Combinational application of the natural products 1-deoxynojirimycin and morin ameliorates insulin resistance and lipid accumulation in prediabetic mice.
DNJ
Insulin resistance
Morin
PPARγ
Prediabetes
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
31
03
2023
revised:
12
09
2023
accepted:
18
09
2023
medline:
23
10
2023
pubmed:
6
10
2023
entrez:
5
10
2023
Statut:
ppublish
Résumé
Prediabetes, a stage characterized by chronic inflammation, obesity and insulin resistance. Morin and 1-deoxynojirimycin (DNJ) are natural flavonoids and alkaloids extracted from Morus nigra L., exhibiting anti-hyperglycemic efficacy. However, the benefits of DNJ are shadowed by the adverse events, and the mechanism of morin in anti-diabetes remains under investigation. In this study, the combinational efficacy and mechanisms of DNJ and morin in ameliorating insulin resistance and pre-diabetes were investigated. The mice model with prediabetes and Alpha mouse liver-12 (AML-12) cell model with insulin resistance were established. The anti-prediabetic efficacy of the drug combination was determined via analyzing the blood glucose, lipid profiles and inflammatory factors. The application of network pharmacology provided guidance for the research mechanism. In our study, the intervention of morin ameliorated the insulin resistance via activating the Peroxisome proliferator-activated receptor γ (PPARγ). However, PPARγ activation leaded to the lipid accumulation in prediabetic mice. The combination of 5 mg/kg dose of DNJ and 25 mg/kg morin effectively hindered the progression of T2DM by 87.56%, which was achieved via inhibition of Suppressors of cytokine signaling 3 (SOCS3) and promotion of PPARγ as well as SOCS2 expression. Furthermore, this treatment exhibited notable capabilities in combating dyslipidemia and adipogenesis, achieved by suppressing the Cluster of differentiation 36/ Sterol-regulatory element binding proteins-1/ Fatty acid synthetase (CD36/Serbp1/Fas) signaling. This research confirmed that the drug combination of DNJ and morin in ameliorating insulin resistance and lipid accumulation, and revealed the potential mechanisms. In summary, the combination of DNJ and morin is an underlying alternative pharmaceutical composition in T2DM prevention.
Sections du résumé
BACKGROUND
BACKGROUND
Prediabetes, a stage characterized by chronic inflammation, obesity and insulin resistance. Morin and 1-deoxynojirimycin (DNJ) are natural flavonoids and alkaloids extracted from Morus nigra L., exhibiting anti-hyperglycemic efficacy. However, the benefits of DNJ are shadowed by the adverse events, and the mechanism of morin in anti-diabetes remains under investigation.
PURPOSE
OBJECTIVE
In this study, the combinational efficacy and mechanisms of DNJ and morin in ameliorating insulin resistance and pre-diabetes were investigated.
METHODS
METHODS
The mice model with prediabetes and Alpha mouse liver-12 (AML-12) cell model with insulin resistance were established. The anti-prediabetic efficacy of the drug combination was determined via analyzing the blood glucose, lipid profiles and inflammatory factors. The application of network pharmacology provided guidance for the research mechanism.
RESULTS
RESULTS
In our study, the intervention of morin ameliorated the insulin resistance via activating the Peroxisome proliferator-activated receptor γ (PPARγ). However, PPARγ activation leaded to the lipid accumulation in prediabetic mice. The combination of 5 mg/kg dose of DNJ and 25 mg/kg morin effectively hindered the progression of T2DM by 87.56%, which was achieved via inhibition of Suppressors of cytokine signaling 3 (SOCS3) and promotion of PPARγ as well as SOCS2 expression. Furthermore, this treatment exhibited notable capabilities in combating dyslipidemia and adipogenesis, achieved by suppressing the Cluster of differentiation 36/ Sterol-regulatory element binding proteins-1/ Fatty acid synthetase (CD36/Serbp1/Fas) signaling.
CONCLUSION
CONCLUSIONS
This research confirmed that the drug combination of DNJ and morin in ameliorating insulin resistance and lipid accumulation, and revealed the potential mechanisms. In summary, the combination of DNJ and morin is an underlying alternative pharmaceutical composition in T2DM prevention.
Identifiants
pubmed: 37797432
pii: S0944-7113(23)00466-X
doi: 10.1016/j.phymed.2023.155106
pii:
doi:
Substances chimiques
1-Deoxynojirimycin
19130-96-2
PPAR gamma
0
morin
8NFQ3F76WR
Flavonoids
0
Drug Combinations
0
Lipids
0
Insulin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
155106Informations de copyright
Copyright © 2023 Elsevier GmbH. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced the outcome.