Shuangshen Xionglian Granule ameliorates atherosclerosis through combined lipid-lowering, anti-inflammatory, and anti-EndMT actions via restoration of FGFR1 phosphorylation and concomitant downregulation of TGF-β/Smad2 signaling.
SSXL ameliorated dyslipidemia and reduced systemic inflammation in high-fat diet-fed ApoE-/- mice.
SSXL alleviated aortic plaque burden in ApoE-/- mice fed a high-fat diet.
An integrated multi-omics approach identified 401 SSXL-responsive disease-associated genes enriched in TGF-β, MAPK, cAMP, and extracellular matrix organization pathways.
SSXL preserved endothelial identity and suppressed endothelial-to-mesenchymal transition (EndMT) in both aortic tissues and human aortic endothelial cells.
SSXL mechanistically restored FGFR1 phosphorylation while downregulating TGF-βRI/TGF-β2 expression and Smad2 phosphorylation.
Pharmacological inhibition of FGFR1 with PD173074 partially abrogated the protective effects of SSXL, confirming FGFR1-mediated suppression of TGF-β/Smad2 signaling as a mechanism of action.
SSXL is a multi-herb traditional Chinese medicine formulation investigated for its multi-target therapeutic potential in atherosclerosis.
This research investigated how a traditional Chinese herbal medicine called Shuangshen Xionglian Granule (SSXL) might protect against atherosclerosis, the buildup of plaques in arteries that can lead to heart attacks and strokes. Using mice genetically prone to atherosclerosis and fed a high-fat diet, the researchers found that SSXL reduced blood lipid levels, lowered inflammation, and reduced the size of arterial plaques. They also studied the drug's effects on human artery cells in the laboratory. To understand how SSXL works, the team used advanced chemical analysis, computer-based drug target prediction, and gene expression analysis together, identifying 401 genes that respond to SSXL treatment and mapping out the biological pathways involved. A key focus of the study was a process called endothelial-to-mesenchymal transition (EndMT), where the cells lining blood vessels lose their normal identity and transform into a different cell type, contributing to plaque formation and arterial stiffening. The researchers found that SSXL blocked this harmful transformation in both mouse aortas and human artery cells. Mechanistically, SSXL appeared to work by reactivating a protective protein called FGFR1 while simultaneously suppressing a pro-disease signaling pathway called TGF-β/Smad2. When the researchers chemically blocked FGFR1, the protective effects of SSXL were reduced, confirming this protein plays an important role in how the medicine works. This research suggests that SSXL may combat atherosclerosis through multiple simultaneous mechanisms — lowering lipids, reducing inflammation, and blocking harmful changes in artery-lining cells — all centered on the FGFR1 and TGF-β/Smad2 signaling pathway. These findings are notable because atherosclerosis is a complex disease that is difficult to treat with single-target drugs, and a multi-target approach may offer advantages. However, this study was conducted in animals and cell cultures, and further research in humans would be needed to understand whether SSXL could be clinically beneficial.
Cui X, Luo H, Zhang R, Chen Y, Li H, Gao J, et al.. (2026). Mechanism of Shuangshen Xionglian Granule in Attenuating EndMT in Atherosclerosis via the FGFR1-TGF-β/Smad2 Axis.. Molecular nutrition & food research. https://doi.org/10.1002/mnfr.70597