A research team at National Taiwan University found that abnormal blood flow activates CB1 receptors in endothelial cells, promoting vascular inflammation and dysfunction. Soy-derived isoflavone prodrugs that inhibit CB1 may help protect blood vessels and prevent atherosclerosis.
Despite advances in lipid-lowering and anti-inflammatory therapies, atherosclerosis remains a major global health challenge. Current treatments mainly target systemic risk factors, while the diseased vascular wall, especially endothelial cells exposed to disturbed blood flow, remains insufficiently addressed.
The research team found that CB1 receptors are markedly upregulated in human and mouse atherosclerotic lesions and in endothelial cells exposed to disturbed flow, driven by transcription factors KLF4, Spi1, and ZNF610. The study is published in the Journal of Biomedical Science.
They also identified the soy isoflavone daidzein as a novel CB1 antagonist. To improve drug properties, the team developed prodrugs genistein 7-O-phosphate (G7P) and daidzein 7-O-phosphate (D7P). Pharmacological or genetic inhibition of CB1 reduced endothelial inflammation, oxidative stress, and endothelial-to-mesenchymal transition, while oral G7P and D7P significantly decreased plaque formation in mouse models.
"These results highlight endothelial CB1 as a mechanosensitive driver of vascular dysfunction and suggest that soy-derived isoflavone prodrugs could offer a promising oral therapy for atherosclerosis," says corresponding author Prof. Tzu-Tang Wei at the Graduate Institute of Pharmacology, National Taiwan University.
To see article on Medical Xpress: https://medicalxpress.com/news/2026-03-soy-isoflavone-prodrugs-cb1-receptor.html