Evaluation of the mechanism of action of Aegle marmelos in a murine model of 3% dextran sulphate sodium induced acute colitis

Authors

  • Alok Nachane Department of Pharmacology, MGM medical college Vashi, Navi Mumbai, Maharashtra, India
  • Sandhya K. Kamat Department of Pharmacology and Therapeutics, Seth G.S. Medical College and K. E. M. Hospital, Mumbai, Maharashtra, India
  • Manoj Radhakrishnan Department of Pharmacology and Therapeutics, Seth G.S. Medical College and K. E. M. Hospital, Mumbai, Maharashtra, India
  • Gita Nataraj Department of Microbiology Seth G.S. Medical College and K. E. M. Hospital, Mumbai, Maharashtra, India
  • Sunil S. Kuyare Department of Microbiology Seth G.S. Medical College and K. E. M. Hospital, Mumbai, Maharashtra, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20250489

Keywords:

Myeloperoxidase, Tumor Necrosis Factor- α, Sulfasalazine, Prebiotic, Disease activity index

Abstract

Background: An earlier study by us in a murine model of dextran sulphate sodium (DSS) induced acute colitis showed that aqueous extract of unripe fruit of Aegle marmelos (780 mg/kg/day) was comparable with Sulfasalazine. In this study we evaluated the same extract for anti-inflammatory, anti-oxidant, and prebiotic activity in the same model.

Methods: 48 adult swiss albino mice (>6 weeks age) of either sex (18-25 grams) were divided into four groups (n=12/) i.e., normal control (distilled water-10 ml/kg/day), Disease control (Distilled water-10 ml/kg/day), Positive Control (Sulfasalazine-100 mg/kg/day) and Test drug (A. marmelos-780 mg/kg/day). The drug/vehicle was administered orally for 14 days from day 1 through day 14. Acute colitis was induced by adding 3% DSS in drinking water from day 8 to 14 in all groups except normal control. The animals were euthanized on day 15, each group were divided into two batches (n=6). One batches were used to estimate colonic myeloperoxidase (MPO) and TNF-α. The other batch was used to cultivate lactobacilli and aerobic microbiota from colonic contents, three animals from this batch were also used to estimate colonic MPO and TNF-α.

Results: Mice administered A. marmelos, and sulfasalazine showed significantly higher colon lengths, colon weight/ length ratios, colonic TNF-α and MPO levels, and both were significantly better than disease control. Lactobacilli and aerobic bacteria counts were significantly higher in A. marmelos group compared to the disease control and were comparable to normal control. However, sulfasalazine showed no improvement in the colonic microbiota counts.

Conclusions: A. marmelos showed anti-inflammatory, anti-oxidant, and prebiotic activity.

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References

Singh P, Ananthakrishnan A, Ahuja V. Pivot to Asia: inflammatory bowel disease burden. Intest Res. 2017;15(1):138. DOI: https://doi.org/10.5217/ir.2017.15.1.138

Ng WK, Wong SH, Ng SC. Changing epidemiological trends of inflammatory bowel disease in Asia. Intest Res. 2016;14(2):111. DOI: https://doi.org/10.5217/ir.2016.14.2.111

Kedia S, Ahuja V. Epidemiology of Inflammatory Bowel Disease in India: The Great Shift East. Inflamm Intest Dis. 2017;2(2):102-15. DOI: https://doi.org/10.1159/000465522

Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2004;53(5):v1-6. DOI: https://doi.org/10.1136/gut.2004.043372

Gogaṭe VM. Ayurvedic pharmacology and therapeutic uses of medicinal plants (Dravyagunavignyan). Bharatiya Vidya Bhavan; 2000;841.

Sharma PPV. Dravyaguna-Vijnana. 4th ed. Varanasi: Chaukhambha Sanskrit Sansthan. Varanasi. 1978;455-7.

Kamat SK, Singh KNM. Evaluation of the effect of Aegle marmelos and Punica granatum in a murine model of dextran sulfate sodium-induced acute colitis. National J Physiol Pharmacy Pharmacol. 2019;9(4):1-8. DOI: https://doi.org/10.5455/njppp.2019.9.1031507022019

Charoensiddhi S, Anprung P. Characterization of bael fruit (Aegle marmelos [L.] correa) hydrolysate as affected by enzyme treatment. J Food Biochem. 2010;34(6):1249-67. DOI: https://doi.org/10.1111/j.1745-4514.2009.00333.x

Park YH, Kim N, Shim YK, Choi YJ, Nam RH, Choi YJ, et al. Adequate dextran sodium sulfate-induced colitis model in mice and effective outcome measurement method. J Cancer Prevention. 2015;20(4):260-7. DOI: https://doi.org/10.15430/JCP.2015.20.4.260

Arul V, Miyazaki S, Dhananjayan R. Studies on the anti-inflammatory, antipyretic and analgesic properties of the leaves of Aegle marmelos Corr. J Ethnopharmacol. 2005;96(1-2):159-63. DOI: https://doi.org/10.1016/j.jep.2004.09.013

Benni JM, Jayanthi MK, Suresha RN. Evaluation of the anti-inflammatory activity of Aegle marmelos (Bilwa) root. Indian J Pharmacol. 2011;43(4):393-7. DOI: https://doi.org/10.4103/0253-7613.83108

Hidalgo-Cantabrana C, Algieri F, Rodriguez-Nogales A. Effect of a ropy Exopolysaccharide-producing Bifidobacterium animalis subsp. Lactis strain orally administered on DSS-induced colitis mice model. Front Microbiol. 2016:7:868. DOI: https://doi.org/10.3389/fmicb.2016.00868

