Role of Oxidative Stress and Inflammatory Cytokines (TNF-α and IL-6) in Acetic Acid-Induced Ulcerative Colitis in Rats: Ameliorated by Otostegia fruticosa

Abstract

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes irritation, inflammation, and ulceration in the linings of the colon and rectum. Otostegia fruticosa is traditionally used to treat various disorders in different parts of the Middle East and sub-Saharan Africa. In the present study, we evaluated the ameliorative effects of crude leaves extract of O. fruticosa (OF.Cr) on acetic acid (AA)-induced UC model in Wistar albino rats. Wistar rats were administered orally with either vehicle (10 mL/kg), OF.Cr (200 and 400 mg/kg), or prednisolone (2 mg/kg) once a day for 6 days. On day 6, UC was induced in rats by intrarectal administration of a single dose of 5% AA (1.0 mL). Disease activity index (DAI) was recorded after one day of colitis induction by assessing the symptoms of colitis and then the rats were euthanized by cervical dislocation, and colon tissues were isolated for the histopathological examination and biochemical analysis of oxidative stress parameters and cytokines (Interleukin-6 and Tumor Necrosis Factor-α). OF.Cr pretreatment exhibits significant prevention against UC, as confirmed by a significant decrease of DAI, colonic ulceration, and reduced inflammatory score as compared to the AA-induced colitis rats. Depletion of total glutathione (GSH) levels and catalase (CAT) activities in the colitis group was significantly restored in the OF.Cr treated groups, while increased lipid peroxidation in the colon tissues was significantly reduced. OF.Cr prevented the activation of the IL-6 and TNF-α pathways in the colonic tissues, which were clearly observed by the decreased levels of IL-6 and TNF-α in the OF.Cr treated animals. Hence, OF.Cr could be developed in the future for the treatment of UC.

Myrica salicifolia Hochst. ex A. Rich. suppress acetic acid-induced ulcerative colitis in rats by reducing TNF-alpha and interleukin-6, oxidative stress parameters and improving mucosal protection

“…2,3 Inflammation is integral in the manifestation of UC and presents with a rise in proinflammatory cytokines which are the consequence of both the innate and adaptive immunity with interleukin (IL)- 1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, as initial perpetrators of inflammation. 4,5 In animal colitis models, the role of TNF-α has been more pronounced as it can trigger apoptosis. 6 Another simultaneous contributor of this inflammatory process is oxidative stress which is due to lipid peroxidation leading to elevated reactive oxygen species (ROS) and metabolites.…”

QbD-based fabrication of transferrin-anchored nanocarriers for targeted drug delivery to macrophages and colon cells for mucosal inflammation healing

“…62 IL-6 is involved in complement system activation and acute phase protein synthesis. 60 Tofa-P/tfr NCs significantly decreased pro-inflammatory cytokines (TNF-α and IL-6) via JAK/STAT inhibition (Fig. 12).…”

“…58,59 The pro-inflammatory cytokines contribute to the disbalanced immune system in the UC with the production of various chemokines, oxidative species, and chemotactic factors. 60,61 For instance, TNF-α is responsible for leukocyte production, endothelial damage, and COX-2 mediated prostaglandin-E2 production. 62 IL-6 is involved in complement system activation and acute phase protein synthesis.…”

Diosmin alleviates ulcerative colitis in mice by increasing Akkermansia muciniphila abundance, improving intestinal barrier function, and modulating the NF-κB and Nrf2 pathways

“…UC pathogenesis is complex, with oxidative stress, intestinal mucosal damage, inflammation, and microbial dysregulation all playing critical roles [ [3] , [4] , [5] ]. When the gut's immune system is active, free radicals and pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) are produced resulting in inflamed intestinal mucosa [ 6 ]. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a genetic factor that improve cell homeostasis in UC by combating reactive oxygen species (ROS) and inflammation [ 7 ].…”