The The Effect of Mango Mistletoes (Dendrophthoe pentandra) Leaves Extract on Percentage of CD4+CD28+, CD8+CD28+, and interleukin-2 Levels of Aged Balb/c Mice

Kusworini Handono; Mirza Zaka Pratama; Inmas Andi Sermoati; Maria Gabriela Yuniati; Ni Putu Sri Haryati; Eviana Norahmawati; Agustina Tri Endharti; Yahya Irwanto; Muhammad Badrus Solikhin; Syaiful Hidayat

doi:10.3889/oamjms.2021.6182

Authors

Kusworini Handono Department of Clinical Pathology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; LAURA (Lupus Autoimmune Rheumatic and Allergy) Research Center, Universitas Brawijaya, Malang, Indonesia
Mirza Zaka Pratama Rheumatology and Immunology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; LAURA (Lupus Autoimmune Rheumatic and Allergy) Research Center, Universitas Brawijaya, Malang, Indonesia
Inmas Andi Sermoati Master Program in Midwifery, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia https://orcid.org/0000-0001-6993-3106
Maria Gabriela Yuniati Master Program in Midwifery, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Diploma III of Midwifery, Politeknik Kesehatan Kartini Bali, Denpasar, Indonesia https://orcid.org/0000-0001-6606-0215
Ni Putu Sri Haryati Master Program in Midwifery, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Bachelor of Midwifery, Faculty of Health, Institute of Technology and Health Bali, Denpasar, Indonesia https://orcid.org/0000-0001-9218-2275
Eviana Norahmawati Department of Anatomical Pathology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia https://orcid.org/0000-0002-8853-0916
Agustina Tri Endharti Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Master Program in Biomedical Science, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia https://orcid.org/0000-0002-2062-5740
Yahya Irwanto Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Muhammad Badrus Solikhin Master Program in Biomedical Science, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Syaiful Hidayat Master Program in Biomedical Science, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.6182

Keywords:

Dendrophthoe pentandra, Immunosenescence, Age, Aged Balb/C mice

Abstract

BACKGROUND: Population aging is considered to be a global phenomenon today. Age-associated immune system dysfunction or “immunosenescence” is indicated by increased susceptibility to infections and chronic diseases, such as hypertension, diabetes mellitus, autoimmune diseases, heart disease, and atherosclerosis. One of the immunosenescence markers is a significant drop in CD28 and reduced proinflammatory cytokine interleukin-2 (IL-2). The mango mistletoes are deemed to have a better affinity for docking the CD28 and IL-2R receptors of α and β subunits than other plants.

AIM: This study aims to determine the effect of ethanol extract of mango mistletoes on IL-2 levels, the percentage of CD4⁺CD28⁺, and the percentage of CD8⁺CD28⁺ in aged female mice.

METHODS: The leaves of mango mistletoes were extracted using 96% ethanol solvent, and the extract was administered to aged female mice (18–20 months) orally with different doses for each group, namely 150, 300, and 600 mg/kg. Mango mistletoe leaves extract was administered once a day for 14 days. Then, the IL-2 levels of the mice were checked from their heart blood samples using Enzyme-Linked Immunosorbent Assay, while the percentages of CD4⁺CD28⁺ and CD8⁺CD28⁺ were examined from the spleen samples using flow cytometry.

RESULTS: The ethanol extract of mango mistletoe leaves was able to increase the percentage of CD4⁺CD28⁺ significantly (p < 0.05) at doses of 300 and 600 mg/kg and increase the percentage of CD8⁺CD28⁺ significantly (p < 0.05) at a dose of 600 mg/kgBW, while other various doses had a strong enough correlation (r = 0.48) to increase IL-2 levels.

CONCLUSION: The ethanol extract of mango mistletoe leaves has the good potential to inhibit the aging process in the immune system, as characterized by an increase in IL-2 levels and the percentage of CD4⁺CD28⁺and CD8⁺CD28⁺.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Public Bank Berhad. World Population Ageing 2019 Highlight. Kuala Lumpur, Malaysia: Public Bank Berhad; 2019.

United Nations. Department of Economic and Social Affairs, Population Division. United States: United Nations; 2017.

Colombo P, Crawley ME, East BS, Hill AR. Aging and the Brain. Encyclopedia of Human Behavior (Second Edition); 2012.

Aiello A, Farzaneh F, Candore G, Caruso C, Accardi G, Turner JE. Immunosenescence and its hallmarks : How to oppose aging strategically ? A review of potential options for therapeutic intervention. Front Immunol. 2019;10:2247. https://doi.org/10.3389/fimmu.2019.02247 PMid:31608061

Jung MK, Shin EC. Aged T cells and cardiovascular disease. Cell Mol Immunol. 2017;14:1009-10. https://doi.org/10.1038/cmi.2017.111.

