Combined Squalene and Tocotrienol-Rich Fraction Attenuates oxLDL-Induced Endothelial Dysfunction Through Modulation of NF-κB–Associated Inflammatory Signalling

Abstract

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.