Asiaticoside inhibits tumor necrosis factor-alpha (TNF-α)-induced soluble adhesion molecules expression in human aortic endothelial cells (HAEC)

Introduction: Increase expression of cell adhesion molecules during endothelial dysfunction allows rolling and firm attachment of leukocytes before the cells migrating out from vessel wall. Therefore, the soluble form of adhesion molecules in human plasma serves as biological markers for endothelial function. Asiaticoside is one of the active compounds derived from Centella asiatica, which is a traditional medicinal plant. Anti-inflammatory and anti-pyretic activities of asiaticoside have been reported previously [1,2]. However, the effect of asiaticoside on endothelial function has not been evaluated yet.

Aim: This study aimed to investigate the effect of asiaticoside on expressions of soluble intercellular adhesion molecules-1 (sICAM-1) and soluble E-selectin (sE-selectin) as well as U937 monocyte adhesion induced by TNF-α in HAEC.

Method: HAECs were pretreated with asiaticoside (50 – 3.125µM) for 6 hrs before induced with TNF-α (10 ng/ml) for another 6 hrs. Levels of sICAM-1 and sE-selectin were determined by using multiplex kit and measured by flow cytometer. U937 monocyte adhesion assay was done by using BCECF-AM-labeled U937 cells co-cultured with HAEC.

Results: Asiaticoside significantly (P < 0.05) suppressed increased levels of sICAM-1 and sE-selectin caused by TNF-α. However, asiaticoside did not significantly attenuate TNF-α stimulated U937 monocyte adhesion to HAEC. Hereby, we propose that asiaticoside exhibits anti-inflammatory activity by decreasing the soluble forms of adhesion molecules released by endothelial cells but this does not lead to further suppression of TNF-α-induced monocyte adhesion. More in-depth studies are needed to explore the mechanism underlies the protective effect of asiaticoside on TNF-α-stimulated HAECs.

Keywords: human aortic endothelial cell, asiaticoside, cell adhesion molecules

References:

[1] Wan JY, Gong X, Jiang R, Zhang Z and Zhang L. Antipyretic and anti-inflammatory effects of asiaticoside in lipopolysaccharide-treated rat through up-regulation of heme oxygenase-1. Phytotherapy Research 2013; 27(8):1136 – 42.

[2] Yun KJ, Kim JY, Kim JB, Lee KW, Jeong SY, Park HJ, Jung HJ, Cho YW, Yun K, Lee KY. Inhibition of LPS-induced NO and PGE2 production by asiatic sicd via NF- κB inactivation in RAW 264.7 macrophages: Possible involvement of the IKK and MAPK pathways. International Immunopharmacology 2008; 8:431 – 441.