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08.09.2022 | Original Paper

Humulus lupulus L. extract and its active constituent xanthohumol attenuate oxidative stress and nerve injury induced by iron overload via activating AKT/GSK3β and Nrf2/NQO1 pathways

verfasst von: Sun Xiao-Lei, Xia Tian-Shuang, Jiang Yi-Ping, Wang Na-Ni, Xu Ling-Chuan, Han Ting, Xin Hai-Liang

Erschienen in: Journal of Natural Medicines | Ausgabe 1/2023

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Abstract

Hops, the dried female clusters from Humulus lupulus L., have traditionally been used as folk medicines for treating insomnia, neuralgia, and menopausal disorders. However, its pharmacological action on iron overload induced nerve damage has not been investigated. This study aims to evaluate the protective effects of hops extract (HLE) and its active constituent xanthohumol (XAN) on nerve injury induced by iron overload in vivo and in vitro, and to explore its underlying mechanism. The results showed that HLE and XAN significantly improved the memory impairment of iron overload mice, mainly manifested as shortened latency time, increased crossing platform times and spontaneous alternation ratio, and increased the expression of related proteins. Additionally, HLE and XAN significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and remarkably decreased malondialdehyde (MDA) level in hippocampus. Also, HLE and XAN apparently reduced reactive oxygen species (ROS) content of PC12 cells induced by iron dextran (ID), and improved the oxidative stress level. Moreover, HLE and XAN significantly upregulated the expression of nuclear factor E2-related factor (Nrf2), NAD(P)H quinone oxidoreductase (NQO1), heme oxygenase-1 (HO-1), SOD, phosphorylated AKT (p-AKT), and phosphorylated GSK3β (p-GSK3β) both in hippocampus and PC12 cells. These findings demonstrated the protective effect of HLE and XAN against iron-induced memory impairment, which is attributed to its antioxidant profile by activation of AKT/GSK3β and Nrf2/NQO1 pathways. Also, it was suggested that hops could be a potential candidate for iron overload-related neurological diseases treatment.

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Liu Y, Nguyen M, Robert A, Meunier B (2019) Metal ions in Alzheimer’s disease: a key role or not? Acc Chem Res 52(7):2026–2035. https://doi.org/10.1021/acs.accounts.9b00248CrossRef

Arber CE, Li A, Houlden H, Wray S (2016) Review: Insights into molecular mechanisms of disease in neurodegeneration with brain iron accumulation: unifying theories. Neuropathol Appl Neurobiol 42(3):220–241. https://doi.org/10.1111/nan.12242CrossRef

Wang XL, Wang WZ, Li L, Perry G, Lee HG, Zhu XW (2014) Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease. Biochim Biophys Acta 1842(8):1240–1247. https://doi.org/10.1016/j.bbadis.2013.10.015CrossRef

Ayton S, Faux NG, Bush AI (2015) Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE. Nat Commun 6:6760. https://doi.org/10.1038/ncomms7760CrossRef

Wang X, Zhang JF, Zhou L, Xu BH, Ren XH, He KW, Nie LL, Li X, Liu JJ, Yang XF, Yuan J (2019) Long-term iron exposure causes widespread molecular alterations associated with memory impairment in mice. Food Chem Toxicol 130:242–252. https://doi.org/10.1016/j.fct.2019.05.038CrossRef

Kalpouzos G, Garzon B, Sitnikov R, Heiland C, Salami A, Persson J, Bäckman L (2017) Higher striatal iron concentration is linked to frontostriatal underactivation and poorer memory in normal aging. Cereb Cortex 27(6):3427–3436. https://doi.org/10.1093/cercor/bhx045CrossRef

Ko YH, Kwon SH, Lee SY, Jang CG (2017) Liquiritigenin ameliorates memory and cognitive impairment through cholinergic and BDNF pathways in the mouse hippocampus. Arch Pharm Res 40(10):1209–1217. https://doi.org/10.1007/s12272-017-0954-6CrossRef

Guo X, Chen ZH, Wang HL, Liu ZC, Wang XP, Zhou BH, Yang C, Zhang XP, Xiao L, Shu C, Chen JX, Wang GH (2015) WSKY, a traditional Chinese decoction, rescues cognitive impairment associated with NMDA receptor antagonism by enhancing BDNF/ERK/CREB signaling. Mol Med Rep 11(4):2927–2934. https://doi.org/10.3892/mmr.2014.3086CrossRef

Jin Y, Sui HJ, Dong Y, Ding Q, Qu WH, Yu SX, Jin YX (2012) Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the AKT/mTOR and AKT/GSK-3β signaling pathways. Acta Pharmacol Sin 33(7):861–872. https://doi.org/10.1038/aps.2012.59CrossRef

10.

