Neuroprotective effects of hesperetin on H2O2-induced damage in neuroblastoma SH-SY5Y cells
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BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates ner ve cells. Neurodegenerative diseases are chronic central ner vous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietar y compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin’s neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H2O2)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H2O2 (400 µM) in hesperetin absence or presence (10–40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4′,6-diamidino-2-phenylindole staining allowed us to obser ve nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H2O2-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H2O2-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF- κB translocation into H2O2-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H2O2-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/ Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophag y pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietar y agent that reduces neurodegenerative disease onset, progression, and prevention.
Abstract
BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates ner ve cells. Neurodegenerative diseases are chronic central ner vous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietar y compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin’s neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H2O2)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H2O2 (400 µM) in hesperetin absence or presence (10–40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4′,6-diamidino-2-phenylindole staining allowed us to obser ve nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H2O2-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H2O2-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF- κB translocation into H2O2-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H2O2-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/ Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophag y pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietar y agent that reduces neurodegenerative disease onset, progression, and prevention.
참고문헌 (84)
- Singh A, "Oxidative stress : a key modulator in neurodegenerative diseases", Molecules, 24, pp.1583~ (2019)
- Simonian NA, "Oxidative stress in neurodegenerative diseases", Annu Rev Pharmacol Toxicol, 36, pp.83~106 (1996)
- Sharifi-Rad M, "Lifestyle, oxidative stress, and antioxidants : back and forth in the pathophysiology of chronic diseases", Front Physiol, 11, pp.694~ (2020)
- Whittemore ER, "A detailed analysis of hydrogen peroxide-induced cell death in primary neuronal culture", Neuroscience, 67, pp.921~932 (1995)
- Lindenboim L, "Bcl-xL inhibits different apoptotic pathways in rat PC12 cells", Neurosci Lett, 253, pp.37~40 (1998)
- Rojkind M, "Role of hydrogen peroxide and oxidative stress in healing responses", Cell Mol Life Sci, 59, pp.1872~1891 (2002)
- Amor S, "Inflammation in neurodegenerative diseases", Immunology, 129, pp.154~169 (2010)
- Hassanzadeh-Taheri M, "Rosmarinic acid attenuates lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats", J Chem Neuroanat, 117, pp.102008~ (2021)
- Ha SK, "6-Shogaol, a ginger product, modulates neuroinflammation : a new approach to neuroprotection", Neuropharmacology, 63, pp.211~223 (2012)
- 배미경, "흰쥐 뇌에서의 Lipopolysaccharide-유도 산화적 스트레스에 대한 OQ21과 Melatonin의 작용", 약 학 회 지, 49(4), pp.347~354 (2005), 대한약학회
