Curcumin protects thymus against D-galactose-induced senescence in mice.
Autoimmune regulator
Curcumin
D-galactose
Senescence
Thymus
Journal
Naunyn-Schmiedeberg's archives of pharmacology
ISSN: 1432-1912
Titre abrégé: Naunyn Schmiedebergs Arch Pharmacol
Pays: Germany
ID NLM: 0326264
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
04
01
2020
accepted:
08
07
2020
pubmed:
21
7
2020
medline:
26
10
2021
entrez:
21
7
2020
Statut:
ppublish
Résumé
Senescence-related decline of thymus affects immune function in the elderly population and contributes to the prevalence of many relevant diseases like cancer, autoimmune diseases, and other chronic diseases. In this study, we investigated the therapeutic effects of curcumin, an agent that could counter aging, and explored its optimal intake and the alteration of autoimmune regulator (Aire) after curcumin treatment in the D-galactose (D-gal)-induced accelerated aging mice. ICR mice were intraperitoneally injected with D-gal for 8 weeks to establish the accelerated aging model and given curcumin with 50, 100, and 200 mg/kg body weight per day by gavage, respectively, for 6 weeks. It indicated that the D-gal-treated mice developed structural changes in the thymi compared with the control group without D-gal and curcumin treatment. As the supplements of curcumin, it resulted in a restoration of the normal thymic anatomy with an increase of proliferating cells and a reduction of apoptotic cells in the thymi of the D-gal-induced aging model mice. Curcumin administration could also expand the expression level of Aire from mRNA level and protein level. The current study demonstrated that curcumin could ameliorate senescence-related thymus involution via upregulating Aire expression, suggesting that curcumin can rejuvenate senescence-associated alterations of thymus induced by D-gal accumulation.
Identifiants
pubmed: 32686020
doi: 10.1007/s00210-020-01945-8
pii: 10.1007/s00210-020-01945-8
doi:
Substances chimiques
Protective Agents
0
Transcription Factors
0
Curcumin
IT942ZTH98
Galactose
X2RN3Q8DNE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
411-420Subventions
Organisme : Youth Development Fund from School of Basic Medical Sciences, Zhengzhou University
ID : No. JCYXY2016-YQ-05
Références
Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41(1):40–59. https://doi.org/10.1016/j.biocel.2008.06.010
doi: 10.1016/j.biocel.2008.06.010
pubmed: 18662800
Alekseyeva IN, Makogon NV, Bryzgina TM, Voznesenskaya TY, Sukhina VS (2011) Effects of NF-kappaB blocker curcumin on oogenesis and immunocompetent organ cells in immune ovarian injury in mice. Bull Exp Biol Med 151(4):432–435. https://doi.org/10.1007/s10517-011-1349-1
doi: 10.1007/s10517-011-1349-1
pubmed: 22448359
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4(6):807–818. https://doi.org/10.1021/mp700113r
doi: 10.1021/mp700113r
Anderson MS, Venanzi ES, Klein L et al (2002) Projection of an immunological self shadow within the thymus by the aire protein. Science (New York, NY) 298(5597):1395–1401. https://doi.org/10.1126/science.1075958
doi: 10.1126/science.1075958
Aw D, Silva AB, Palmer DB (2007) Immunosenescence: emerging challenges for an ageing population. Immunology 120(4):435–446. https://doi.org/10.1111/j.1365-2567.2007.02555.x
doi: 10.1111/j.1365-2567.2007.02555.x
pubmed: 17313487
pmcid: 2265901
Aw D, Silva AB, Maddick M, von Zglinicki T, Palmer DB (2008) Architectural changes in the thymus of aging mice. Aging Cell 7(2):158–167. https://doi.org/10.1111/j.1474-9726.2007.00365.x
doi: 10.1111/j.1474-9726.2007.00365.x
pubmed: 18241323
