The combination of indirubin and isatin attenuates dextran sodium sulfate induced ulcerative colitis in mice

Abstract

Indirubin and isatin have been used in the treatment of inflammatory diseases due to their anti-inflammatory properties. This study aimed to evaluate the combined effect of indirubin and isatin on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). UC was induced by the administration of 3% (w/v) DSS solution, and then the model mice were administered indirubin (10 mg/kg body mass) and (or) isatin (10 mg/kg body mass) by gavage once daily for 7 days. The results showed that indirubin and isatin, individually or combined, significantly inhibited weight loss, lowered disease activity index (DAI), ameliorated pathological changes, decreased the levels of pro-inflammatory mediators and myeloperoxidase (MPO) activity, increased the expression of anti-inflammatory cytokines and Foxp3, suppressed CD4 T cell infiltration, and inhibited oxidative stress and epithelial cell apoptosis. Additionally, indirubin and isatin, both individually and combined, can also inhibit activation of the NF-κB and MAPK pathways induced by DSS. The protective effect of combination therapy against UC was superior to that of single-agent treatment. These results suggest that indirubin combined with isatin attenuates DSS-induced UC, and changes to the NF-κB and MAPK signaling pathways may mediate the protective effects of indirubin and isatin in UC.

Chlorogenic Acid Attenuates Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice through MAPK/ERK/JNK Pathway

“…The infiltration of immune cells in the colon and rectal mucosa is regulated by the activation of NF- κ B to regulate the development of the UC. The activation of NF- κ B is mainly achieved through the phosphorylation and dissociation of its inhibitor I κ B, and the phosphorylation expression of I κ B and NF- κ B p65 increased in DSS-induced colitis model [59]. We found chlorogenic acid can reduce the phosphorylation level of I κ B and NF- κ B p65 protein, thus inhibiting the activity of NF- κ B. MAPK/ERK/JNK pathway is the main signal transduction pathway of many factors, which is related to intestinal injury, and the three most representative pathways are ERK pathway, JNK pathway, and p38/MAPK pathway [60–63].…”

Mechanisms of indigo naturalis on treating ulcerative colitis explored by GEO gene chips combined with network pharmacology and molecular docking

“…Tryptanthrin also improves the body weight and pathology of DSS mice and increases the survival rate. Indirubin regulates the TNF-α/NF-κB p65 and IL-6/STAT3 signaling pathways by inhibiting the degradation of IαBκ and the phosphorylation of STAT3 57 , 58 . Tryptanthrin also improves the body weight and pathology of DSS mice and increases the survival rate.…”

Natural Products Modulate Cell Apoptosis: A Promising Way for the Treatment of Ulcerative Colitis

“…tinctoria]. In 2018, an investigation by Gao et al demonstrated that the combination of Indirubin and Isatin inhibited cell apoptosis in DSS-induced UC mice through mediating the MAPK pathway, decreasing caspase-3, and increasing bcl-2 (Gao et al, 2018). Qing Chang Hua Shi granule (QCHS) also showed inhibitory effects on reducing UCinduced colonic apoptosis in vitro and in vivo by mediating MEK/ ERK pathway and decreasing the expression of such apoptosisrelated proteins as bax, bcl-2, caspase-3, -9, Fas, and Fas-L (Zhu et al, 2019a).…”