Synergistic protective effect of paeoniflorin and beta-ecdysterone against rotenone-induced neurotoxicity in PC12 cells

摘要

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 beta-ecdysterone (beta-Ecd) synergize to protect PC12 cells against toxicity induced by PD-related neurotoxin rotenone. The combination of PF and beta-Ecd, hereafter referred to as the PF/beta-Ecd, at suboptimal concentrations increased the viability of rotenone-exposed PC12 cells in a synergistic manner. PF and beta-Ecd cooperate to attenuate the rotenone-induced apoptosis by decrease in Bax expression, caspase-9 activity, and caspase-3 activity. PF or PF/beta-Ecd, but not beta-Ecd, inhibited rotenone-triggered protein kinase C-delta kinase C-delta (PKC delta) upregulation and nuclear factor kappa B (NF-kappa B) activation. beta-Ecd or PF/beta-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/beta-Ecd could be completely blocked by PKC delta inhibitor rottlerin plus Akt specific inhibitor LY294002. Dual blockade of the PKC delta/NF-kappa B pathway by PF and activation of Akt/Nrf2 pathway by beta-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 beta-Ecd against PD.