Bielak-Zmijewska A, Grabowska W, Ciolko A, Bojko A, Mosieniak G, Bijoch Ł, Sikora E (2019) The role of curcumin in the modulation of ageing. Int J Mol Sci 20(5). https://doi.org/10.3390/ijms20051239
Brelinska R (2003) Thymic epithelial cells in age-dependent involution. Microsc Res Tech 62(6):488–500. https://doi.org/10.1002/jemt.10410
doi: 10.1002/jemt.10410
pubmed: 14635142
Calabrese EJ (2014) Hormesis: from mainstream to therapy. J Cell Commun Signal 8(4):289–291. https://doi.org/10.1007/s12079-014-0255-5
doi: 10.1007/s12079-014-0255-5
pubmed: 25366126
pmcid: 4390802
Cepeda S, Cantu C, Orozco S, Xiao Y, Brown Z, Semwal MK, Venables T, Anderson MS, Griffith AV (2018) Age-associated decline in thymic B cell expression of Aire and Aire-dependent self-antigens. Cell Rep 22(5):1276–1287. https://doi.org/10.1016/j.celrep.2018.01.015
doi: 10.1016/j.celrep.2018.01.015
pubmed: 29386114
pmcid: 5813500
Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21(4B):2895–2900
pubmed: 11712783
Chinn IK, Blackburn CC, Manley NR, Sempowski GD (2012) Changes in primary lymphoid organs with aging. Semin Immunol 24(5):309–320. https://doi.org/10.1016/j.smim.2012.04.005
doi: 10.1016/j.smim.2012.04.005
pubmed: 22559987
pmcid: 3415579
Dardenne M, Boukaiba N, Gagnerault MC, Homo-Delarche F, Chappuis P, Lemonnier D, Savino W (1993) Restoration of the thymus in aging mice by in vivo zinc supplementation. Clin Immunol Immunopathol 66(2):127–135. https://doi.org/10.1006/clin.1993.1016
doi: 10.1006/clin.1993.1016
pubmed: 8453784
Demirovic D, Rattan SI (2011) Curcumin induces stress response and hormetically modulates wound healing ability of human skin fibroblasts undergoing ageing in vitro. Biogerontology 12(5):437–444. https://doi.org/10.1007/s10522-011-9326-7
doi: 10.1007/s10522-011-9326-7
pubmed: 21380847
Deng HB, Cheng CL, Cui DP, Li DD, Cui L, Cai NS (2006) Structural and functional changes of immune system in aging mouse induced by D-galactose. Biomedical and environmental sciences : BES 19(6):432–438
pubmed: 17319267
Dey S, Sreenivasan K (2014) Conjugation of curcumin onto alginate enhances aqueous solubility and stability of curcumin. Carbohydr Polym 99:499–507. https://doi.org/10.1016/j.carbpol.2013.08.067
doi: 10.1016/j.carbpol.2013.08.067
pubmed: 24274536
Du HM, Wang YJ, Liu X et al (2019) Defective central immune tolerance induced by high-dose D-galactose resembles aging. Biochemistry (Mosc) 84(6):617–626. https://doi.org/10.1134/S000629791906004X
doi: 10.1134/S000629791906004X
Ernszt D, Banfai K, Kellermayer Z, Pap A, Lord JM, Pongracz JE, Kvell K (2017) PPARgamma deficiency counteracts thymic senescence. Front Immunol 8:1515. https://doi.org/10.3389/fimmu.2017.01515
doi: 10.3389/fimmu.2017.01515
pubmed: 29163553
pmcid: 5681731
Fujisawa S, Atsumi T, Ishihara M, Kadoma Y (2004) Cytotoxicity, ROS-generation activity and radical-scavenging activity of curcumin and related compounds. Anticancer Res 24(2B):563–569
pubmed: 15160995
Gui J, Mustachio LM, Su DM, Craig RW (2012) Thymus size and age-related thymic involution: early programming, sexual dimorphism, progenitors and stroma. Aging Dis 3(3):280–290
pubmed: 22724086
pmcid: 3375084
Guo L, J-h C, T-t W et al (2019) Gallic acid attenuates thymic involution in the D-galactose induced accelerated aging mice. Immunobiology 225:151870. https://doi.org/10.1016/j.imbio.2019.11.005
doi: 10.1016/j.imbio.2019.11.005
pubmed: 31822433
Haynes BF, Sempowski GD, Wells AF, Hale LP (2000) The human thymus during aging. Immunol Res 22(2–3):253–261. https://doi.org/10.1385/IR:22:2-3:253
doi: 10.1385/IR:22:2-3:253
pubmed: 11339360
Heng TS, Goldberg GL, Gray DH, Sutherland JS, Chidgey AP, Boyd RL (2005) Effects of castration on thymocyte development in two different models of thymic involution. J Immunol 175(5):2982–2993. https://doi.org/10.4049/jimmunol.175.5.2982
