Tryptanthrin Protects Mice against Dextran Sulfate Sodium-Induced Colitis through Inhibition of TNF-α/NF-κB and IL-6/STAT3 Pathways

Abstract

Inflammatory bowel disease (IBD) is a notable health problem and may considerably affect the quality of human life. Previously, the protective roles of tryptanthrin (TRYP) against dextran sulfate sodium (DSS) induced colitis has been proved, but the concrete mechanism remained elusive. It has been suggested that TRYP could diminish the weight loss and improve the health conditions of mice with DSS induced colitis. Hematoxylin and eosin staining revealed that TRYP could improve the histopathological structure of the colon tissue. Two signaling pathways (TNF-α/NF-κBp65 and IL-6/STAT3) were investigated using immunochemistry and western blot. The detected concentrations of the two cytokines TNF-α and IL-6 showed that their levels decreased after TRYP treatment of the colitis. The protein expression level of NF-κBp65 in cytoplasm increased after TRYP treatment of the induced colitis. However, the protein level of NF-κBp65 in the nucleus decreased after administration of TRYP. The expression level of IκBα, the inhibitory protein of NF-κBp65, was tested and the results suggested that TRYP could inhibit the degradation of IκBα. The phosphorylation level of STAT3 was inhibited by TRYP and the expression level of STAT3 and p-STAT3 decreased after administration of TRYP. We conclude that TRYP improves the health condition of mice with DSS induced colitis by regulating the TNF-α/NF-κBp65 and IL-6/STAT3 signaling pathways via inhibiting the degradation of IκBα and the phosphorylation of STAT3.

Tryptanthrin promotes keratinocyte and fibroblast responses in vitro after infection with Trichophyton benhamiae DSM6916

“…Hence, inhibition of caspase-1 by TRP could be one possible mode of action explaining the reduced IL-1β protein secretion despite unaffected mRNA levels. Another possible regulation of anti-inflammatory effects of TRP is by inhibiting the degradation of IκBα 34 . The inhibitory molecule IκBα sequesters NF-κB in an inactivate form in the cytoplasm and blocks its translocation to the nucleus 35 , leading to an absent positive feedback for further TNF-α production.…”

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

“…A total of 29 active ingredients were obtained from TSMSP, BATMAN-TCM, and TCMID, and nine core active components were selected according to the screening criteria of ADME OB ≥ 30% and DL ≥ 0.18. However, tryptanthrin was the third most effective component of indigo, and the related literature confirmed that it showed protective effects in an experimental UC animal model 21,22 . Therefore, it was included although it did not meet the OB and DL criteria.…”

“…Tryptanthrin also improves the body weight and pathology of DSS mice and increases the survival rate. It regulates the TNF-α/NF-κB p65 and IL-6/STAT3 signaling pathways by inhibiting the degradation of IαBκ and the phosphorylation of STAT3 22 . Spleen cells from mice with colitis treated with tryptanthrin produce less IL-2 and IFN-γ after mitogen stimulation than those from untreated mice.…”

Protective Effect of Cicer arietinum L. (Chickpea) Ethanol Extract in the Dextran Sulfate Sodium-Induced Mouse Model of Ulcerative Colitis

“…The activation of these transcription factors is also significantly higher in intestinal epithelial cells from patients with active UC compared with patients with inactive disease or healthy controls, and these levels correlated with colitis severity [1]. The functional interactions between NF-κB and STAT3 enhance inflammation in the intestinal mucosa and have been investigated in other studies [25,26]. In contrast, abrogation of NF-κB and STAT3 activation has been reported to be associated with improvements in intestinal homeostasis in DSS-administrated mice [27].…”