Integrated metabolomics and network pharmacology analysis to reveal the mechanisms of naringin against atherosclerosis.

Abstract

Objectives: The purpose of this study was to explore the mechanism of naringin in atherosclerotic mice from the perspective of network pharmacology and non-targeted metabolomics.

Methods: ApoE-/- mice were induced to establish an atherosclerotic model to explore the pharmacodynamics and potential mechanism of naringin in atherosclerosis (AS). Pathological section and blood lipid levels were used to evaluate the intervention effects. The core targets, metabolites, and related pathways of naringin alleviating atherosclerotic were predicted through network pharmacology and metabolomics analysis. Furthermore, the inflammatory factors and pathway-related protein expression were detected using ELISA and Western blot methods.

Key findings: It turned out that compared with the model group, the naringin could reduce the development degree in atherosclerotic mice. The network pharmacology suggested that PI3K-AKT pathway was an important mechanism for naringin to interfere with AS. Serum metabolic data were collected and analyzed, and a total of 27 potential biomarkers were identified, involving vitamin B6 metabolism, arginine metabolism, and retinol metabolism. The experiment verified that naringin inhibited inflammation in AS through the PI3K-AKT/TLR4/NF-κB pathway.

Conclusions: This study provides a strategy combining metabolomics and network pharmacology to explore the alleviation of AS by naringin and offers a new idea for its application.