Cambogin suppresses dextran sulphate sodium‐induced colitis by enhancing Treg cell stability and function

Abstract

Background and PurposeInflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, and an impaired immune response plays a critical role in IBD. The current drugs and therapies for IBD treatment are of limited use, therefore, there is a need to find novel drugs or therapies for this disease. We investigated the effect of cambogin in a mouse model of dextran sulphate sodium (DSS)‐induced colitis and whether cambogin attenuates inflammation via a Treg‐cell‐mediated effect on the immune response.Experimental ApproachChronic colitis was established in mice using 2% DSS, and cambogin (10 mg·kg−1, p.o.) was administered for 10 days. Body weight, colon length and colon histology were assessed. Cytokine production was measured using elisa and quantitative real‐time PCR. To evaluate the mechanism of cambogin, human CD4+CD25hiCD127lo Treg cells were isolated from peripheral blood mononuclear cells. Major signalling profiles involved in Treg cell stability were measured.Key ResultsCambogin attenuated diarrhoea, colon shortening and colon histological injury and IL‐6, IFN‐γ and TNF‐α production in DSS‐treated mice. Cambogin also up‐regulated Treg cell numbers in both the spleen and mesenteric lymph nodes. Furthermore, cambogin (10 μM) prevented Foxp3 loss in human primary Treg cells in vitro, and promoted USP7‐mediated Foxp3 deubiquitination and increased Foxp3 protein expression in LPS‐treated cells.Conclusions and ImplicationsThe effect of cambogin on DSS‐induced colitis is expedited by a Treg‐cell‐mediated modification of the immune response, suggesting that cambogin could be applied as a novel agent for treating colitis and other Treg cell‐related diseases.

YYFZBJS ameliorates colorectal cancer progression in ApcMin/+ mice by remodeling gut microbiota and inhibiting regulatory T-cell generation

“…What is more, Treg can inhibit the function of effector T helper cells and cytotoxic T cells, and also act on antigen presenting cells to reduce their capacity to activate naive T cells [64]. Recently, our group described an important involvement of the immune response in DSS-induced colitis in mice through regulating Treg cell stability and function, to promote cancer development [65].…”

Protective effects of oxymatrine against DSS-induced acute intestinal inflammation in mice via blocking the RhoA/ROCK signaling pathway

“…Many people suffer from IBD worldwide [36]. Intestinal mucosal barrier damage [1], abnormal overproduction of pro-inflammatory cytokines in inflammatory mucosa [37], oxidative stress and immune dysfunction are key factors in the pathogenesis of UC [36,38–39]. Thus, we sought to determine whether OMT suppressed inflammation in the colon by attenuating IEB dysfunction, modulating pro-inflammatory cytokines, relieving oxidative stress and restoring the balance between Th17 and Treg cells.…”

Gaudichaudione H Inhibits Inflammatory Responses in Macrophages and Dextran Sodium Sulfate-Induced Colitis in Mice

“…Cambogin isolated from Garcinia esculenta Y. H. Li. inhibited DSS-induced colitis in mice through the upregulation of Treg cell stability and function (Lu et al, 2018). In addition, other compounds such as 1,3,5,7-tetrahyd roxy-8isoprenylxanthone (TIE) from the twigs of G. esculenta, kolaviron from the seeds of Garcinia kola, and b-mangostin from Garcinia mangostana Linn.…”