Rajaram A, Vanaja GR, Vyakaranam P, Rachamallu A, Reddy GV, Anilkumar K, et al. Anti-inflammatory profile of Aegle marmelos (L) Correa (Bilva) with special reference to young roots grown in different parts of India. J Ayur integrative Med. 2018;9(2):90-8. DOI: https://doi.org/10.1016/j.jaim.2017.03.006

Ibrahim M, Parveen B, Zahiruddin S, Gautam G, Parveen R, Khan MA, et al. Analysis of polyphenols in Aegle marmelos leaf and ameliorative efficacy against diabetic mice through restoration of antioxidant and anti‐inflammatory status. J Food Biochemistr. 2021;46(4):e13852. DOI: https://doi.org/10.1111/jfbc.13852

Kasinathan NK, Subramaniya BR, Pandian I, Sivasithamparam ND. Aegle marmelos fruit extract abates dextran sodium sulfate induced acute colitis in mice: Repression of pro-inflammatory cytokines during colonic inflammation. Biomed Prev Nutr. 2014;4(2):307-17. DOI: https://doi.org/10.1016/j.bionut.2014.03.002

Behera JP, Mohanty B, Ramani YR, Rath B, Pradhan S. Effect of aqueous extract of Aegle marmelos unripe fruit on inflammatory bowel disease. Indian J Pharmacol. 2012;44(5):614-8. DOI: https://doi.org/10.4103/0253-7613.100389

Gibson PR, Jewell DP. Sulphasalazine and derivatives, natural killer activity and ulcerative colitis. Clinical Science. 1985;69(2):177-84. DOI: https://doi.org/10.1042/cs0690177

Kang BY, Chung SW, Im SY, Choe YK, Kim TS. Sulfasalazine prevents T-helper 1 immune response by suppressing interleukin-12 production in macrophages. Immunology. 1999;98(1):98-103. DOI: https://doi.org/10.1046/j.1365-2567.1999.00849.x

Rodenburg RJ, Ganga A, Van Lent PL, Van De Putte LB, Van Venrooij WJ. The anti-inflammatory drug sulfasalazine inhibits tumor necrosis factor α expression in macrophages by inducing apoptosis. Arthrit Rheumat. 2000;43(9):1941-50. DOI: https://doi.org/10.1002/1529-0131(200009)43:9<1941::AID-ANR4>3.0.CO;2-O

Xiao L, Feng Q, Liang S, Sonne SB, Xia Z, Qiu X, et al. A catalog of the mouse gut metagenome. Nat Biotechnol. 2015;33(10):1103-8. DOI: https://doi.org/10.1038/nbt.3353

Naito Y, Takagi T, Handa O, Ishikawa T, Nakagawa S, Yamaguchi T, et al. Enhanced intestinal inflammation induced by dextran sulfate sodium in tumor necrosis factor-alpha deficient mice. J Gastroenterol Hepatol. 2003;18(5):560-9. DOI: https://doi.org/10.1046/j.1440-1746.2003.03034.x

Jones-Hall YL, Nakatsu CH. The Intersection of TNF, IBD and the Microbiome. Gut Microbes. 2016;7(1):58-62. DOI: https://doi.org/10.1080/19490976.2015.1121364

Pynam H, Dharmesh SM. Antioxidant and anti-inflammatory properties of marmelosin from Bael (Aegle marmelos L.); Inhibition of TNF-α mediated inflammatory/tumor markers. Biomed Pharmacother. 2018;106:98-108. DOI: https://doi.org/10.1016/j.biopha.2018.06.053

Rathee D, Kamboj A, Sachdev RK, Sidhu S. Hepatoprotective effect of Aegle marmelos augmented with piperine co-administration in paracetamol model. Rev Bras Farmacogn. 2018;28:65-72. DOI: https://doi.org/10.1016/j.bjp.2017.11.003

Anatoliotakis N, Deftereos S, Bouras G, Giannopoulos G, Tsounis D, Angelidis C, et al. Myeloperoxidase: expressing inflammation and oxidative stress in cardiovascular disease. Curr Top Med Chem. 2013;13(2):115-38. DOI: https://doi.org/10.2174/1568026611313020004

Ghatule RR, Gautam MK, Goel S, Singh A, Joshi VK, Goel RK. Protective effects of Aegle marmelos fruit pulp on 2,4,6-trinitrobenzene sulfonic acid-induced experimental colitis. Pharmacogn Mag. 2014;10(1):S147-52. DOI: https://doi.org/10.4103/0973-1296.127366

Gautam MK, Ghatule RR, Singh A, Purohit V, Gangwar M, Kumar M, et al. Healing effects of Aegle marmelos (L.) Correa fruit extract on experimental colitis. Indian J Exp Biol. 2013;51(2):157-64.

Shen Z-H, Zhu C-X, Quan Y-S, Yang Z-Y, Wu S, Luo W-W, et al. Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J Gastroenterol. 2018;24(1):5-14. DOI: https://doi.org/10.3748/wjg.v24.i1.5

Martyniak A, Medyńska-Przęczek A, Wędrychowicz A, Skoczeń S, Tomasik PJ. Prebiotics, probiotics, synbiotics, paraprobiotics and postbiotic compounds in IBD. Biomolecules. 2021;11(12):1903. DOI: https://doi.org/10.3390/biom11121903

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Published

2025-02-25

How to Cite

Nachane, A., Kamat, S. K., Radhakrishnan, M., Nataraj, G., & Kuyare, S. S. (2025). Evaluation of the mechanism of action of Aegle marmelos in a murine model of 3% dextran sulphate sodium induced acute colitis. International Journal of Basic & Clinical Pharmacology, 14(2), 275–280. https://doi.org/10.18203/2319-2003.ijbcp20250489

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