title: Panaxatriol saponins attenuated oxygen-glucose deprivation injury in PC12 cells via activation of PI3K/Akt and Nrf2 signaling pathway.
abstract: Panaxatriol saponins (PTS), the main components extracted from Panax notoginseng, have been shown to be efficacious in the prevention and treatment of cerebrovascular diseases in China. NF-E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant and cytoprotective responses to oxidative stress, has received particular attention as a molecular target for pharmacological intervention of ischemic diseases. The aim of this study was to characterize the effect of PTS on the activation of Nrf2 signaling pathway and the potential role in its protective effect. We found that PTS induced heme oxygenase-1 (HO-1) expression in PC12 cells via activating Nrf2 signaling pathway. Phosphatidylinositol 3-kinase (PI3K)/Akt kinase was involved in the upstream of this PTS activated pathway. Moreover, combination of the main components in PTS significantly enhanced the expression of Nrf2 mediated phase II enzymes. Importantly, the protective effect of PTS against oxygen-glucose deprivation-reperfusion (OGD-Rep) induced cell death was significantly attenuated by PI3K inhibitor and antioxidant response element (ARE) decoy oligonucleotides, suggesting that both PI3K/Akt and Nrf2 signaling pathway are essential during this protective process. Taken together, our results suggest that PTS may activate endogenous cytoprotective mechanism against OGD-Rep induced oxidative injury via the activation of PI3K/Akt and Nrf2 signaling pathway.
authors: College of Pharmacy, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Road, Wenjiang District, Chengdu, Sichuan 611137, China.
authors: Yongliang
authors: Y
authors: Huang
authors: College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.
authors: Jie
authors: J
authors: Yu
authors: Huasun Group Co., Ltd., Chengdu, Sichuan 610072, China.
authors: Fang
authors: F
authors: Wan
authors: Huasun Group Co., Ltd., Chengdu, Sichuan 610072, China.
authors: Wenwu
authors: W
authors: Zhang
authors: Huasun Group Co., Ltd., Chengdu, Sichuan 610072, China.
authors: Huarong
authors: H
authors: Yang
authors: Huasun Group Co., Ltd., Chengdu, Sichuan 610072, China.
authors: Li
authors: L
authors: Wang
authors: College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.
authors: Hongyi
authors: H
authors: Qi
authors: College of Pharmacy, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Road, Wenjiang District, Chengdu, Sichuan 611137, China.
authors: Chunjie
authors: C
authors: Wu
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000235:genetics; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D036145:Ginsenosides; D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D012503:Saponins; C004563:panaxatriol; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D010100:Oxygen