Eucommia ulmoides Oliv. bark. attenuates 6-hydroxydopamine-induced neuronal cell death through inhibition of oxidative stress in SH-SY5Y cells

Ethno pharmacological relevance: Eucommia ulmoides Oliv. Bark. (EUE) has commonly been used to fortify the muscles and lungs, lower blood pressure, prevent miscarriage, improve liver and kidney tone, and promote longevity as a traditional tonic medicine in Korea, China, and Japan. Aim of the study: In this study, we investigated the mechanisms by which EUE protects neuronal cells from apoptosis induced by the Parkinson's disease (PD)-related neurotoxin, 6-hydroxydopamine (6-OHDA). Materials and methods: We determined the neuroprotective effects of EUE on 6-OHDA-induced neuronal cell death, cytotoxicity, reactive oxygen species (ROS) production, and mitochondrial membrane dysfunction. Moreover, we examined whether EUE suppressed phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K)/Akt, and glycogen synthase kinase-3 beta (GSK-3 beta). Furthermore, the neuroprotective effects of EUE on 6-OHDA-induced activation of nuclear factor-kappa B (NF-kappa B) was studied in SH-SY5Y cells. Results: Pretreatment of SH-SY5Y cells with EUE significantly reduced 6-OHDA-induced cell death and cytotoxicity. EUE inhibited 6-OHDA-induced generation of ROS, which conferred cytoprotection against 6-OHDA-induced oxidative injury. EUE treatment also strikingly inhibited 6-OHDA-induced mitochondrial dysfunction. In addition, EUE suppressed phosphorylation of JNK, PI3K/Akt, and GSK-3 beta. Furthermore, EUE blocked 6-OHDA-induced NF-kappa B nuclear translocation, an event downstream from JNK, PI3K/Akt, and GSK-3 beta phosphorylation. Moreover, chlorogenic acid (CGA), one of the active constituents of EUE, was also able to reduce 6-OHDA-induced toxicity in SH-SY5Y cells. Conclusion: Taken together, these results suggest that EUE attenuates oxidative stress through activation of JNK, PI3K/Akt, GSK-3 beta, and NF-kappa B pathways, thereby protecting cells from neuronal cell death. (C) 2014 Elsevier Ireland Ltd. All rights reserved.