Safranal prevents rotenone-induced oxidative stress and apoptosis in an in vitro model of Parkinson's disease through regulating Keap1/Nrf2 signaling pathway

Abstract

Safranal, a major constituent of saffron, possesses antioxidant and anti-apoptotic properties showing considerable neuroprotective effects. However, whether safranal shows therapeutic effect on Parkinson's disease (PD) remains unknown. In this study, we aimed to investigate the potential effect of safranal on PD using an in vitro model of PD induced by rotenone. We found that safranal significantly inhibited rotenoneinduced cell death in a dose-dependent manner. Moreover, safranal also markedly suppressed the reactive oxygen species (ROS) generation and cell apoptosis induced by rotenone. Further investigation showed that safranal inhibited the expression of kelch-like ECH-associated protein 1 (Keap1) and promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in rotenone-induced dopaminergic neurons. Meanwhile, the downstream antioxidant enzyme genes of Nrf2 including glutathione S transferase (GST), glutamate-cysteine ligase catalytic subunit (GCLc), NADPH-quinone oxidoreductase 1 (NQO1) and heme oxygenase1 (HO-1) were also induced by safranal in rotenone-induced dopaminergic neurons. However, the knockdown of Nrf2 significantly abrogated the protective effect of safranal on rotenone-induced neurotoxicity. Taken together, our study suggests that safranal protects against rotenone-induced neurotoxicity associated with Nrf2 signaling pathway implying that safranal may serve as a potent and promising therapeutic drug for the treatment of PD.

Safranal Attenuates Excitotoxin-Induced Oxidative OLN-93 Cells Injury

“…In a mouse model of asthma, safranal significantly suppressed oxidative stress in the bronchial epithelial cells by inhibiting of inducible nitric oxide synthase and decreasing nitric oxide production [52]. Subsequently, Pan and colleagues showed that safranal ameliorats the ROS production and cell apoptosis mediated by rotenone via regulating nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element signaling pathway, in an in vitro model of Parkinson's disease [53]. In streptozotocininduced diabetic neuropathy model, safranal exhibited potent antioxidant properties by decreasing the levels of MDA in the sciatic nerve tissue [54].…”

Phytotherapic use of the Crocus sativus L. (Saffron) and its potential applications: A brief overview

“…Pan and collaborators (), in an in vitro model of Parkinson's disease, demonstrated that safranal could act as preventive agent against rotenone‐induced oxidative stress and apoptosis by regulating Keap1/Nrf2 signaling pathway. have studied the therapeutic potential of crocetin in a rat model of Parkinson's disease induced by 6‐hydroxydopamine.…”

Anti-oxidative effects of catechins and theaflavins on glutamate-induced HT22 cell damage

“…12,13 The ROS directly contribute to numerous neuronal injuries. [14][15][16][17][18] Therefore, emerging antioxidants have been investigated to remove intracellular ROS and serve as potential therapeutic agents in multiple neurological diseases. [19][20][21] The antioxidant properties of polyphenolic compounds have been widely studied.…”