Combined Squalene and Tocotrienol-Rich Fraction Attenuates oxLDL-Induced Endothelial Dysfunction Through Modulation...

Atherosclerosis is the principal underlying pathology of cardiovascular diseases (CVDs), with endothelial dysfunction representing one of the earliest events in its initiation and progression. Oxidised low-density lipoprotein (oxLDL) plays a pivotal role in this process by promoting inflammatory activation and endothelial dysfunction. Squalene and tocotrienol-rich fraction (SQTRF), both derived from palm oil, possess antioxidant and anti-inflammatory properties. However, their combined effects on endothelial dysfunction remain poorly understood. This study investigated the protective effects of SQTRF against oxLDL-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to oxLDL (50 μg/mL) and treated with SQTRF or TRF, with atorvastatin included as a positive control. Endothelial function was assessed by measuring cell viability, proliferation, migration, angiogenesis, and inflammatory gene expression using established in vitro assays and quantitative real-time PCR (qRT-PCR). OxLDL significantly enhanced endothelial migration and inflammatory gene expression without causing marked cytotoxicity. SQTRF preserved cell viability and significantly attenuated oxLDL-induced migration and angiogenesis. SQTRF demonstrated enhanced attenuation of endothelial proliferation and migration compared with TRF alone. These functional improvements were accompanied by downregulation of NF-κB, suggesting suppression of NF-κB-mediated inflammatory activation. Collectively, these findings demonstrate that SQTRF mitigates oxLDL-induced endothelial dysfunction through modulation of inflammatory and angiogenic responses. This study provides mechanistic evidence supporting the potential of SQTRF as a natural therapeutic candidate for attenuating early endothelial dysfunction associated with atherogenesis, warranting further validation in in vivo models and clinical studies.