Sesquiterpene compound α-cyperone relieves the injury in neurons undergoing oxygen-glucose deprivation/reoxygenation
Keywords:AK-7, alpha-cyperone, Neuron, oxygen-glucose deprivation/reoxygenation, Sirtuin 2, Western blot
The present study aimed to explore the effects of α-cyperone, an extract of Cyperus rotundus, on PC12 cells, as well as the underlying mechanism. Following the cells were induced by oxygen-glucose deprivation/reoxygena-tion (OGD/R), the viability, morphology, inflammation, oxidative stress and apoptotic levels in the cells were evaluated. To explore the mechanism of α-cyperone, cells were treated with 3-TYP, a sirtuin-3 (SIRT3) inhibitor, and then the effects of 3-TYP on the function of α-cyperone were assessed. α-Cyperone was found to reduce OGD/R-induced damage to neuronal viability and alleviate inflammation, oxidative stress, and apoptosis. In addition, α-cyperone could elevate SIRT3 and decline acetyl-forkhead box O1 (FOXO1) levels, and 3-TYP broke the effects of α-cyperone on the aforementioned aspects in the PC12 cells. In conclusion, α-cyperone activated SIRT3 and FOXO1 deacetylation, and alleviated OGD/R-induced cell inflammation, oxidative stress, and apoptosis.
Akinyemi RO, Owolabi MO, Ihara M, Damasceno A, Ogunniyi A, Dotchin C, Paddick SM, Ogeng’o J, Walker R, Kalaria RN. Stroke, cerebrovascular diseases and vascular cognitive impairment in Africa. Brain Res Bull. 2019; 145: 97-108.
Black M, Wang W, Wang W. Ischemic stroke: From next generation sequencing and GWAS to community genomics? Omics 2015; 19: 451-60.
Cheng Z, Zhang M, Ling C, Zhu Y, Ren H, Hong C, Qin J, Liu T, Wang J. Neuroprotective effects of ginsenosides against cerebral ischemia. Molecules 2019; 24: 1102.
Chi OZ, Mellender SJ, Kiss GK, Chiricolo A, Liu X, Patel N, Jacinto E, Weiss HR. Lysophosphatidic acid increased infarct size in the early stage of cerebral ischemia-reperfusion with increased BBB permeability. J Stroke Cerebrovasc Dis. 2020; 29: 105029.
Dabaghian FH, Hashemi M, Entezari M, Movassaghi S, Goushegir SA, Kalantari S, Movafagh A, Sharifi ZN. Effect of Cyperus rotundus on ischemia-induced brain damage and memory dysfunction in rats. Iranian J Basic Med Sci. 2015; 18: 199-204.
Datta A, Sarmah D, Mounica L, Kaur H, Kesharwani R, Verma G, Veeresh P, Kotian V, Kalia K, Borah A, Wang X. Cell death pathways in ischemic stroke and targeted pharmacotherapy. Transl Stroke Res. 2020; 11: 1185-202.
Eslami A, Lujan J. Western blotting: Sample preparation to detection. JoVE. 2010: e2359.
Farahani K, Hashemi M. Investigating the effect of hydro-alcoholic extract of Cyperus rotundus L. on the expression of Bcl-x1 antiapoptotic gene in rats' hippocampus tissue following global ischemic-reperfusion injury. Acta Med Iranica. 2016; 54: 256-60.
Gao P, Ding N, Lv J, Ramzan MN, Wen Q. α-Cyperone inhibitory effects on tumor-derived DNA trigger microglia by STING pathway. J Ethnopharmacol. 2021; 264: 113246.
Hazra A, Gogtay N. Biostatistics Series Module 3: Comparing Groups: Numerical variables. Indian J Dermatol. 2016; 61: 251-60.
He Z, Ning N, Zhou Q, Khoshnam SE, Farzaneh M. Mitochondria as a therapeutic target for ischemic stroke. Free Rad Biol Med. 2020; 146: 45-58.
Herpich F, Rincon F. Management of acute ischemic stroke. Crit Care Med. 2020; 48: 1654-63.
Hu QP, Cao XM, Hao DL, Zhang LL. Chemical composition, antioxidant, DNA damage protective, cytotoxic and antibacterial activities of Cyperus rotundus rhizomes essential oil against foodborne pathogens. Sci Rep. 2017; 7: 45231.
Huang B, He D, Chen G, Ran X, Guo W, Kan X, Wang W, Liu D, Fu S, Liu J. α-Cyperone inhibits LPS-induced inflammation in BV-2 cells through activation of Akt/Nrf2/HO-1 and suppression of the NF-κB pathway. Food Funct. 2018; 9: 2735-43.
Kamala A, Middha SK, Gopinath C, Sindhura HS, Karigar CS. In vitro antioxidant potentials of Cyperus rotundus L. rhizome extracts and their phytochemical analysis. Pharmacogn Mag. 2018a; 14: 261-67.
Kamala A, Middha SK, Karigar CS. Plants in traditional medicine with special reference to Cyperus rotundus L.: A review. 3 Biotech. 2018b; 8: 309.
Kanagali SN, Patil BM, Khanal P, Unger BS. Cyperus rotundus L. reverses the olanzapine-induced weight gain and metabolic changes-outcomes from network and experimental pharmacology. Comput Biol Med. 2021: 105035.
