PUBLICATION

Hormetic effect of panaxatriol saponins confers neuroprotection in PC12 cells and zebrafish through PI3K/AKT/mTOR and AMPK/SIRT1/FOXO3 pathways

Authors
Zhang, C., Li, C., Chen, S., Li, Z., Ma, L., Jia, X., Wang, K., Bao, J., Liang, Y., Chen, M., Li, P., Su, H., Lee, S.M., Liu, K., Wan, J.B., He, C.
ID
ZDB-PUB-170124-5
Date
2017
Source
Scientific Reports   7: 41082 (Journal)
Registered Authors
Wang, Kai
Keywords
Cellular neuroscience, Growth factor signalling, Parkinson's disease, Stress signalling, TOR signalling
MeSH Terms
  • Sirtuin 1/genetics
  • Zebrafish/genetics*
  • PC12 Cells
  • Rats
  • Protein Kinases/genetics
  • Phosphatidylinositol 3-Kinases/genetics
  • Neuroprotection/drug effects
  • Gene Expression Regulation/drug effects
  • Panax notoginseng/chemistry
  • Signal Transduction/drug effects
  • Animals
  • Proto-Oncogene Proteins c-akt/genetics
  • Hormesis/drug effects*
  • Hormesis/genetics
  • Ginsenosides/administration & dosage*
  • Ginsenosides/chemistry
  • Forkhead Box Protein O3/genetics
  • Saponins/administration & dosage*
  • Saponins/chemistry
  • TOR Serine-Threonine Kinases/genetics
(all 20)
PubMed
28112228 Full text @ Sci. Rep.
Abstract
Hormesis is an adaptive response of living organisms to a moderate stress. However, its biomedical implication and molecular mechanisms remain to be intensively investigated. Panaxatriol saponins (PTS) is the major bioactive components extracted from Panax notoginseng, a widely used herbal medicine for cerebrovascular diseases. This study aims to examine the hormetic and neuroprotective effects of PTS in PC12 cells and zebrafish Parkinson's disease (PD) models. Our results demonstrated that PTS stimulated PC12 cell growth by about 30% at low doses, while PTS at high doses inhibited cell growth, which is a typical hormetic effect. Moreover, we found that low dose PTS pretreatment significantly attenuated 6-OHDA-induced cytotoxicity and up-regulated PI3K/AKT/mTOR cell proliferation pathway and AMPK/SIRT1/FOXO3 cell survival pathway in PC12 cells. These results strongly suggested that neuroprotective effects of PTS may be attributable to the hormetic effect induced by PTS through activating adaptive response-related signaling pathways. Notably, low dose PTS could significantly prevent the 6-OHDA-induced dopaminergic neuron loss and improve the behavior movement deficiency in zebrafish, whereas relative high dose PTS exhibited neural toxicity, further supporting the hormetic and neuroprotective effects of PTS. This study indicates that PTS may have the potential in the development of future therapeutic medicines for PD.
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Citation
Zhang, C., Li, C., Chen, S., Li, Z., Ma, L., Jia, X., Wang, K., Bao, J., Liang, Y., Chen, M., Li, P., Su, H., Lee, S.M., Liu, K., Wan, J.B., He, C. (2017) Hormetic effect of panaxatriol saponins confers neuroprotection in PC12 cells and zebrafish through PI3K/AKT/mTOR and AMPK/SIRT1/FOXO3 pathways. Scientific Reports. 7:41082.