Effects of compound Qinbai Decoction on regulation of ERK/JNK signaling pathway in treating ulcerative colitis and its mechanism
Objective To study the regulatory effects of compound Qinbai Decoction(QBD)on the extracellular regulated protein kinases(ERK)/c-Jun N-terminal kinase(JNK)signaling pathway,as well as its effects on inflammatory factors in the serum of mice with ulcerative colitis(UC).Methods Sixty SPF grade healthy male BALB/C mice were used to establish a UC model using 3%dextran sulfate sodium(DSS).After successful modeling,they were randomized into model group(enema with normal saline),mesalazine group(enema with 0.196 g/kg mesalazine solution),and compound QBD group(enema with 1.092 g/kg compound Qinbai Granule),with 20 mice in each group.The enema was administered twice a day for 3 consecutive weeks.An additional 20 normally fed mice were used as blank group.Before treatment and on the 7th,14th,and 21st day after treatment,the body mass,stool characteristics,and bloody stool situation of the mice were observed,and the disease activity index(DAI)was calculated.The mice were anesthetized for blood and colon tissue collection after completion of administration.HE staining was used to observe the pathological changes of colon tissues in each group of mice;ELISA method was applied to check changes in the content of inflammatory factors such as interleukin-22,IL-6,IL-10,and tumor necrosis factor-α(TNF-α)in mice serum in each group;Western blot was employed to examine the expressions of p90 Ribosomal protein S6 kinase(p90 RSK),JNK,phosphorylated c-Jun N-terminal kinase(p-JNK),extracellular regulated protein kinases 1/2(ERK 1/2),and phospho extracellular regulated protein kinases 1/2(p-ERK 1/2)in the colon tissue of mice in each group.Results On the 7th,14th,and 21st day of treatment,the body mass of mice in the mesalazine and compound QBD groups were significantly higher than those in the model group(P<0.05,P<0.01),and the DAI score was significantly lower than that in model group(P<0.05,P<0.01).Under the light microscope,compared with the model group,the pathological changes in the colon tissue of mice in the mesalazine and the compound QBD groups showed varying degrees of recovery,with reduced inflammation infiltration.After administration,compared with the blank group,the model group showed a significant increase in the protein expressions of p90RSK,p-JNK,p-ERK 1/2,as well as IL-6 and TNF-α(P<0.01).Compared with the model group,the mesalazine and the QBD groups showed a significant decrease in the protein expressions of p90RSK,p-JNK,p-ERK 1/2,as well as IL-6 and TNF-α(P<0.05,P<0.01),while the content of anti-inflammatory factors IL-22 and IL-10 significantly increased(P<0.01).Conclusion Compound QBD may promote the expressions of anti-inflammatory factors IL-22 and IL-10 and inhibit the expressions of proinflammatory factors IL-6 and TNF-α,reduce intestinal inflammatory response,promote intestinal epithelial cell proliferation,improve intestinal mucosal barrier,and promote the repair of intestinal mucosal tissue damage in UC mice by inhibiting the ERK/JNK signaling pathway.
ulcerative colitiscompound Qinbai Decoctioninflammatory factorp90 Ribosomal protein S6 Kinasec-Jun N-terminal kinasephosphorylated c-Jun N-terminal kinaseextracellular regulated protein kinases 1/2phospho extracellular regulated protein kinases 1/2