Protective Effect of Arzanol Against HO-Induced Oxidative Stress Damage in Differentiated and Undifferentiated SH-SY5Y Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jul 13

PMID 39000492

Authors

Franca Piras

Valeria Sogos

Federica Pollastro

Antonella Rosa

Affiliations

Soon will be listed here.

Abstract

Oxidative stress can damage neuronal cells, greatly contributing to neurodegenerative diseases (NDs). In this study, the protective activity of arzanol, a natural prenylated α-pyrone-phloroglucinol heterodimer, was evaluated against the HO-induced oxidative damage in trans-retinoic acid-differentiated (neuron-like) human SH-SY5Y cells, widely used as a neuronal cell model of neurological disorders. The pre-incubation (for 2 and 24 h) with arzanol (5, 10, and 25 μM) significantly preserved differentiated SH-SY5Y cells from cytotoxicity (MTT assay) and morphological changes induced by 0.25 and 0.5 mM HO. Arzanol reduced the generation of reactive oxygen species (ROS) induced by 2 h oxidation with HO 0.5 mM, established by 2',7'-dichlorodihydrofluorescein diacetate assay. The 2 h incubation of differentiated SH-SY5Y cells with HO determined a significant increase in the number of apoptotic cells versus control cells, evaluated by propidium iodide fluorescence assay (red fluorescence) and NucView 488 assay (green fluorescence). Arzanol pre-treatment (2 h) exerted a noteworthy significant protective effect against apoptosis. In addition, arzanol was tested, for comparison, in undifferentiated SH-SY5Y cells for cytotoxicity and its ability to protect against HO-induced oxidative stress. Furthermore, the PubChem database and freely accessible web tools SwissADME and pkCSM-pharmacokinetics were used to assess the physicochemical and pharmacokinetic properties of arzanol. Our results qualify arzanol as an antioxidant agent with potential neuroprotective effects against neuronal oxidative stress implicated in NDs.

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References

Selvaraj S, Krishnaswamy S, Devashya V, Sethuraman S, Krishnan U . Influence of membrane lipid composition on flavonoid-membrane interactions: Implications on their biological activity. Prog Lipid Res. 2014; 58:1-13. DOI: 10.1016/j.plipres.2014.11.002. View

Scarian E, Viola C, Dragoni F, Di Gerlando R, Rizzo B, Diamanti L . New Insights into Oxidative Stress and Inflammatory Response in Neurodegenerative Diseases. Int J Mol Sci. 2024; 25(5). PMC: 10931808. DOI: 10.3390/ijms25052698. View

Ornano L, Venditti A, Sanna C, Ballero M, Maggi F, Lupidi G . Chemical composition and biological activity of the essential oil from Helichrysum microphyllum Cambess. ssp. tyrrhenicum Bacch., Brullo e Giusso growing in La Maddalena Archipelago, Sardinia. J Oleo Sci. 2014; 64(1):19-26. DOI: 10.5650/jos.ess14171. View

Sanchez-Martinez J, Valdes A, Gallego R, Suarez-Montenegro Z, Alarcon M, Ibanez E . Blood-Brain Barrier Permeability Study of Potential Neuroprotective Compounds Recovered From Plants and Agri-Food by-Products. Front Nutr. 2022; 9:924596. PMC: 9243654. DOI: 10.3389/fnut.2022.924596. View

Fuller M, Futerman A . The brain lipidome in neurodegenerative lysosomal storage disorders. Biochem Biophys Res Commun. 2018; 504(3):623-628. DOI: 10.1016/j.bbrc.2018.03.042. View

Piras F, Sogos V, Pollastro F, Appendino G, Rosa A . Arzanol, a natural phloroglucinol α-pyrone, protects HaCaT keratinocytes against HO-induced oxidative stress, counteracting cytotoxicity, reactive oxygen species generation, apoptosis, and mitochondrial depolarization. J Appl Toxicol. 2023; 44(5):720-732. DOI: 10.1002/jat.4570. View

Biedler J, Helson L, Spengler B . Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res. 1973; 33(11):2643-52. View

