Valencene ameliorates ox-LDL induced foam cell formation by suppressing inflammation and modulating key proteins involved in the atherogenesis on THP-1 derived macrophages

Abstract

Atherosclerosis is a distinct risk factor for cardiovascular and cerebrovascular disorders, which are significant contributors to global mortality. It is defined by macrophage-derived foam cell development followed by persistent inflammation, plaque formation, fibrosis and thrombosis. Studies have shown valencene, a sesquiterpene obtained from Valencia oranges, has several health-promoting properties. However, its protective effect against atherosclerosis and foam cell models remains unexplored. The present investigation revealed that valencene treatment suppresses foam cell generation and accumulation of lipids in THP-1-derived cells macrophage models activated with oxidized low-density lipoprotein (ox-LDL), maintained in vitro. The intracellular lipid content was qualitatively and semi-quantitatively analyzed by Oil Red O staining, and the compound's cytotoxicity was assessed through the MTT assay, considering both time-dependent and dose-dependent factors. The RT-qPCR results showed promising anti-inflammatory and anti-oxidant enzyme status upon valencene treatment. The H2DCFDA staining revealed valencene's ability to reduce the oxidative stress induced by ox-LDL. Further, high-throughput proteomic profiling was carried out to identify the target proteins affected by valencene treatment and thereby explore its mechanism of action on foam cell models. Proteomic studies revealed that valencene treatment regulates the expression of several proteins associated with ox-LDL-induced inflammation, defective cholesterol homeostasis and cholesterol efflux pathways.