Spinosin protects N2a cells from H2O2-induced neurotoxicity through inactivation of p38MAPK

Abstract

Objectives Previous studies have suggested that spinosin (SPI) exerted neuroprotective effects through inhibition of oxidative damage, but the underlying mechanisms are still unclear. Herein, the mechanisms underlying the protective effects of SPI against oxidative stress induced by hydrogen peroxide (H 2 O 2) were examined in neuro-2a (N2a) mouse neuroblastoma cells. Methods N2a cells were pretreated with H 2 O 2 for 2 h, followed by a 24-h incubation with SPI. Intracellular reactive oxygen species (ROS) production was analysed by flow cytometry. Levels of Aβ 1-42 production were determined by ELISA assay. Levels of expression of c-Jun N-terminal kinase (JNK), p-JNK, extracellular signal-regulated kinase (ERK), pERK , p38 mitogen-activated protein kinase (p38MAPK), p-p38MAPK, p-Tau (Ser199), p-Tau (Ser202), p-Tau (Ser396), synaptophysin (SYP) and postsynaptic scaffold postsynaptic density-95 (PSD-95) were detected by Western blot analysis. Key findings Our results showed that H 2 O 2 treatment enhanced intracellular ROS production in N2a cells. SPI prevented H 2 O 2-induced oxidative damage via inhibiting Aβ 1-42 production, decreasing Tau phosphorylation and improving synaptic structural plasticity. Notably, H 2 O 2-increased p38MAPK activation was attenuated by SPI administration, and p38MAPK inhibitor BIRB796 markedly reduced H 2 O 2-induced oxidative damage in N2a cells. Conclusions Our findings suggest that SPI protects N2a cells from H 2 O 2induced oxidative damage through inactivation of p38MAPK.

Exploration of Ziziphi Spinosae Semen in Treating Insomnia Based on Network Pharmacology Strategy

“…Jujuboside A can inhibit cancer cell growth through various mechanisms such as cell cycle arrest, proliferation inhibition, stem cell inhibition, and promotion of aging and can contaminate antitoxins [ 25 , 26 ], and our analysis results show that there are many intersections of targets associated with it and insomnia targets. Spinosin exerts neuroprotective effects by inhibiting oxidative damage and has a significant antidepressant effect, and there is a great association between spinosin and insomnia [ 27 , 28 ]. Although the kinetic values of these two components are relatively low, they have very excellent biological activity and are closely related to our study.…”

The pharmacology, pharmacokinetics, and toxicity of spinosin: A mini review

“…Spinosin showed the inhibitory effect on the intracellular ROS production induced by H 2 O 2 in N2a cells. The in-depth mechanism research indicated spinosin inhibited A β (1–42) production, decreased Tau phosphorylation, and improved synaptic structural plasticity induced by H 2 O 2 through inhibiting the p38MAPK activation ( Xu et al, 2020 ).…”

“…Jujuboside A, jujuboside B, and spinosin are major components of total saponins and total flavones, respectively ( Zhu et al, 2015 ). Spinosin is a C -glycoside flavonoid isolated from the ethanol extract of ZJS’s dried seeds ( Huang et al, 2014 ), as one of the main bioactive components of ZJS, numerous explorations of the pharmacological effects of it have been reported, such as hypnosis effects ( Wang et al, 2008 , 2010 , 2012 ; Wang et al, 2016a ), improvement of cognitive function ( Jung et al, 2014 ; Ko et al, 2015 ; Xu et al, 2020 ), anxiolytic effect ( Wang and Yan, 2022 ), inhibition of melanin synthesis ( Moon et al, 2019 ), and antioxidant effects ( Zhang et al, 2020a ).…”

Antidepressant-Like Effects of Ethanol Extract of Ziziphus jujuba Mill Seeds in Mice

“…Very recently, Ziziphus mucronata showed an antidepressant effect in chronically stressed rats due to its capacities for antioxidant activity, and probably the modulation of monoamines transmission [37]. Spinosin, a major constituent of SZS, has been reported to have the activities of neurogenesis for cognitive improvement [38][39][40], sleep reduction for the treatment of insomnia [41], neuroprotection [42], and cardioprotection [43]. However, the antidepressant activity of spinosin was not previously reported.…”