Skip to main content
Erschienen in: European Journal of Nutrition 2/2019

13.03.2018 | Original Contribution

Xanthohumol exerts protective effects in liver alterations associated with aging

verfasst von: Cristina Fernández-García, Lisa Rancan, Sergio D. Paredes, César Montero, Mónica de la Fuente, Elena Vara, Jesús A. F. Tresguerres

Erschienen in: European Journal of Nutrition | Ausgabe 2/2019

Einloggen, um Zugang zu erhalten

Abstract

Background and aims

Aging is associated with a deregulation of biological systems that lead to an increase in oxidative stress, inflammation, and apoptosis, among other effects. Xanthohumol is the main preylated chalcone present in hops (Humulus lupulus L.) whose antioxidant, anti-inflammatory and chemopreventive properties have been shown in recent years. In the present study, the possible protective effects of xanthohumol on liver alterations associated with aging were evaluated.

Methods

Male young and old senescence-accelerated prone mice (SAMP8), aged 2 and 10 months, respectively, were divided into four groups: non-treated young, non-treated old, old treated with 1 mg/kg/day xanthohumol, and old treated with 5 mg/kg/day xanthohumol. Male senescence-accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed and livers were collected. mRNA (AIF, BAD, BAX, Bcl-2, eNOS, HO-1, IL-1β, NF-κB2, PCNA, sirtuin 1 and TNF-α) and protein expressions (BAD, BAX, AIF, caspase-3, Blc-2, eNOS, iNOS, TNF-α, IL1β, NF-κB2, and IL10) were measured by RT-PCR and Western blotting, respectively. Mean values were analyzed using ANOVA.

Results

A significant increase in mRNA and protein levels of oxidative stress, pro-inflammatory and proliferative markers, as well as pro-apoptotic parameters was shown in old non-treated SAMP8 mice compared to the young SAMP8 group and SAMR1 mice. In general, age-related oxidative stress, inflammation and apoptosis were significantly decreased (p < 0.05) after XN treatment. In most cases, this effect was dose-dependent.

