DIHYDROARTEMISININ ATTENUATES TNBS-INDUCED COLITIS IN MICE BY INHIBITING JAK2/STAT3 SIGNALING AND NF-κB ACTIVATION

Objective: To investigate the effect of dihydroartemisinin on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice by regulating Janus kinase 2 (JAK2)/mouse anti-signal transducer and activator of transcription 3 (STAT3) signaling and activation of nuclear factor-kappa B (NF-kappa B). Methods: Thirty-three BALB mice were collected. Eleven mice were randomly selected as blank control group, and the remaining 22 mice were induced to establish a Crohn's disease model by TNBS enema. After successful modeling, the mice were randomly divided into a Crohn's disease group and a dihydroartemisinin group with 11 mice in each group. Mgmiddotkg-1 dihydroartemisinin was injected intraperitoneally, and the mice in the model group were intraperitoneally injected with an equal volume of normal saline. The levels of serum inflammatory factors (IL-6, IL-10, TNF-alpha), cell barrier associated proteins (claudin-1, ZO-1), (JAK2, p-JAK2, STAT3, p-STAT3) and NF-kappa B signaling pathways (Toll-like receptor 4 (TLR4), p-p65, p65) in the colon tissue of the mice were compared among the three groups' protein expression levels. Results: The levels of IL-6 and TNF-alpha in the Crohn's disease group were significantly higher than those in the blank control group, and the level of IL-10 was significantly lower than that in the blank control group (P<0.05). The levels of IL-6 and TNF-alpha in the dihydroartemisinin group were significantly lower than those in the Crohn's disease group, while the level of IL-10 in dihydroartemisinin group was significantly higher than that in the Crohn's disease group (P<0.05). The protein expression levels of claudin-1 and ZO-1 in the Crohn's disease group were significantly lower than those in blank control group (P<0.05). The protein expression levels of claudin-1 and ZO-1 in the dihydroartemisinin group were significantly higher than those in the Crohn's disease group (P<0.05). The expression levels of p-Akt and p-STAT3 protein in the Crohn's disease group were significantly higher than those in the blank control group (P<0.05). The expression levels of p-Akt and p-STAT3 in the dihydroartemisinin group were significantly lower than those in Crohn's disease group (P<0.05). The expression levels of TLR4 and p-p65 protein in the Crohn's disease group were significantly higher than those in the control group. The expression levels of TLR4 and p-p65 protein in the dihydroartemisinin group were significantly lower than those in the Crohn's disease group (P<0.05). Conclusion: Dihydroartemisinin can effectively alleviate TNBS-induced inflammatory response in mice with Crohn's disease and improve the protective effect of the intestinal mucosal barrier structure, which may be achieved by blocking the JAK2/STAT3 signaling pathway and NF-kappa B activation.