doi: 10.4049/jimmunol.175.5.2982
pubmed: 16116185
Heng TS, Reiseger JJ, Fletcher AL et al (2012) Impact of sex steroid ablation on viral, tumour and vaccine responses in aged mice. PLoS One 7(8):e42677. https://doi.org/10.1371/journal.pone.0042677
doi: 10.1371/journal.pone.0042677
pubmed: 22880080
pmcid: 3411797
Hoehle SI, Pfeiffer E, Solyom AM, Metzler M (2006) Metabolism of curcuminoids in tissue slices and subcellular fractions from rat liver. J Agric Food Chem 54(3):756–764. https://doi.org/10.1021/jf058146a
doi: 10.1021/jf058146a
pubmed: 16448179
Hubert FX, Kinkel SA, Webster KE, Cannon P, Crewther PE, Proeitto AI, Wu L, Heath WR, Scott HS (2008) A specific anti-Aire antibody reveals aire expression is restricted to medullary thymic epithelial cells and not expressed in periphery. J Immunol 180(6):3824–3832. https://doi.org/10.4049/jimmunol.180.6.3824
doi: 10.4049/jimmunol.180.6.3824
pubmed: 18322189
Jaruga E, Bielak-Zmijewska A, Sikora E, Skierski J, Radziszewska E, Piwocka K, Bartosz G (1998) Glutathione-independent mechanism of apoptosis inhibition by curcumin in rat thymocytes. Biochem Pharmacol 56(8):961–965
doi: 10.1016/S0006-2952(98)00144-0
Jin QH, Shen HX, Wang H, Shou QY, Liu Q (2013) Curcumin improves expression of SCF/c-kit through attenuating oxidative stress and NF-κB activation in gastric tissues of diabetic gastroparesis rats. Diabetology & metabolic syndrome 5(1):12. https://doi.org/10.1186/1758-5996-5-12
doi: 10.1186/1758-5996-5-12
Koizumi K, Kawanai T, Hashimoto E, Kanbara Y, Masuda T, Kanemaru K, Okano Y, Oyama Y (2011) Cytometric analysis on cytotoxicity of curcumin on rat thymocytes: proapoptotic and antiapoptotic actions of curcumin. Toxicology in vitro : an international journal published in association with BIBRA 25(4):985–990. https://doi.org/10.1016/j.tiv.2011.03.010
doi: 10.1016/j.tiv.2011.03.010
Kumar A, Sasmal D, Jadav SS, Sharma N (2015) Mechanism of immunoprotective effects of curcumin in DLM-induced thymic apoptosis and altered immune function: an in silico and in vitro study. Immunopharmacol Immunotoxicol 37(6):488–498. https://doi.org/10.3109/08923973.2015.1091004
doi: 10.3109/08923973.2015.1091004
pubmed: 26471321
Kuroda N, Mitani T, Takeda N, Ishimaru N, Arakaki R, Hayashi Y, Bando Y, Izumi K, Takahashi T, Nomura T, Sakaguchi S, Ueno T, Takahama Y, Uchida D, Sun S, Kajiura F, Mouri Y, Han H, Matsushima A, Yamada G, Matsumoto M (2005) Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice. Journal of immunology (Baltimore, Md : 1950) 174(4):1862–1870
doi: 10.4049/jimmunol.174.4.1862
Labat-Moleur F, Guillermet C, Lorimier P, Robert C, Lantuejoul S, Brambilla E, Negoescu A (1998) TUNEL apoptotic cell detection in tissue sections: critical evaluation and improvement. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 46(3):327–334. https://doi.org/10.1177/002215549804600306
doi: 10.1177/002215549804600306
Lao CD, Ruffin MT, Normolle D et al (2006) Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 6:10. https://doi.org/10.1186/1472-6882-6-10
doi: 10.1186/1472-6882-6-10
pubmed: 16545122
pmcid: 1434783
Lin N, Zhang H, Su Q (2012) Advanced glycation end-products induce injury to pancreatic beta cells through oxidative stress. Diabetes Metab 38(3):250–257. https://doi.org/10.1016/j.diabet.2012.01.003
doi: 10.1016/j.diabet.2012.01.003
pubmed: 22386833
Liu B, Liu Z, Chen T, Li H, Qiang B, Yuan J, Peng X, Qiu M (2007) Selective expression of Bhlhb5 in subsets of early-born interneurons and late-born association neurons in the spinal cord. Developmental dynamics : an official publication of the American Association of Anatomists 236(3):829–835. https://doi.org/10.1002/dvdy.21061
