Nootkatone Alleviates Type 2 Diabetes in db/db Mice Through AMPK Activation and ERK Inhibition: An Integrated In Vitro and In Vivo Study

Nootkatone Alleviates Type 2 Diabetes in db/db Mice Through AMPK Activation and ERK Inhibition: An Integrated In Vitro and In Vivo Study

Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disorder that imposes a substantial healthcare burden globally. Recent advances highlight the potential of natural products in ameliorating T2DM. In this study, we investigated the therapeutic efficacy of nootkatone (Nok), a natural sesqu...

Full description

Saved in:
Bibliographic Details
Main Authors: Yingjie Li, Linlin Zheng, Mimi Chen, Ruodi Li, Yansu Yu, Lu Qiao, Jialu Liu, Xiaopo Zhang, Yong Zhang, Yuxin Zhang, Wei Zheng
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Molecules
Subjects:
nootkatone
diabetes
liver
pancreatic
network pharmacology
db/db mice
Online Access:https://www.mdpi.com/1420-3049/30/10/2111
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disorder that imposes a substantial healthcare burden globally. Recent advances highlight the potential of natural products in ameliorating T2DM. In this study, we investigated the therapeutic efficacy of nootkatone (Nok), a natural sesquiterpene ketone, in T2DM and elucidated its underlying mechanisms. In vivo experiments demonstrated that Nok administration markedly improved dysregulated glucose metabolism and ameliorated serum biochemical abnormalities in db/db mice. Leveraging a network pharmacology-based approach, we identified putative molecular targets of Nok. Subsequent in vitro analyses revealed that Nok significantly enhanced glucose consumption in cultured cells. Mechanistically, Nok robustly activated AMP-activated protein kinase (AMPK) while suppressing mitogen-activated protein kinase (MAPK) signaling. Western blot validation further indicated that Nok downregulated the phosphorylation of MAPK1/3 (ERK2/1), attenuating MAPK pathway activation and thereby alleviating metabolic dysfunction-associated fatty liver disease (MAFLD) progression in the diabetic model. Collectively, our findings suggest that Nok exerts anti-diabetic effects via dual modulation of AMPK activation and MAPK inhibition, effectively restoring metabolic homeostasis and mitigating inflammation in T2DM. This study positions Nok as a promising natural compound for therapeutic intervention in T2DM and associated metabolic disorders.
ISSN:1420-3049

Similar Items