Aspalathin-rich unfermented Aspalathus linearsis extract mitigates vascular endothelial inflammation by inhibiting the TNF-α/Hexokinase 2/NF-κB signaling pathway
Year: 2025
Type: article
Abstract: Inflammation of vascular endothelium initiates cardiovascular diseases. We investigated if unfermented green Aspalathus linearis (rooibos) extract (GRT) and its main flavonoid aspalathin may suppress inflammation in cardiovascular endothelial cells . Human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) were used as cell models, while β-aminopropionitrile (BAPN)-induced inflammation in mice was used as animal models . Tube formation assay, transwell migration assay, wound healing assay and monolayer permeability assay were used to examine the inflammatory effects on vascular endothelial cells , while cytokine array, qRT-PCR, ELISA , reporter gene assay, fluorescent microscopy, western blot , IHC staining and Seahorse mitochondrial analyzer were used to dissect the molecular mechanisms lying underneath. TNF-α decreased angiogenesis and VE-cadherin expression but increased cellular migration, monolayer permeability, secretion of inflammation cytokines IL-6 and IL-8, as well as NF-κB activity in HCAEC and HUVEC cells. Treatment with GRT or aspalathin reversed these TNF-α-induced inflammatory effects. We discovered that hexokinase 2 (HK2) was essential in regulation of TNF-α-induced inflammation in vascular endothelial cells, but was inhibited by GRT or aspalathin. Overexpression of HK2 induced NF-κB phosphorylation, activity and inflammatory effects. However, these phenomenon was repressed by GRT, aspalathin or HK2 knockdown. GRT or aspalathin reversed the TNF-α-enhanced interaction between HK2 and YB-1, vimentin or drebrin . Gavage of GRT repressed the expression of IL-6 and HK-2 in aortic tissues in BAPN-induced inflammation murine model . Our study demonstrated that GRT or aspalathin can suppress the TNF-α-induced inflammation in human vascular endothelial cells via inhibition of TNF-α/HK2/NF-κB signaling axis.
Institutions: National Health Research Institutes, Wan Fang Hospital, Taipei Medical University, South African Medical Research Council, University of Zululand, Stellenbosch University, National Sun Yat-sen University, Institute for Deciduous Fruit, Vines and Wine, National Chung Hsing University, China Medical University, National Central University
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,530
OpenAlex ID: W4409150136