Citrus Peel Xanthophylls Orchestrate Lipid-Glucose-Inflammation Axis Reprogramming in Cardiometabolic Syndrome:...

Area of Science:

• Nutritional Biochemistry
• Pharmacology
• Metabolic Disorders

Background:

• Cardiometabolic syndrome (CMS) is characterized by dysregulated lipid, glucose, and inflammatory pathways.
• Citrus peel xanthophylls show potential for multitarget effects, but their mechanisms are unclear.

Purpose of the Study:

• To investigate the mechanistic basis and therapeutic efficacy of citrus peel xanthophyll fraction (CPXF) in managing CMS.
• To elucidate CPXF's effects on the lipid-glucose-inflammation axis using integrated in silico and in vivo methods.

Main Methods:

• CPXF characterization using UHPLC-HRMS/MS.
• Network pharmacology and molecular docking for target identification.
• In vivo validation in a rat model of diet-induced CMS, assessing metabolic, inflammatory, and oxidative parameters.

Main Results:

• Dominant compounds identified as β-cryptoxanthin, violaxanthin, and lutein.
• Key targets included PPARG, AMPK, SREBP1, and MMP9 with strong binding affinities.
• CPXF significantly improved glucose homeostasis, insulin resistance, lipid profile, reduced inflammation (TNF-α, IL-6, CRP), and attenuated oxidative stress.

Conclusions:

• CPXF demonstrates synergistic, multitarget effects on the lipid-glucose-inflammation axis.
• Mechanisms involve AMPK activation, PPAR-γ modulation, and SREBP-1c suppression.
• CPXF shows promise as a food-derived strategy for CMS management.