The Effect of Neem (Azadirachta indica) Leaf Extracts on Interleukin-10 Expression and Histological Score in Dextran Sodium Sulfate-induced Colitis Mice

Authors

  • Riska Habriel Ruslie Department of Child Health, Faculty of Medicine, Universitas Prima Indonesia, Medan, North Sumatera, Indonesia
  • Darmadi Darmadi Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, Haji Adam Malik General Hospital, Medan, North Sumatera, Indonesia
  • Gontar Alamsyah Siregar Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, Haji Adam Malik General Hospital, Medan, North Sumatera, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2020.4809

Keywords:

Azadirachta indica, Colitis, Histological score, Interleukin-10, Neem

Abstract

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic or relapsing inflammation of the intestine which consists of Crohn’s disease and ulcerative colitis. Interleukin (IL)-10 is an anti-inflammatory cytokine which plays important role in the pathogenesis of IBD. Neem (Azadirachta indica) is rich of azadiractoids which possesses anti-inflammatory activity.

AIM: The objective of the study was to determine the effect of neem leaf extract on IL-10 expression and histological score in dextran sodium sulfate (DSS)-induced colitis rats.

METHODS: The first phase compared 7 DSS-induced colitis rats (case group) with seven healthy rats (control group). All of them were sacrificed. The second phase compared 28 DSS-induced colitis rats treated with mesalazine (Group I) and 56 rats treated with neem leaf extract (Groups II and III). Seven rats from each group were sacrificed on days 7, 14, 21, and 28. Colon samples were harvested and underwent histopathological examination and immunohistochemical analysis to determine IL-10 expression and histological score.

RESULTS: IL-10 expression and histological score were higher in case group compared to control group. There was similar IL-10 expression between Groups I and II on day 28 while the similarity was observed since day 7 between Groups I and III. Mean histological score was higher in Group II compared to Group I and it was similar between Group I and Group III on days 21 and 28.

CONCLUSION: Neem leaf extract increased the expression of anti-inflammatory cytokine, in particular IL-10, and improved histological score in DSS-induced colitis rats.

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References

Matsuoka K, Kobayashi Y, Ueno F, Matsui T, Hirai F, Inoue, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease. J Gastroenterol. 2018;53(3):305-53 PMid:29429045

Sharara AI, Awadhi SA, Alharbi O, Dhahab HA, Mounir M, Salese L, et al. Epidemiology, disease burden, and treatment challenges of ulcerative colitis in Africa and the Middle East. Expert Rev Gastroenterol Hepatol. 2018;12(9):883-97. https:// doi.org/10.1080/17474124.2018.1503052 PMid:30096985

Sun M, He C, Cong Y, Liu Z. Regulatory immune cells in regulation of intestinal inflammatory response to microbiota. Mucosal Immunol. 2015;8(5):969-78. https://doi.org/10.1038/ mi.2015.49 PMid:26080708

Muzes G, Molnar B, Tulassay Z, Sipos F. Changes of the cytokine profile in inflammatory bowel diseases. World J Gastroenterol. 2012;18(41):5848-61. https://doi.org/10.3748/wjg.v18.i41.5848 PMid:23139600

Valsecchi C, Tagliacarne SC, Brambilla I, Klersy C, Benazzo M, Montagna L, et al. Detection of IL10-producing B cell (B10) in adenoids of atopic children with adenoidal hypertrophy. Ital J Pediatr. 2018;44(1):30. https://doi.org/10.1186/s13052-018-0471-3 PMid:29486786

Barman S, Kayama H, Okuzaki D, Ogino T, Osawa H, Matsuno H, et al. Identification of a human intestinal myeloid cell subset that regulates gut homeostasis. Int Immunol. 2016;28(11):533-45. https://doi.org/10.1093/intimm/dxw034 PMid:27421871

Liu B, Tonkonogy SL, Sartor RB. Antigen-presenting cell production of IL-10 inhibits T-helper 1 and 17 cell responses and supresses colitis in mice. Gastroenterology. 2011;141(2):653- 62. https://doi.org/10.1053/j.gastro.2011.04.053 PMid:21679711

Ranatunga DC, Ramakrishnan A, Uprety P, Wang F, Zhang H, Margolick JB, et al. A protective role for human IL-10-expressing CD4+ T cells in colitis. J Immunol. 2012;189(3):1243-52. https:// doi.org/10.4049/jimmunol.1103421 PMid:22753934

Nielsen OH, Seidelin JB, Munck LK, Rogler G. Use of biological molecules in the treatment of inflammatory bowel disease. J Intern Med. 2011;270(1):15-28. PMid:21241384

