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Int. J. Mol. Sci. 2015, 16(9), 22350-22367;

Gardenamide A Protects RGC-5 Cells from H2O2-Induced Oxidative Stress Insults by Activating PI3K/Akt/eNOS Signaling Pathway

National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China
Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China
Faculty of Health Sciences, University of Macao, Macao, China
Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Guangzhou 510632, China
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 27 July 2015 / Revised: 24 August 2015 / Accepted: 31 August 2015 / Published: 15 September 2015
(This article belongs to the Section Biochemistry)
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Gardenamide A (GA) protects the rat retinal ganglion (RGC-5) cells against cell apoptosis induced by H2O2. The protective effect of GA was completely abrogated by the specific phosphoinositide 3-kinase (PI3K) inhibitor LY294002, and the specific protein kinase B (Akt) inhibitor Akt VIII respectively, indicating that the protective mechanism of GA is mediated by the PI3K/Akt signaling pathway. The specific extracellular signal-regulated kinase (ERK1/2) inhibitor PD98059 could not block the neuroprotection of GA. GA attenuated the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) induced by H2O2. Western blotting showed that GA promoted the phosphorylation of ERK1/2, Akt and endothelial nitric oxide synthase (eNOS), respectively, and effectively reversed the H2O2-inhibited phosphorylation of these three proteins. LY294002 completely inhibited the GA-activated phosphorylation of Akt, while only partially inhibiting eNOS. This evidence implies that eNOS may be activated directly by GA. PD98059 attenuated only partially the GA-induced phosphorylation of ERK1/2 with/without the presence of H2O2, indicating that GA may activate ERK1/2 directly. All these results put together confirm that GA protects RGC-5 cells from H2O2 insults via the activation of PI3K/Akt/eNOS signaling pathway. Whether the ERK1/2 signaling pathway is involved requires further investigations. View Full-Text
Keywords: gardenamide A; oxidative stress; cell apoptosis; neuroprotection; neurotoxicity gardenamide A; oxidative stress; cell apoptosis; neuroprotection; neurotoxicity

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Wang, R.; Peng, L.; Zhao, J.; Zhang, L.; Guo, C.; Zheng, W.; Chen, H. Gardenamide A Protects RGC-5 Cells from H2O2-Induced Oxidative Stress Insults by Activating PI3K/Akt/eNOS Signaling Pathway. Int. J. Mol. Sci. 2015, 16, 22350-22367.

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