Eriodictyol attenuates dextran sodium sulphate-induced colitis in mice by regulating the sonic hedgehog signalling pathway.

Abstract:

CONTEXT:Eriodictyol (EDT) is a flavonoid with strong anti-inflammatory, anti-apoptotic, and antioxidant properties. OBJECTIVE:To investigate the protective effect and mechanism of EDT in ulcerative colitis (UC). MATERIALS AND METHODS:UC model was induced by 3% dextran sulphate sodium (DSS) solution for 7 days, meanwhile, EDT and Smoothened (Smo) inhibitor cyclopamine (Cyc) were intraperitoneally injected. In the first experiment, C57BL/6 mice divided into blank control, DSS, DSS + EDT (20 or 40 mg/kg) groups. In second experiment, added Cyc (5 mg/kg) and EDT + Cyc groups. All mice were sacrificed on day 8. Disease activity index (DAI), colon length and colon histology as well as MDA levels, SOD, and GSH-Px activities were measured. The expression of Sonic hedgehog (Shh), Patched, Smo, glioblastoma-1, zonula occludens-1 (ZO-1), occludin, cleaved caspase 3, Bax and Bcl-2 in colon was detected using RT-PCR and Western blotting. RESULTS:After EDT treatment, compared with the DSS group, DAI (2.33 ± 0.516 vs. 3.67 ± 0.516), colon shortening (5.27 ± 0.476 vs. 4.53 ± 0.528 cm) and histological score (6.67 ± 1.211 vs. 12 ± 1.265) was significantly decreased. EDT also reduced inflammation, oxidative stress and apoptosis in colon. Additionally, EDT increased the expression of the tight junction proteins ZO-1 (35%) and occludin (66.3%). Mechanistically, EDT upregulated the Shh signalling pathway. However, Cyc-mediated inhibition of the Shh pathway partially abolished the effects of EDT. DISCUSSION AND CONCLUSIONS:These results indicate EDT attenuates DSS-induced colitis by activating the Shh pathway. Further clinical trials are needed to demonstrate its efficacy on UC.

journal_name

Pharm Biol

journal_title

Pharmaceutical biology

authors

Wang R,Shen L,Li H,Peng H

doi

10.1080/13880209.2021.1948066

keywords:

["IBD","epithelial barrier destruction","inflammation","oxidative stress"]

subject

Has Abstract

pub_date

2021-12-01 00:00:00

pages

974-985

issue

1

eissn

1388-0209

issn

1744-5116

journal_volume

59

pub_type

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