Asiatic acid exhibits anti-inflammatory activities in human aortic endothelial cells

The early stage of atherogenesis is characterized by an increase in endothelial permeability and expression of cell adhesion molecules, which subsequently promotes the cell migration across the vascular endothelium. In this study, asiatic acid, also known as (2α,3β,4α)-2,3,23-Trihydroxy-urs-12-en-28-oic acid) was purchased from ChromaDex with purity of 93.7%. Asiatic acid, a triterpenoids derived from Centella asiatica, has been known to exhibit anti-cancer [1] and anti-diabetic activities [2]. However, its effect on endothelial barrier function has not been evaluated yet. We aimed to examine the effects of asiatic acid on tumor necrosis factor-α (TNF-α)-induced (i) endothelial hyperpermeability by using FITC-dextran permeability assay, (ii) increased level of soluble E selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1) by flow cytometry as well as (iii) increased attachment of monocytes (U937 cells) to endothelial cells by adhesion assay. Human aortic endothelial cells (HAECs) were pretreated with asiatic acid (40 – 10µM) for 6 hours followed by stimulation with TNF-α for 6 hours. Results showed that asiatic acid significantly inhibits (P < 0.05) increased permeability with the maximal suppression was shown at 40µM. Besides, cells pretreated with asiatic acid also suppressed the increased expression of sE-selectin and sICAM-1 in TNF-α treated HAECs. However, it fails to suppress TNF-α-induced monocyte adhesion to HAECs. In conclusion, asiatic acid improves endothelial dysfunction by inhibiting increased permeability and the soluble forms of cell adhesion molecules. Its anti-inflammatory effects however, did not involve reduction of the interaction between monocytes and endothelial cells.

Keywords: human aortic endothelial cell, asiatic acid, adhesion molecules, monocyte adhesion

References:

[1] Hsu YL, Kuo PL, Lin LT, and Lin CC. Asiatic Acid, a Triterpene, Induces Apoptosis and Cell Cycle Arrest through Activation of Extracellular Signal-Regulated Kinase and p38 Mitogen-Activated Protein Kinase Pathways in Human Breast Cancer Cells. J Pharmacol Exp There 2005; 313: 333 – 344

[2] Ramachandran V, Saravanan R, Senthilraja P. Antidiabetic and antihyperlipidemic activity of asiatic acid in diabetic rats, role of HMG CoA: in vivo and in silico approaches. Phytomedicine 2014; 21: 225 – 232