Diosmetin attenuate experimental ulcerative colitis in rats via suppression of NF-κB, TNF-α and IL-6 signalling pathways correlated with down-regulation of apoptotic events

Introduction Ulcerative colitis (UC) is a chronic inflammation of colon in which the innermost tissue of colon and rectum develops deep-rooted inflammation. Diosmetin is the aglycone of the flavonoid glycoside diosmin, commonly found in citrus fruits. Therapeutically diosmetin is indicated to demonstrate anticancer, antimicrobial, antioxidant, oestrogenic and anti-inflammatory activity. Methods In this research, we studied the action of diosmetin on TNBS (2,4,6-trinitrobenzene sulfonic acid)-induced UC in rats. Male Wister rats were anesthetised with pentobarbital and TNBS introduced by performing an enema. Diosmetin treatment was provided through oral gavage for the next 28 days. Animals were sacrificed on the 29th day and colon tissues were collected for further examinations. Results Diosmetin treatment decreased colonic ulceration dramatically and decreased the percentage of inflammation in the colonic mucosa. Depletion of the TNBS assisted of superoxide dismutase and catalase was substantially restricted, while lipid peroxidation was recorded in the colonic tissue as malondialdehyde content was also decreased. After treatment with diosmetin, the occurrence of TNF-α, IL-6and NF-κB was considerably lowered and the number of apoptotic cells observed was significantly reduced. Conclusion Taken together, these observations demonstrated the potential of diosmetin against ulcer formation and development.

CD40 Receptor Knockout Protects against Microcystin-LR (MC-LR) Prolongation and Exacerbation of Dextran Sulfate Sodium (DSS)-Induced Colitis

Inflammatory Bowel Disease (IBD) is one of the most common gastrointestinal (GI) disorders around the world, and includes diagnoses such as Crohn’s disease and ulcerative colitis. The etiology of IBD is influenced by genetic and environmental factors. One environmental perturbagen that is not well studied within the intestines is microcystin-leucine arginine (MC-LR), which is a toxin produced by cyanobacteria in freshwater environments around the world. We recently reported that MC-LR has limited effects within the intestines of healthy mice, yet interestingly has significant toxicity within the intestines of mice with pre-existing colitis induced by dextran sulfate sodium (DSS). MC-LR was found to prolong DSS-induced weight loss, prolong DSS-induced bloody stools, exacerbate DSS-induced colonic shortening, exacerbate DSS-induced colonic ulceration, and exacerbate DSS-induced inflammatory cytokine upregulation. In addition, we previously reported a significant increase in expression of the pro-inflammatory receptor CD40 in the colons of these mice, along with downstream products of CD40 activation, including plasminogen activator inhibitor-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP-1). In the current study, we demonstrate that knocking out CD40 attenuates the effects of MC-LR in mice with pre-existing colitis by decreasing the severity of weight loss, allowing a full recovery in bloody stools, preventing the exacerbation of colonic shortening, preventing the exacerbation of colonic ulceration, and preventing the upregulation of the pro-inflammatory and pro-fibrotic cytokines IL-1β, MCP-1, and PAI-1. We also demonstrate the promising efficacy of a CD40 receptor blocking peptide to ameliorate the effects of MC-LR exposure in a proof-of-concept study. Our findings suggest for the first time that MC-LR acts through a CD40-dependent mechanism to exacerbate colitis.

Severe Human Intestinal Spirochetosis: An Unusual Cause of Diffuse Colonic Ulcerations in a Patient Living with HIV

We describe a case of a homosexual male with human immunodeficiency virus (HIV) and CD4 count of 246 presenting with acute severe bloody diarrhea. Infectious work up was negative, and colonoscopy revealed severe diffuse colonic ulcerations. Histopathologic analysis and Treponemal pallidum immunostaining confirmed the diagnosis of intestinal spirochetosis. There was no evidence of co-infection with other pathogens. His symptoms completely resolved after a 14-day course of metronidazole. This case is notable as colonic ulceration of any severity in patients living with HIV is rarely identified with intestinal spirochetosis. Hence, it should be considered in the differential diagnosis of colonic ulcerations.