Cryptotanshinone ameliorates dextran sulfate sodium-induced murine acute and chronic ulcerative colitis via suppressing STAT3 activation and Th17 cell differentiation

Ulcerative colitis (UC) is a chronically relapsing inflammatory disease in the intestinal tract. Current unsatisfactory treatments prompt people to seek for alternative therapies and drug candidates. Cryptotanshinone (CTS), a diterpene quinoneextractedfromthe roots ofSalviamiltiorrhiza, has recently been shown to inhibit acute colitis by reducing pro-inflammatory mediators. However, whether CTS can protect against chronic UC and its effect on T lymphocytes remain unknown. In this study, CTS (20, 60 mg/kg) showed potent inhibitory activity against dextran sulfate sodium (DSS)-induced acute UC, as determined by weight loss, disease activity, colon length and histology. Similarly, in a model of DSS-induced chronic colitis, the administration of CTS prevented the disease progression with longer colon length, lower histological scores, and less expression of fibrosis-related collagen and α-smooth muscle actin in the colon. CTS also reduced the proportion of CD4+IL-17A+ Th17 cells in spleen and mesenteric lymph nodes of mice with acute or chronic colitis. However, CTS at 20 mg/kg had no effect on regulatory T cells (Tregs). In addition, CTS reduced the phosphorylation of signal transduction and transcription activator 3 (STAT3) in DSS-treated colon tissue. Further study showed that CTS concentration-dependently suppressed the differentiation of naïve CD4+ T cells into Th17 cells. CTS could not inhibit the activation and proliferation of T lymphocytes or attenuate the secretion of cytokines including IL-10, IL-2, IL-6 and IFN-γ, but could inhibit the production of IL-17A and TNF-α in Con A-stimulated splenocytes. CTS suppressed IL-6-induced phosphorylation and nuclear translocation of STAT3. In conclusion, our study demonstrated that CTS alleviated acute and chronic UC by suppressing STAT3 activation and Th17 cell differentiation, suggesting that it may be a promising candidate drug for the treatment of UC.