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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Immunosuppressive Effects of Annona muricata L. Leaf Extract on Cellular and Humoral Immune Responses in Male Wistar Rats

Author(s): Siti Mariam Abdul Wahab, Khairana Husain, Ibrahim Jantan*, Laiba Arshad, Md. Areeful Haque, Norsyahida Mohd Fauzi, Mohd Azlan Nafiah and Srijit Das

Volume 24, Issue 11, 2023

Published on: 13 January, 2023

Page: [1465 - 1477] Pages: 13

DOI: 10.2174/1389201024666221221113020

Price: $65

Abstract

Background: Annona muricata L. (Annonaceae) (AM)'s remarkable anti-inflammatory and anti-cancer activities make it a targeted plant to be explored for its immunomodulatory properties. Traditional practitioners have employed various components of AM to cure a variety of ailments, including cancer, diabetes, and inflammation.

Objective: The present study evaluated the immunosuppressive effects of 80% ethanol extract of of AM leaves in male Wistar rats on different parameters of humoral and cellular immune responses.

Methods: AM leaf extract (AMLE) was analyzed using UHPLC-MS/MS to profile its secondary metabolites. AMLE was rich in polyphenols which include (epi)catechin-(epi)catechin-(epi) catechin, caffeic acid, coumaroylquinic acid, hyperin, kaempferol, quinic acid and rutin. The rats were administered 100, 200 and 400 mg/kg bw of the extract daily for 14 days. The effects of AMLE on innate immune responses were determined by evaluating phagocytosis, neutrophils migration, reactive oxygen species (ROS) release, CD11b/CD18 integrin expression, and ceruloplasmin, lysozyme and myeloperoxidase (MPO) levels. The adaptive immune parameters were evaluated by immunizing the rats with sheep red blood cells (sRBC) on day 0 and administered orally with AMLE for 14 days.

Results: AMLE established significant immunosuppressive effects on the innate immune parameters by inhibiting the neutrophil migration, ROS production, phagocytic activity and expression of CD11b/CD18 integrin in a dose-dependent pattern. AMLE also suppressed ceruloplasmin, MPO and lysozyme expressions in the rat plasma dose-dependently. AMLE dose-dependently inhibited T and B lymphocytes proliferation, Th1 and Th2 cytokine production, CD4+ and CD8+ co-expression in splenocytes, immunoglobulins (IgM and IgG) expression and the sRBC-induced swelling rate of rat paw in delayed-type hypersensitivity (DTH).

Conclusion: The strong inhibitory effects on the different parameters of humoral and cellular responses indicate that AMLE has potential to be an important source of effective immunosuppressive agents.