Ge XH, Shao L, Zhu GJ (2018) Oxymatrine attenuates brain hypoxic-ischemic injury from apoptosis and oxidative stress: role of p-AKT/GSK3beta/ HO-1/Nrf-2 signaling pathway. Metab Brain Dis 33(6):1869–1875. https://doi.org/10.1007/s11011-018-0293-4CrossRef

11.

Li SW, Jiang X, Luo YH, Zhou BR, Shi M, Liu FY, Sha AL (2019) Sodium/calcium overload and Sirt1/Nrf2/OH-1 pathway are critical events in mercuric chloride-induced nephrotoxicity. Chemosphere 234:579–588. https://doi.org/10.1016/j.chemosphere.2019.06.095CrossRef

12.

Jo C, Gundemir S, Pritchard S, Jin YN, Rahman I, Johnson GV (2014) Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52. Nat Commun 5:3496. https://doi.org/10.1038/ncomms4496CrossRef

13.

Xia TS, Lin LY, Zhang QY, Jiang YP, Li CH, Liu XY, Qin LP, Xin HL (2021) Humulus lupulus L. extract prevents ovariectomy-induced osteoporosis in mice and regulates activities of osteoblasts and osteoclasts. Chin J Integr Med 27(1):31–38. https://doi.org/10.1007/s11655-019-2700-zCrossRef

14.

Bolton JL, Dunlap TL, Hajirahimkhan A, Mbachu O, Chen SN, Chadwick L, Nikolic D, van Breemen RB, Pauli GF, Dietz BM (2019) The multiple biological targets of hops and bioactive compounds. Chem Res Toxicol 32(2):222–233. https://doi.org/10.1021/acs.chemrestox.8b00345CrossRef

15.

Sasaoka N, Sakamoto M, Kanemori S, Kan M, Tsukano C, Takemoto Y, Kakizuka A (2014) Long-term oral administration of hop flower extracts mitigates Alzheimer phenotypes in mice. PLoS ONE 9(1):e87185. https://doi.org/10.1371/journal.pone.0087185CrossRef

16.

Yao J, Zhang BX, Ge CP, Peng SJ, Fang JG (2015) Xanthohumol, a polyphenol chalcone present in hops, activating Nrf2 enzymes to confer protection against oxidative damage in PC12 cells. J Agric Food Chem 63(5):1521–1531. https://doi.org/10.1021/jf505075nCrossRef

17.

Olas B, Kolodziejczyk J, Wachowicz B, Jędrejek D, Stochmal A, Oleszek W (2011) The extract from hop cones (Humulus lupulus) as a modulator of oxidative stress in blood platelets. Platelets 22(5):345–352. https://doi.org/10.3109/09537104.2010.549597CrossRef

18.

Liu XW, Song ZB, Bai J, Nauwynck H, Zhao YX, Jiang P (2019) Xanthohumol inhibits PRRSV proliferation and alleviates oxidative stress induced by PRRSV via the Nrf2-HMOX1 axis. Vet Res 50(1):61. https://doi.org/10.1186/s13567-019-0679-2CrossRef

19.

Fernández-García C, Rancan L, Paredes SD, Montero C, de la Fuente M, Vara E, Tresguerres JAF (2019) Xanthohumol exerts protective effects in liver alterations associated with aging. Eur J Nutr 58(2):653–663. https://doi.org/10.1007/s00394-018-1657-6CrossRef

20.

Jiao Y, Cao YZ, Lu XY, Wang JJ, Saitgareeva A, Kong XT, Song C, Li J, Tian K, Zhang SQ, Bai M, Li S, Zhang HX, Wang LH (2020) Xanthohumol protects neuron from cerebral ischemia injury in experimental stroke. Mol Biol Rep 47(4):2417–2425. https://doi.org/10.1007/s11033-019-05128-4CrossRef

21.