Li J, O W, Li W, Jiang Z, Ghanbari H . Oxidative stress and neurodegenerative disorders. Int J Mol Sci. 2013; 14(12):24438-75. PMC: 3876121. DOI: 10.3390/ijms141224438. View

Kunzler A, Zeidan-Chulia F, Gasparotto J, Girardi C, Klafke K, Petiz L . Changes in Cell Cycle and Up-Regulation of Neuronal Markers During SH-SY5Y Neurodifferentiation by Retinoic Acid are Mediated by Reactive Species Production and Oxidative Stress. Mol Neurobiol. 2016; 54(9):6903-6916. DOI: 10.1007/s12035-016-0189-4. View

10.

Bhat A, Dar K, Anees S, Zargar M, Masood A, Sofi M . Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother. 2015; 74:101-10. DOI: 10.1016/j.biopha.2015.07.025. View

11.

Zhao X, Fang J, Li S, Gaur U, Xing X, Wang H . Artemisinin Attenuated Hydrogen Peroxide (HO)-Induced Oxidative Injury in SH-SY5Y and Hippocampal Neurons via the Activation of AMPK Pathway. Int J Mol Sci. 2019; 20(11). PMC: 6600327. DOI: 10.3390/ijms20112680. View

12.

Dinicola S, Mariggio M, Morabito C, Guarnieri S, Cucina A, Pasqualato A . Grape seed extract triggers apoptosis in Caco-2 human colon cancer cells through reactive oxygen species and calcium increase: extracellular signal-regulated kinase involvement. Br J Nutr. 2013; 110(5):797-809. DOI: 10.1017/S0007114512006095. View

13.

Deshpande P, Gogia N, Singh A . Exploring the efficacy of natural products in alleviating Alzheimer's disease. Neural Regen Res. 2019; 14(8):1321-1329. PMC: 6524497. DOI: 10.4103/1673-5374.253509. View

14.

Rosa A, Pollastro F, Atzeri A, Appendino G, Melis M, Deiana M . Protective role of arzanol against lipid peroxidation in biological systems. Chem Phys Lipids. 2010; 164(1):24-32. DOI: 10.1016/j.chemphyslip.2010.09.009. View

15.

He W, Lv C, Chen Z, Shi M, Zeng C, Hou D . The Regulatory Effect of Phytochemicals on Chronic Diseases by Targeting Nrf2-ARE Signaling Pathway. Antioxidants (Basel). 2023; 12(2). PMC: 9952802. DOI: 10.3390/antiox12020236. View

16.

Ferlazzo N, Cirmi S, Maugeri A, Russo C, Lombardo G, Gangemi S . Neuroprotective Effect of Bergamot Juice in 6-OHDA-Induced SH-SY5Y Cell Death, an Model of Parkinson's Disease. Pharmaceutics. 2020; 12(4). PMC: 7238189. DOI: 10.3390/pharmaceutics12040326. View

17.

Venkatesan R, Ji E, Kim S . Phytochemicals that regulate neurodegenerative disease by targeting neurotrophins: a comprehensive review. Biomed Res Int. 2015; 2015:814068. PMC: 4446472. DOI: 10.1155/2015/814068. View

18.

Rosa A, Atzeri A, Nieddu M, Appendino G . New insights into the antioxidant activity and cytotoxicity of arzanol and effect of methylation on its biological properties. Chem Phys Lipids. 2017; 205:55-64. DOI: 10.1016/j.chemphyslip.2017.05.001. View

19.

Pavelescu L . On reactive oxygen species measurement in living systems. J Med Life. 2015; 8 Spec Issue:38-42. PMC: 4564046. View

20.

Park C, Lee H, Noh J, Jin C, Kim G, Hyun J . Hemistepsin A protects human keratinocytes against hydrogen peroxide-induced oxidative stress through activation of the Nrf2/HO-1 signaling pathway. Arch Biochem Biophys. 2020; 691:108512. DOI: 10.1016/j.abb.2020.108512. View