Abstract
Endothelial cells are the fundamental components of blood vessels that regulate several physiological processes including immune responses, angiogenesis, and vascular tone. Endothelial dysfunction contributes to the development of various diseases such as acute lung injury, and endothelial inflammation is a vital part of endothelial dysfunction. Dauricine is an extract isolated from Menispermum dauricum DC, a traditional Chinese medical plant that can be used for pharyngitis. In this work, we found that IL-1β-induced overexpression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin was inhibited by dauricine in primary human umbilical vein endothelial cells (HUVECs). Correspondingly, adhesion of human acute monocytic leukemia cell line (THP-1) to HUVECs was decreased by dauricine. Further studies showed that dauricine inhibited the activation of nuclear factor-κB (NF-κB) pathway in HUVECs stimulated with IL-1β. In vivo, dauricine protected mice from lipopolysaccharide (LPS)-induced acute lung injury. In lung tissues, the activation of NF-κB pathway and the expression of its downstream genes (ICAM-1, VCAM-1, and E-selectin) were decreased by dauricine, consistent with what was found in vitro. In summary, we concluded that dauricine could alleviate endothelial inflammation by suppressing NF-κB pathway, which might serve as an effective candidate for diseases related with endothelial inflammation.
Highlights
The vascular endothelium forms the inner surface of the cardiovascular system
To investigate the effect of dauricine on endothelial cells, we first conducted the MTT assay to explore its cytotoxicity on human umbilical vein endothelial cells (HUVECs)
To explore the role of dauricine on IL-1β-induced endothelial inflammation, first, we assessed its function on monocyte–endothelial cell adhesion
Summary
The vascular endothelium forms the inner surface of the cardiovascular system. It is a natural blood–organ barrier and an endocrine tissue that plays pivotal roles in immune responses, angiogenesis, hemostasis, and the regulation of vascular tone (Boulanger, 2016; Sturtzel, 2017). Endothelial dysfunction has been noticed in various pathological states, including atherosclerosis, hypertension, kidney disease, and sepsis (Gimbrone and GarcíaCardeña, 2016; Konukoglu and Uzun, 2017; Jourde-Chiche et al, 2019; Joffre et al, 2020). Aggravated endothelial inflammation, which is characterized by overexpressed cytokines and adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and selectins (Konukoglu and Uzun, 2017), is an important pathological process in endothelial dysfunction. Several molecules and pathways that regulate endothelial inflammation have been elucidated, among which the classic nuclear factor-κB (NF-κB) proinflammatory pathway attracted wide attention (Brasier, 2010; Rao et al, 2019).
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