doi: 10.1002/dvdy.21061
Liu J, Liu J, Xu H et al (2014) Novel tumor-targeting, self-assembling peptide nanofiber as a carrier for effective curcumin delivery. Int J Nanomedicine 9:197–207. https://doi.org/10.2147/IJN.S55875
doi: 10.2147/IJN.S55875
pubmed: 24399876
Ma Z, Wang N, He H, Tang X (2019) Pharmaceutical strategies of improving oral systemic bioavailability of curcumin for clinical application. J Control Release 316:359–380. https://doi.org/10.1016/j.jconrel.2019.10.053
doi: 10.1016/j.jconrel.2019.10.053
pubmed: 31682912
Moghaddam NSA, Oskouie MN, Butler AE, Petit PX, Barreto GE, Sahebkar A (2019) Hormetic effects of curcumin: what is the evidence? J Cell Physiol 234(7):10060–10071. https://doi.org/10.1002/jcp.27880
doi: 10.1002/jcp.27880
pubmed: 30515809
Moreira-Filho CA, Bando SY, Bertonha FB, Ferreira LR, Vinhas CF, Oliveira LHB, Zerbini MCN, Furlanetto G, Chaccur P, Carneiro-Sampaio M (2018) Minipuberty and sexual dimorphism in the infant human thymus. Sci Rep 8(1):13169. https://doi.org/10.1038/s41598-018-31583-3
doi: 10.1038/s41598-018-31583-3
pubmed: 30177771
pmcid: 6120939
Odinokov D, Hamblin MR (2018) Aging of lymphoid organs: can photobiomodulation reverse age-associated thymic involution via stimulation of extrapineal melatonin synthesis and bone marrow stem cells? 11(8):e201700282 doi: https://doi.org/10.1002/jbio.201700282
Pan MH, Huang TM, Lin JK (1999) Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 27(4):486–494
pubmed: 10101144
Pera A, Campos C, Lopez N et al (2015) Immunosenescence: implications for response to infection and vaccination in older people. Maturitas 82(1):50–55. https://doi.org/10.1016/j.maturitas.2015.05.004
doi: 10.1016/j.maturitas.2015.05.004
pubmed: 26044074
Perniola R (2018) Twenty years of AIRE. Front Immunol 9:98. https://doi.org/10.3389/fimmu.2018.00098
doi: 10.3389/fimmu.2018.00098
pubmed: 29483906
pmcid: 5816566
Petrie HT, Zuniga-Pflucker JC (2007) Zoned out: functional mapping of stromal signaling microenvironments in the thymus. Annu Rev Immunol 25:649–679. https://doi.org/10.1146/annurev.immunol.23.021704.115715
doi: 10.1146/annurev.immunol.23.021704.115715
pubmed: 17291187
Rai D, Singh JK, Roy N, Panda D (2008) Curcumin inhibits FtsZ assembly: an attractive mechanism for its antibacterial activity. The Biochemical journal 410(1):147–155. https://doi.org/10.1042/BJ20070891
doi: 10.1042/BJ20070891
pubmed: 17953519
Rattan SI, Ali RE (2007) Hormetic prevention of molecular damage during cellular aging of human skin fibroblasts and keratinocytes. Ann N Y Acad Sci 1100:424–430. https://doi.org/10.1196/annals.1395.047
doi: 10.1196/annals.1395.047
pubmed: 17460207
Reuter S, Eifes S, Dicato M, Aggarwal BB, Diederich M (2008) Modulation of anti-apoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells. Biochem Pharmacol 76(11):1340–1351. https://doi.org/10.1016/j.bcp.2008.07.031
doi: 10.1016/j.bcp.2008.07.031
pubmed: 18755156
Rezzani R, Nardo L, Favero G, Peroni M, Rodella LF (2014) Thymus and aging: morphological, radiological, and functional overview. Age (Dordr) 36(1):313–351. https://doi.org/10.1007/s11357-013-9564-5
doi: 10.1007/s11357-013-9564-5
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS (1998) Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 64(4):353–356. https://doi.org/10.1055/s-2006-957450
doi: 10.1055/s-2006-957450
pubmed: 9619120
Sikora E, Bielak-Zmijewska A, Piwocka K, Skierski J, Radziszewska E (1997) Inhibition of proliferation and apoptosis of human and rat T lymphocytes by curcumin, a curry pigment. Biochem Pharmacol 54(8):899–907. https://doi.org/10.1016/s0006-2952(97)00251-7
