The Mango’s Mistletoe Leaves Extract Ameliorates Lupus by Inhibiting the Anti-dsDNA Antibody Production, the Percentages of CD8+CD28− and CD4+CD28− T Cells

Kusworini Handono; Sri Sunarti; Mirza Zaka Pratama; Saiful Hidayat; Muhammad Badrus Solikhin; Inmas Andi Sermoati; Maria Gabriela Yuniati

doi:10.3889/oamjms.2022.8093

Authors

Kusworini Handono Department of Clinical Pathology, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia
Sri Sunarti Department of Internal Medicine, Geriatric Division, Brawijaya University, Malang, East Java, Indonesia
Mirza Zaka Pratama Department of Internal Medicine, Rheumatology and Immunology Division, Brawijaya University, Malang, East Java, Indonesia https://orcid.org/0000-0003-0906-9939
Saiful Hidayat Magister Program in Biomedical Sciences, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia https://orcid.org/0000-0001-7756-7679
Muhammad Badrus Solikhin Magister Program in Biomedical Sciences, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia
Inmas Andi Sermoati Magister Program in Midwife Sciences, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia
Maria Gabriela Yuniati Magister Program in Midwife Sciences, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia https://orcid.org/0000-0001-6606-0215

DOI:

https://doi.org/10.3889/oamjms.2022.8093

Keywords:

Anti-dsDNA antibodies, Mango’s mistletoe leaf, Systemic lupus erythematosus, The percentages of CD8 28− T cells, The percentages of CD4 28− T cells

Abstract

BACKGROUND: In SLE patients, repeated antigen stimulations induce a progressive reduction in CD28 expression on the surface of T cells and the chronic inflammation condition. Mango’s mistletoe is a parasitic plant that has anti-inflammation, antiproliferation, and immunomodulatory activities.

AIM: This study aimed to investigate the effect of mango’s mistletoe leaves extract (MLE) in inhibiting anti-dsDNA antibodies and ameliorating the percentages of CD8⁺CD28⁻ and CD4⁺CD28⁻ T cells in a pristane-induced lupus mice model.

METHODS: Lupus induction was undertaken by an injection of pristane 0.5 ml intraperitoneally in 6–8-week-old female balb/c mice. Mice with lupus signs were grouped randomly into the treatment groups which received MLE at doses of 150, 300, and 600 mg/kgbw/d for 28 days, respectively, and the positive control group without MLE. On day 29, anti-dsDNA antibody levels were analyzed using an ELISA. One of the immunosenescence markers (CD28⁻ T cells) was investigated using a flow cytometer. ANOVA test was used for statistical analysis.

RESULTS: The mango’s mistletoe leaves extract (MLE) significantly decreased the number of anti-dsDNA antibodies (*p < 0.05), the percentages of CD8⁺CD28⁻ T cells (*p < 0.05) and CD4⁺CD28⁻ T cells (*p < 0.05).

CONCLUSION: We resume that the mango’s mistletoe leaves can ameliorate lupus by inhibiting anti-dsDNA antibody production and the percentages of CD8⁺CD28⁻and CD4⁺CD28⁻T cells.

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References

Kosmaczewska A, Ciszak L, Stosio M, Szteblich A, Madej M, Frydecka I, et al. CD4+ CD28null T cells are expanded in moderately active systemic lupus erythematosus and secrete proinflammatory interferon-gamma, depending on the Disease Activity Index. Lupus. 2020;29(7):705-14. https://doi. org/10.1177/0961203320917749 PMid:32279585 DOI: https://doi.org/10.1177/0961203320917749

Hanaoka H, Okazaki Y, Satoh T, Kaneko Y, Yasuoka H, Seta N, et al. Circulating anti-double-stranded DNA antibody-secreting cells in patients with systemic lupus erythematosus: a novel biomarker for disease activity. Lupus. 2021;21(12):1284-93. https://doi.org/10.1177/0961203312453191 PMid:22740429 DOI: https://doi.org/10.1177/0961203312453191

Stojan G, Petri M. Epidemiology of systemic lupus erythematosus: An update. Curr Opin Rheumatol. 2018;30(2):144-50. https://doi.org/10.1097/BOR.0000000000000480 PMid:29251660 DOI: https://doi.org/10.1097/BOR.0000000000000480

Kariniemi S, Rantalaiho V, Virta LJ, Puolakka K, Isler TS, Elfving P. Multimorbidity among incident Finnish systemic lupus erythematosus patients during 2000-2017. Lupus. 2020;30(1):165-71. https://doi.org/10.1177/0961203320967102 PMid:33086917 DOI: https://doi.org/10.1177/0961203320967102

Balkrishna A, Thakur P, Singh S, Dev SN, Varshney A. Mechanistic paradigms of natural plant metabolites as remedial candidates for systemic lupus erythematosus. Cells. 2020;9(4):104. https://doi.org/10.3390/cells9041049 PMid:32331431 DOI: https://doi.org/10.3390/cells9041049