- 최원희, "느릅나무 추출물의 항산화 효과 및 L-glutamate 유래 PC12 세포독성 보호효과", 한국식품과학회지, 37(3), pp.479~483 (2005), 한국식품과학회
- Good PF, "Evidence of neuronal oxidative damage in Alzheimer’s disease", Am J Pathol, 149, pp.21~28 (1996)
- Radi E, "Apoptosis and oxidative stress in neurodegenerative diseases", J Alzheimers Dis, 42(Suppl 3), pp.S125~S152 (2014)
- Saraste A, "Morphologic and biochemical hallmarks of apoptosis", Cardiovasc Res, 45, pp.528~537 (2000)
- 김정희, "국내산 참다래 추출물의 신경독성 방어효과", 한국자원식물학회지, 23(2), pp.165~171 (2010), 한국자원식물학회
- Chen B, "Protective effects of(E)-2-(1-hydroxyl-4-oxocyclohexyl)ethyl caffeine against hydrogen peroxide-induced injury in PC12 cells", Neurochem Res, 40, pp.531~541 (2015)
- Tian X, "Protective effects of Arctium lappa L. roots against hydrogen peroxide-induced cell injury and potential mechanisms in SH-SY5Y cells", Cell Mol Neurobiol, 35, pp.335~344 (2015)
- Chang KC, "The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases", Cell Biosci, 12, pp.1~ (2022)
- Nixon RA, "The role of autophagy in neurodegenerative disease", Nat Med, 19, pp.983~997 (2013)
- Tong W, "Liraglutide ameliorates nonalcoholic fatty liver disease by enhancing mitochondrial architecture and promoting autophagy through the SIRT1", SIRT3-FOXO3a pathway, 2016, pp.46, 933~943
- Yang L, "Curcumin alleviates D-galactose-induced cardiomyocyte senescence by promoting autophagy via the SIRT1", AMPK, Evid Based Complement Alternat Med, pp.2022, 2022[DOI]
- 신옥, "Oligonol promotes anti-aging pathways via modulation of SIRT1-AMPK-Autophagy Pathway", Nutrition Research and Practice, 10(1), pp.3~10 (2016), 한국영양학회
- Bockaert J, "mTOR in brain physiology and pathologies", Physiol Rev, 95, pp.1157~1187 (2015)
- Carosi JM, "Rapamycin and Alzheimer disease : a double-edged sword?", Autophagy, 15, pp.1460~1462 (2019)
- Velmurugan BK, "Neuroprotective role of phytochemicals", Molecules, 23, pp.2485~ (2018)
- Parhiz H, "Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin : an updated review of their molecular mechanisms and experimental models", Phytother Res, 29, pp.323~331 (2015)
- Morin B, "The citrus flavonoids hesperetin and nobiletin differentially regulate low density lipoprotein receptor gene transcription in HepG2 liver cells", J Nutr, 138, pp.1274~1281 (2008)
- Marletta MA, "Nitric oxide synthase structure and mechanism", J Biol Chem, 268, pp.12231~12234 (1993)
- Morgan MJ, "Crosstalk of reactive oxygen species and NF-κB signaling", Cell Res, 21, pp.103~115 (2011)
- Yue J, "Understanding MAPK signaling pathways in apoptosis", Int J Mol Sci, 21, pp.2346~ (2020)
- Larson EB, "Prospects for delaying the rising tide of worldwide, late-life dementias", Int Psychogeriatr, 22, pp.1196~1202 (2010)
- Teleanu DM, "An overview of oxidative stress, neuroinflammation, and neurodegenerative diseases", Int J Mol Sci, 23, pp.5938~ (2022)
- Nita M, "The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults", Oxid Med Cell Longev, 2016, pp.3164734~ (2016)
- Liu JT, "Microglia and astroglia : the role of neuroinflammation in lead toxicity and neuronal injury in the brain", Neuroimmunol Neuroinflamm, 2, pp.131~137 (2015)
- Amato A, "Natural compounds as beneficial antioxidant agents in neurodegenerative disorders : a focus on Alzheimer’s disease", Antioxidants, 8, pp.608~ (2019)
- Shimmyo Y, "Epigallocatechin-3-gallate and curcumin suppress amyloid beta-induced beta-site APP cleaving enzyme-1 upregulation", Neuroreport, 19, pp.1329~1333 (2008)
- Song X, "Silibinin ameliorates anxiety", depression-like behaviors in amyloid β-treated rats by upregulating BDNF, Physiol Behav, pp.2017, 179[DOI]
