[Huangqin Decoction alleviates ulcerative colitis in mice by reducing endoplasmic reticulum stress]

【黄芩汤通过降低内质网应激缓解小鼠溃疡性结肠炎】

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Abstract

OBJECTIVE: To evaluate the therapeutic effect of Huangqin Decoction (HQD) on ulcerative colitis (UC) in mice and explore its mechanism. METHODS: Male Balb/c mice were randomly divided into normal control group, model group, mesalazine group (5-ASA, 200 mg/kg), and low-, medium-and high-dose HQD groups (2.275, 4.55 and 9.1 g/kg, respectively). With the exception of those in the normal control group, all the mice were exposed to 3% DSS solution in drinking water for 7 days to establish UC models. After treatment with the indicated drugs, the mice were assessed for colon injury and apoptosis using HE, AB-PAS and TUNEL staining, and the expression levels of inflammatory factors were detected with ELISA. Western blotting, immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier, mechanical barrier and endoplasmic reticulum stress (ERS). RESULTS: HQD treatment significantly reduced DAI score and macro score of UC mice, decreased colonic epithelial cell apoptosis, lowered expressions of IL-6, TNF-α, IL-1β and IL-8, and enhanced the expressions of MUC2 and TFF3. HQD treatment also upregulated the protein expressions of claudin-1, occludin and E-cadherin, reduced the expressions of GRP78, CHOP, caspase-12 and caspase-3, decreased the phosphorylation levels of PERK, eIF2α and IRE1α, and increased the Bcl-2/Bax ratio in the colon tissues of UC mice. CONCLUSION: HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.

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