Van den Hoogen LL, Sims GP, Van Roon JA, Fritsch-Stork RD. Aging and systemic lupus erythematosus immunosenescence and beyond. Curr Aging Sci. 2015;8(2):158-77. https://doi.org/10.2174/1874609808666150727111904 PMid:26212055 DOI: https://doi.org/10.2174/1874609808666150727111904

Davis LS, Hutcheson J, Mohan C. The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus. J Interferon Cytokine Res. 2011;31(10):781-9. https://doi.org/10.1089/jir.2011.0047 PMid:21787222 DOI: https://doi.org/10.1089/jir.2011.0047

Liu D, Li P, Song S, Liu Y, Wang Q, Chang Y, et al. Pro-apoptotic effect of Epigallo-catechin-3-gallate on B lymphocytes through regulating BAFF/PI3K/Akt/mTOR signaling in rats with collagen-induced arthritis. Eur J Pharmacol. 2012;690(1-3):214-25. https://doi.org/10.1016/j.ejphar.2012.06.026 PMid:22760071 DOI: https://doi.org/10.1016/j.ejphar.2012.06.026

Pan L, Lu MP, Wang JH, Xu M, Yang SR. Immunological pathogenesis and treatment of systemic lupus erythematosus. World J. Pediatr. 2020;16(1):19-30. https://doi.org/10.1007/s12519-019-00229-3 PMid:30796732 DOI: https://doi.org/10.1007/s12519-019-00229-3

Mou D, Espinosa J, Lo DJ, Kirk AD. CD28 Negative T cells: is their loss our gain? Am J Transplant. 2014;14(11):2460-6. https://doi.org/10.1111/ajt.12937 PMid:25323029 DOI: https://doi.org/10.1111/ajt.12937

Bryl E, Vallejo AN, Weyand CM, Goronzy JJ. Down-regulation of CD28 expression by TNF-α. J Immunol. 2001;167(6):3231-8. https://doi.org/10.4049/jimmunol.167.6.3231 PMid:11544310 DOI: https://doi.org/10.4049/jimmunol.167.6.3231

Minning S, Xiaofan Y, Anqi X, Bingjie G, Dinglei S, Mingshun Z, et al. Imbalance between CD8þCD28þ and CD8þCD28-T-cell subsets and its clinical significance in patients with systemic lupus erythematosus. Lupus. 2019;28(10):1214-23. https://doi.org/10.1177/0961203319867130 PMid:31399013 DOI: https://doi.org/10.1177/0961203319867130

Strioga M, Pasukoniene V, Characiejus D. CD8+CD28- and CD8+CD57+ T cells and their role in health and disease. Immunology. 2011;134(1):17-32. https://doi.org/10.1111/j.1365-2567.2011.03470.x PMid:21711350 DOI: https://doi.org/10.1111/j.1365-2567.2011.03470.x

Roy S. Immunosenescence in rheumatoid arthritis: Use of CD28 negative T cells to predict treatment response. Indian J Rheumatol. 2014;9(2):62-8. https://doi.org/10.4103/0973-3698.185982 DOI: https://doi.org/10.1016/j.injr.2014.01.011

Kalim H, Wahono CS, Permana BPO, Pratama MZ, Handono K. Association between senescence of T cells and disease activity in patients with systemic lupus erythematosus. Reumatologia. 2021;59(5):292-301. https://doi.org/10.5114/reum.2021.110318. PMid 34819703 DOI: https://doi.org/10.5114/reum.2021.110318

Moore E, Putterman C. Are lupus animal models useful for understanding and developing new therapies for human SLE? J Autoimmune. 2020;112:102490. https://doi.org/10.1016/j.jaut.2020.102490 PMid:32535128 DOI: https://doi.org/10.1016/j.jaut.2020.102490

Kristiningrum N, Ridlo M, Pratoko DK. Phytochemical screening and determination of total phenolic content of Dendophthoe pentandra L. leave ethanolic extract on mango host. Ann Trop Med Public Health. 2020;23(3):23-32. https://doi.org/10.36295/asro.2020.2334 DOI: https://doi.org/10.36295/ASRO.2020.2334

Li W, Titov AA, Morel L. An update on lupus animal models. Curr Opin Rheumatol. 2017;29(5):434-41. https://doi.org/10.1097/BOR.0000000000000412 PMid:28537986 DOI: https://doi.org/10.1097/BOR.0000000000000412

Halkom A, Wu H, Lu Q. Contribution of mouse models in our understanding of lupus. Int Rev Immunol. 2020;39(4):174-187. https://doi.org/10.1080/08830185.2020.1742712 PMid:32202964 DOI: https://doi.org/10.1080/08830185.2020.1742712