- Kumar V, "Cerebrospinal fluid choline, and acetylcholinesterase activity in familial vs. nonfamilial Alzheimer’s disease patients", Arch Gerontol Geriatr, 7, pp.111~117 (1988)
- Roohbakhsh A, "Molecular mechanisms behind the biological effects of hesperidin and hesperetin for the prevention of cancer and cardiovascular diseases", Life Sci, 124, pp.64~74 (2015)
- Elstner EF, "Oxygen activation and oxygen toxicity", Annu Rev Plant Physiol, 33, pp.73~96 (1982)
- Finkel T, "Oxidants, oxidative stress and the biology of ageing", Nature, 408, pp.239~247 (2000)
- Ma J, "Neuroprotective effects of proanthocyanidins, natural flavonoids derived from plants, on rotenone-induced oxidative stress and apoptotic cell death in human neuroblastoma SH-SY5Y cells", Front Neurosci, 12, pp.369~ (2018)
- Ling APK, "Neuroprotective roles of asiaticoside on hydrogen peroxideinduced toxicity in SH-SY5Y cells", J Fundam Appl Sci, 9, pp.636~649 (2017)
- Andreasson KI, "Targeting innate immunity for neurodegenerative disorders of the central nervous system", J Neurochem, 138, pp.653~693 (2016)
- Mukaida N, "Novel insight into molecular mechanism of endotoxin shock : biochemical analysis of LPS receptor signaling in a cell-free system targeting NF-κB and regulation of cytokine production", action through β2 integrin in vivo, 1996, pp.59, 145~151
- Liu T, "NF-κB signaling in inflammation", Signal Transduct Target Ther, 2, pp.17023~ (2017)
- Schmedtje JF Jr, "Hypoxia induces cyclooxygenase-2 via the NF-κB p65 transcription factor in human vascular endothelial cells", J Biol Chem, 272, pp.601~608 (1997)
- Baldwin AS Jr, "The NF-κB and I κB proteins : new discoveries and insights", Annu Rev Immunol, 14, pp.649~683 (1996)
- 박재현, "LPS에 의해 활성화된 미세아교세포에서 미역쇠 추출물의 신경염증 보호 효과", Journal of Nutrition and Health, 50(1), pp.25~31 (2017), 한국영양학회
- Shal B, "Anti-neuroinflammatory potential of natural products in attenuation of Alzheimer’s disease", Front Pharmacol, 9, pp.548~ (2018)
- Naoi M, "Neuroprotection of multifunctional phytochemicals as novel therapeutic strategy for neurodegenerative disorders : antiapoptotic and antiamyloidogenic activities by modulation of cellular signal pathways", Future Neurol, 14, pp.FNL9~ (2019)
- 박찬흠, "H2O2로 유도된 C6 신경교세포의 세포사멸에 대한 감초 추출물과 감초 활성물질의 보호효과", 한국약용작물학회지, 25(5), pp.315~321 (2017), 한국약용작물학회[DOI]
- Elmore S, "Apoptosis : a review of programmed cell death", Toxicol Pathol, 35, pp.495~516 (2007)
- Su B, "Mitogen-activated protein kinase cascades and regulation of gene expression", Curr Opin Immunol, 8, pp.402~411 (1996)
- Ruffels J, "Activation of ERK1", 2, JNK and PKB by hydrogen peroxide in human SHSY5Y neuroblastoma cells : role of ERK1, Eur J Pharmacol, pp.2004, 483[DOI]
- Son Y, "Mitogen-activated protein kinases and reactive oxygen species : how can ROS activate MAPK pathways?", J Signal Transduct, 2011, pp.792639~ (2011)
- Cagnol S, "ERK and cell death : mechanisms of ERK-induced cell death--apoptosis, autophagy and senescence", FEBS J, 277, pp.2~21 (2010)
- Subramaniam S, "ERK and cell death : ERK1", 2 in neuronal death, 2010, pp.277, 22~29
- Ouyang M, "Critical role of ASK1 in the 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells", J Neurochem, 97, pp.234~244 (2006)
- Kim SD, "Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis", Biochem Biophys Res Commun, 328, pp.326~334 (2005)
- Feng HJ, "Silencing of FANCD2 enhances the radiosensitivity of metastatic cervical lymph node-derived head and neck squamous cell carcinoma HSC4 cells", Int J Oncol, 50, pp.1241~1250 (2017)
