Graviola mitigates acetic acid–induced ulcerative colitis in rats: insight on apoptosis and Wnt/Hh signaling crosstalk

Abstract

In this study, we elucidated the potential protective effects of graviola leaves, compared with sulfasalazine, against acetic acid (AA)–induced ulcerative colitis (UC) in rats. Twenty-eight mature male rats were divided into four groups, Sham, Colitis, Colitis/Sulfa, and Colitis/Graviola, and were treated orally with either saline, saline, sulfasalazine (100 mg/kg/day), or graviola (100 mg/kg/day), respectively, for 7 days. On the 4th day, UC was induced by transrectal administration of 4% AA. Colon tissues were excised for macroscopic and histopathological evaluation and immunohistochemical analysis of caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax). Also, levels of oxidative mediators, Wnt family member1 (Wnt1), smoothened (Smo), and glioblastoma-1 (Gli1) were evaluated. Macroscopic and histopathological examination revealed that both graviola and sulfasalazine significantly mitigated colonic damage. Besides, both treatments significantly alleviated AA-induced oxidative stress, as evidenced by reduced nitric oxide (No) and malondialdehyde (MDA) levels and myeloperoxidase (MPO) activity and raised reduced glutathione (GSH) content. Both treatments significantly attenuated AA-induced apoptosis via downregulating the expression of Bax and caspase-3 and upregulating the expression of the anti-apoptotic protein, Bcl-2. Furthermore, downregulation of mRNA expression of Wnt1 with concomitant upregulation of Smo and Gli1 was observed in rats treated with either sulfasalazine or graviola. Based on these observations, graviola may attenuate AA-induced UC, at least partially, by modulating apoptosis and Wingless/Int1 (Wnt) and hedgehog (Hh) signaling crosstalk. Graphical abstract