Synergistic protective effect of paeoniflorin and β-ecdysterone against rotenone-induced neurotoxicity in PC12 cells
| Autor: | Xiaojie Zhang, Tianjiao Xu, Chunlei Yu, Miaoxian Dong, Han Liu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research genetic structures Clinical Biochemistry Pharmaceutical Science Apoptosis Pharmacology medicine.disease_cause PC12 Cells Neuroprotection 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glucosides Rotenone medicine Animals LY294002 Protein kinase A Protein kinase B Neurons Chemistry Biochemistry (medical) Neurotoxicity Drug Synergism Cell Biology medicine.disease Rats Ecdysterone Neuroprotective Agents 030104 developmental biology Monoterpenes Rottlerin 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Apoptosis. 21:1354-1365 |
| ISSN: | 1573-675X 1360-8185 |
| Popis: | There are several factors, like oxidative stress and neurons loss, involving neurodegenerative diseases such as Parkinson's disease (PD). The combination of antioxidant and anti-apoptotic agent is becoming a promising approach to fight against PD. This study evaluates the hypothesis that paeoniflorin (PF) and β-ecdysterone (β-Ecd) synergize to protect PC12 cells against toxicity induced by PD-related neurotoxin rotenone. The combination of PF and β-Ecd, hereafter referred to as the PF/β-Ecd, at suboptimal concentrations increased the viability of rotenone-exposed PC12 cells in a synergistic manner. PF and β-Ecd cooperate to attenuate the rotenone-induced apoptosis by decrease in Bax expression, caspase-9 activity, and caspase-3 activity. PF or PF/β-Ecd, but not β-Ecd, inhibited rotenone-triggered protein kinase C-δkinase C-δ (PKCδ) upregulation and nuclear factor κB (NF-κB) activation. β-Ecd or PF/β-Ecd, but not PF, enhanced serine/threonine protein kinase (Akt) activation, promoted nuclear factor E2-related factor 2 (Nrf2) nuclear accumulation, suppressed reactive oxygen species (ROS) production. Neuroprotection of PF/β-Ecd could be completely blocked by PKCδ inhibitor rottlerin plus Akt specific inhibitor LY294002. Dual blockade of the PKCδ/NF-κB pathway by PF and activation of Akt/Nrf2 pathway by β-Ecd results in a synergistic neuroprotective effect against rotenone-induced neurotoxicity in vitro. These findings provide the rationale for determining the in vivo activity of combined therapy with PF and β-Ecd against PD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink