Neuroprotective Effects of Sparassis crispa Ethanol Extract through the AKT/NRF2 and ERK/CREB Pathway in Mouse Hippocampal Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Fungal Material
2.2. Extraction and Separation
2.3. Cell Culture
2.4. Cell Viability Assay
2.5. Annexin Ⅴ/Propidium Iodide (PI) Assay
2.6. Intracellular ROS Measurement
2.7. Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR)
2.8. Western Blot
2.9. High Performance Liquid Chromatography (HPLC) Analysis
2.10. Statstical Analysis
3. Results
3.1. Effects of SCE on Glutamate-induced Excitotoxicity and ROS Generation in HT22 Cells
3.2. Protective Effect of SCE-E against Glutamate-Induced Cell Death in HT22 Cells
3.3. Protective Effect of SCE-E against Glutamate-Induced Oxidative Stress in HT22 Cells
3.4. SCE-E Regulates Gene Expression of Bdnf, Nrf2, and Catalase in HT22 Cells
3.5. SCE-E Regulates ERK-Mediated CREB-BDNF Signaling and AKT-Mediated Nrf2 Signaling
3.6. HPLC Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Stamets, P.; Zwickey, H. Medicinal Mushrooms: Ancient Remedies Meet Modern Science. Integr. Med. Encinitas Calif. 2014, 13, 46–47. [Google Scholar]
- Spencer, S.J.; Korosi, A.; Layé, S.; Shukitt-Hale, B.; Barrientos, R.M. Food for thought: How nutrition impacts cognition and emotion. NPJ Sci. Food 2017, 1, 7. [Google Scholar] [CrossRef] [PubMed]
- Davis, J.J.; Fournakis, N.; Ellison, J. Ketogenic Diet for the Treatment and Prevention of Dementia: A Review. J. Geriatr. Psychiatry Neurol. 2020, 34, 3–10. [Google Scholar] [CrossRef] [PubMed]
- Businaro, R.; Vauzour, D.; Sarris, J.; Münch, G.; Gyengesi, E.; Brogelli, L.; Zuzarte, P. Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease and Depression. Front. Nutr. 2021, 8, 669846. [Google Scholar] [CrossRef] [PubMed]
- Kubota, C.; Torii, S.; Hou, N.; Saito, N.; Yoshimoto, Y.; Imai, H.; Takeuchi, T. Constitutive Reactive Oxygen Species Generation from Autophagosome/Lysosome in Neuronal Oxidative Toxicity. J. Biol. Chem. 2010, 285, 667–674. [Google Scholar] [CrossRef] [PubMed]
- Barnham, K.J.; Masters, C.L.; Bush, A.I. Neurodegenerative diseases and oxidative stress. Nat. Rev. Drug Discov. 2004, 3, 205–214. [Google Scholar] [CrossRef] [PubMed]
- Meldrum, B.S. Glutamate as a Neurotransmitter in the Brain: Review of Physiology and Pathology. J. Nutr. 2000, 130, 1007S–1015S. [Google Scholar] [CrossRef] [PubMed]
- Kritis, A.A.; Stamoula, E.G.; Paniskaki, K.A.; Vavilis, T.D. Researching glutamate—Induced cytotoxicity in different cell lines: A comparative/collective analysis/study. Front. Cell. Neurosci. 2015, 9, 91. [Google Scholar] [CrossRef] [PubMed]
- Sato, K.; Yamanaka, Y.; Asakura, Y.; Nedachi, T. Glutamate levels control HT22 murine hippocampal cell death by regulating biphasic patterns of Erk1/2 activation: Role of metabolic glutamate receptor 5. Biosci. Biotechnol. Biochem. 2016, 80, 712–718. [Google Scholar] [CrossRef] [PubMed]
- Fukui, M.; Song, J.-H.; Choi, H.J.; Choi, H.J.; Zhu, B.T. Mechanism of glutamate-Induced neurotoxicity in HT22 mouse hippocampal cells. Eur. J. Pharmacol. 2009, 617, 1–11. [Google Scholar] [CrossRef] [PubMed]
- de Vries, H.E.; Witte, M.; Hondius, D.; Rozemuller, A.J.M.; Drukarch, B.; Hoozemans, J.; van Horssen, J. Nrf2-induced antioxidant protection: A promising target to counteract ROS-mediated damage in neurodegenerative disease? Free Radic. Biol. Med. 2008, 45, 1375–1383. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, T.; Sherratt, P.J.; Pickett, C.B. Regulatory Mechanisms Controlling Gene Expression Mediated by the Antioxidant Response Element. Annu. Rev. Pharmacol. Toxicol. 2003, 43, 233–260. [Google Scholar] [CrossRef] [PubMed]
- Koundouros, N.; Poulogiannis, G. Phosphoinositide 3-Kinase/Akt Signaling and Redox Metabolism in Cancer. Front. Oncol. 2018, 8, 160. [Google Scholar] [CrossRef] [PubMed]
- Zarneshan, S.N.; Fakhri, S.; Khan, H. Targeting Akt/CREB/BDNF signaling pathway by ginsenosides in neurodegenerative diseases: A mechanistic approach. Pharmacol. Res. 2022, 177, 106099. [Google Scholar] [CrossRef] [PubMed]
- Hannan, M.A.; Dash, R.; Sohag, A.A.M.; Haque, M.N.; Moon, I.S. Neuroprotection Against Oxidative Stress: Phytochemicals Targeting TrkB Signaling and the Nrf2-ARE Antioxidant System. Front. Mol. Neurosci. 2020, 13, 116. [Google Scholar] [CrossRef] [PubMed]
- Albert-Gascó, H.; Ros-Bernal, F.; Castillo-Gómez, E.; Olucha-Bordonau, F.E. MAP/ERK Signaling in Developing Cognitive and Emotional Function and Its Effect on Pathological and Neurodegenerative Processes. Int. J. Mol. Sci. 2020, 21, 4471. [Google Scholar] [CrossRef] [PubMed]
- Alonso, M.; Medina, J.H.; Pozzo-Miller, L. ERK1/2 Activation Is Necessary for BDNF to Increase Dendritic Spine Density in Hippocampal CA1 Pyramidal Neurons. Learn. Mem. 2004, 11, 172–178. [Google Scholar] [CrossRef] [PubMed]
- Yoo, J.-M.; Lee, B.D.; Sok, D.-E.; Ma, J.Y.; Kim, M.R. Neuroprotective action of N-acetyl serotonin in oxidative stress-induced apoptosis through the activation of both TrkB/CREB/BDNF pathway and Akt/Nrf2/Antioxidant enzyme in neuronal cells. Redox Biol. 2017, 11, 592–599. [Google Scholar] [CrossRef] [PubMed]
- Sou, H.-D.; Ryoo, R.; Ryu, S.-R.; Ka, K.-H.; Park, H.; Joo, S.-H. Morphological and genetic characteristics of newly crossbred cauliflower mushroom (Sparassis latifolia). J. Microbiol. 2013, 51, 552–557. [Google Scholar] [CrossRef]
- Kimura, T. Natural Products and Biological Activity of the Pharmacologically Active Cauliflower Mushroom Sparassis crispa. BioMed Res. Int. 2013, 2013, 982317. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.; Hu, B.; Han, M.; Guo, Y.; Cheng, Y.; Qian, H. Purification, structural characterization and neuroprotective effect of a neutral polysaccharide from Sparassis crispa. Int. J. Biol. Macromol. 2022, 201, 389–399. [Google Scholar] [CrossRef] [PubMed]
- Bang, S.; Chae, H.-S.; Lee, C.; Choi, H.G.; Ryu, J.; Li, W.; Lee, H.; Jeong, G.-S.; Chin, Y.-W.; Shim, S.H. New Aromatic Compounds from the Fruiting Body of Sparassis crispa (Wulf.) and Their Inhibitory Activities on Proprotein Convertase Subtilisin/Kexin Type 9 mRNA Expression. J. Agric. Food Chem. 2017, 65, 6152–6157. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.; Guo, Y.; Cheng, Y.; Zhao, W.; Zheng, Y.; Qian, H. Ultrasonic-assisted enzymatic extraction of Sparassis crispa polysaccharides possessing protective ability against H2O2-induced oxidative damage in mouse hippocampal HT22 cells. RSC Adv. 2020, 10, 22164–22175. [Google Scholar] [CrossRef]
- Tönnies, E.; Trushina, E. Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease. J. Alzheimers Dis. 2017, 57, 1105–1121. [Google Scholar] [CrossRef]
- Jin, M.C.; Yoo, J.-M.; Sok, D.-E.; Kim, M.R. Neuroprotective Effect of N-Acyl 5-Hydroxytryptamines on Glutamate-Induced Cytotoxicity in HT-22 Cells. Neurochem. Res. 2014, 39, 2440–2451. [Google Scholar] [CrossRef]
- Houghton, P.J.; Howes, M.-J. Natural Products and Derivatives Affecting Neurotransmission Relevant to Alzheimer’s and Parkinson’s Disease. Neurosignals 2005, 14, 6–22. [Google Scholar] [CrossRef] [PubMed]
- Tonelli, C.; Chio, I.I.C.; Tuveson, D.A. Transcriptional Regulation by Nrf2. Antioxid. Redox Signal. 2018, 29, 1727–1745. [Google Scholar] [CrossRef] [PubMed]
- Yuan, H.; Xu, Y.; Luo, Y.; Wang, N.-X.; Xiao, J.-H. Role of Nrf2 in cell senescence regulation. Mol. Cell. Biochem. 2020, 476, 247–259. [Google Scholar] [CrossRef]
- Yu, C.; Xiao, J.-H. The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging. Oxidative Med. Cell. Longev. 2021, 2021, 6635460. [Google Scholar] [CrossRef] [PubMed]
- Ortuño-Sahagún, D.; González, R.M.; Verdaguer, E.; Huerta, V.C.; Torres-Mendoza, B.M.; Lemus, L.; Rivera-Cervantes, M.C.; Camins, A.; Zárate, C.B. Glutamate Excitotoxicity Activates the MAPK/ERK Signaling Pathway and Induces the Survival of Rat Hippocampal Neurons In Vivo. J. Mol. Neurosci. 2013, 52, 366–377. [Google Scholar] [CrossRef] [PubMed]
- Grimes, M.T.; Powell, M.; Gutierrez, S.M.; Darby-King, A.; Harley, C.W.; McLean, J.H. Epac activation initiates associative odor preference memories in the rat pup. Learn. Mem. 2015, 22, 74–82. [Google Scholar] [CrossRef] [PubMed]
- Sakamoto, K.M.; Frank, D.A. CREB in the Pathophysiology of Cancer: Implications for Targeting Transcription Factors for Cancer Therapy. Clin. Cancer Res. 2009, 15, 2583–2587. [Google Scholar] [CrossRef] [PubMed]
- Pak, M.E.; Yang, H.J.; Li, W.; Kim, J.K.; Go, Y. Yuk-Gunja-Tang attenuates neuronal death and memory impairment via ERK/CREB/BDNF signaling in the hippocampi of experimental Alzheimer’s disease model. Front. Pharmacol. 2022, 13, 1014840. [Google Scholar] [CrossRef] [PubMed]
- Welch, K.; Helpern, J.; Ewing, J.; Robertson, W.; D’Andrea, G. Biochemical Effects of Cerebral Ischemia: Relevance To Migraine. Cephalalgia 1985, 5 (Suppl. S2), 35–42. [Google Scholar] [CrossRef] [PubMed]
- Fukui, M.; Zhu, B.T. Mitochondrial superoxide dismutase SOD2, but not cytosolic SOD1, plays a critical role in protection against glutamate-induced oxidative stress and cell death in HT22 neuronal cells. Free Radic. Biol. Med. 2010, 48, 821–830. [Google Scholar] [CrossRef] [PubMed]
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Pak, M.E.; Li, W. Neuroprotective Effects of Sparassis crispa Ethanol Extract through the AKT/NRF2 and ERK/CREB Pathway in Mouse Hippocampal Cells. J. Fungi 2023, 9, 910. https://doi.org/10.3390/jof9090910
Pak ME, Li W. Neuroprotective Effects of Sparassis crispa Ethanol Extract through the AKT/NRF2 and ERK/CREB Pathway in Mouse Hippocampal Cells. Journal of Fungi. 2023; 9(9):910. https://doi.org/10.3390/jof9090910
Chicago/Turabian StylePak, Malk Eun, and Wei Li. 2023. "Neuroprotective Effects of Sparassis crispa Ethanol Extract through the AKT/NRF2 and ERK/CREB Pathway in Mouse Hippocampal Cells" Journal of Fungi 9, no. 9: 910. https://doi.org/10.3390/jof9090910