Anti-Inflammatory and Anti-Apoptotic Effects of Stybenpropol A on Human Umbilical Vein Endothelial Cells.

Li Zhang,Shumei Wang,Minghua Xian,Qiuming Liang,Feifei Wang,Feng Wang,Qing Zhang

doi:10.3390/ijms20215383

Abstract

Inflammation is a key mediator in the progression of atherosclerosis (AS). Benzoinum, a resin secreted from the bark of Styrax tonkinensis, has been widely used as a form of traditional Chinese medicine in clinical settings to enhance cardiovascular function, but the active components of the resin responsible for those pharmaceutical effects remain unclear. To better clarify these components, a new phenylpropane derivative termed stybenpropol A was isolated from benzoinum and characterized via comprehensive spectra a nalysis. We further assessed how this phenylpropane derivative affected treatment of human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α). Our results revealed that stybenpropol A reduced soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-8 (IL-8), and interleukin-1β (IL-1β) expression by ELISA, inhibited apoptosis, and accelerated nitric oxide (NO) release in TNF-α-treated HUVECs. We further found that stybenpropol A decreased VCAM-1, ICAM-1, Bax, and caspase-9 protein levels, and increased the protein levels of Bcl-2, IKK-β, and IκB-α. This study identified a new, natural phenylpropane derivative of benzoinum, and is the first to reveal its cytoprotective effects in the context of TNF-α-treated HUVECs via regulation of the NF-κB and caspase-9 signaling pathways.

Highlights

Atherosclerosis (AS) is a common driver of cardiovascular and cerebrovascular disease, resulting in high and rising rates of disability and mortality globally [1,2]
We found that tumor necrosis factor-α (TNF-α) treat5mofe1n2t markedly increased the secretions of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), IL-1β, and IL-8 by human umbilical vein endothelial cells (HUVECs), whereas the stybenpropol A pretreatment significantly reduced this upregulation (Figure 5A–D)
We provided novel evidence suggesting that stybenpropol A may protect TNF-α-stimulated HUVECs against inflammation and apoptosis, suppress the release of proinflammatory factors and soluble cell adhesion molecules, and promote the synthesis of nitric oxide (NO) by regulating the NF-κB and caspase-9 signaling pathways

Summary

Introduction

Atherosclerosis (AS) is a common driver of cardiovascular and cerebrovascular disease, resulting in high and rising rates of disability and mortality globally [1,2]. In the best-characterized model of such inflammation, the vascular–tone imbalance between endothelin-1 (ET-1) and nitric oxide (NO) in dysfunctional endothelial cells results in the increased expression of adhesion molecules and proinflammatory factors in the vascular wall [4,5,6]. These factors, in turn, drive cholesterol accumulation proinflammatory foam cell formation and driving AS. Inhibition of endothelial cell apoptosis and reductions in this iannfdlammomnoactyotreyexrterasvpaosnatsioenraecproresssethnet aartepriraolminitsiminag, stuabrsgeeqtuefnotrlycpornomstoratiinnginpgroitnhfleamomccautorrryence and developfmoaemntceolfl fAorSm. ation and driving AS Such inflammation-induced endothelial dysfunction and Statiitsnass(sHocMiatGed-CprooAgrarmedmuecdtcaeslel dienahthibairteokrse)y adrievetrhseofpAriSmaandryastshoecriaatpedeudtisiceaasegpenatthsoluosgeyd[7f–o9r].

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Discussion

Conclusion