Xanthohumol Protects Neuron from Cerebral Ischemia Injury in Experimental Stroke

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2020 Feb 29

PMID 32108303

Citations 10

Authors

Yang Jiao

Yuze Cao

Xiaoyu Lu

Jianjian Wang

Aigul Saitgareeva

Xiaotong Kong

Chang Song

Jie Li

Kuo Tian

Shuoqi Zhang

Ming Bai

Shuang Li

Huixue Zhang

Lihua Wang

Affiliations

Soon will be listed here.

Abstract

Treatment of antioxidants is necessary to protect ischemic stroke associated neuronal damage. Xanthohumol (XN), a natural flavonoid extracted from hops, has been reported to have potential function as an antioxidant and can be used for neuro protection. However, the role of XN in ischemic stroke remains unclear. Here, we studied the neuroprotective effects of XN through experimental stroke models. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) was used as in vivo and in vitro model, respectively. We found that the treatment of XN improved MCAO-induced brain injury by reducing infarct size, improving neurological deficits, reversing neuronal damage, reducing oxidative stress injury and cell apoptosis. Further experimental studies showed that XN could revive neuronal apoptosis induced by OGD by preventing oxidative stress injury. In addition, our study suggested that these effects were related to the inhibition of phosphorylation of p38-MAPK and the mediation of nuclear Nrf2 activation. In conclusion, the neuroprotective effects of XN showed in this study make XN a promising supplement for ischemic stroke protection.

Citing Articles

Mechanism of Action and Therapeutic Potential of Xanthohumol in Prevention of Selected Neurodegenerative Diseases.

Dlugosz A, Blaszak B, Czarnecki D, Szulc J Molecules. 2025; 30(3).

PMID: 39942798 PMC: 11821245. DOI: 10.3390/molecules30030694.

Screening and Antioxidant Activities Evaluation of Peptides From Abalone ( Ino).

Wu J, Wang X, Qiao K, Pan N, Chen X, Liu Z Food Sci Nutr. 2025; 13(2):e70028.

PMID: 39926104 PMC: 11807725. DOI: 10.1002/fsn3.70028.

Targeting the neurovascular unit: Therapeutic potential of traditional Chinese medicine for the treatment of stroke.

Wu B, Zhou D, Mei Z Heliyon. 2024; 10(19):e38200.

PMID: 39386825 PMC: 11462356. DOI: 10.1016/j.heliyon.2024.e38200.

Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson's disease model.

Lu H, Chai J, Xu Z, Wu J, He S, Liao H Zool Res. 2023; 45(1):108-124.

PMID: 38114437 PMC: 10839659. DOI: 10.24272/j.issn.2095-8137.2023.101.

Xanthohumol attenuates renal ischemia/reperfusion injury by inhibiting ferroptosis.

Tang Z, Feng Y, Nie W, Li C Exp Ther Med. 2023; 26(6):571.

PMID: 37954118 PMC: 10632967. DOI: 10.3892/etm.2023.12269.

References

Pinto C, Cestero J, Rodriguez-Galdon B, Macias P . Xanthohumol, a prenylated flavonoid from hops ( L.), protects rat tissues against oxidative damage after acute ethanol administration. Toxicol Rep. 2017; 1:726-733. PMC: 5598346. DOI: 10.1016/j.toxrep.2014.09.004. View

Qu Y, Mao M, Zhao F, Zhang L, Mu D . Proapoptotic role of human growth and transformation-dependent protein in the developing rat brain after hypoxia-ischemia. Stroke. 2009; 40(8):2843-8. DOI: 10.1161/STROKEAHA.109.553644. View

Sun K, Fan J, Han J . Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage. Acta Pharm Sin B. 2015; 5(1):8-24. PMC: 4629119. DOI: 10.1016/j.apsb.2014.11.002. View

Li C, Zhang W, Frei B . Quercetin inhibits LPS-induced adhesion molecule expression and oxidant production in human aortic endothelial cells by p38-mediated Nrf2 activation and antioxidant enzyme induction. Redox Biol. 2016; 9:104-113. PMC: 4961307. DOI: 10.1016/j.redox.2016.06.006. View