Lim HS, Jang Y, Moon BC, Park G. NF-κB signaling contributes to the inhibitory effects of Bombyx batryticatus on neuroinflammation caused by MPTP toxicity. Bangladesh J Pharmacol. 2021; 16: 96-102.
Lu J, Li W, Gao T, Wang S, Fu C, Wang S. The association study of chemical compositions and their pharmacological effects of Cyperi rhizoma (Xiangfu), a potential traditional Chinese medicine for treating depression. J Ethnopharmacol. 2021: 114962.
Ma Y, Zhao Y, Zhang R, Liang X, Yin Z, Geng Y, Shu G, Song X, Zou Y, Li L, Yin L. α-Cyperone inhibits PMA-induced EPCR shedding through PKC pathway. Biol Pharm Bull. 2017: b17-00183.
Maida CD, Norrito RL, Daidone M, Tuttolomondo A, Pinto A. Neuroinflammatory mechanisms in ischemic stroke: Focus on cardioembolic stroke, background, and therapeutic approaches. Int J Mol Sci. 2020; 21.
Orellana-Urzúa S, Rojas I, Líbano L, Rodrigo R. Pathophysiology of ischemic stroke: Role of oxidative stress. Curr Pharm Des. 2020; 26: 4246-60.
Paul S, Candelario-Jalil E. Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies. Exp Neurol. 2021; 335: 113518.
Rocha FG, de Mello Brandenburg M, Pawloski PL, da Silva Soley B, Costa SC, Meinerz CC, Baretta IP, Otuki MF, Cabrini DA. Preclinical study of the topical anti-inflammatory activity of Cyperus rotundus L. extract (Cyperaceae) in models of skin inflammation. J Ethnopharmacol. 2020; 254: 112709.
Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008; 3: 1101-08.
Shen S, Hou Y, Wu Y. Tongxinluo preserves the renal function in diabetic kidney disease via protecting the HK-2 cells from the patterns of programmed cell death. Bangladesh J Pharmacol. 2021; 16: 52-64.
Silva GS, Nogueira RG. Endovascular treatment of acute ischemic stroke. Continuum (Minneap Minn). 2020; 26: 310-31.
Sun B, Ou H, Ren F, Huan Y, Zhong T, Gao M, Cai H. Propofol inhibited autophagy through Ca(2+)/CaMKKβ/AMPK/mTOR pathway in OGD/R-induced neuron injury. Mol Med. 2018; 24: 58.
Sunil AG, Kesavanarayanan KS, Kalaivani P, Sathiya S, Ranju V, Priya RJ, Pramila B, Paul FS, Venkhatesh J, Babu CS. Total oligomeric flavonoids of Cyperus rotundus ameliorates neurological deficits, excitotoxicity and behavioral alterations induced by cerebral ischemic-reperfusion injury in rats. Brain Res Bull. 2011; 84: 394-405.
Wang KJ, Zhang WQ, Liu JJ, Cui Y, Cui JZ. Piceatannol protects against cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress via the Sirt1/FoxO1 signaling pathway. Mol Med Rep. 2020a; 22: 5399-411.
Wang M, Chen Z, Yang L, Ding L. Sappanone A protects against inflammation, oxidative stress and apoptosis in cerebral ischemia-reperfusion injury by alleviating endoplasmic reticulum stress. Inflammation 2021; 44: 934-45.
Wang S, Tang Q, Ge F, Guo Q. Typhae pollen polysaccharides protect hypoxia-induced PC12 cell injury via regulation of miR-34a/SIRT1. Int J Immunopathol Pharmacol. 2020b; 34: 2058738420910005.
Wang XX, Zhang B, Xia R, Jia QY. Inflammation, apoptosis and autophagy as critical players in vascular dementia. Euro Rev Med Pharm Sci. 2020c; 24: 9601-14.
You J, Feng L, Xin M, Ma D, Feng J. Cerebral ischemic post-conditioning plays a neuroprotective role through regulation of central and peripheral glutamate. Bio Med Res Int. 2018; 2018: 6316059.
Zeng R, Wang X, Zhou Q, Fu X, Wu Q, Lu Y, Shi J, Klaunig JE, Zhou S. Icariin protects rotenone-induced neurotoxicity through induction of SIRT3. Toxicol Appl Pharmacol. 2019; 379: 114639.
Zhang B, Cui S, Bai X, Zhuo L, Sun X, Hong Q, Fu B, Wang J, Chen X, Cai G. SIRT3 overexpression antagonizes high glucose accelerated cellular senescence in human diploid fibroblasts via the SIRT3–FOXO1 signaling pathway. Age 2013; 35: 2237-53.
Zhang H, Li S, Lu J, Jin J, Zhu G, Wang L, Yan Y, He L, Wang B, Wang X, Yu H. α-Cyperone (CYP) down-regulates NF-κB and MAPKs signaling, attenuating inflammation and extracellular matrix degradation in chondrocytes, to ameliorate osteoarthritis in mice. Aging 2021; 13: 17690-706.
Zhao H, Luo Y, Chen L, Zhang Z, Shen C, Li Y, Xu R. Sirt3 inhibits cerebral ischemia-reperfusion injury through normalizing Wnt/β-catenin pathway and blocking mitochondrial fission. Cell Stress Chaperones. 2018; 23: 1079-92.
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