Effect of diosmin and diosmetin on the level of pro-inflammatory factors in the endothelium artificially induced with inflammatory stimuli

Introduction: Diosmin and its aglycone diosmetin are phlebotropic drugs used in the treatment of chronic venous insufficiency (CVI). Diosmin increases the elasticity and tension of blood vessel walls, exhibits an antiedematous effect, and acts as an anti-inflammatory agent. As it is commonly known that the endothelium layer plays a significant role in the physiology and pathophysiology of the cardiovascular system, this paper investigates the effect of diosmin and diosmetin on modulating the levels of pro-inflammatory factors in an endothelial cell culture (HUVEC) stimulated by lipopolysaccharide (LPS) or phorbol (PMA).Material and methods: A normal human umbilical vein/vascular endothelium cell line HUV-EC-C (HUVEC) was stimulated with lipopolysaccharide (LPS) or phorbol 12-myristate-13-acetate (PMA). Cell viability was assessed using NR and MTT assays. The levels of human IL-10, IL-6, IL-10, COX-2, and PGE2 were measured using ELISA kits.Results: Depending on the agent used to initiate inflammation, different levels of factors associated with this state were obtained. Diosmetin significantly decreased the levels of pro-inflammatory IL-10 and IL-6 as well as COX-2 in PMA-treated cells. Meanwhile, diosmin did not affect the interleukins but it lowered COX-2 and increased PGE-2. Upon the LPS stimulation of HUVEC cells, diosmetin increased the levels of PGE2, IL-10, COX-2, and nitric oxide (NO), while diosmin increased NO and IL-6.Conclusion: Diosmin and diosmetin have different impacts on the levels of pro-inflammatory factors depending on the inflammation inducer. Diosmetin more effectively modulated inflammation than diosmin, suggesting that the attachment of the sugar moiety to the aglycone attenuates its activity.