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Study on the Action Mechanism of 6-Shogaol in the Treatment of Ulcerative Colitis from the Signaling Pathway of Notch and TLR4/ NF-κB / 中国药学杂志
Chinese Pharmaceutical Journal ; (24): 1331-1338, 2020.
Article in Chinese | WPRIM | ID: wpr-857607
ABSTRACT

OBJECTIVE:

To explore the effect and mechanism of 6-gingerenol on ulcerative colitis based on TLR4/NF-κB signaling pathway related to immune inflammation and Notch signaling pathway related to mucosal repair.

METHODS:

Forty Kunming mice were randomly divided into the control group (n=10), the model group (n=10), the sulfasalazine group (n=10) and the 6-gingerenol group (n=10). Ulcerative colitis model mice were induced by oral administration of 2% dextran sulfate sodium(DSS) except those in the control group. The mice in the sulfasalazine group and the 6-gingerenol group were given sulfasalazine and 6-gingerenol (ig 100 mg•kg-1) respectively, and mice in the other groups were given normal saline. The serum and colon were isolated after 20-days treatment. The expressions of Hes-1, Math-1, MUC2 and olfm4 proteins in colonic tissues were detected by immunofluorescence. The expression levels of notch-1, Hes-1, Math-1, TLR4, NF-κBp65 mRNA and proteins in colonic tissues were detected by RT-PCR and Western blot. The levels of TNF-α and IL-1β in serum were detected by ELISA.

RESULTS:

Compared with the model group, the expressions of Notch-1, Hes-1, TLR4 and NF-κB p65 proteins and the relative expressions of mRNA in colon epithelial tissue of mice in sulfasalazine group and 6-gingerenol group were significantly decreased, while the relative expression of mRNA in Math-1 protein was significantly increased, and the contents of TNF-α and IL-1β in serum were significantly decreased. The expression of olfm4 protein was significantly decreased and the expression of MUC2 protein was significantly increased in 6-gingerenol group, but there was no significant change in olfm4 and MUC2 proteins expressions in sulfasalazine group. Compared with sulfasalazine group, the expressions of Notch-1 and Hes-1 proteins and the relative expression of mRNA in colon epithelial tissue in the 6-gingerenol group were significantly decreased, the relative expression of mRNA and protein of Math-1 were significantly increased, the expression of olfm4 protein was significantly decreased, and the expression of MUC2 protein was significantly increased, but the expressions of TLR4 and NF-κBp65 proteins and mRNA, and the TNF-α and IL-1β in serum were not significantly changed in 6-gingerenol group.

CONCLUSION:

6-Gingerenol could treat ulcerative colitis though inhibiting intestinal immune inflammation and promoting the repair of damaged colonic mucosa. The mechanism is related to its inhibition on activation of Notch and TLR4/NF-κB signaling pathway.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Pharmaceutical Journal Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Pharmaceutical Journal Year: 2020 Type: Article