Huang Qin decoction increases SLC6A4 expression and blocks the NFκB-mediated NLRP3/Caspase1/GSDMD pathway to disrupt colitis-associated carcinogenesis

© 2024. The Author(s)..

Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.

Errataetall:

ErratumIn: Funct Integr Genomics. 2024 Apr 25;24(3):80. - PMID 38658401

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:24

Enthalten in:

Functional & integrative genomics - 24(2024), 2 vom: 12. März, Seite 55

Sprache:

Englisch

Beteiligte Personen:

Tao, Yili [VerfasserIn]
Wang, Lai [VerfasserIn]
Ye, Xiaofeng [VerfasserIn]
Qian, Xin [VerfasserIn]
Pan, Danye [VerfasserIn]
Dong, Xiaoyu [VerfasserIn]
Jiang, Qian [VerfasserIn]
Hu, Po [VerfasserIn]

Links:

Volltext

Themen:

4Q81I59GXC
Chinese medicine preparation
Journal Article
MODE-K cells
Mesalamine
NLR Family, Pyrin Domain-Containing 3 Protein
Pyroptosis

Anmerkungen:

Date Completed 13.03.2024

Date Revised 26.04.2024

published: Electronic

ErratumIn: Funct Integr Genomics. 2024 Apr 25;24(3):80. - PMID 38658401

Citation Status MEDLINE

doi:

10.1007/s10142-024-01334-x

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369576748