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Journal of Traditional Chinese Medicine >

2023 , Vol. 43 >Issue 5: 868 - 875

DOI: https://doi.org/10.19852/j.cnki.jtcm.20220907.001

Spinosin protects Neuro-2a/APP695 cells from oxidative stress damage by inactivating p38

  • Xiaoying ZHANG ,
  • Ruixuan WANG ,
  • Yiqing WANG ,
  • Fanxing XU ,
  • Tingxu YAN ,
  • Bo WU ,
  • Ming ZHANG ,
  • Ying JIA
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  • 1 School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
    2 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
    3 Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
    4 Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China
    5 Gynecology Department, Shenyang Women's and Children's Hospital, Shenyang 110011, China

Received date: 2022-07-11

  Accepted date: 2022-09-02

  Online published: 2023-08-29

Supported by

National Natural Science Foundation of China: Study on the Basis and Mechanism of Antidepressant Substances in Which Schisandra Chinensis Regulates the Endocannabinoid System in the Body and Participates in "Gut-Brain Dialogue"(82173961);National Natural Science Foundation of China: to Investigate the Pharmacological Substance Basis and Mechanism of Suanzaoren Decoction in Improving Depression by Crosstalk Regulating "Gut Microbiota-Gut-Brain" Axis Based on TLR4-NF-κB/NLRP3 and Wnt/β-Catenin Signaling Pathways(82003926);Doctoral Scientific Research Foundation of Liaoning Province: Study on the Mechanism of Antidepressant Action of Schisandra Chinensis Mediated by Intestinal Flora(2019-BS-233);High-Level Innovation and Entrepreneurship Team of Liaoning Province: "Healthy Liaoning" Functional Food Quality and Safety Innovation Team, "Xingliao Talent Plan" High-Level Innovation and Entrepreneurship Team(XLYC2008029);Guizhou Provincial Natural Science Foundation: Probing the Chemical Components and the Detailed Working Mechanisms of Danggui Buxue Tang for Mitigating the Menopausal Syndrome(QKH-J[2020]1Y377)

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Abstract

OBJECTIVE: To explore the protective mechanism of spinosin (SPI) on Alzheimer's disease (AD) model cells, Neuro-2a/APP695 (N2a/APP695), against H2O2-induced oxidative stress damage, to reflect the influence of oxidative stress on the development of AD, and to provide a valuable basis for the research and development of therapeutic drug for AD.
METHODS: N2a/APP695 cells were exposed to H2O2 and then treated with spinosin. Firstly, the secretion level of amyloid β (Aβ)1-42 and the production of malondialdehyde (MDA) and lactate dehydrogenase (LDH) were detected by enzyme linked immunosorbent assay kits. Secondly, the oligomerization degree of Aβ1-42 was performed by Thioflavin T staining. Thirdly, the expression levels of p-Tau (Ser199/202/396), synaptophysin (SYP), postsynaptic density protein 95 (PSD95), and mitogen-activated protein kinase (MAPK) family-related proteins were detected by Western blot analysis. In addition, FITC-labeled phalloidin was used in cytoskeleton staining to reflect synaptic function.
RESULTS: This study showed that H2O2 stimulated N2a/APP695 cells to produce excessive MDA and LDH and secrete a large amount of Aβ, promoted the aggregation of Aβ, induced Tau protein hyperphosphorylation, and led to synaptic dysfunction. Spinosin reversed these changes caused by H2O2 by inactivating p38, which was verified by treatment with the p38 inhibitor BIRB796.
CONCLUSION: Spinosin protects N2a/APP695 cells from oxidative stress damage caused by H2O2 through inactivating p38.

Key words： Alzheimer disease; spinosin; oxidative stress; p38 mitogen-activated protein kinases

Cite this article

Xiaoying ZHANG , Ruixuan WANG , Yiqing WANG , Fanxing XU , Tingxu YAN , Bo WU , Ming ZHANG , Ying JIA . Spinosin protects Neuro-2a/APP695 cells from oxidative stress damage by inactivating p38[J]. Journal of Traditional Chinese Medicine, 2023 , 43(5) : 868 -875 . DOI: 10.19852/j.cnki.jtcm.20220907.001

