Drimenol, isodrimeninol and polygodial isolated from Drimys winteri reduce monocyte adhesion to stimulated human endothelial cells

The vascular endothelium is a continuous monolayer of endothelial cells that are in direct contact with the blood and its dysfunction is the starting process in the development of many pathological inflammatory disorders, such as atherosclerosis, which can result in death. The expression of adhesion molecules such as vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1) is a key stage in modulating vascular inflammation, where the adhesion of monocytes and their transmigration into the intima starting a cascade of inflammatory reactions. Looking for natural compounds with inhibitory activity of VACM1 and ICAM1, we isolated drimenol, isodrimeninol and polygodial as the main secondary metabolites from barks of Drimys winteri (Dw) and evaluated their effects in the adhesion response of monocytes cells (THP1) to a monolayer of human umbilical vein endothelial cells (HUVEC) in coculture assays. The results showed that the molecules and total extract Dw decrease the adhesion of THP1 to HUVECs, at 10 μg/mL. The adhesion activity is explained due to the inhibition of VCAM1 and ICAM1 evidenced by qRT-PCR and Western-blot assays. In conclusion, drimane sesquiterpenoids could be used as a molecular scaffold in the development of drugs for inflammatory vascular diseases.

Keywords: Drimys winteri; adhesion molecules VCAM1 and ICAM1; drimane sesquiterpenoids; endothelial cells.