Ran Y, Zhu M, Li S, Zhang Z, Wang X, Zhang Y . Related Research and Recent Progress of Ischemic Penumbra. World Neurosurg. 2018; 116:5-13. DOI: 10.1016/j.wneu.2018.04.193. View

Sun J, Nan G . The Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway as a Discovery Target in Stroke. J Mol Neurosci. 2016; 59(1):90-8. DOI: 10.1007/s12031-016-0717-8. View

Yao J, Zhang B, Ge C, Peng S, Fang J . Xanthohumol, a polyphenol chalcone present in hops, activating Nrf2 enzymes to confer protection against oxidative damage in PC12 cells. J Agric Food Chem. 2015; 63(5):1521-31. DOI: 10.1021/jf505075n. View

Zhang R, Xu M, Wang Y, Xie F, Zhang G, Qin X . Nrf2-a Promising Therapeutic Target for Defensing Against Oxidative Stress in Stroke. Mol Neurobiol. 2016; 54(8):6006-6017. DOI: 10.1007/s12035-016-0111-0. View

Gilgun-Sherki Y, Rosenbaum Z, Melamed E, Offen D . Antioxidant therapy in acute central nervous system injury: current state. Pharmacol Rev. 2002; 54(2):271-84. DOI: 10.1124/pr.54.2.271. View

10.

DOrsi B, Mateyka J, Prehn J . Control of mitochondrial physiology and cell death by the Bcl-2 family proteins Bax and Bok. Neurochem Int. 2017; 109:162-170. DOI: 10.1016/j.neuint.2017.03.010. View

11.

Bederson J, Pitts L, Tsuji M, Nishimura M, Davis R, Bartkowski H . Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 1986; 17(3):472-6. DOI: 10.1161/01.str.17.3.472. View

12.

Yang J, Mukda S, Chen S . Diverse roles of mitochondria in ischemic stroke. Redox Biol. 2018; 16:263-275. PMC: 5854930. DOI: 10.1016/j.redox.2018.03.002. View

13.

Bai J, Mei Y . Overexpression of aldehyde dehydrogenase-2 attenuates neurotoxicity induced by 4-hydroxynonenal in cultured primary hippocampal neurons. Neurotox Res. 2010; 19(3):412-22. DOI: 10.1007/s12640-010-9183-1. View

14.

Iadecola C, Anrather J . The immunology of stroke: from mechanisms to translation. Nat Med. 2011; 17(7):796-808. PMC: 3137275. DOI: 10.1038/nm.2399. View

15.

Sanderson T, Reynolds C, Kumar R, Przyklenk K, Huttemann M . Molecular mechanisms of ischemia-reperfusion injury in brain: pivotal role of the mitochondrial membrane potential in reactive oxygen species generation. Mol Neurobiol. 2012; 47(1):9-23. PMC: 3725766. DOI: 10.1007/s12035-012-8344-z. View

16.

Puig B, Brenna S, Magnus T . Molecular Communication of a Dying Neuron in Stroke. Int J Mol Sci. 2018; 19(9). PMC: 6164443. DOI: 10.3390/ijms19092834. View

17.

Liu M, Hansen P, Wang G, Qiu L, Dong J, Yin H . Pharmacological profile of xanthohumol, a prenylated flavonoid from hops (Humulus lupulus). Molecules. 2015; 20(1):754-79. PMC: 6272297. DOI: 10.3390/molecules20010754. View

18.

Doddapattar P, Radovic B, Patankar J, Obrowsky S, Jandl K, Nusshold C . Xanthohumol ameliorates atherosclerotic plaque formation, hypercholesterolemia, and hepatic steatosis in ApoE-deficient mice. Mol Nutr Food Res. 2013; 57(10):1718-28. PMC: 3771820. DOI: 10.1002/mnfr.201200794. View

19.

Cheong S, Lee D . Taurine Chloramine Prevents Neuronal HT22 Cell Damage Through Nrf2-Related Heme Oxygenase-1. Adv Exp Med Biol. 2017; 975 Pt 1:145-157. DOI: 10.1007/978-94-024-1079-2_13. View

20.

Dostalek P, Karabin M, Jelinek L . Hop Phytochemicals and Their Potential Role in Metabolic Syndrome Prevention and Therapy. Molecules. 2017; 22(10). PMC: 6151408. DOI: 10.3390/molecules22101761. View