Laurolitsine ameliorates type 2 diabetes by regulating the hepatic LKB1-AMPK pathway and gut microbiota.
Phytomedicine
; 106: 154423, 2022 Nov.
Article
em En
| MEDLINE
| ID: mdl-36075181
ABSTRACT
BACKGROUND:
Type 2 diabetes mellitus (DM) is a highly prevalent chronic metabolic disease. Effective antidiabetic drugs are needed to improve and expand the available treatments. Using the ob/ob diabetic mouse model, we previously demonstrated that the alkaloid-rich extract from Litsea glutinosa bark (CG) has potent antidiabetic effects and that laurolitsine (LL) is the richest alkaloid in CG.PURPOSE:
We conducted a systematic investigation of the antidiabetic effects and potential mechanisms of LL in vitro and in vivo.METHODS:
The antidiabetic effects of LL and its mechanisms of action were explored in HL-7702 hepatocytes in vitro and in db/db mice in vivo by a series of experiments, including cellular toxicity analysis, glucose consumption analysis, serum/liver biochemical analysis, pathological examinations, Western blots, RNA-seq analysis, and gut microbiota analysis.RESULTS:
LL stimulated glucose consumption and activated AMP-activated protein kinase (AMPK) without inducing lactic acid production or cytotoxicity in vitro. LL had potent antidiabetic effects with hypoglycemic activity in vivo. It improved insulin resistance, glucose tolerance and lipid metabolism; protected liver, renal and pancreatic functions; and promoted weight loss in db/db mice. Transcriptomic analysis suggested that the antidiabetic effects of LL involved the regulation of mitochondrial oxidative phosphorylation. We further demonstrated that LL effectively activated the hepatic liver kinase B1 (LKB1)/AMPK pathway by regulating the ADP/ATP ratio. Simultaneously, LL significantly modulated the gut microbial community, specifically decreasing the abundances of Mucispirillum schaedleri and Anaerotruncus_sp_G3_2012, which might also contribute to its antidiabetic effects.CONCLUSION:
These results suggest that LL is a promising antidiabetic drug candidate that may improve glucolipid metabolism via modulation of the hepatic LKB1/AMPK pathway and the gut microbiota.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Microbioma Gastrointestinal
Limite:
Animals
Idioma:
En
Revista:
Phytomedicine
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China