PHARMACOLOGICAL INVESTIGATION OF CITRULLUS COLOCYNTHIS LINN. FRUIT EXTRACT FOR ULCERATIVE COLITIS IN EXPERIMENTAL RATS

Objective: The present study was aimed to investigate the protective effect of Citrullus colocynthis Linn. fruit extract for Acetic Acid induced and Dextran Sulphate Sodium (DSS) induced ulcerative colitis in rats. Methods: The preliminary screening of different extracts was the basis of selection of ethanol extract of Citrullus colocynthis fruits for detail study on Acetic Acid and Dextran Sulphate Sodium induced model. Ethanol extract suspension (0.5% CMC-Na) was administered in animal groups for pharmacological evaluation. The wistar rats were divided into 5 groups consisting 6 animals in each. UC was induced by single intra-rectal administration of 150μl of 5 % acetic acid to rats fasted for 12 h prior to the administration. The rats observed for macroscopical characteristic, histological changes and alterations in biochemical parameters (Myeloperoxidase (MPO) and malondialdehyde (MDA) content, antioxidant components and pro-inflammatory components). Similarly, Dextran sodium sulfate (3%w/v) was used for another model. Sulfasalazine was used as standard for the comparisons in both models. Results: Ethanolic extract of Citrullus colocynthis fruits (EECC) significantly improved clinical symptoms in a dose-dependent manner. EECC at 300 mg/kg produced a significant (P<0.05) reduction to 2.55±0.06, corresponding to 66.09% protection disease activity index, reduced MPO activity to 32.05±1.66 OD/g tissue. Administration of EECC significantly lowered MDA levels from 73.77±3.42 to 44.08±2.60 OD/g tissue. At 300 mg/kg, EECC increased SOD, CAT, and GSH levels close to normal values, demonstrating potent antioxidant activity in Acetic acid and Dextran sodium sulfate induced colitis model. animals treated with EECC showed substantial restoration of mucosal architecture, reduced inflammatory cell infiltration, decreased edema, and preservation of epithelial integrity. Conclusion: Ethanol extract of Citrullus colocynthis fruits possess significant anti-ulcerative colitis in both acetic acid and DSS-induced ulcerative colitis models through reduction of disease activity index, suppression of MPO and MDA levels, restoration of antioxidant enzymes and reduction of pro-inflammatory cytokines. Therefore, the anti-ulcerative colitis activity of ethanol extract appears to be mediated through a combination of antioxidant, anti-inflammatory and cytokine-modulating mechanisms.