Sun XL, Zhang JB, Guo YX, Xia TS, Xu LC, Rahmand K, Wang GP, Li XJ, Han T, Wang NN, Xin HL (2021) Xanthohumol ameliorates memory impairment and reduces the deposition of β-amyloid in APP/PS1 mice via regulating the mTOR/LC3II and Bax/Bcl-2 signaling pathways. J Pharm Pharmacol 73(9):1230–1239. https://doi.org/10.1093/jpp/rgab052CrossRef

22.

Liu EJ, Xie AJ, Zhou QZ, Li MZ, Zhang SJ, Li SH, Wang WJ, Wang XC, Wang Q, Wang JZ (2017) GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory. Sci Rep 7(1):5781. https://doi.org/10.1038/s41598-017-06173-4CrossRef

23.

Wharton W, Baker LD, Gleason CE, Dowling M, Barnet JH, Johnson S, Carlsson C, Craft S, Asthana S (2011) Short-term hormone therapy with transdermal estradiol improves cognition for postmenopausal women with Alzheimer’s disease: results of a randomized controlled trial. J Alzheimers Dis 26(3):495–505. https://doi.org/10.3233/JAD-2011-110341CrossRef

24.

Żołnierczyk AK, Mączka WK, Grabarczyk M, Wińska K, Woźniak E, Anioł M (2015) Isoxanthohumol-biologically active hop flavonoid. Fitoterapia 103:71–82. https://doi.org/10.1016/j.fitote.2015.03.007CrossRef

25.

Morimoto-Kobayashi Y, Ohara K, Takahashi C, Kitao S, Wang G, Taniguchi Y, Katayama M, Nagai K (2015) Matured hop bittering components induce thermogenesis in brown adipose tissue via sympathetic nerve activity. PLoS ONE 10(6):e0131042. https://doi.org/10.1371/journal.pone.0131042CrossRef

26.

Zanoli P, Rivasi M, Zavatti M, Brusiani F, Baraldi M (2005) New insight in the neuropharmacological activity of Humulus lupulus L. J Ethnopharmacol 102(1):102–106. https://doi.org/10.1016/j.jep.2005.05.040CrossRef

27.

Sun LN, Jin Y, Dong LM, Sumi R, Jahan R, Hu DH, Li Z (2015) Coccomyxa gloeobotrydiformis improves learning and memory in intrinsic aging rats. Int J Biol Sci 11(7):825–832. https://doi.org/10.7150/ijbs.10861CrossRef

28.

Miyazaki S, Fujita Y, Oikawa H, Takekoshi H, Soya H, Ogata M, Fujikawa T (2020) Combination of syringaresinol-di-O-beta-D-glucoside and chlorogenic acid shows behavioral pharmacological anxiolytic activity and activation of hippocampal BDNF-TrkB signaling. Sci Rep 10(1):18177. https://doi.org/10.1038/s41598-020-74866-4CrossRef

29.

Nakamura T, Okui T, Hasegawa K, Ryumon S, Ibaragi S, Ono K, Kunisada Y, Obata K, Masui M, Shimo T, Sasaki A (2020) High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer. Oncol Rep 44(6):2547–2558. https://doi.org/10.3892/or.2020.7788CrossRef

30.

Chen DY, Bambah-Mukku D, Pollonini G, Alberini CM (2012) Glucocorticoid receptors recruit the CaMKII alpha-BDNF-CREB pathways to mediate memory consolidation. Nat Neurosci 15(12):1707–1714. https://doi.org/10.1038/nn.3266CrossRef

31.

Caracciolo L, Marosi M, Mazzitelli J, Latifi S, Sano Y, Galvan L, Kawaguchi R, Holley S, Levine MS, Coppola G, Portera-Cailliau C, Silva AJ, Carmichael ST (2018) CREB controls cortical circuit plasticity and functional recovery after stroke. Nat Commun 9(1):2250. https://doi.org/10.1038/s41467-018-04445-9CrossRef

32.

Yao J, Wang XQ, Li YJ, Shan K, Yang H, Wang YN, Yao MD, Liu C, Li XM, Shen Y, Liu JY, Cheng H, Yuan J, Zhang YY, Jiang Q, Yan B (2016) Long non-coding RNA MALAT1 regulates retinal neurodegeneration through CREB signaling. EMBO. Mol Med 8(4):346–362. https://doi.org/10.15252/emmm.201505725CrossRef

33.