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[1]
Bonilla, F.A.; Oettgen, H.C. Adaptive immunity. J. Allergy Clin. Immunol., 2010, 125(2), S33-S40.
[http://dx.doi.org/10.1016/j.jaci.2009.09.017] [PMID: 20061006]
[2]
Arshad, L.; Jantan, I.; Bukhari, S.N.A.; Jamil, S. Inhibitory effects of α, β-unsaturated carbonyl-based compounds and their pyrazoline derivatives on the phagocytosis of human neutrophils. Med. Chem. Res., 2018, 27(5), 1460-1471.
[http://dx.doi.org/10.1007/s00044-018-2163-3]
[3]
Berger, J.R.; Houff, S.A.; Major, E.O. Monoclonal antibodies and progressive multifocal leukoencephalopathy. MAbs, 2009, 1(6), 583-589.
[http://dx.doi.org/10.4161/mabs.1.6.9884] [PMID: 20073129]
[4]
Mythili, M.; Nair, S.; Gunasekaran, S. Effect of cyclophosphamide pretreatment on hematological indices of Indian Bonnet monkeys. Indian J. Pharmacol., 2004, 36, 175-176.
[5]
Patil, U.; Jaydeokar, A.; Bandawane, D. Immunomodulators: A pharmacological review. Int. J. Pharm. Pharm. Sci., 2012, 4, 30-36.
[6]
Alamgir, M.; Uddin, S.J. Recent advances on the ethnomedicinal plants as immunomodulatory agents. Ethnomedicine, 2010, 1, 227-244.
[7]
Arreola, R.; Quintero-Fabián, S.; López-Roa, R.I.; Flores-Gutiérrez, E.O.; Reyes-Grajeda, J.P.; Carrera-Quintanar, L.; Ortuño-Sahagún, D. Immunomodulation and anti-inflammatory effects of garlic compounds. J. Immunol. Res., 2015, 2015, 1-13.
[http://dx.doi.org/10.1155/2015/401630] [PMID: 25961060]
[8]
Ilangkovan, M.; Jantan, I.; Mesaik, M.A.; Bukhari, S.N.A. Inhibitory effects of the standardized extract of Phyllanthus amarus on cellular and humoral immune responses in Balb/c mice. Phytother. Res., 2016, 30(8), 1330-1338.
[http://dx.doi.org/10.1002/ptr.5633] [PMID: 27137750]
[9]
Shahbazi, S.; Bolhassani, A. Immunostimulants: Types and functions. J. Med. Microbiol. Infec. Dis., 2016, 4(3-4), 45-51.
[10]
Abdul Wahab, S.M.; Jantan, I.; Haque, M.A.; Arshad, L. Exploring the leaves of Annona muricata L. as a source of potential anti-inflammatory and anticancer agents. Front. Pharmacol., 2018, 9, 661.
[http://dx.doi.org/10.3389/fphar.2018.00661] [PMID: 29973884]
[11]
Laksmitawati, D.R.; Prasanti, A.P.; Larasinta, N.; Syauta, G.A.; Hilda, R.; Ramadaniati, H.U.; Widyastuti, A.; Karami, N.; Afni, M.; Rihibi-ha, D.D.; Kusuma, H.S.W.; Widowati, W. Anti-Inflammatory potential of gandarusa (Gendarussa vulgaris Nees) and soursoup (Annona muricata L.) extracts in LPS stimulated-macrophage cell (RAW264. 7). J. Nat. Rem., 2016, 16(2), 73-81.
[http://dx.doi.org/10.18311/jnr/2016/5367]
[12]
Moghadamtousi, S.Z.; Rouhollahi, E.; Hajrezaie, M.; Karimian, H.; Abdulla, M.A.; Kadir, H.A. Annona muricata leaves accelerate wound healing in rats via involvement of Hsp70 and antioxidant defence. Int. J. Surg., 2015, 18, 110-117.
[http://dx.doi.org/10.1016/j.ijsu.2015.03.026] [PMID: 25899210]
[13]
Quilez, A.M.; Montserrat-de la Paz, S.; De la Puerta, R.; Fernández-Arche, M.A.; Gargia-Gimenez, M.D. Validation of ethnopharmacologi-cal use as anti-inflammatory of a decoction from Annona muricata leaves. Afr. J. Tradit. Complement. Altern. Med., 2015, 12(4), 14-20.
[http://dx.doi.org/10.4314/ajtcam.v12i4.3]
[14]
