期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 242, 期 1, 页码 18-28出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2009.09.009
关键词
Ginsenoside Rb1; Heme oxygenase-1; NF-E2 related factor 2; Phosphatidylinositol 3-kinase; Estrogen receptor; Cytoprotection
资金
- National institute of Toxicological Research, KFDA [07142KFDA570, 08152KFDA424]
- Korea Healthcare Technology RD Project [A084869]
- Ministry for Health, Welfare & Family Affairs, Republic of Korea
Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is a popular traditional herbal medicine. Ginsenoside Rb1 (Rb1), an active component commonly found in ginseng root, is a phytoestrogen that exerts estrogen-like activity. In this study, we demonstrate that the phytoestrogen Rb1 inhibits 6-hydroxydopamine (6-OHDA)-induced oxidative injury via an ER-dependent G beta 1/PI3K/Akt and heme oxygenase-1 (HO-1) pathway. Pretreatment of SH-SY5Y cells with Rb1 significantly reduced 6-OHDA-induced caspase-3 activation and subsequent cell death. Rb1 also up-regulated HO-1 expression, which conferred cytoprotection against 6-OHDA-induced oxidative injury. Moreover, Rb1 induced both Nrf2 nuclear translocation, which is upstream of HO-1 expression and PI3K activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. Also, Rb1-mediated increases in PI3K activation and HO-1 induction were reversed by co-treatment with ICI 182,780 and pertussis toxin. Taken together, these results suggest that Rb1 augments the cellular antioxidant defenses through ER-dependent HO-1 induction via the G beta 1/PI3K/Akt-Nrf2 signaling pathway, thereby protecting cells from oxidative stress. Thus our Study indicates that Rb1 has a partial cytoprotective role in dopaminergic cell Culture systems. (C) 2009 Elsevier Inc. All rights reserved.
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