Morris J, Gonzales CB, De La Chapa JJ, Cabang AB, Fountzilas C, Patel M, et al. The highly pure neem leaf extract, SCNE, inhibits tumorigenesis in oral squamous cell carcinoma via disruption of pro-tumor inflammatory cytokines and cell signaling. Front Oncol. 2019;9:980. https://doi.org/10.3389/ fonc.2019.00890 PMid:31572681

Hao F, Kumar S, Yadav N, Chandra D. Neem components as potential agents for cancer prevention and treatment. Biochim Biophys Acta. 2014;1846(1):247-57. PMid:25016141

Patel MJ, Tripathy S, Mukhopadhyay KD, Wangjam T, Cabang AB, Morris J, et al. A supercritical CO2 extract of neem leaf (A. indica) and its bioactive liminoid, nimbolide, suppresses colon cancer in preclinical models by modulating pro-inflammatory pathways. Mol Carcinog. 2018;57(9):1156-65. https://doi.org/10.1002/mc.22832 PMid:29697164

Gautam MK, Goel S, Ghatule RR, Singh A, Joshi VK, Goel RK. Azadirachta indica attenuates colonic mucosal damage in experimental colitis induced by trinitrobenzene sulfonic acid. Indian J Pharm Sci. 2013;75(5):602-6. https://doi. org/10.4103/0973-1296.127366 PMid:24403663

Biswas K, Ishita C, Ranajit K, Banerjee UB. Biological activities and medicinal properties of neem (Azadirachta indica A. Juss). Curr Sci. 2002;82(11):1136-45.

Laroui H, Ingersoll SA, Liu HC, Baker MT, Ayyadurai S, Charania MA, et al. Dextran sodium sulfate (DSS) induces colitis in mice by forming nano-lipocomplexes with medium-chain-length fatty acids in the colon. PLoS One. 2012;7(3):e32084. https://doi.org/10.1371/journal.pone.0032084 PMid:22427817

Lubis M, Siregar GA, Bangun H, Ilyas S. The effect of roselle flower petals extract (Hibiscus sabdariffa Linn.) on reducing inflammation in dextran sodium sulfateinduced colitis. Med Glas (Zenica). 2020;17(2):395-401. https://doi.org/10.17392/1095-20 PMid:32329325

Fries W, Salvatore C. Ulcerative colitis: Pathogenesis. Curr Drug Targets. 2011;12(10):1373-82. PMid:21466489

Kennedy RJ, Hoper M, Deodhar K, Erwin PJ, Kirk SJ, Gardiner KR. Interleukin 10-deficient colitis: New similarities to human inflammatory bowel disease. Br J Surg. 2000;87(10):1346- 51. https://doi.org/10.1046/j.1365-2168.2000.01615.x PMid:11044159

Keubler LM, Buettner M, Hager C, Bleich A. A multihit model: Colitis lessons from the interleukin-10-deficient mouse. Inflamm Bowel Dis. 2015;21(8):1967-75. https://doi.org/10.1097/ mib.0000000000000468 PMid:26164667

Li B, Alli R, Vogel P, Geiger TL. IL-10 modulates DSS-induced colitis through a macrophage-ROS-NO axis. Mucosal Immunol. 2014;7(4):869-78. https://doi.org/10.1038/mi.2013.103 PMid:24301657

Bose A, Baral R. Natural killer cell mediated cytotoxicity of tumor cells initiated by neem leaf preparation is associated with CD40- CD40L-mediated endogenous production of interleukin-12. Hum Immunol. 2007;68(10):823-31. https://doi.org/10.1016/j. humimm.2007.08.002 PMid:17961770

Yuan B, Zhou S, Lu Y, Liu J, Jin XWan H, et al. Changes in expression and distribution of claudins, increased epithelial apoptosis, and a mannan-binding lectin-associated immune response lead to barrier dysfunction in dextran sodium sulfate-induced rat colitis. Gut Liver. 2015;9(6):743-40. https://doi. org/10.5009/gnl14155 PMid:25717051

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Published

2020-07-20

How to Cite

1.
Ruslie RH, Darmadi D, Siregar GA. The Effect of Neem (Azadirachta indica) Leaf Extracts on Interleukin-10 Expression and Histological Score in Dextran Sodium Sulfate-induced Colitis Mice. Open Access Maced J Med Sci [Internet]. 2020 Jul. 20 [cited 2022 Jul. 1];8(A):578-82. Available from: https://oamjms.eu/index.php/mjms/article/view/4809

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