Rexach JE, Clark PM, Mason DE, Neve RL, Peters EC, Hsieh-Wilson LC (2012) Dynamic O-GlcNAc modification regulates CREB-mediated gene expression and memory formation. Nat Chem Biol 8(3):253–261. https://doi.org/10.1038/nchembio.770CrossRef

34.

Cabello-Verrugio C, Simon F, Trollet C, Santibañez JF (2017) Oxidative stress in disease and aging: mechanisms and therapies 2016. Oxid Med Cell Longev 2017:4310469. https://doi.org/10.1155/2017/4310469CrossRef

35.

Xu WZ, Li F, Xu ZK, Sun B, Cao JW, Liu YG (2012) Role of peroxiredoxin 2 in the protection against ferrous sulfate-induced oxidative and inflammatory injury in PC12 cells. Cell Mol Neurobiol 38(3):735–745. https://doi.org/10.1007/s10571-017-0540-yCrossRef

36.

Huo TT, Jia YQ, Yin CL, Luo XT, Zhao JR, Wang ZQ, Lv PY (2019) Iron dysregulation in vascular dementia: focused on the AMPK/autophagy pathway. Brain Res Bull 153:305–313. https://doi.org/10.1016/j.brainresbull.2019.09.006CrossRef

37.

Wang L, Yin YL, Liu XZ, Shen P, Zheng YG, Lan XR, Lu CB, Wang JZ (2020) Current understanding of metal ions in the pathogenesis of Alzheimer’s disease. Transl Neurodegener 9:10. https://doi.org/10.1186/s40035-020-00189-zCrossRef

38.

Rana AK, Singh D (2018) Targeting glycogen synthase kinase-3 for oxidative stress and neuroinflammation: opportunities, challenges and future directions for cerebral stroke management. Neuropharmacology 139:124–136. https://doi.org/10.1016/j.neuropharm.2018.07.006CrossRef

39.

Yao K, Zhao YF, Zu HB (2019) Melatonin receptor stimulation by agomelatine prevents Abeta-induced tau phosphorylation and oxidative damage in PC12 cells. Drug Des Devel Ther 13:387–396. https://doi.org/10.2147/DDDT.S182684CrossRef

40.

Rival T, Page RM, Chandraratna DS, Sendall TJ, Ryder E, Liu B, Lewis H, Rosahl T, Hider R, Camargo LM, Shearman MS, Crowther DC, Lomas DA (2009) Fenton chemistry and oxidative stress mediate the toxicity of the beta-amyloid peptide in a Drosophila model of Alzheimer’s disease. Eur J Neurosci 29(7):1335–1347. https://doi.org/10.1111/j.1460-9568.2009.06701.xCrossRef

41.

Song XH, Long DX (2020) Nrf2 and ferroptosis: a new research direction for neurodegenerative diseases. Front Neurosci 14:267. https://doi.org/10.3389/fnins.2020.00267CrossRef

42.

Hur W, Gray NS (2011) Small molecule modulators of antioxidant response pathway. Curr Opin Chem Biol 15(1):162–173. https://doi.org/10.1016/j.cbpa.2010.12.009CrossRef

Titel: Humulus lupulus L. extract and its active constituent xanthohumol attenuate oxidative stress and nerve injury induced by iron overload via activating AKT/GSK3β and Nrf2/NQO1 pathways
verfasst von: Sun Xiao-Lei
Xia Tian-Shuang
Jiang Yi-Ping
Wang Na-Ni
Xu Ling-Chuan
Han Ting
Xin Hai-Liang
Publikationsdatum: 08.09.2022
Verlag: Springer Nature Singapore
Erschienen in: Journal of Natural Medicines / Ausgabe 1/2023
Print ISSN: 1340-3443
Elektronische ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-022-01642-1

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Humulus lupulus L. extract and its active constituent xanthohumol attenuate oxidative stress and nerve injury induced by iron overload via activating AKT/GSK3β and Nrf2/NQO1 pathways

Abstract

Weitere Artikel der Ausgabe 1/2023

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17β-neriifolin from unripe fruits of Cerbera manghas suppressed cell proliferation via the inhibition of HOXA9-dependent transcription and the induction of apoptosis in the human AML cell line THP-1

Anti-influenza A virus activity of flavonoids in vitro: a structure–activity relationship

Content and distribution of prunasin in Perilla frutescens

Seasonal variation in the total saponin content of platycodon roots cultivated in Japan

Effect of drying and processing on diterpenes and other chemical constituents of ginger

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