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Synergism and mechanism of Astragaloside IV combined with Ginsenoside Rg1 against autophagic injury of PC12 cells induced by oxygen glucose deprivation/reoxygenation.
Biomed Pharmacother. 2017 May; 89:124-134.BP

Abstract

The aim of this study was to explore the effect by which the combination of Astragaloside IV (AST IV) and Ginsenoside Rg1 (Rg1) resisted autophagic injury in PC12 cells induced by oxygen glucose deprivation/reoxygenation (OGD/R). We studied the nature of the interaction between AST IV and Rg1 that inhibited autophagy through the Isobologram method, and investigated the synergistic mechanism via the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways. Our results showed that, based on the 50% inhibiting concentration (IC50), AST IV combined with Rg1 at a 1:1 ratio resulted in a synergistic effect, whereas the combination of the two had an antagonistic effect on autophagy at ratios of 1:2 and 2:1. Meanwhile, AST IV and Rg1 alone increased cell survival and decreased lactate dehydrogenase (LDH) leakage induced by OGD/R, reduced autophagosomes and the LC3 II positive patch, down-regulated the LC3 II/LC3 I ratio and up-regulated the p62 protein; the 1:1 combination enhanced these effects. Mechanistic study showed that Rg1 and the 1:1 combination increased the phosphorylation of PI3K I, Akt and mTOR; the effects of the combination were greater than those of the drugs alone. AST IV and the 1:1 combination suppressed the expression of PI3K III and Becline-1, and the combination elevated Bcl-2 protein expression; the effects of the combination were better than those of the drugs alone. These results suggest that after 2 h-OGD followed by reoxygenation for 24h, PC12 cells suffer excessive autophagy and damage, which are blocked by AST IV or Rg1; moreover, the combination of AST IV and Rg1 at a 1:1 ratio of their IC50 concentrations has a synergistic inhibition on autophagic injury. The synergistic mechanism may be associated with the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways.

Authors+Show Affiliations

Molecular Pathology Laboratory, Hunan Provincial Key Laboratory for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China.Molecular Pathology Laboratory, Hunan Provincial Key Laboratory for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China.Molecular Pathology Laboratory, Hunan Provincial Key Laboratory for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China.Molecular Pathology Laboratory, Hunan Provincial Key Laboratory for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China.Hunan Education Department's Key Laboratory of Cell Biology and Molecular Technology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China.Hunan Education Department's Key Laboratory of Cell Biology and Molecular Technology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China.Hunan Education Department's Key Laboratory of Cell Biology and Molecular Technology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China.Molecular Pathology Laboratory, Hunan Provincial Key Laboratory for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China. Electronic address: dchangq@sohu.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28219050

Citation

Huang, Xiao-Ping, et al. "Synergism and Mechanism of Astragaloside IV Combined With Ginsenoside Rg1 Against Autophagic Injury of PC12 Cells Induced By Oxygen Glucose Deprivation/reoxygenation." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 89, 2017, pp. 124-134.
Huang XP, Ding H, Yang XQ, et al. Synergism and mechanism of Astragaloside IV combined with Ginsenoside Rg1 against autophagic injury of PC12 cells induced by oxygen glucose deprivation/reoxygenation. Biomed Pharmacother. 2017;89:124-134.
Huang, X. P., Ding, H., Yang, X. Q., Li, J. X., Tang, B., Liu, X. D., Tang, Y. H., & Deng, C. Q. (2017). Synergism and mechanism of Astragaloside IV combined with Ginsenoside Rg1 against autophagic injury of PC12 cells induced by oxygen glucose deprivation/reoxygenation. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 89, 124-134. https://doi.org/10.1016/j.biopha.2017.02.015
Huang XP, et al. Synergism and Mechanism of Astragaloside IV Combined With Ginsenoside Rg1 Against Autophagic Injury of PC12 Cells Induced By Oxygen Glucose Deprivation/reoxygenation. Biomed Pharmacother. 2017;89:124-134. PubMed PMID: 28219050.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergism and mechanism of Astragaloside IV combined with Ginsenoside Rg1 against autophagic injury of PC12 cells induced by oxygen glucose deprivation/reoxygenation. AU - Huang,Xiao-Ping, AU - Ding,Huang, AU - Yang,Xiao-Qian, AU - Li,Jing-Xian, AU - Tang,Biao, AU - Liu,Xiao-Dan, AU - Tang,Ying-Hong, AU - Deng,Chang-Qing, Y1 - 2017/02/20/ PY - 2016/09/29/received PY - 2017/02/03/revised PY - 2017/02/07/accepted PY - 2017/2/22/pubmed PY - 2018/2/28/medline PY - 2017/2/21/entrez KW - Astragaloside IV KW - Autophagic injury KW - Ginsenoside Rg1 KW - PC12 cells OGD/R KW - PI3K I/Akt/mTOR KW - PI3K III/Beclin-1/Bcl-2 KW - Synergism SP - 124 EP - 134 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 89 N2 - The aim of this study was to explore the effect by which the combination of Astragaloside IV (AST IV) and Ginsenoside Rg1 (Rg1) resisted autophagic injury in PC12 cells induced by oxygen glucose deprivation/reoxygenation (OGD/R). We studied the nature of the interaction between AST IV and Rg1 that inhibited autophagy through the Isobologram method, and investigated the synergistic mechanism via the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways. Our results showed that, based on the 50% inhibiting concentration (IC50), AST IV combined with Rg1 at a 1:1 ratio resulted in a synergistic effect, whereas the combination of the two had an antagonistic effect on autophagy at ratios of 1:2 and 2:1. Meanwhile, AST IV and Rg1 alone increased cell survival and decreased lactate dehydrogenase (LDH) leakage induced by OGD/R, reduced autophagosomes and the LC3 II positive patch, down-regulated the LC3 II/LC3 I ratio and up-regulated the p62 protein; the 1:1 combination enhanced these effects. Mechanistic study showed that Rg1 and the 1:1 combination increased the phosphorylation of PI3K I, Akt and mTOR; the effects of the combination were greater than those of the drugs alone. AST IV and the 1:1 combination suppressed the expression of PI3K III and Becline-1, and the combination elevated Bcl-2 protein expression; the effects of the combination were better than those of the drugs alone. These results suggest that after 2 h-OGD followed by reoxygenation for 24h, PC12 cells suffer excessive autophagy and damage, which are blocked by AST IV or Rg1; moreover, the combination of AST IV and Rg1 at a 1:1 ratio of their IC50 concentrations has a synergistic inhibition on autophagic injury. The synergistic mechanism may be associated with the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/28219050/Synergism_and_mechanism_of_Astragaloside_IV_combined_with_Ginsenoside_Rg1_against_autophagic_injury_of_PC12_cells_induced_by_oxygen_glucose_deprivation/reoxygenation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(16)31789-9 DB - PRIME DP - Unbound Medicine ER -