Drimenol, isodrimeninol and polygodial isolated from Drimys winteri reduce monocyte adhesion to stimulated human endothelial cells. (December 2020)

• Record Type: Journal Article
• Authors: Burgos, Viviana; Paz, Cristian; Saavedra, Kathleen; Saavedra, Nicolás; Foglio, Mary Ann; Salazar, Luis A.
• Is Part Of: Food and chemical toxicology. Volume 146(2020)
• Publication Date: 2020-12
• Subjects: Drimys winteri -- Drimane sesquiterpenoids -- Adhesion molecules VCAM1 and ICAM1 -- Endothelial cells; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2020.111775
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: 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 VCAM1 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. Highlights: The sesquiterpenoids Drimenol, Polygodial and Isodrimeninol were isolated from barks of the Chilean native tree Drimys winteri. Drimys winteri, Drimenol, Polygodial and Isodrimeninol reduced the monocyte adhesion to HUVECs at 10 μg/mL. Drimys winteri, Drimenol, Polygodial and Isodrimeninol reduced gene and protein expression of VCAM-1 at 10 μg/mL. Drimys winteri and Polygodial reduced the protein expression of ICAM-1 at 10 μg/mL.