doi: 10.1016/s0006-2952(97)00251-7
pubmed: 9354590
Song P, Chen Y (2015) Public policy response, aging in place, and big data platforms: creating an effective collaborative system to cope with aging of the population. Bioscience trends 9(1):1–6. https://doi.org/10.5582/bst.2015.01025
doi: 10.5582/bst.2015.01025
pubmed: 25787904
Song X, Bao M, Li D, Li YM (1999) Advanced glycation in D-galactose induced mouse aging model. Mech Ageing Dev 108(3):239–251
doi: 10.1016/S0047-6374(99)00022-6
Song Y, Sonawane ND, Salinas D, Qian L, Pedemonte N, Galietta LJV, Verkman AS (2004) Evidence against the rescue of defective DeltaF508-CFTR cellular processing by curcumin in cell culture and mouse models. J Biol Chem 279(39):40629–40633. https://doi.org/10.1074/jbc.M407308200
doi: 10.1074/jbc.M407308200
pubmed: 15280357
Sun L, Guo J, Brown R, Amagai T, Zhao Y, Su DM (2010) Declining expression of a single epithelial cell-autonomous gene accelerates age-related thymic involution. Aging Cell 9(3):347–357. https://doi.org/10.1111/j.1474-9726.2010.00559.x
doi: 10.1111/j.1474-9726.2010.00559.x
pubmed: 20156205
pmcid: 2894280
Sutherland JS, Goldberg GL, Hammett MV, Uldrich AP, Berzins SP, Heng TS, Blazar BR, Millar JL, Malin MA, Chidgey AP, Boyd RL (2005) Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol 175(4):2741–2753. https://doi.org/10.4049/jimmunol.175.4.2741
doi: 10.4049/jimmunol.175.4.2741
pubmed: 16081852
Tsvetkov P, Asher G, Reiss V, Shaul Y, Sachs L, Lotem J (2005) Inhibition of NAD(P)H:quinone oxidoreductase 1 activity and induction of p53 degradation by the natural phenolic compound curcumin. Proc Natl Acad Sci U S A 102(15):5535–5540. https://doi.org/10.1073/pnas.0501828102
doi: 10.1073/pnas.0501828102
pubmed: 15809436
pmcid: 556252
Uddin MN, Nishio N, Ito S, Suzuki H, Isobe K (2010) Toxic effects of D-galactose on thymus and spleen that resemble aging. J Immunotoxicol 7(3):165–173. https://doi.org/10.3109/15476910903510806
doi: 10.3109/15476910903510806
pubmed: 20050818
Varalakshmi C, Ali AM, Pardhasaradhi BV, Srivastava RM, Singh S, Khar A (2008) Immunomodulatory effects of curcumin: in-vivo. Int Immunopharmacol 8(5):688–700. https://doi.org/10.1016/j.intimp.2008.01.008
doi: 10.1016/j.intimp.2008.01.008
pubmed: 18387511
Velardi E, Dudakov JA, van den Brink MR (2015) Sex steroid ablation: an immunoregenerative strategy for immunocompromised patients. Bone Marrow Transplant 50(Suppl 2):S77–S81. https://doi.org/10.1038/bmt.2015.101
doi: 10.1038/bmt.2015.101
pubmed: 26039214
pmcid: 5067941
Yan Z, Dai Y, Fu H, Zheng Y, Bao D, Yin Y, Chen Q, Nie X, Hao Q, Hou D, Cui Y (2018) Curcumin exerts a protective effect against premature ovarian failure in mice. J Mol Endocrinol 60(3):261–271. https://doi.org/10.1530/JME-17-0214
doi: 10.1530/JME-17-0214
pubmed: 29437881
pmcid: 5863768
Yang H, Youm YH, Dixit VD (2009) Inhibition of thymic adipogenesis by caloric restriction is coupled with reduction in age-related thymic involution. Journal of immunology (Baltimore, Md : 1950) 183(5):3040–3052. https://doi.org/10.4049/jimmunol.0900562
doi: 10.4049/jimmunol.0900562
Zhang J, Wang Y, Aili A, et al. (2019) Th1 biased progressive autoimmunity in aged Aire-deficient mice accelerated thymic epithelial cell senescence. Aging Dis 10(3):497-509 doi: https://doi.org/10.14336/AD.2018.0608
Zhou YY, Ji XF, Fu JP, Zhu XJ, Li RH, Mu CK, Wang CL, Song WW (2015) Gene transcriptional and metabolic profile changes in mimetic aging mice induced by D-galactose. PLoS One 10(7):e0132088. https://doi.org/10.1371/journal.pone.0132088
doi: 10.1371/journal.pone.0132088
pubmed: 26176541
pmcid: 4503422