Puerarin Inhibits Adhesion Molecule Expression in TNF-α-Stimulated Human Endothelial Cells via Modulation of the Nuclear Factor ĸB Pathway

Abstract

Background: The isoflavone puerarin is the most abundant isoflavone-C-glucoside extracted from the root (radix puerariae) of the plant Pueraria lobata and possesses many biological activities. In this report, the ability of puerarin to modulate intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial leukocyte adhesion molecule 1 (E-selectin), and to induce changes in the nuclear factor ĸB (NF-ĸB) pathway in human umbilical vein endothelial cells (HUVECs) was examined. Methods: The protein and mRNA levels of tumor-necrosis-factor-α (TNF-α)-induced ICAM-1, VCAM-1 and E-selectin were determined in HUVECs. Inhibitor ĸB (I-ĸB) phosphorylation and p65 NF-ĸB expression in HUVECs were also examined. Results: Puerarin inhibited the expression of TNF-α-induced ICAM-1, VCAM-1 and E-selectin proteins and mRNAs in HUVECs. Subsequently, we determined that the inhibition of ICAM-1, VCAM-1 and E-selectin expression was due to a dose-dependent suppression of phosphorylation and degradation of I-ĸB, which resulted in a reduction of p65 NF-ĸB nuclear translocation. Conclusion: These data suggested that the effect of puerarin-mediated inhibition of TNF-α-induced ICAM-1, VCAM-1 and E-selectin expression is attributed to suppressed NF-ĸB activation on the transcriptional level.

Suppressive Effects of Puerariae Radix on the Breast Tumor Incidence in Rats Treated with DMBA

“…ICAM-1 is a multi-functional transmembrane protein, well known for its importance in stabilizing cell-cell interactions, proliferation, and adhesion (Kotteas et al, 2014). Previous studies have indicated that the inhibitory effects of puerarin on ICAM-1 expression were found to not only exist in human umbilical vein endothelial cells (Hu et al, 2010), but also to limit early-stage renal damage in diabetic rats (Pan et al, 2015). The present study showed that PR decreased the levels of ICAM-1 in DMBA-induced breast tumors in rats, an observation supported by the studies described previously.…”

Paeoniflorin attenuates hepatic ischemia/reperfusion injury via anti-oxidative, anti-inflammatory and anti-apoptotic pathways

“…Furthermore, TNF-α may stimulate monocytes and macrophages to secrete IL-1, which in turn further induces the production of TNF-α (8). Following excessive TNF-α production in the acute phase of HI/R injury, due to toxic stimulation within the body, IL-1 serves as a pro-inflammatory cytokine that activates various immune and inflammatory cells (9). The levels of IL-1 not only reflect the extent of the inflammatory response, but also direct clinical treatment (9).…”

“…Following excessive TNF-α production in the acute phase of HI/R injury, due to toxic stimulation within the body, IL-1 serves as a pro-inflammatory cytokine that activates various immune and inflammatory cells (9). The levels of IL-1 not only reflect the extent of the inflammatory response, but also direct clinical treatment (9). IL-6 is secreted by activated macrophages, lymphocytes and epithelial cells, and may be induced by IL-1β and TNF-α (10).…”

Metabolic profile of puerarin in rats after intragastric administration of puerarin solid lipid nanoparticles

“…7 In diet-induced hypercholesterolemic rats, puerarin markedly reduces the total cholesterol by the promotion of cholesterol and bile acid excretion in the liver. 6 Puerarin also improves endothelial function by inhibiting cellular factors, such as adhesive molecules 8 and C-reactive protein, 9 and stimulating endothelial nitric oxide synthase phosphorylation and nitric oxide production via activation of an estrogen receptor-mediated phosphatidylinositol 3-kinase/Akt-and calmodulin-dependent kinase II/AMP-activated protein kinase-dependent pathway. Understanding the metabolic pathway of puerarin will contribute to our understanding of its therapeutic as well as toxic effects.…”