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Qing Hua Chang Yin ameliorates chronic colitis in mice by inhibiting PERK-ATF4-CHOP pathway of ER stress and the NF-κB signalling pathway.
- Source :
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Pharmaceutical biology [Pharm Biol] 2024 Dec; Vol. 62 (1), pp. 607-620. Date of Electronic Publication: 2024 Jul 22. - Publication Year :
- 2024
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Abstract
- Context: Ulcerative colitis has been clinically treated with Qing Hua Chang Yin (QHCY), a traditional Chinese medicine formula. However, its precise mechanisms in mitigating chronic colitis are largely uncharted.<br />Objective: To elucidate the therapeutic efficiency of QHCY on chronic colitis and explore its underlying molecular mechanisms.<br />Materials and Methods: A total ion chromatogram fingerprint of QHCY was analysed. Chronic colitis was induced in male C57BL/6 mice using 2% dextran sodium sulphate (DSS) over 49 days. Mice were divided into control, DSS, DSS + QHCY (0.8, 1.6 and 3.2 g/kg/d dose, respectively) and DSS + mesalazine (0.2 g/kg/d) groups ( n  = 6). Mice were intragastrically administered QHCY or mesalazine for 49 days. The changes of disease activity index (DAI), colon length, colon histomorphology and serum pro-inflammatory factors in mice were observed. RNA sequencing was utilized to identify the differentially expressed transcripts (DETs) in colonic tissues and the associated signalling pathways. The expression of endoplasmic reticulum (ER) stress-related protein and NF-κB signalling pathway-related proteins in colonic tissues was detected by immunohistochemistry staining.<br />Results: Forty-seven compounds were identified in QHCY. Compared with the DSS group, QHCY significantly improved symptoms of chronic colitis like DAI increase, weight loss, colon shortening and histological damage. It notably reduced serum levels of IL-6, IL-1β and TNF-α. QHCY suppressed the activation of PERK-ATF4-CHOP pathway of ER stress and NF-κB signalling pathways in colonic tissues.<br />Discussion and Conclusions: The findings in this study provide novel insights into the potential of QHCY in treating chronic colitis patients.
- Subjects :
- Animals
Male
Mice
Chronic Disease
Colitis drug therapy
Colitis chemically induced
Colitis pathology
Disease Models, Animal
Colitis, Ulcerative drug therapy
Colitis, Ulcerative chemically induced
Colitis, Ulcerative pathology
Dose-Response Relationship, Drug
Mice, Inbred C57BL
Signal Transduction drug effects
Endoplasmic Reticulum Stress drug effects
Drugs, Chinese Herbal pharmacology
NF-kappa B metabolism
eIF-2 Kinase metabolism
Activating Transcription Factor 4 metabolism
Dextran Sulfate
Transcription Factor CHOP metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1744-5116
- Volume :
- 62
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Pharmaceutical biology
- Publication Type :
- Academic Journal
- Accession number :
- 39034914
- Full Text :
- https://doi.org/10.1080/13880209.2024.2378012