α-Cyperone Attenuates H2O2-Induced Oxidative Stress and Apoptosis in SH-SY5Y Cells via Activation of Nrf2

Abstract

a-Cyperone, extracted from Cyperus rotundus, has been reported to inhibit microgliamediated neuroinflammation. Oxidative stress and apoptosis play crucial roles in the course of Parkinson's disease (PD). PD is a common neurodegenerative disease characterized by selective death of dopaminergic neurons. This study was designed to investigate the neuroprotective effects of a-cyperone against hydrogen peroxide (H 2 O 2)induced oxidative stress and apoptosis in dopaminergic neuronal SH-SY5Y cells. Neurotoxicity was assessed by MTT assay and the measurement of lactic dehydrogenase (LDH) release. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The apoptosis of SH-SY5Y cells was evaluated by annexin-V-FITC staining. The translocation of NF-E2related factor 2 (Nrf2) was determined by western blot and immunofluorescence staining. Western blot analysis was conducted to determine the expression level of cleavedcaspase-3, the pro-apoptotic factor Bax, and the anti-apoptotic factor, Bcl-2. The results showed that a-cyperone substantially decreased H 2 O 2-induced death, release of LDH, and the production of ROS in SH-SY5Y cells. In addition, we found that a-cyperone attenuated H 2 O 2-induced cellular apoptosis. Moreover, a-cyperone remarkably reduced the expression of cleaved-caspase-3 and Bax, and upregulated Bcl-2. Furthermore, acyperone enhanced the nuclear translocation of Nrf2. Pretreatment with brusatol (BT, an Nrf2 inhibitor) attenuated a-cyperone-mediated suppression of ROS, cleaved-caspase-3, and Bax, as well as a-cyperone-induced Bcl-2 upregulation in H 2 O 2-treated SH-SY5Y cells. a-cyperone neuroprotection required Nrf2 activation. In conclusion, a-cyperone attenuated H 2 O 2-induced oxidative stress and apoptosis in SH-SY5Y cells via the activation of Nrf2, suggesting the potential of this compound in the prevention and treatment of PD.

Anticapsular and Antifungal Activity of α-Cyperone

“…Hence, we performed the PI uptake assay with the α-Cyperone treated C. krusei cells and we did not find the PI uptake ( Figure 3 ), suggesting α-Cyperone may not be targeting the fungal membrane. It is worth mentioning that α-Cyperone inhibits the proliferation of cancer cells through the ROS-mediated signaling pathways [ 19 ]. Fungi as eukaryotic cells, α-Cyperone may function similarly or to related pathways in them, which remain to be determined.…”

“…According to Liu et al [ 18 ], α-Cyperone showed a protective effect on lipopolysaccharide (LPS)-induced acute lung injury/inflammatory response in mice by downregulating the NF-κB and NLRP3 signaling pathways, mainly by upregulating SIRT1. In another study, the neuroprotective effect of α-Cyperone against H 2 O 2 -induced oxidative stress and apoptosis in dopaminergic neuronal SH-SY5Y cells was demonstrated [ 19 ]. Anticancer activity of α-Cyperone has also been reported [ 20 ].…”

“…Although various pharmacological activities of α-Cyperone against mammalian cells are known [ 18 , 19 ], the antifungal and anticapsular activities of α-Cyperone against fungal pathogens Candida and Cryptococcus species are unknown. In this study, we investigated the antifungal activity of α-Cyperone against various human fungal pathogens, its antifungal synergistic activity, and the anticapsular activity of α-Cyperone on Cryp.…”

Editorial: Oxidative Stress: How Has It Been Considered in the Design of New Drug Candidates for Neurodegenerative Diseases?

“…In this context, several hypotheses have been recently proposed to explain the complexity and multifactorial pathogenesis of AD, including OS as not only a central player, but, perhaps, one of the main causative factors of NDs, unifying a series of other sequential or individual pathophysiological events ( Singh et al, 2019 ). According to this consensus, oxidative damage in the brain of patients is resultant from excessive production of free radicals induced by fragments of insoluble and/or overproduced proteins, such as β-amyloid peptide, α-synuclein, tau and huntingtin, with functional alteration in the mitochondria, inadequate energy supply, production of inflammatory mediators and alteration of antioxidant defenses ( Islam, 2016 ; Liu et al, 2017 ). Thus, the modulation of the cellular oxidative process should lead to a new concept in the design of drugs and, possibly, a new way of searching for more effective disease-modifying chemical entities, reinforcing the hope of at least real clinical relief, if healing is not yet possible ( Ghosh et al, 2011 ; Rekatsina et al, 2020 ).…”

“…The collection of research articles and reviews that composed this Research Topic clearly demonstrate some advances to better understand the role of OS in the mechanisms associated with the genesis of NDs and the ability of some natural products to modulate these phenomena. In this context, the paper by Huang et al (2020) describes the neuroprotective effects of α-cyperone, a terpene isolated from Cyperus rotundus , against hydrogen peroxide (H 2 O 2 )-induced OS and apoptosis in dopaminergic neuronal SH-SY5Y cells, used as models to study PD. Their findings indicated that α-cyperone, which is well-known to inhibit neuroinflammation, was able to decrease H 2 O 2 -induced death and production of ROS in SH-SY5Y cells, through a mechanism dependent on the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2), which is a key transcription factor for the regulation of antioxidant proteins expression.…”