Saponins from Allium macrostemon Bulbs Attenuate Endothelial Inflammation and Acute Lung Injury via the NF-κB/VCAM-1 Pathway

Abstract

Endothelial inflammation is a multifaceted physiological process that plays a pivotal role in the pathogenesis and progression of diverse diseases, encompassing but not limited to acute lung infections like COVID-19, coronary artery disease, stroke, sepsis, metabolic syndrome, certain malignancies, and even psychiatric disorders such as depression. This inflammatory response is characterized by augmented expression of adhesion molecules and secretion of pro-inflammatory cytokines. In this study, we discovered that saponins from Allium macrostemon bulbs (SAMB) effectively inhibited inflammation in human umbilical vein endothelial cells induced by the exogenous inflammatory mediator lipopolysaccharide or the endogenous inflammatory mediator tumor necrosis factor-α, as evidenced by a significant reduction in the expression of pro-inflammatory factors and vascular cell adhesion molecule-1 (VCAM-1) with decreased monocyte adhesion. By employing the NF-κB inhibitor BAY-117082, we demonstrated that the inhibitory effect of SAMB on VCAM-1 expression may be attributed to the NF-κB pathway’s inactivation, as characterized by the suppressed IκBα degradation and NF-κB p65 phosphorylation. Subsequently, we employed a murine model of lipopolysaccharide-induced septic acute lung injury to substantiate the potential of SAMB in ameliorating endothelial inflammation and acute lung injury in vivo. These findings provide novel insight into potential preventive and therapeutic strategies for the clinical management of diseases associated with endothelial inflammation.

Saponins from Allii Macrostemonis Bulbus attenuate atherosclerosis by inhibiting macrophage foam cell formation and inflammation

“…Of note, endothelial dysfunction is recognized as an underlying cause of atherosclerosis. The anti-atherosclerotic action of SAMB may also be attributed to its inhibitory role on endothelial dysfunction, which was possibly supported by the suppressive impact of SAMB on VCAM-1 expression in endothelial cells 42 . Thus, further studies detecting endothelial dysfunction markers such as ZO-1, ICAM-1, and VCAM-1 in the aortic roots by immunofluorescence staining are recommended.…”

“…SAMB significantly reduced phosphorylated NF-κB p65 and the levels of pro-inflammatory factors, including IL-6, TNF-α, and IL-1β in LPS-treated BMDMs. Indeed, we previously utilized the NF-κB inhibitor BAY-117082 to investigate whether SAMB achieved anti-inflammatory effects by inhibiting NF-κB signaling in human umbilical vein endothelial cells (HUVECs) 42 . Our findings suggested that SAMB's downregulation of VCAM-1 expression in endothelial cells, a key inflammatory factor, may be attributed to the inhibition of the NF-κB pathway 42 .…”

“…Indeed, we previously utilized the NF-κB inhibitor BAY-117082 to investigate whether SAMB achieved anti-inflammatory effects by inhibiting NF-κB signaling in human umbilical vein endothelial cells (HUVECs) 42 . Our findings suggested that SAMB's downregulation of VCAM-1 expression in endothelial cells, a key inflammatory factor, may be attributed to the inhibition of the NF-κB pathway 42 . These results also allow us to speculate that SAMB may exert a similar anti-inflammatory action by inhibiting the NF-κB pathway in BMDMs.…”

“…As a class B scavenger receptor family member, CD36 can recognize various endogenously derived hazardous molecules (e.g., ox-LDL), thereby triggering the initiation of sterile inflammation 43 . CD36 is implicated in priming and activating NLRP3 inflammasome 42 , 43 . Sheedy et al demonstrated that macrophage CD36 sequestered ox-LDL, leading to the activation of NF-κB downstream of the heterotrimeric CD36-TLR4-TLR6 complex, thereby inducing up-regulation of NF-κB-driven NLRP3 expression 44 .…”