Liu, N.; Yang, H.L.; Wang, P.; Lu, Y.C.; Yang, Y.J.; Wang, L.; Lee, S.C. Functional proteomic analysis revels that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway. J. Ethnopharmacol., 2016, 189, 210-217.
[http://dx.doi.org/10.1016/j.jep.2016.05.045] [PMID: 27224241]
[15]
Md Roduan, M.R.; Hamid, R.A.; Sulaiman, H.; Mohtarrudin, N. Annona muricata leaves extracts prevent DMBA/TPA-induced skin tu-morigenesis via modulating antioxidants enzymes system in ICR mice. Biomed. Pharmacother., 2017, 94, 481-488.
[http://dx.doi.org/10.1016/j.biopha.2017.07.133] [PMID: 28779710]
[16]
OECD. Guidance document on the recognition, assessment, and use of clinical signs as humane endpoints for experimental animals used in safety evaluation. 2000. Available from: http://www.oecd.org/officialdocuments/publicdisplay documentpdf/?cote=env/jm/mono(2000)7&doclanguage=en (Accessed on: March 21, 2015).
[17]
Huyan, X.H.; Lin, Y.P.; Gao, T.; Chen, R.Y.; Fan, Y.M. Immunosuppressive effect of cyclophosphamide on white blood cells and lym-phocyte subpopulations from peripheral blood of Balb/c mice. Int. Immunopharmacol., 2011, 11(9), 1293-1297.
[http://dx.doi.org/10.1016/j.intimp.2011.04.011] [PMID: 21530682]
[18]
Ahmad, W.; Jantan, I.; Kumolosasi, E.; Bukhari, S.N.A. Immunostimulatory effects of the standardized extract of Tinospora crispa on innate immune responses in Wistar Kyoto rats. Drug Des. Devel. Ther., 2015, 9, 2961-2973.
[PMID: 26089645]
[19]
Park, J.Y.; Arnaout, M.A.; Gupta, V. A simple, no-wash cell adhesion-based high-throughput assay for the discovery of small-molecule regulators of the integrin CD11b/CD18. SLAS Discov., 2007, 12(3), 406-417.
[http://dx.doi.org/10.1177/1087057106299162] [PMID: 17438069]
[20]
Farrar, J.D.; Asnagli, H.; Murphy, K.M. T helper subset development: roles of instruction, selection, and transcription. J. Clin. Invest., 2002, 109(4), 431-435.
[http://dx.doi.org/10.1172/JCI0215093] [PMID: 11854312]
[21]
Koffuor, G.; Amoateng, P.; Andey, T. Immunomodulatory and erythropoietic effects of aqueous extract of the fruits of Solanum torvum Swartz (Solanaceae). Pharmacognosy Res., 2011, 3(2), 130-134.
[http://dx.doi.org/10.4103/0974-8490.81961] [PMID: 21772757]
[22]
Billerey-Larmonier, C.; Uno, J.K.; Larmonier, N.; Midura, A.J.; Timmermann, B.; Ghishan, F.K.; Kiela, P.R. Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent. Inflamm. Bowel Dis., 2008, 14(6), 780-793.
[http://dx.doi.org/10.1002/ibd.20348] [PMID: 18200517]
[23]
Coxon, A.; Rieu, P.; Barkalow, F.J.; Askari, S.; Sharpe, A.H.; von Andrian, U.H.; Arnaout, M.A.; Mayadas, T.N. A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: A homeostatic mechanism in inflammation. Immunity, 1996, 5(6), 653-666.
[http://dx.doi.org/10.1016/S1074-7613(00)80278-2] [PMID: 8986723]
[24]
Loike, J.D.; Cao, L.; Budhu, S.; Marcantonio, E.E.; Khoury, J.E.; Hoffman, S.; Yednock, T.A.; Silverstein, S.C. Differential regulation of beta1 integrins by chemoattractants regulates neutrophil migration through fibrin. J. Cell Biol., 1999, 144(5), 1047-1056.
[http://dx.doi.org/10.1083/jcb.144.5.1047] [PMID: 10085300]
[25]
