Abstract
Atherosclerosis is a cardiovascular disease that affects most people to at least some extent by old age. Many factors contribute to atherogenesis, and although it is extremely common, the mechanisms behind the pathogenesis of the disease remain poorly understood. Endothelial dysfunction is thought to be one of the main causes of atherosclerosis along with numerous other factors, such as oxidative stress and proinflammatory cytokine upregulation. The culmination of the complications that lead to atherogenesis is the formation of a fatty plaque on the intima of the arterial endothelium. In this study, we explore these aspects and others in regard to the treatment potential of dehydrocostus lactone (DHL), which is naturally occurring in certain flora such as the Saussurea lappa costus plant. Having long been used in traditional Chinese medicine, the effects of this plant are only just beginning to be studied by modern science. Among our most noteworthy findings are that DHL exerts an inhibitory effect against the increased expression of VCAM-1 and E-selectin induced by exposure to oxidized low-density lipoprotein (ox-LDL), which has been linked to the development and progression of atherosclerosis. The introduction of DHL also significantly diminished the downstream effects of VCAM-1 and E-selectin, such as the attachment of monocytes to the endothelium and the release of proinflammatory cytokines and chemokines, including TNF-α, MCP-1, and HMGB1. Furthermore, DHL is capable of rescuing the expression of KLF2, an important regulator of VCAM-1 and E-selectin expression. Together, our findings demonstrate the potential of DHL as a prophylactic or therapeutic treatment against ox-LDL-induced atherosclerosis via inhibition of the attachment of monocytes to endothelial cells.