Research Center of Medicinal Chemistry and Chemical Biology, Chongqing Technology and Business University, Chongqing 400067, PR China.
Biol Pharm Bull. 2010;33(11):1841-6. doi: 10.1248/bpb.33.1841.
Oxidative stress in brain is emerging as a potential causal factor in aging and age-related neurodegenerative disorders. A large body of evidence shows that induction of endogenous antioxidative proteins seems to be a reasonable strategy for delaying the progression of cell injury. In this study, geniposide upregulates the expression of heme oxygenase-1 (HO-1) to attenuate the cell apoptosis induced by 3-morpholinosydnonimine hydrochloride (SIN-1) in primary cultured hippocampal neurons. Furthermore, geniposide induces the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and activation of phosphatidylinositol 3'-kinase (PI3K) in the presence of oxidative stress, and both LY294002 (a specific inhibitor of PI3K) and Zinc protoporphyrin (ZnPP, an inhibitor of HO-1) decrease the cytoprotective action of geniposide in hippocampal neurons. Taken together, the novel cytoprotective mechanism of geniposide to antagonize oxidative stress may be involved in PI3K- and Nrf2-mediated upregulation of the antioxidative enzyme HO-1.
脑内氧化应激被认为是衰老和与年龄相关的神经退行性疾病的潜在原因。大量证据表明，诱导内源性抗氧化蛋白的表达似乎是延缓细胞损伤进展的合理策略。在这项研究中，京尼平苷通过上调血红素加氧酶-1（HO-1）的表达来减轻原代培养海马神经元中 3-吗啉代-sydnonimine 盐酸盐（SIN-1）诱导的细胞凋亡。此外，京尼平苷在氧化应激条件下诱导核转录因子-E2 相关因子 2（Nrf2）的核易位和磷脂酰肌醇 3′-激酶（PI3K）的激活，而 LY294002（PI3K 的特异性抑制剂）和锌原卟啉（HO-1 的抑制剂）降低了京尼平苷在海马神经元中的细胞保护作用。总之，京尼平苷拮抗氧化应激的新型细胞保护机制可能涉及 PI3K 和 Nrf2 介导的抗氧化酶 HO-1 的上调。
