Citrus Changshan Huyou Extracts as Natural GLP-1R Agonists Attenuate Atherosclerosis via the GLP-1R/PKA/CREB Pathway: A Functional Food Pers
This research evaluates Citrus Changshan Huyou extracts (HY) as natural food-origin glucagon-like peptide-1 receptor agonists, demonstrating their ability to attenuate atherosclerosis through activation of the intestinal
Atherosclerosis (AS)-triggered cardiovascular diseases constitute a major global public health crisis. The pathological progression of AS is characterized by abnormal lipid accumulation, inflammatory cell infiltration, and atherosclerotic plaque buildup in arterial walls. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are well known for hypoglycemic effects, and accumulating evidence proves they exert extra cardiovascular protective effects. This research aimed to explore whether Citrus Changshan Huyou extracts (HY) function as natural food-origin GLP-1RAs and further verify their anti-atherosclerotic activity and underlying mechanisms.
Cellular assays confirmed that HY possessed prominent GLP-1R agonistic activity with negligible cytotoxicity, and all five intrinsic flavonoid components of HY independently activated GLP-1R. The five major flavonoid monomers of HY (eriocitrin, neoeriocitrin, narirutin, naringin, and neohesperidin) were isolated and individually validated for GLP-1R activating capacity at the cellular level. These findings establish the pharmacological basis for utilizing these citrus-derived compounds in functional food development.
In animal experiments, HY intervention markedly relieved excessive weight gain, corrected disordered blood lipid levels, and shrank atherosclerotic plaque lesions in the aorta, without any detectable toxic reactions. A high-fat diet-induced ApoE−/− mouse model was established to assess the in vivo efficacy and biosafety of HY. The results demonstrate that HY is safe and potent when administered orally to mice with metabolic risk profiles.
Mechanistically, HY activated intestinal GLP-1R/PKA/CREB signaling, which further suppressed the expression of vascular senescence-associated proteins and alleviated inflammatory infiltration in aortic tissues. This study verifies that HY is a safe and potent natural GLP-1RA derived from edible citrus raw materials with robust anti-atherosclerotic performance. The intestinal GLP-1R/PKA/CREB pathway mediates the dual protective effects of HY against vascular senescence and aortic inflammation.
The authors' findings provide solid experimental support for the development of novel cardiovascular-protective functional food raw materials based on Changshan Huyou extracts. These results suggest that Citrus Changshan Huyou may serve as a viable alternative to synthetic GLP-1RAs in dietary interventions, provided further clinical validation is conducted.
This research note is intended solely for laboratory research and development purposes. The data presented herein describes preclinical findings from controlled animal models and cell culture systems. No human clinical trials have been conducted, and no therapeutic dosages or medical claims are made regarding the use of Citrus Changshan Huyou extracts in humans. All results should be interpreted within the context of established scientific literature and regulatory guidelines for functional food ingredients.