Cynarin ameliorates dextran sulfate sodium-induced acute colitis in mice through the STAT3/NF-κB pathway.

OBJECTIVE: Cynarin is a derivative of hydroxycinnamic acid presented in various medicinal plants, such as Cynara scolymus L. and Onopordum illyricum L. To date, the antioxidant and antihypertensive activities of cynarin have been reported. However, whether cynarin has a therapeutic impact on ulcerative colitis (UC) is unclear. Therefore, the aim of this study was to explore the potential effect of cynarin on dextran sulfate sodium (DSS)-induced acute colitis in vivo and on lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced RAW264.7 and J774A.1 cellular inflammation model in vitro. METHODS AND RESULTS: In this study, we investigated that cynarin alleviated clinical symptoms in animal models, including disease activity index (DAI) and histological damage. Furthermore, cynarin can attenuate colon inflammation through decreasing the proportion of neutrophils in peripheral blood, reducing the infiltration of neutrophils, and macrophages in colon tissue, inhibiting the release of pro-inflammatory cytokines and suppressing the expression of STAT3 and p65. In cellular inflammation models, cynarin inhibited the expression of M1 macrophage markers, such as TNF-α, IL-1ß, and iNOS. Besides, cynarin suppressed the expression of STAT3 and p65 as well as the phosphorylation of STAT3, p65. Cynarin inhibited the polarization of RAW264.7 and J774A.1 cells toward M1 and alleviated LPS/IFN-γ-induced cellular inflammation. CONCLUSION: Considering these results, we conclude that cynarin mitigates experimental UC partially through inhibiting the STAT3/NF-кB signaling pathways and macrophage polarization toward M1. Accordingly, cynarin might be a potential and effective therapy for UC.

Isochlorogenic acid A alleviates dextran sulfate sodium-induced ulcerative colitis in mice through STAT3/NF-кB pathway.

Isochlorogenic acid A (ICGA-A) is a dicaffeoylquinic acid widely found in various medicinal plants or vegetables, such as Lonicerae japonicae Flos and chicory, and multiple properties of ICGA-A have been reported. However, the therapeutic effect of ICGA-A on colitis is not clear, and thus were investigated in our present study, as well as the underlying mechanisms. Here we found that ICGA-A alleviated clinical symptoms of dextran sodium sulfate (DSS) induced colitis model mice, including disease activity index (DAI) and histological damage. In addition, DSS-induced inflammation was significantly attenuated in mice given ICGA-A supplementation. ICGA-A reduced the fraction of neutrophils in peripheral blood and the infiltration of neutrophils and macrophages in colon tissue, and reduced pro-inflammatory cytokine production and tight junctions in mouse models. Furthermore, ICGA-A down-regulated expression of STAT3 and up-regulated the protein level of IκBα. Our in vitro studies confirmed that ICGA-A inhibited the mRNA expression of pro-inflammatory cytokines. ICGA-A blocked the phosphorylation of STAT3, p65, and IκBα, suppressed the expression STAT3 and p65. In addition, the present study also demonstrated that ICGA-A had no obvious toxicity on normal cells and organs. Taken together, we conclude that ICGA-A mitigates experimental ulcerative colitis (UC) at least in part by inhibiting the STAT3/NF-кB signaling pathways. Hence, ICGA-A may be a promising and effective drug for treating UC.

Corilagin induces apoptosis, autophagy and ROS generation in gastric cancer cells in vitro.

Corilagin, a unique component of the tannin family, has been identified in several medicinal plants. In previous literature, corilagin exhibited a marked anticancer property in a variety of human cancer cells. However, the biological effects of corilagin on gastric cancer and the mechanisms involved remain to be fully elucidated. In the present study, it was reported that corilagin induced inhibition of cell growth in SGC7901 and BGC823 cells in a concentration­dependent manner. It was found that corilagin exhibited less toxicity towards normal GES­1 cells. Furthermore, the study showed that corilagin induced the apoptosis of gastric cancer cells mainly via activating caspase­8, ­9, ­3 and poly ADP­ribose polymerase proteins. Simultaneously, it was verified that corilagin triggered autophagy in gastric cancer cells and the inhibition of autophagy improved the activity of corilagin on cell growth suppression. In addition, corilagin significantly increased intracellular reactive oxygen species production, which is important in inhibiting the growth of gastric cancer cells. Finally, it was shown that necroptosis cannot be induced by corilagin­incubation in SGC7901 and BGC823 cell lines. Consequently, these findings indicate that corilagin may be developed as a potential therapeutic drug for gastric cancer.