Ischemic heart disease (IHD) was identified by the World Health Organization (WHO) as the leading global cause of death [32]. Atherosclerosis, which is a pathological process characterized by the accumulation of fatty deposits and inflammation within arterial walls is the primary cause of IHD [12]. In the early stage of atherosclerosis, inflammation occurs in the endothelial cells lining the blood vessels [7]. This inflammatory process can be caused by tumor necrosis factor-α (TNF-α), which is a key pro-inflammatory cytokine in atherosclerosis [26].

Activation of endothelial cells by TNF- α may result in increased expression of cell adhesion molecules such as intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cell surfaces [16]. These adhesion molecules facilitate the migration of monocyte into the tunica intima by binding with its ligands [16]. Monocyte chemoattractant protein-1 (MCP-1) further accelerates atherosclerosis progression by potently attracting and activating leukocytes, particularly monocytes [28].

Nuclear factor-kappa B (NF-κB) is a family of pro-inflammatory transcription factors. TNF-α-mediated signal transduction to NF-κB serves as a central pathway connecting activated leukocytes and endothelium [4]. TNF-α triggers the canonical NF-κB cell signaling pathway by activating IκB kinase (IKK), leading to the phosphorylation and degradation of the NF-κB inhibitor (IκB). This results in NF-κB dimers moving from the cytoplasm to the nucleus, binding to specific promoter regions of target genes, and regulating their transcription [4]. In endothelial cells, crucial NF-κB target genes are adhesion molecules, including ICAM-1 and VCAM-1 [21]. Targeting the IKK/NF-κB cell signaling pathway or specific downstream genes offers a promising approach to effectively control or prevent chronic inflammatory diseases such as atherosclerosis [3].

Christia vespertilionis (L.f.) Bakh.f. (CV) from family Leguminosae (Fabaceae) is commonly known as Rerama leaves in Malaysia due to their butterfly-like leaf shape [30]). The Java-Melayu community in Parit Jelutong, Batu Pahat, Johor, Malaysia uses the infusion of CV leaves supplying energy and treating fever, cancer, hypertension and diabetes [10]. To date, CV has been shown to possess pharmacological effects such as anti-cancer [13], antioxidant [20], antidiabetic [20]and anti-plasmodial [31]. To the best of our knowledge, research on the anti-atherosclerotic effects of CV has not yet been investigated. However, studies have reported that compounds present in christia, such as orientin and isoorientin, have been shown to possess anti-atherogenic effects [11], [14]. This study is the first to explore the anti-atherogenic effect of CV extract on endothelial cells activated by TNF-α.