Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells
Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells
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DOI：
10.1016/j.taap.2009.09.009
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发表时间：
2010-01-01
影响因子：
3.8
通讯作者：
Jeong, Hye Gwang
中科院分区：
文献类型：
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作者：
Hwang, Yong Pil;Jeong, Hye Gwang
植物雌激素是一类具有雌激素样生物活性的多酚类非甾体植物化合物。人参为人参（Panax ginseng C.A.）的根。Meyer（五加科），是一种受欢迎的传统草药。人参皂苷Rb 1（Rb 1）是人参根中常见的活性成分，是一种具有雌激素样活性的植物雌激素。在这项研究中，我们证明，植物雌激素Rb 1抑制6-羟基多巴胺（6-OHDA）诱导的氧化损伤通过ER依赖的G β 1/PI 3 K/Akt和血红素加氧酶-1（HO-1）途径。Rb 1预处理SH-SY 5 Y细胞可显著降低6-OHDA诱导的caspase-3激活和随后的细胞死亡。Rb 1还上调HO-1的表达，从而对6-OHDA诱导的氧化损伤提供细胞保护。此外，Rb 1诱导Nrf 2核转位，这是HO-1表达和PI 3 K激活的上游，参与诱导Nrf 2核转位，HO-1表达和细胞保护的途径。此外，Rb 1介导的PI 3 K活化和HO-1诱导的增加通过与ICI 182，780和百日咳毒素的共同处理而逆转。综上所述，这些结果表明，Rb 1通过G β 1/PI 3 K/Akt-Nrf 2信号通路通过ER依赖性HO-1诱导增强细胞的抗氧化防御，从而保护细胞免受氧化应激。因此，我们的研究表明，Rb 1在多巴胺能细胞培养系统中具有部分细胞保护作用。(C)2009 Elsevier Inc. All rights reserved.
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.