Yoshida, N.; Yoshikawa, T.; Tanaka, Y.; Fujita, N.; Kassai, K.; Naito, Y.; Kondo, M. A new mechanism for anti-inflammatory actions of proton pump inhibitors - inhibitory effects on neutrophil-endothelial cell interactions. Aliment. Pharmacol. Ther., 2000, 14(1), 74-81.
[http://dx.doi.org/10.1046/j.1365-2036.2000.014s1074.x]
[26]
Ley, K.; Laudanna, C.; Cybulsky, M.I.; Nourshargh, S. Getting to the site of inflammation: The leukocyte adhesion cascade updated. Nat. Rev. Immunol., 2007, 7(9), 678-689.
[http://dx.doi.org/10.1038/nri2156] [PMID: 17717539]
[27]
Hofman, P.; Piche, M.; Far, D.F.; Le Negrate, G.; Selva, E.; Landraud, L.; Alliana-Schmid, A.; Boquet, P.; Rossi, B. Increased Escherichia coli phagocytosis in neutrophils that have transmigrated across a cultured intestinal epithelium. Infect. Immun., 2000, 68(2), 449-455.
[http://dx.doi.org/10.1128/IAI.68.2.449-455.2000] [PMID: 10639403]
[28]
Wang, T.; He, C. TNF-α and IL-6: The link between immune and bone system. Curr. Drug Targets, 2020, 21(3), 213-227.
[http://dx.doi.org/10.2174/18735592MTAwhMzkdy] [PMID: 31433756]
[29]
Rodríguez, M.; Rivas, G. Label-free electrochemical aptasensor for the detection of lysozyme. Talanta, 2009, 78(1), 212-216.
[http://dx.doi.org/10.1016/j.talanta.2008.11.002] [PMID: 19174227]
[30]
Yamamoto, Y.; Gaynor, R.B. Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer. J. Clin. Invest., 2001, 107(2), 135-142.
[http://dx.doi.org/10.1172/JCI11914] [PMID: 11160126]
[31]
De La Fuente, M.; Victor, V. Anti-oxidants as modulators of immune function. Immunol. Cell Biol., 2000, 78(1), 49-54.
[http://dx.doi.org/10.1046/j.1440-1711.2000.00884.x] [PMID: 10651929]
[32]
Gao, X.; Kuo, J.; Jiang, H.; Deeb, D.; Liu, Y.; Divine, G.; Chapman, R.A.; Dulchavsky, S.A.; Gautam, S.C. Immunomodulatory activity of curcumin: Suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro. Biochem. Pharmacol., 2004, 68(1), 51-61.
[http://dx.doi.org/10.1016/j.bcp.2004.03.015] [PMID: 15183117]
[33]
Kang, B.Y.; Song, Y.J.; Kim, K.M.; Choe, Y.K.; Hwang, S.Y.; Kim, T.S. Curcumin inhibits Th1 cytokine profile in CD4+ T cells by sup-pressing interleukin-12 production in macrophages. Br. J. Pharmacol., 1999, 128(2), 380-384.
[http://dx.doi.org/10.1038/sj.bjp.0702803] [PMID: 10510448]
[34]
Stamm, C.; Barthelmann, J.; Kunz, N.; Toellner, K.M.; Westermann, J.; Kalies, K. Dose-dependent induction of murine Th1/Th2 respons-es to sheep red blood cells occurs in two steps: Antigen presentation during second encounter is decisive. PLoS One, 2013, 8(6)e67746
[http://dx.doi.org/10.1371/journal.pone.0067746] [PMID: 23840769]
[35]
Benacerraf, B. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J. Immunol., 1978, 120(6), 1809-1812.
[PMID: 77879]
[36]
Loveland, B.E.; McKenzie, I.F. Delayed-type hypersensitivity and allograft rejection in the mouse: Correlation of effector cell phenotype. Immunology, 1982, 46(2), 313-320.
[PMID: 7044959]
[37]
Ryan, E.P.; Pollack, S.J.; Murant, T.I.; Bernstein, S.H.; Felgar, R.E.; Phipps, R.P. Activated human B lymphocytes express cyclooxygen-ase-2 and cyclooxygenase inhibitors attenuate antibody production. J. Immunol., 2005, 174(5), 2619-2626.
[http://dx.doi.org/10.4049/jimmunol.174.5.2619] [PMID: 15728468]

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