Conclusions

XN was shown to modulate inflammation, apoptosis, and oxidative stress in aged livers, exerting a protective effect in hepatic alterations.
Literatur
1.
Zurück zum Zitat Sanz A, Stefanatos RK (2008) The mitochondrial free radical theory of aging: a critical view. Curr Aging Sci 1(1):10–21CrossRefPubMed Sanz A, Stefanatos RK (2008) The mitochondrial free radical theory of aging: a critical view. Curr Aging Sci 1(1):10–21CrossRefPubMed
2.
Zurück zum Zitat Schmucker D (2005) Age-related changes in liver structure and function: implications for disease? Exp Gerontol 40(8–9):650–659CrossRefPubMed Schmucker D (2005) Age-related changes in liver structure and function: implications for disease? Exp Gerontol 40(8–9):650–659CrossRefPubMed
3.
Zurück zum Zitat Preedy V (2014) Aging. Chapter 1. Oxidative stress and frailty: a closer look at the origin of a human aging phenotype Preedy V (2014) Aging. Chapter 1. Oxidative stress and frailty: a closer look at the origin of a human aging phenotype
4.
Zurück zum Zitat Aikata H, Takaishi H, Kawakami Y, Takahashi S, Kitamoto M, Nakanishi T et al (2000) Telomere reduction in human liver tissues with age and chronic inflammation. Exp Cell Res 256(2):578–582CrossRefPubMed Aikata H, Takaishi H, Kawakami Y, Takahashi S, Kitamoto M, Nakanishi T et al (2000) Telomere reduction in human liver tissues with age and chronic inflammation. Exp Cell Res 256(2):578–582CrossRefPubMed
5.
Zurück zum Zitat Jaskelioff M, Muller F, Paik J, Thomas E, Jiang S, Adams A, Sahin E, Kost-Alimova M, Protopopov A, Cadiñanos J, Horner J, Maratos-Flier E, DePinho R (2010) Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469(7328):102–106CrossRefPubMedPubMedCentral Jaskelioff M, Muller F, Paik J, Thomas E, Jiang S, Adams A, Sahin E, Kost-Alimova M, Protopopov A, Cadiñanos J, Horner J, Maratos-Flier E, DePinho R (2010) Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469(7328):102–106CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Aravinthan A, Alexander G (2016) Senescence in chronic liver disease: is the future in ageing? J Hepatol 65:825–834CrossRefPubMed Aravinthan A, Alexander G (2016) Senescence in chronic liver disease: is the future in ageing? J Hepatol 65:825–834CrossRefPubMed
7.
Zurück zum Zitat Pinto C, Cestero J, Rodríguez-Galdón B, Macías P (2014) Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus L.), protects rat tissues against oxidative damage after acute ethanol administration. Toxicol Rep 1:726–733CrossRefPubMedPubMedCentral Pinto C, Cestero J, Rodríguez-Galdón B, Macías P (2014) Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus L.), protects rat tissues against oxidative damage after acute ethanol administration. Toxicol Rep 1:726–733CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Vanhoecke B, Derycke L, Van Marck V, Depypere H, De Keukeleire D, Bracke M (2005) Antiinvasive effect of xanthohumol, a prenylated chalcone present in hops (Humulus lupulus L.) and beer. Int J Cancer 117(6):889–895CrossRefPubMed Vanhoecke B, Derycke L, Van Marck V, Depypere H, De Keukeleire D, Bracke M (2005) Antiinvasive effect of xanthohumol, a prenylated chalcone present in hops (Humulus lupulus L.) and beer. Int J Cancer 117(6):889–895CrossRefPubMed
9.
Zurück zum Zitat Zhang B, Chu W, Wei P, Liu Y, Wei T (2015) Xanthohumol induces generation of reactive oxygen species and triggers apoptosis through inhibition of mitochondrial electron transfer chain complex I. Free Radical Biol Med 89:486–497CrossRef Zhang B, Chu W, Wei P, Liu Y, Wei T (2015) Xanthohumol induces generation of reactive oxygen species and triggers apoptosis through inhibition of mitochondrial electron transfer chain complex I. Free Radical Biol Med 89:486–497CrossRef
10.
Zurück zum Zitat Ungvari Z, Kaley G, de Cabo R, Sonntag WE, Csiszar A (2010) Mechanisms of vascular aging: new perspectives. J Gerontol Ser A Biol Sci Med Sci 65(10):1028–1041CrossRef Ungvari Z, Kaley G, de Cabo R, Sonntag WE, Csiszar A (2010) Mechanisms of vascular aging: new perspectives. J Gerontol Ser A Biol Sci Med Sci 65(10):1028–1041CrossRef
11.
Zurück zum Zitat Takeda T, Hosokawa M, Takeshita S, Irino M, Higuchi K, Matsushita T et al (1981) A new murine model of accelerated senescence. Mech Ageing Dev 17(2):183–194CrossRefPubMed Takeda T, Hosokawa M, Takeshita S, Irino M, Higuchi K, Matsushita T et al (1981) A new murine model of accelerated senescence. Mech Ageing Dev 17(2):183–194CrossRefPubMed
12.
Zurück zum Zitat Yagi H, Katoh S, Akiguchi I, Takeda T (1988) Age-related deterioration of ability of acquisition in memory and learning in senescence accelerated mouse: SAM-P/8 as an animal model of disturbances in recent memory. Brain Res 474(1):86–93CrossRefPubMed Yagi H, Katoh S, Akiguchi I, Takeda T (1988) Age-related deterioration of ability of acquisition in memory and learning in senescence accelerated mouse: SAM-P/8 as an animal model of disturbances in recent memory. Brain Res 474(1):86–93CrossRefPubMed
13.
Zurück zum Zitat Tresguerres JA, Kireev R, Forman K, Cuesta S, Tresguerres AF, Vara E (2012) Effect of chronic melatonin administration on several physiological parameters from old wistar rats and SAMP8 mice. Curr Aging Sci 5(3):242–253CrossRefPubMed Tresguerres JA, Kireev R, Forman K, Cuesta S, Tresguerres AF, Vara E (2012) Effect of chronic melatonin administration on several physiological parameters from old wistar rats and SAMP8 mice. Curr Aging Sci 5(3):242–253CrossRefPubMed
14.
Zurück zum Zitat Paredes SD, Forman KA, Garcia C, Vara E, Escames G, Tresguerres JA (2014) Protective actions of melatonin and growth hormone on the aged cardiovascular system. Hormone Mol Biol Clin Investig 18(2):79–88CrossRef Paredes SD, Forman KA, Garcia C, Vara E, Escames G, Tresguerres JA (2014) Protective actions of melatonin and growth hormone on the aged cardiovascular system. Hormone Mol Biol Clin Investig 18(2):79–88CrossRef
15.
Zurück zum Zitat Puig A, Rancan L, Paredes SD, Carrasco A, Escames G, Vara E et al (2016) Melatonin decreases the expression of inflammation and apoptosis markers in the lung of a senescence-accelerated mice model. Exp Gerontol 75:1–7CrossRefPubMed Puig A, Rancan L, Paredes SD, Carrasco A, Escames G, Vara E et al (2016) Melatonin decreases the expression of inflammation and apoptosis markers in the lung of a senescence-accelerated mice model. Exp Gerontol 75:1–7CrossRefPubMed
16.