Flurkey K, Currer JM, Harrison DE. Mouse models in aging research. In: The Mouse in Biomedical Research. Ch. 20. United States: Academic Press; 2007. p. 637-72.

Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S, et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science. 2020;370(6518):856-60. https://doi.org/10.1126/science.abd2985 PMid:33082293

Maun HR, Jackman JK, Choy DF, Loyet KM, Staton TL, Jia G, et al. An allosteric anti-tryptase antibody for the treatment of mast cell-mediated severe asthma. Cell. 2019;179:417-31.e19. https://doi.org/10.1016/j.cell.2019.09.009 PMid:31585081

Johnson M. Laboratory mice and rats. Mater Methods. 2012;2:113. https://doi.org/10.13070/mm.en.2.113

Boldizsar F, Mikecz K, Glant TT. Immunosenescence and its potential modulation: Lessons from mouse models. Expert Rev Clin Immunol. 2010;6(3):353-7. https://doi.org/10.1586/eci.10.16 PMid:20441421

Esquivel N, García Y, Lores B, Gutiérrez M, Rodríguez C. Characterization of aged male BALB/ccenp mice as a model of dementia. Lab Anim Res. 2020;36:7. https://doi.org/10.1186/ s42826-020-00038-0

Fulton RB, Weiss KA, Pewe LL, Harty JT, Varga SM. Aged mice exhibit a severely diminished CD8 T cell response following respiratory syncytial virus infection. J Virol. 2013;87(23):12694- 700. https://doi.org/10.1128/jvi.02282-12 PMid:24049171

Goldmann O, Lehne S, Medina E. Age-related susceptibility to Streptococcus pyogenes infection in mice: Underlying immune dysfunction and strategy to enhance immunity. J Pathol. 2010;220(5):521-9. https://doi.org/10.1002/path.2664 PMid:20020512

Palmer S, Albergante L, Blackburn CC, Newman TJ. Thymic involution and rising disease incidence with age. Proc Natl Acad Sci U S A. 2018;115(8):1883. https://doi.org/10.1073/pnas.1714478115 PMid:29432166

Castelo-Branco C, Soveral I. The immune system and aging: A review. Gynecol Endocrinol. 2014;30(1):16-22. https://doi.org/10.3109/09513590.2013.852531 PMid:24219599

De Araújo AL, Silva LC, Fernandes JR, Benard G. Preventing or reversing immunosenescence: Can exercise be an immunotherapy? Immunotherapy. 2013;5(8):879-93. https://doi.org/10.2217/imt.13.77 PMid:23902557

Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13:227-42. https://doi.org/10.1038/nri3405

Weng NP, Akbar AN, Goronzy J. CD28(-) T cells: Their role in the age-associated decline of immune function. Trends Immunol. 2009;30(7):306-12. https://doi.org/10.1016/j.it.2009.03.013 PMid:19540809

Endharti AT, Wulandari A, Listyana A, Norahmawati E, Permana S. Dendrophthoe pentandra (L.) miq extract effectively inhibits inflammation, proliferation and induces p53 expression on colitis-associated colon cancer. BMC Complement Altern Med. 2016;16(1):374. https://doi.org/10.1186/s12906-016-1345-0 PMid:27670445

Hosseinzade A, Sadeghi O, Biregani AN, Soukhtehzari S, Brandt GS, Esmaillzadeh A. Immunomodulatory effects of flavonoids: Possible induction of T CD4+ regulatory cells through suppression of mTOR pathway signaling activity. Front Immunol. 2019;10:1-12. https://doi.org/10.3389/fimmu.2019.00051 PMid:30766532

Endale M, Park SC, Kim S, Kim SH, Yang Y, Cho JY, et al. Quercetin disrupts tyrosine-phosphorylated phosphatidylinositol 3-kinase and myeloid differentiation factor-88 association, and inhibits MAPK/ AP-1 and IKK/NF-κB-induced inflammatory mediators production in RAW 264.7 cells. Immunobiology. 2013;218(12):1452-67. https://doi.org/10.1016/j.imbio.2013.04.019 PMid:23735482

Matcham F, Carroll A, Chung N, Crawford V, Galloway J, Hames A, et al. Smoking and common mental disorders in patients with chronic conditions: An analysis of data collected via a web-based screening system. Gen Hosp Psychiatry. 2017;45:12-8. https://doi.org/10.1016/j.genhosppsych.2016.11.006 PMid:28274333