Rottman JB, Willis CR. Mouse models of systemic lupus erythematosus reveal a complex pathogenesis. Vet Pathol. 2010;47(4):664-76. https://doi.org/10.1177/0300985810370005 PMid:20448279 DOI: https://doi.org/10.1177/0300985810370005

Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-86. https://doi.org/10.1002/art.34473 PMid:22553077 DOI: https://doi.org/10.1002/art.34473

Ponte LG, Pavan IC, Mancini MC, da Silva LG, Morelli AP, Severino MB, et al. The hallmarks of flavonoids in cancer. Molecules. 2021;26(7):2029. https://doi.org/10.3390/molecules26072029 PMid:33918290 DOI: https://doi.org/10.3390/molecules26072029

Bacalao MA, Satterthwaite AB. Recent advances in lupus B cell biology: PI3K, IFNγ, and chromatin. Front Immunol. 2020;11:615673. https://doi.org/10.3389/fimmu.2020.615673 PMid:33519824 DOI: https://doi.org/10.3389/fimmu.2020.615673

Chyuan IT, Tzeng HT, Chen JY. Signaling pathways of Type I and Type III interferons and targeted therapies in systemic lupus erythematosus. Cells. 2019;8(9):963. https://doi.org/10.3390/cells8090963 PMid:31450787 DOI: https://doi.org/10.3390/cells8090963

Kirou KA, Gkrouzman E. Anti-interferon alpha treatment in SLE. Clin Immunol. 2013;148(3):303-12. https://doi.org/10.1016/j.clim.2013.02.013 PMid:23566912 DOI: https://doi.org/10.1016/j.clim.2013.02.013

Ioannone F, Miglio C, Raguzzini A, Serafini M. Flavonoids and immune function. In: Calder PC, Yaqoob P, editors. Diet, Immunity, and Inflammation. 1st ed. Cambridge: Woodhead Publishing; 2013. p. 379-415. DOI: https://doi.org/10.1533/9780857095749.3.379

Guritno T, Barlianto W, Wulandari D, Amru WA. Effect Nigella sativa extract for balancing immune response in pristane-induced lupus mice model. J Appl Pharm Sci. 2020;11(7):146-152. https://doi.org/10.7324/JAPS.2021.110716 DOI: https://doi.org/10.7324/JAPS.2021.110716

Tiji S, Benayad O, Berrabah M, El Mounsi I, Mimouni M. Phytochemical profile and antioxidant activity of Nigella sativa L growing in Morocco. Sci World J. 2021;2021:6623609. https://doi.org/10.1155/2021/6623609 PMid:33986636 DOI: https://doi.org/10.1155/2021/6623609

Kalim H, Pratama MZ, Mahardini E, Winoto ES, Krisna PA, Handono K. Accelerated immune aging was correlated with lupus-associated brain fog in reproductive-age systemic lupus erythematosus patients. Int J Rheum Dis. 2019;23(5):620-6. https://doi.org/10.1111/1756-185X.13816 PMid:32107852 DOI: https://doi.org/10.1111/1756-185X.13816

Coleman MJ, Zimmerly KM, Yang XO. Accumulation of CD28 senescent t-cells is associated with poorer outcomes in COVID19 patients. Biomolecules. 2021;11(10):1425. https://doi.org/10.3390/biom11101425 PMid:34680058 DOI: https://doi.org/10.3390/biom11101425

Kim ME, Ha TK, Yoon JH, Lee JL. Myricetin induces cell death of human colon cancer cells via BAX/BCL2-dependent pathway. Anticancer Res. 2014;34(2):701-6. PMid:24511002

Farzaei MH, Singh AK, Kumar R, Croley CR, Pandey AK, Coy-Barrera E. Targeting inflammation by flavonoids: Novel therapeutic strategy for metabolic disorders. Int J Mol Sci. 2019;20(19):4957. https://doi.org/10.3390/ijms20194957 PMid:31597283 DOI: https://doi.org/10.3390/ijms20194957

Lanna A, Henson SM, Escors D, Akbar AN. The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells. Nat. Immunol. 2014;15(10):965-72. https://doi.org/10.1038/ni.2981 PMid:25151490 DOI: https://doi.org/10.1038/ni.2981

Liu X, Mo W, Ye J, Li L, Zhang Y, Hsueh EC, et al. Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition. Nat Commun. 2018;9(1):249. https://doi.org/10.1038/s41467-017-02689-5 PMid:29339767 DOI: https://doi.org/10.1038/s41467-017-02689-5

Masad RJ, Haneefa SM, Mohamed YA, Sbiei AA, Bashir G, Cabezudo MJ, et al. The immunomodulatory effects of honey and associated flavonoids in cancer. Nutrients. 2021;13(4):1269. https://doi.org/10.3390/nu13041269 PMid:33924384 DOI: https://doi.org/10.3390/nu13041269