Geniposide induces the expression of heme oxygenase-1 via PI3K/Nrf2-signaling to enhance the antioxidant capacity in primary hippocampal neurons.
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.
Research Center of Medicinal Chemistry and Chemical Biology, Chongqing Technology and Business University, Chongqing 400067, PR China.
Fei
F
Yin
Jianhui
J
Liu
Xuxu
X
Zheng
Lixia
L
Guo
He
H
Xiao
D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005638:Fruit; D032062:Gardenia / Q000737:chemistry*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D039823:Iridoids / Q000494:pharmacology*; D008981:Molsidomine / Q000031:analogs & derivatives; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
D000975:Antioxidants; D039823:Iridoids; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; D011524:Protoporphyrins; C007835:geniposide; C017803:zinc protoporphyrin; C002385:linsidomine; D008981:Molsidomine; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases