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

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• 作者：Seung-Hwan Kwon ; Shi-Xun Ma ; Sa-Ik Hong ; Sun Yeou Kim ; Seok-Yong Lee ; Choon-Gon Jang
• 关键词：AD ; Alzheimer's disease ; A尾 ; Amyloid beta ; CGA ; Chlorogenic acid ; EUE ; Eucommia ulmoides Oliv. Bark. ; DCFH-DA ; 2 ; 7'-Dichlorofluorescein diacetate ; DMEM ; Dulbecco's modified Eagle's medium ; DMSO ; Dimethyl sulfoxide ; FBS ; Fetal bovine serum ; GSK-3尾 ; Glycogen synthase kinase-3 beta ; 6-OHDA ; 6-Hydroxydopamine ; H2O2 ; Hydrogen peroxide ; JNK ; c-Jun N-terminal kinase ; LDH ; Lactate dehydrogenase ; MMP ; Mitochondrial membrane potential ; MPTP ; 1-Methyl-4-phenyl-1 ; 2 ; 3 ; 6-tetrahydropyridine ; MTT ; 3-(4 ; 5-Dime
• 刊名：Journal of Ethnopharmacology
• 出版年：27 February, 2014
• 年：2014
• 卷：152
• 期：1
• 页码：173-182
• 全文大小：2493 K

文摘

Ethnopharmacological 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尾). Furthermore, the neuroprotective effects of EUE on 6-OHDA-induced activation of nuclear factor-kappa B (NF-魏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尾. Furthermore, EUE blocked 6-OHDA-induced NF-魏B nuclear translocation, an event downstream from JNK, PI3K/Akt, and GSK-3尾 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尾, and NF-魏B pathways, thereby protecting cells from neuronal cell death.