Li X, Shen J, Jiang Y, Shen T, You L, Sun X, et al. Anti-inflammatory effects of chloranthalactone B in LPS-stimulated RAW264.7 cells. Int J Mol Sci. 2016;17(11):1938. https://doi.org/10.3390/ijms17111938 PMid:27879664

Weichhart T, Hengstschläger M, Linke M. Regulation of innate immune cell function by mTOR. Nat Rev Immunol. 2015;15(10):599-614. https://doi.org/10.1038/nri3901 PMid:26403194

Rostamzadeh D, Yousefi M, Haghshenas MR, Ahmadi M, Dolati S, Babaloo Z. mTOR signaling pathway as a master regulator of memory CD8(+) T-cells, Th17, and NK cells development and their functional properties. J Cell Physiol. 2019;234(8):12353-68. https://doi.org/10.1002/jcp.28042 PMid:30710341

Elsyana V, Bintang M, Priosoeryanto BP. Cytotoxicity and antiproliferative activity assay of clove mistletoe (Dendrophthoe pentandra (L.) Miq.) leaves extracts. Adv Pharmacol Sci. 2016;2016:3242698. https://doi.org/10.1155/2016/3242698

Kurniasih N, Kusmiyati M, Sari RP, Wafdan R. Potensi daun sirsak (Annona muricata Linn), daun binahong (Anredera cordifolia (Ten) Steenis), dan daun benalu mangga (Dendrophthoe pentandra) sebagai antioksidan pencegah. J Istek. 2015;9:556. https://doi.org/10.35617/jfi.v9i1.556

Fitrilia T. Ekstrak Benalu Cengkeh (Dendrophthoe petandra (L.) Miq) Sebagai Agen Antioksidan Dan Antidiabetes Secara in vitro. India: IPB University Scientific Repository; 2015.

Endharti AT, Permana S. Extract from mango mistletoes Dendrophthoe pentandra ameliorates TNBS-induced colitis by regulating CD4+ T cells in mesenteric lymph nodes. BMC Complement Altern Med. 2017;17:468. https://doi.org/10.1186/s12906-017-1973-z

Ang HY, Subramani T, Yeap SK, Omar AR, Ho WY, Abdullah MP, et al. Immunomodulatory effects of Potentilla indica and Dendrophthoe pentandra on mice splenocytes and thymocytes. Exp Ther Med. 2014;7(6):1733-7. https://doi.org/10.3892/etm.2014.1657 PMid:24926376

Haralambieva IH, Painter SD, Kennedy RB, Ovsyannikova IG, Lambert ND, Goergen KM, et al. The impact of immunosenescence on humoral immune response variation after influenza A/H1N1 vaccination in older subjects. PLoS One. 2015;10(3):e0122282. https://doi.org/10.1371/journal.pone.0122282 PMid:25816015

Pawelec G. The aging immune system : Dysregulation, compensatory mechanisms, and prospects for intervention. In: Handbook of the Biology of Aging. 8th ed. United States: Academic Press; 2016. p. 407-31. https://doi.org/10.1016/b978-0-12-815962-0.00016-0

Whaley MM, Connon SB. The aging process. In: Lohman HL, Byers-Connon S, Padilla RL, editors. Occupational Therapy with Elders. 4th ed. Amsterdam, Netherlands: Elsevier Health Sciences; 2019. p. 30-40. https://doi.org/10.1016/b978-0-323-49846-3.00003-2

Sekar M. Pemberian ekstrak benalu mangga terhadap perubahan histologis hepar tikus yang diinduksi kodein. Biosaintifika J Biol Biol Educ. 2014;6:80-6. https://doi.org/10.15294/biosaintifika.v6i2.3103

Nurfaat DL, Indriyati W, Farmakologi L, Farmasi F, Padjadjaran U. Uji toksisitas akut ekstrak etanol benalu mangga (Dendrophthoe petandra) terhadap mencit swiss webster. IJPST. 2016;3(2):53-65. https://doi.org/10.35799/jm.4.2.2015.9132

Connolly CK. Advances in Infectious Diseases. Vol. 9. Berlin: Springer; 2012. https://doi.org/10.7861/clinmedicine.9-6-632

Montoya-Ortiz G. Immunosenescence, aging, and systemic lupus erythematous. Autoimmune Dis. 2013;2013:1-15. https://doi.org/10.1155/2013/267078.

Xuan TD, Khanh TD. Chemistry and pharmacology of Bidens pilosa: An overview. J Pharm Investig. 2016;46(2):91-132. https://doi.org/10.1007/s40005-016-0231-6 PMid:32226639