Carvacrol protects neuroblastoma SH-SY5Y cells against Fe2+-induced apoptosis by suppressing activation of MAPK/JNK-NF-κB signaling pathway

Abstract

Aim: Carvacrol (2-methyl-5-isopropylphenol), a phenolic monoterpene in the essential oils of the genera Origanum and Thymus, has been shown to exert a variety of therapeutic effects. Here we examined whether carvacrol protected neuroblastoma SH-SY5Y cells against Fe 2+ -induced apoptosis and explored the underlying mechanisms. Methods: Neuroblastoma SH-SY5Y cells were incubated with Fe 2+ for 24 h, and the cell viability was assessed with CCK-8 assay. TUNEL assay and flow cytometric analysis were performed to evaluate cell apoptosis. The mRNA levels of pro-inflammatory cytokines and NF-κB p65 were determined using qPCR. The expression of relevant proteins was determined using Western blot analysis or immunofluorescence staining. Results: Treatment of SH-SY5Y cells with Fe 2+ (50-200 μmol/L) dose-dependently decreased the cell viability, which was significantly attenuated by pretreatment with carvacrol (164 and 333 μmol/L). Treatment with Fe 2+ increased the Bax level and caspase-3 activity, and decreased the Bcl-2 level, resulting in cell apoptosis. Furthermore, treatment with Fe 2+ significantly increased the gene expression of IL-1β, IL-6 and TNF-α, and induced the nuclear translocation of NF-κB. Treatment with Fe 2+ also significantly increased the phosphorylation of p38, ERK, JNK and IKK in the cells. Pretreatment with carvacrol significantly inhibited Fe 2+ -induced activation of NF-κB, expression of the pro-inflammatory cytokines, and cell apoptosis. Moreover, pretreatment with carvacrol inhibited Fe 2+ -induced phosphorylation of JNK and IKK, but not p38 and ERK in the cells. Conclusion: Carvacrol protects neuroblastoma SH-SY5Y cells against Fe 2+ -induced apoptosis, which may result from suppressing the MAPK/JNK-NF-κB signaling pathways.

Genistein‐3′‐sodium sulphonate protects against lipopolysaccharide‐induced lung vascular endothelial cell apoptosis and acute lung injury via BCL‐2 signalling

“…When it is activated by phosphorylation, NF-κB translocates into the nucleus, where active NF-κB binds to specific DNA sequences and regulates the expression of many downstream genes, such as BCL-2. 8 In the present study, we further found that GSS inhibited the activation of NF-κB and attenuated LPS-induced NF-κB translocation from the cytoplasm into the nucleus in ECs. Our data suggested that NF-κB/BCL-2 signalling might be involved in the GSS-induced anti-apoptotic effects on LPSstimulated ECs in vitro.…”

“…BCL-2 family proteins play an important role in cellular apoptosis process by regulating mitochondrial membrane permeability. 7 NF-κB regulates BCL-2 family proteins in immune responses, 8 and inhibition of NF-κB activity has been shown to protect against LPS-induced EC apoptosis. 9 Interestingly, our previous studies revealed that LPS-induced activation of NF-κB in ECs was mediated in a Myd88dependent manner and a Myd88-independent manner (GEF-H1 signalling pathway).…”

Particularly interesting Cys-His-rich protein is highly expressed in human intracranial aneurysms and resists aneurysmal rupture

“…The function of the ternary complex of IPP as a signalling platform is achieved by directly interacting with factors that function as upstream regulators of numerous different signalling pathways (21). The present study summarized the known binding partners of PINCH signaling, which are important in processes as diverse as cell adhesion, migration, proliferation, differentiation, survival and apoptosis (22,23). The results demonstrated a decrease in the pro-apoptotic proteins Bax and caspase3 and an increase in the anti-apoptotic protein Bcl-2 in the RA and UA groups compared to those of the control group (Fig.…”

Programmed cell death in periodontitis: recent advances and future perspectives

“…The experiment demonstrated that the activity of caspase‐3 was inhibited in the presence of carvacrol. These findings indicated that carvacrol might be an apoptotic inhibitor (Nafees et al , ; Cui et al , ).…”

Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons

“…Abnormally high iron concentrations in the brain have been widely reported in AD patients [7,8] , and the well-known APP/PS1 transgenic mouse AD animal model [9] . Additionally, excess iron has been proven to cause neuronal damage in multiple in vitro and in vivo studies [10][11][12] because excess iron can generate reactive oxygen species (ROS) [13] and is closely associated with mitochondrial dysfunction [14] . Correspondingly, therapeutic strategies targeting iron dyshomeostasis have recently attracted considerable attention and have been both preclinically and clinically demonstrated to effectively decrease the progression of the neurological symptoms of AD [15][16][17][18] .…”