Zurück zum Zitat Rancan L, Paredes SD, García I, Muñoz P, García C, López de Hontanar G, de la Fuente M, Vara E, Tresguerres JAF (2017) Protective effect of xanthohumol against age-related brain damage. J Nutr Biochem 49:133–140CrossRefPubMed Rancan L, Paredes SD, García I, Muñoz P, García C, López de Hontanar G, de la Fuente M, Vara E, Tresguerres JAF (2017) Protective effect of xanthohumol against age-related brain damage. J Nutr Biochem 49:133–140CrossRefPubMed
17.
Zurück zum Zitat Montoliu C, Vallés S, Renau-Piqueras J, Guerri C (2002) Ethanol-induced oxygen radical formation and lipid peroxidation in rat brain: effect of chronic alcohol consumption. J Neurochem 63(5):1855–1862CrossRef Montoliu C, Vallés S, Renau-Piqueras J, Guerri C (2002) Ethanol-induced oxygen radical formation and lipid peroxidation in rat brain: effect of chronic alcohol consumption. J Neurochem 63(5):1855–1862CrossRef
18.
Zurück zum Zitat Chomcznyski P, Sacchi N (2006) The single-step method of RNA isolation by acid guanidinium thiocynate-phenol-chloroform extraction: twenty something years on. Nat Protoc 1:581–585CrossRef Chomcznyski P, Sacchi N (2006) The single-step method of RNA isolation by acid guanidinium thiocynate-phenol-chloroform extraction: twenty something years on. Nat Protoc 1:581–585CrossRef
19.
Zurück zum Zitat Shmittgen DT, Livak KJ (2001) Analysis of relative gene expression data using real-time quantitive PCR and the 2-∆∆CT method. Methods 25:402–408CrossRef Shmittgen DT, Livak KJ (2001) Analysis of relative gene expression data using real-time quantitive PCR and the 2-∆∆CT method. Methods 25:402–408CrossRef
20.
Zurück zum Zitat Pasparakis M, Alexopoulou L, Episkopou V, Kollias G (1996) Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J Exp Med 184(4):1397–1411CrossRefPubMed Pasparakis M, Alexopoulou L, Episkopou V, Kollias G (1996) Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J Exp Med 184(4):1397–1411CrossRefPubMed
21.
Zurück zum Zitat Lee IS, Lim J, Gal J, Kang JC, Kim HJ, Kang BY et al (2011) Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells. Neurochem Int 58(2):153–160CrossRefPubMed Lee IS, Lim J, Gal J, Kang JC, Kim HJ, Kang BY et al (2011) Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells. Neurochem Int 58(2):153–160CrossRefPubMed
22.
Zurück zum Zitat Gieling R, Wallace K, Han Y (2009) Interleukin-1 participates in the progression from liver injury to fibrosis. Am J Physiol Gastrointest Liver Physiol 296(6):G1324-G1331CrossRefPubMedCentral Gieling R, Wallace K, Han Y (2009) Interleukin-1 participates in the progression from liver injury to fibrosis. Am J Physiol Gastrointest Liver Physiol 296(6):G1324-G1331CrossRefPubMedCentral
23.
Zurück zum Zitat Tak P, Firestein G (2001) NF-κB: a key role in inflammatory diseases. J Clin Investig 107(1):7–11CrossRef Tak P, Firestein G (2001) NF-κB: a key role in inflammatory diseases. J Clin Investig 107(1):7–11CrossRef
24.
Zurück zum Zitat Peluso I, Raguzzini A, Serafini M (2013) Effect of flavonoids on circulating levels of TNF-alpha and IL-6 in humans: a systematic review and meta-analysis. Mol Nutr Food Res 57(5):784–801CrossRefPubMed Peluso I, Raguzzini A, Serafini M (2013) Effect of flavonoids on circulating levels of TNF-alpha and IL-6 in humans: a systematic review and meta-analysis. Mol Nutr Food Res 57(5):784–801CrossRefPubMed
25.
Zurück zum Zitat Garcia-Lafuente A, Guillamon E, Villares A, Rostagno MA, Martinez JA (2009) Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease. Inflamm Res 58(9):537–552CrossRefPubMed Garcia-Lafuente A, Guillamon E, Villares A, Rostagno MA, Martinez JA (2009) Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease. Inflamm Res 58(9):537–552CrossRefPubMed
26.
Zurück zum Zitat Paredes SD, Rancan L, Kireev R, González A, Louzao P, González P, Rodríguez-Bobada C, García C, Vara E, Tresguerres J (2015) Melatonin counteracts at a transcriptional level the inflammatory and apoptotic response secondary to ischemic brain injury induced by middle cerebral artery blockade in aging rats. BioRes Open Access 4(1):407–416CrossRefPubMedPubMedCentral Paredes SD, Rancan L, Kireev R, González A, Louzao P, González P, Rodríguez-Bobada C, García C, Vara E, Tresguerres J (2015) Melatonin counteracts at a transcriptional level the inflammatory and apoptotic response secondary to ischemic brain injury induced by middle cerebral artery blockade in aging rats. BioRes Open Access 4(1):407–416CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Meador BM, Krzyszton CP, Johnson RW, Huey KA (2008) Effects of IL-10 and age on IL-6, IL-1beta, and TNF-alpha responses in mouse skeletal and cardiac muscle to an acute inflammatory insult. J Appl Physiol 104(4):991–997CrossRefPubMed Meador BM, Krzyszton CP, Johnson RW, Huey KA (2008) Effects of IL-10 and age on IL-6, IL-1beta, and TNF-alpha responses in mouse skeletal and cardiac muscle to an acute inflammatory insult. J Appl Physiol 104(4):991–997CrossRefPubMed
28.
Zurück zum Zitat Lu B, Chen H, Lu HG (2012) The relationship between apoptosis and aging. Adv Biosci Biotechnol 3:705–711CrossRef Lu B, Chen H, Lu HG (2012) The relationship between apoptosis and aging. Adv Biosci Biotechnol 3:705–711CrossRef
29.
Zurück zum Zitat Daugas E, Nochy D, Ravagnan L, Loeffler M, Susin SA, Zamzami N et al (2000) Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis. FEBS Lett 476(3):118–123CrossRefPubMed Daugas E, Nochy D, Ravagnan L, Loeffler M, Susin SA, Zamzami N et al (2000) Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis. FEBS Lett 476(3):118–123CrossRefPubMed
30.
Zurück zum Zitat Cau SB, Carneiro FS, Tostes RC (2012) Differential modulation of nitric oxide synthases in aging: therapeutic opportunities. Front Physiol 3:218PubMedPubMedCentral Cau SB, Carneiro FS, Tostes RC (2012) Differential modulation of nitric oxide synthases in aging: therapeutic opportunities. Front Physiol 3:218PubMedPubMedCentral
31.
Zurück zum Zitat Schipper HM (2000) Heme oxygenase-1: role in brain aging and neurodegeneration. Exp Gerontol 35(6–7):821–830CrossRefPubMed Schipper HM (2000) Heme oxygenase-1: role in brain aging and neurodegeneration. Exp Gerontol 35(6–7):821–830CrossRefPubMed
32.
33.
Zurück zum Zitat Guarente L (2007) Sirtuins in aging and disease. Cold Spring Harb Symp Quant Biol:483–488 Guarente L (2007) Sirtuins in aging and disease. Cold Spring Harb Symp Quant Biol:483–488
Metadaten
Titel
Xanthohumol exerts protective effects in liver alterations associated with aging
verfasst von
Cristina Fernández-García
Lisa Rancan
Sergio D. Paredes
César Montero
Mónica de la Fuente
Elena Vara
Jesús A. F. Tresguerres
Publikationsdatum
13.03.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nutrition / Ausgabe 2/2019
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-018-1657-6

