated the activation of NF-κB signaling pathway induced by H(2)O(2) thoroughly in PC12 cells, and Rg1 suppressed phosphorylation and nuclear translocation of NF-κB/p65, phosphorylation and degradation of inhibitor protein of κB (IκB) as well as the phosphorylation of IκB-kinase complex (IKK) by western blotting or indirect immunofluorescence assay. Besides, Rg1 also inhibited the activation of Akt and the extracellular signal-regulated kinase 1/2 (ERK1/2). Furthermore, the protection of Rg1 on H(2)O(2)-injured PC12 cells was attenuated by pretreatment with two NF-κB pathway inhibitors (JSH-23 or BOT-64). In conclusion, our results suggest that Rg1 could rescue the cell injury by H(2)O(2) via down-regulation NF-κB signaling pathway as well as Akt and ERK1/2 activation, which put new evidence on the neuroprotective mechanism of Rg1 against the oxidative stress and the regulatory role of H(2)O(2) in NF-κB pathway in PC12 cells.
authors.affiliation: Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Kou
authors.forename: Bo-Yang
authors.initials: BY
authors.lastname: Yu
mesh_terms: D000818:Animals; D000975:Antioxidants; D001562:Benzimidazoles; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005456:Fluorescent Dyes; D036145:Ginsenosides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018696:Neuroprotective Agents; D016716:PC12 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000975:Antioxidants; D001562:Benzimidazoles; D004396:Coloring Agents; D005456:Fluorescent Dyes; D036145:Ginsenosides; D020672:I-kappa B Proteins; D016328:NF-kappa B; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C022616:thiazolyl blue; C017807:bisbenzimide ethoxide trihydrochloride; C035054:ginsenoside Rg1