Protective effect of Sesbania grandiflora on acetic acid induced ulcerative colitis in mice by inhibition of TNF-α and IL-6.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Sesbania grandiflora (Linn) belonging to the family Fabaceae is commonly known as sesbania, agathi, and katurai. The plant is accredited for alleviating a spectrum of ailments including inflammation, colitis, diarrhea, dysentery, leprosy, gout, rheumatism, jaundice, bronchitis, convulsion and anxiety. It is also used as antitumour, anthelmintic, and laxatives in Ayurveda and Siddha system of Indian traditional medicine. AIM: To reveal protective effect of Sesbania grandiflora in acetic acid induced ulcerative colitis in mice. MATERIALS AND METHOD: Polyphenol, flavonoid and flavanone contents of different extracts of S. grandiflora leaves were quantified and correlated with their antioxidant capacity in-vitro (DPPH assay) for identification of potential fraction. In further studies hydroalocholic extract (HASG, 100 and 200 mg/kg) was evaluated for protective effect towards acetic acid induced ulcerative colitis (UC) animals administered with 150 µl of 5% acetic acid once, intrarectally. The colonic mucosal injury was assessed by estimating disease activity index (DAI), which took into account weight loss, stool consistency and occult/gross bleeding. Macroscopic changes like colon length, spleen weights, ulcer area and ulcer index were determined. Haematological parameters like WBC count, RBC count, Hb (g/dL), HCT (%), PLT count and FFA level were determined. Biochemical analysis was carried out for asserting the levels of tissue myeloperoxidase (MPO) accumulation, SOD concentrations, reduced GSH and lipid peroxidation in UC induced and treated animals. The cardinal inflammatory biomarkers like nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin (IL-6) were determined. Histopathological investigation was carried out and scores were calculated. RESULTS: HASG showed presence of highly polymerized polyphenols and flavonoids amongst other extracts of S. grandiflora, which is correlated to its rich antioxidant potential (IC50 =19.21). HPLC fingerprinting quantifies the presence of quercetin in concentration of 81.7 µg/mg of HASG. HASG (200 mg/kg) and Prednisolone (2 mg/kg) significantly reduced DAI and macroscopic scores. The haematological changes in experimental animals were restored upon treatment with HASG and Prednisolone. HASG showed potent antioxidant activity (In-vivo) by restoring the levels of SOD, GSH, MPO, MDA and NO. HASG was found to inhibit FFA levels, which may indicate inhibition of TLR4 receptor mediated inflammation. The levels of serological biomarkers like TNF-α and IL-6 were found to be suppressed. Histopathological investigation reveals decrease signs of ulceration, necrosis, cellular infiltration, hyperaemia in HASG treated animals. The results of HASG (200 mg/kg) were found to be comparable with Prednisolone (2 mg/kg) significantly. CONCLUSION: The protective action of HASG against acetic acid induced UC is attributed to the antioxidant like action (In-vitro and In-vivo) of highly polymerized polyphenols and flavonoids especially quercetin. Also HASG was found to reduce the levels of TNF-α and IL-6, thereby suppressing their inflammatory response in UC.