Sulfuretin Attenuates MPP+-Induced Neurotoxicity through Akt/GSK3β and ERK Signaling Pathways

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease. It is caused by the death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress and mitochondrial dysfunction contribute to the loss of dopaminergic neurons in PD. Sulfuretin is a potent antioxidant that is reported to be beneficial in the treatment of neurodegenerative diseases. In this study, we examined the protective effect of sulfuretin against 1-methyl-4-phenyl pyridinium (MPP+)-induced cell model of PD in SH-SY5Y cells and the underlying molecular mechanisms. Sulfuretin significantly decreased MPP+-induced apoptotic cell death, accompanied by a reduction in caspase 3 activity and polyADP-ribose polymerase (PARP) cleavage. Furthermore, it attenuated MPP+-induced production of intracellular reactive oxygen species (ROS) and disruption of mitochondrial membrane potential (MMP). Consistently, sulfuretin decreased p53 expression and the Bax/Bcl-2 ratio. Moreover, sulfuretin significantly increased the phosphorylation of Akt, GSK3β, and ERK. Pharmacological inhibitors of PI3K/Akt and ERK abolished the cytoprotective effects of sulfuretin against MPP+. An inhibitor of GSK3β mimicked sulfuretin-induced protection against MPP+. Taken together, these results suggest that sulfuretin significantly attenuates MPP+-induced neurotoxicity through Akt/GSK3β and ERK signaling pathways in SH-SY5Y cells. Our findings suggest that sulfuretin might be one of the potential candidates for the treatment of PD.

In Vitro and In Vivo Neuroprotective Effects of Stellettin B Through Anti-Apoptosis and the Nrf2/HO-1 Pathway

“…With respect to apoptosis of dopaminergic cells in PD [27,52,53], ERK, and P38 activators such as sulfuretin and chrysotoxine have shown efficacy in in vitro models of PD, by blocking apoptosis. Pariyar et al showed that sulfuretin protects neuronal cells against MPP + -induced damage through the activation of ERK and its downstream anti-apoptosis effector, Bcl-2, in SH-SY5Y cells [54]; however, sulfuretin has not been studied in an in vivo PD model. In addition, sulfuretin protected dopaminergic neurons from amyloid beta neurotoxicity in an in vitro model of Alzheimer’s disease [55].…”

The Akt pathway in oncology therapy and beyond (Review)

“…Sulfuretin reduced caspase-3 and PARP activity accompanied by a reduction of intracellular reactive oxygen species (ROS) production and recovered the normal mitochondrial membrane potential. The mechanism involved the augmentation of the phosphorylation of Akt, GSK-3β and Erk pathway, confirmed by the disappearance of the cytoprotective effects of sulfuretin following the administration of PI3K/Akt and Erk inhibitors ( 78 ). Vitexin, a glucoside derivative of apigenin and several other flavonoids had similar protective effects on cell and mouse models of PD ( 79 ).…”

Further Study on Chemical Constituents From the Heartwood of Dalbergia Ton

“…This compound was also isolated from the heartwood of D. odorifera [11]. Sulfuretin possesses antiinflammatory [23], anti-cancer [24] and neuroprotective activities [25].…”