References

1. Xu FX, Zhang XY, Wang JY, et al. Spinosin protects N2a cells from H2O2-induced neurotoxicity through inactivation of p38MAPK. J Pharm Pharmacol 2020; 72: 1607-14.
2. Ennerfelt HE, Lukens JR. The role of innate immunity in Alzheimer's disease. Immunol Rev 2020; 297: 225-46.
3. Qi Y, Guo L, Jiang YB, Shi YJ, Sui HJ, Zhao L. Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles. Drug Deliv 2020; 27: 745-55.
4. Pooler AM, Noble W, Hanger DP. A role for tau at the synapse in Alzheimer's disease pathogenesis. Neuropharmacology 2014; 76 Pt A: 1-8.
5. Tu S, Okamoto S, Lipton SA, Xu H. Oligomeric Aβ-induced synaptic dysfunction in Alzheimer's disease. Mol Neurodegener 2014; 9: 48.
6. Teixeira JP, de Castro AA, Soares FV, da Cunha EFF, Ramalho TC. Future therapeutic perspectives into the Alzheimer's disease targeting the oxidative stress hypothesis. Molecules 2019; 24: 4410.
7. Tabassum R, Jeong NY. Potential for therapeutic use of hydrogen sulfide in oxidative stress-induced neurodegenerative diseases. Int J Med Sci 2019; 16: 1386-96.
8. Zuroff L, Daley D, Black KL, Koronyo HM. Clearance of cerebral Aβ in Alzheimer's disease: reassessing the role of microglia and monocytes. Cell Mol Life Sci 2017; 74: 2167-201.
9. Choi EY, Kang SS, Lee SK, Han BH. Polyphenolic biflavonoids inhibit amyloid-beta fibrillation and disaggregate preformed amyloid-beta fibrils. Biomol Ther (Seoul) 2020; 28: 145-51.
10. Duan Q, Si E. MicroRNA-25 aggravates Aβ1-42-induced hippocampal neuron injury in Alzheimer's disease by downregulating KLF2 via the Nrf2 signaling pathway in a mouse model. J Cell Biochem 2019; 120: 15891-905.
11. Michalska P, Mayo P, MC Fernández, et al. Antioxidant, anti-inflammatory and neuroprotective profiles of novel 1,4-dihydropyridine derivatives for the treatment of Alzheimer's disease. Antioxidants (Basel) 2020; 9: 650.
12. Song Y, Li N, Gu J, et al. β-Hydroxybutyrate induces bovine hepatocyte apoptosis via an ROS-p38 signaling pathway. J Dairy Sci 2016; 99: 9184-98.
13. Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ 2015; 350: h369.
14. Fang X, Hao J, Zhou H, Zhu LX, Wang JH, Song FQ. Pharmacological studies on the sedative-hypnotic effect of Semen Ziziphi spinosae (Suanzaoren) and Radix et Rhizoma Salviae miltiorrhizae (Danshen) extracts and the synergistic effect of their combinations. Phytomedicine 2010; 17: 75-80.
15. Xu FX, He BS, Xiao F, et al. Neuroprotective effects of spinosin on recovery of learning and memory in a mouse model of Alzheimer's disease. Biomol Ther (Seoul) 2019; 27: 71-7.
16. Zhang XY, Wang JY, Gong GW, et al. Spinosin inhibits Aβ1-42production and aggregation via activating Nrf2/HO-1 pathway. Biomol Ther (Seoul) 2020; 28: 259-66.
17. Karthick C, Nithiyanandan S, Essa MM, Guillemin GJ, Jayachandran SK, Anusuyadevi M. Time-dependent effect of oligomeric amyloid-β1-42-induced hippocampal neurodegeneration in rat model of Alzheimer's disease. Neurol Res 2019; 41: 139-50.
18. Arias E, SS Gallego, Villarroya M, García AG, López MG. Unequal neuroprotection afforded by the acetylcholinesterase inhibitors galantamine, donepezil, and rivastigmine in SH-SY5Y neuroblastoma cells: role of nicotinic receptors. J Pharmacol Exp Ther 2005; 315: 1346-53.
19. Tang Y, Min Z, Xiang XJ, et al. Estrogen-related receptor alpha is involved in Alzheimer's disease-like pathology. Exp Neurol 2018; 305: 89-96.
20. Prasad K. AGE-RAGE stress: a changing landscape in pathology and treatment of Alzheimer's disease. Mol Cell Biochem 2019; 459: 95-112.
21. Xiao L, Liao F, Ide R, et al. Enzyme-digested Colla Corii Asini (E'jiao) prevents hydrogen peroxide-induced cell death and accelerates amyloid beta clearance in neuronal-like PC12 cells. Neural Regen Res 2020; 15: 2270-2.
22. Hu Y, Zhou KY, Wang ZJ, Lu Y, Yin M. N-stearoyl-l-Tyrosine inhibits the cell senescence and apoptosis induced by H2O2 in HEK293/Tau cells via the CB2 receptor. Chem Biol Interact 2017; 272: 135-44.
23. Su B, Wang X, Lee HG, et al. Chronic oxidative stress causes increased tau phosphorylation in M17 neuroblastoma cells. Neurosci Lett 2010; 468: 267-71.
24. Tamagno E, Robino G, Obbili A, et al. H2O2 and 4-hydroxynonenal mediate amyloid beta-induced neuronal apoptosis by activating JNKs and p38MAPK. Exp Neurol 2003; 180: 144-55.
25. Schn?der L, Hao W, Qin Y, et al.Deficiency of neuronal p38α MAPK attenuates amyloid pathology in Alzheimer disease mouse and cell models through facilitating lysosomal degradation of BACE1. J Biol Chem 2016; 291: 2067-79.
26. Hanger DP, Anderton BH, Noble W. Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med 2009; 15: 112-9.
27. Su JH, Cummings BJ, Cotman CW. Early phosphorylation of tau in Alzheimer's disease occurs at Ser-202 and is preferentially located within neurites. Neuroreport 1994; 5: 2358-62.
28. Yao E, Tang Y, Liu X, Wang MH. TPPU protects tau from H2O2-induced hyperphosphorylation in HEK293/tau cells by regulating PI3K/AKT/GSK-3β pathway. Hua Zhong Ke Ji Da Xue Xue Bao 2016; 36: 785-90.
29. Borovac J, Bosch M, Okamoto K. Regulation of actin dynamics during structural plasticity of dendritic spines: signaling messengers and actin-binding proteins. Mol Cell Neurosci 2018; 91: 122-30.
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