Weitere Artikel der Ausgabe 2/2019

European Journal of Nutrition 2/2019 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Battle of Experts: Sport vs. Spritze bei Adipositas und Typ-2-Diabetes

11.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Im Battle of Experts traten zwei Experten auf dem Diabeteskongress gegeneinander an: Die eine vertrat die Auffassung „Sport statt Spritze“ bei Adipositas und Typ-2-Diabetes, der andere forderte „Spritze statt Sport!“ Am Ende waren sie sich aber einig: Die Kombination aus beidem erzielt die besten Ergebnisse.

Vorsicht, erhöhte Blutungsgefahr nach PCI!

10.05.2024 Koronare Herzerkrankung Nachrichten

Nach PCI besteht ein erhöhtes Blutungsrisiko, wenn die Behandelten eine verminderte linksventrikuläre Ejektionsfraktion aufweisen. Das Risiko ist umso höher, je stärker die Pumpfunktion eingeschränkt ist.

Triglyzeridsenker schützt nicht nur Hochrisikopatienten

10.05.2024 Hypercholesterinämie Nachrichten

Patienten mit Arteriosklerose-bedingten kardiovaskulären Erkrankungen, die trotz Statineinnahme zu hohe Triglyzeridspiegel haben, profitieren von einer Behandlung mit Icosapent-Ethyl, und zwar unabhängig vom individuellen Risikoprofil.

Gibt es eine Wende bei den bioresorbierbaren Gefäßstützen?

In den USA ist erstmals eine bioresorbierbare Gefäßstütze – auch Scaffold genannt – zur Rekanalisation infrapoplitealer Arterien bei schwerer PAVK zugelassen worden. Das markiert einen Wendepunkt in der Geschichte dieser speziellen Gefäßstützen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.