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M-06: Evaluation of the Effect of Aegle Marmelos in a Murine Model of Trinitrobenzene Sulfonic acid (TNBS) Induced Coliti

Poster Presenter

Abhishek Rajan Mane

Student
Seth G S Medical College & KEM Hospital
India

Objectives

Standardisation of Trinitrobenzene Sulfonic acid induced colitis model in BALB/c mice. This was followed by evaluation of the effect of Aegle marmelos in TNBS induced acute colitis, by Colon length by weight ratio, Disease Activity Index (DAI) and Histopathological examination of Colon.

Method

Study was conducted from October 2018 to January 2019 in the Central Animal House, KEM Hospital, Mumbai. BALB/c mice were injected with TNBS following which, they were observed for stool consistency, bleeding per rectum and weight loss. Animals were sacrificed on day 3 for assessment of colitis.

Results

Standardization (Phase I) of TNBS induced colitis was done, followed by evaluation of the effect of Aegle marmelos in acute colitis. In Phase I, 8 mice were taken in each of the disease control and normal control group. Assessment of Disease activity index (DAI) was done on the day of induction, and 3 days after that. Colon length, colon length by weight ratio, macroscopic and histopathological examination was done on day 3, after sacrifice. Macroscopic examination of the colon showed extensive necrosis, patchy haemorrhage with visible shortening of length. Colon length by weight ratio was significantly higher (p<0.001) in the disease control group (21.20 ? 1.30)mg/cm than the normal control group (32.30 ? 2.90)mg/cm. DAI was higher (p<0.001) for the disease control group (7.5 ? 2) as compared to the normal control group (0.5 ? 0.7). Histopathological grading score for TNBS colitis was significantly higher in disease control group (21.9 ? 3) than the normal control group (1.2 ? 1.32). After Phase I, the effect of Aegle marmelos in colitis was evaluated (Phase II), with a low dose (0.78 g/kg/day) and a high dose (1.56 g/kg/day), with sulfasalazine being the positive control. 8 mice were included in each of the disease control, positive control and Aegle marmelos (low dose & high dose) groups. Macroscopic scoring of colitis (tissue necrosis and haemorrhage) was significantly less in the high dose Aegle marmelos group (1.83 ? 0.8) with a p value less than 0.05. The Disease activity index was also reduced in this group (5 ? 1.2) than the disease control group (9 ? 1.6). High dose of Aegle marmelos group also showed significantly low histopathological grading score (14.5 ? 6) with a p value less than 0.05. Thus, high dose Aegle marmelos group showed marked decrease in colitis severity, with reduced bleeding per rectum and weight loss.

Conclusion

Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract which has a high incidence and prevalence in India. It is a matter of great concern in developing Asian, African and South American countries. The treatment options which are currently available, aim at decreasing the clinical features of colitis rather than completely curing the disease. The anti-inflammatory agents which are commonly used for treatment of colitis (sulfasalazine and corticosteroids) have limited efficacy and are associated with a plethora of adverse effects. This warrants the search for new therapeutic options for the treatment of Crohn’s disease and Inflammatory bowel disease as a whole. Aegle marmelos (unripe fruit) is prescribed by the Ayurvedic physicians for multiple diarrheal disorders. In the above study, animals treated with high dose of Aegle marmelos, showed significantly reduced inflammatory changes after TNBS induction, as compared to the disease control group. Bleeding per rectum and weight loss was also reduced. Thus, high dose Aegle marmelos was found to be comparable to the standard dose of Sulfasalazine in experimentally induced acute colitis. In the world of Evidence Based Medicine (EBM), where struggle for discovery and development of new molecules is a continuous learning curve, Aegle marmelos can be used as a supplementary drug, for the management of Crohn’s disease. It is important that clinical studies be conducted in patients of Crohn’s disease to confirm the efficacy of Aegle marmelos alone and as an add-on to sulfasalazine. Not only will this decrease the side effect due to the use of anti-inflammatory agents, but will also boost the overall immunity and condition of the gastrointestinal tract.