Coptisine alleviates colitis through modulating gut microbiota and inhibiting TXNIP/NLRP3 inflammasome.
J Ethnopharmacol
; 335: 118680, 2024 Dec 05.
Article
en En
| MEDLINE
| ID: mdl-39117021
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Ulcerative colitis (UC) is a disease involving the enteric canal which is characterised by chronisch inflammatory reaction. Coptisine (COP), the distinctive component of Coptis chinensis Franch., is famous for its anti-inflammation, antioxidation, anti-bacteria, and anti-cancer. Earlier researches certified that COP is a prospective remedy for colitis, but the mechanism of colitis and the therapeutical target of COP are deficiently elucidated. AIM OF THIS STUDY In this follow-up study, we adopted dextran sulfate sodium (DSS)-elicited UC model to further elucidate the possible mechanism of COP on UC in mice. MATERIALS AND METHODS:
COP and the positive drug sulfasalazine (SASP) were administered by oral gavage in DSS-induced colitis mouse model. Oxidative stress, inflammatory cytokines, intestinal barrier permeability, protein expression of the TXNIP/NLRP3 inflammasome pathway and intestinal microbiome structure were assessed.RESULTS:
Among this investigation, our team discovered that COP could mitigate DSS-elicited UC in murines, with prominent amelioration in weight loss, disease activity index, intestinal permeability (serum diamine oxidase and D-lactate), contracted colonal length and histologic alterations. Furthermore, COP greatly lowered the generation of pro-inflammatory factors, malondialdehyde (MDA) activity and reactive oxygen species (ROS) level, while increased superoxide dismutase (SOD) activity in colonal tissues. Additionally, COP downmodulated the proteic expressions of thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, IL-1ß and IL-18. Enteric microbiome sequencing displayed that DSS and COP tremendously influenced the constitution and diversity of enteric microbes in DSS-elicited UC murines. Besides, COP elevated the abundance of probiotic bacteria Bacteroidota, Akkermansia_muciniphila and Bacteroides_acidifaciens, lowered the proportions of potential pathogenic bacteria, such as Lachnospiraceae, Acetatifactor_muris, Clostridium_XlVa, Alistipes and Oscillibacter, and reduced the ratio of Bacillota/Bacteroidota, which vastly helped to reverse the enteric microbiome to a balanceable condition. Alterations in these bacteria were strongly correlated with the colitis relative index.CONCLUSION:
The mechanism of COP against UC is connected with the suppression of TXNIP/NLRP3 inflammasome signalling pathway and the adjustment of the enteric microbiome profiles. The proofs offer new understandings upon the anti-UC function of COP, which might be a prospective candidate against UC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Berberina
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Proteínas Portadoras
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Colitis Ulcerosa
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Sulfato de Dextran
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Inflamasomas
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Microbioma Gastrointestinal
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Proteína con Dominio Pirina 3 de la Familia NLR
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Ratones Endogámicos C57BL
Límite:
Animals
Idioma:
En
Revista:
J Ethnopharmacol
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Irlanda