- Su JC, "Novel indoloquinoline derivative, IQDMA, induces G2", M phase arrest and apoptosis in A549 cells through JNK, Life Sci, pp.2009, 85[DOI]
- Lee S, "Protective effects of red ginseng oil against Aβ25-35-induced neuronal apoptosis and inflammation in PC12 cells", Int J Mol Sci, 18, pp.2218~ (2017)
- Tang S, "Neuroprotective effects of savinin on LPS-induced neuroinflammation in vivo via regulating MAPK", NF-κB pathway and NLRP3inflammasome activation, 2023, pp.28, 1575~
- Wang MM, "The relationship between autophagy and brain plasticity in neurological diseases", Front Cell Neurosci, 13, pp.228~ (2019)
- 김희주, "Neuroprotective Effect of Chebulagic Acid via Autophagy Induction in SH-SY5Y Cells", Biomolecules & Therapeutics, 22(4), pp.275~281 (2014), 한국응용약물학회
- Shirgadwar SM, "Neuroprotective effect of phloretin in rotenoneinduced mice model of Parkinson’s disease: modulating mTOR-NRF2-p62 mediated autophagy-oxidative stress crosstalk", J Alzheimers Dis (2022)
- Xi X, "Pioglitazone protects tubular cells against hypoxia", reoxygenation injury through enhancing autophagy via AMPK-mTOR signaling pathway, 2019, pp.863, 172695~
- Hill JL, "Traumatic brain injury decreases AMP-activated protein kinase activity and pharmacological enhancement of its activity improves cognitive outcome", J Neurochem, 139, pp.106~119 (2016)
- Tang SJ, "A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus", Proc Natl Acad Sci U S A, 99, pp.467~472 (2002)
- Hoeffer CA, "mTOR signaling : at the crossroads of plasticity, memory and disease", Trends Neurosci, 33, pp.67~75 (2010)
- Ravikumar B, "Rapamycin pre-treatment protects against apoptosis", Hum Mol Genet, 15, pp.1209~1216 (2006)
- Hardie DG, "AMPK : a nutrient and energy sensor that maintains energy homeostasis", Nat Rev Mol Cell Biol, 13, pp.251~262 (2012)
- Wang Z, "Autophagy protects against PI3K", Akt, Neurosci Lett, pp.2017, 656[DOI]
- Stacchiotti A, "Natural compounds and autophagy : allies against neurodegeneration", Front Cell Dev Biol, 8, pp.555409~ (2020)
- Wu Y, "Resveratrol-activated AMPK", SIRT1, Neurosignals, pp.2011, 19[DOI]
- Chen J, "Quercetin attenuates tau hyperphosphorylation and improves cognitive disorder via suppression of ER stress in a manner dependent on AMPK pathway", J Funct Foods, 22, pp.463~476 (2016)
- Zhao Y, "Glutamine protects against oxidative stress injury through inhibiting the activation of PI3K", Akt signaling pathway in parkinsonian cell model, 2019, pp.24, 4~
- Wu Y, "(-)-Epigallocatechin-3-gallate provides neuroprotection via AMPK activation against traumatic brain injury in a mouse model", Naunyn Schmiedebergs Arch Pharmacol, 393, pp.2209~2220 (2020)
- Vingtdeux V, "AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-β peptide metabolism", J Biol Chem, 285, pp.9100~9113 (2010)
- Tramutola A, "Alteration of mTOR signaling occurs early in the progression of Alzheimer disease(AD) : analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD", J Neurochem, 133, pp.739~749 (2015)
- Griffin RJ, "Activation of Akt", PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer’s disease pathology, 2005, pp.93, 105~117
- Wang Y, "Role of mammalian target of rapamycin signaling in autophagy and the neurodegenerative process using a senescence accelerated mouse-prone 8 model", Exp Ther Med, 14, pp.1051~1057 (2017)
- Gao L, "Chlorogenic acid alleviates Aβ25-35-induced autophagy and cognitive impairment via the mTOR", TFEB signaling pathway, 2020, pp.14, 1705~1716