Effect of a rosmarinic acid supplemented hemodialysis fluid on inflammation of human vascular endothelial cells

Abstract

Chronic systemic inflammation and repetitive damage of vascular endothelia by incompatible dialysis system are probable causes of cardiovascular disease in patients on dialysis. The present study aimed to assess in vitro biocompatibility and anti-inflammatory effect of hemodialysis fluid supplemented with rosmarinic acid (RA) using human umbilical vein endothelial cells (HUVEC). HUVECs (5×106 cells/mL) were pre-exposed to 1 μg/mL of lipopolysaccharides (LPS) and incubated with RA-supplemented hemodialysis fluid (HDF). Cytotoxicity was assessed qualitatively by morphologic assessment and quantitatively by MTT assay. Expressions of proinflammatory mediators were assessed using quantitative real-time PCR and production of NO was quantified. Phosphorylation of AKT and nuclear localization of nuclear factor kappa B (NF-κB) were examined using western blotting. Exposure of HUVECs to RA-supplemented HDF had no influence on morphology and viability. Inhibition of proinflammatory mediator production in HUVECs by RA supplementation to HDF was significant in a dose-dependent manner. Exposure to RA-supplemented HDF resulted in a decrease in nitric oxide synthase expression and reduction of NO production in LPS-stimulated HUVECs. RA supplementation of HDF suppressed Akt activation in LPS-stimulated HUVECs. In addition, the level of cellular IκB was increased in parallel to a reduced nuclear translocation of NF-κB in LPS-induced endothelial cells. Our results suggest that RA-supplemented HDF is biocompatible and significantly suppressed inflammation induced in endothelial cells. In this respect, the use of HDF supplemented with RA could alleviate inflammation and improve long-term treatment of patients with renal failure on dialysis. Further clinical studies are required to confirm the effects.

A Review of the Anti-Inflammatory Effects of Rosmarinic Acid on Inflammatory Diseases

“…Using HDF to supplement RosA could reduce inflammation and ameliorate long-term treatment in patients with dialysis-induced renal failure. (Wang et al, 2017) Cardiac I/R injury RosA pretreatment suppressed the expressions of inflammatory cytokines (IL-6, TNF-a, and CRP), upregulated PPARg level and downregulated NF-kB level. RosA attenuated heart damage by activating PPARg and downregulating NF-kBmediated pathways, thereby suppressing inflammation and cardiomyocyte apoptosis in cardiac I/R injury models.…”

Implication of dietary phenolic acids on inflammation in cardiovascular disease

“…In a left anterior descending coronary artery ligation myocardial infarction model, rosmarinic acid ameliorates cardiac dysfunction and fibrosis, likely due to modulation of ACE expression and ACE2 expression via the AT1R/p38 MAPK pathway . Wang et al (2017) investigated the anti-inflammatory effects and in vitro biocompatibility of rosmarinic acid supplemented hemodialysis fluid in a HUVECs model. Rosmarinic acid inhibits proinflammatory mediator production in a dose-dependent manner.…”

Rosmarinic Acid Inhibits Platelet Aggregation and Neointimal Hyperplasia In Vivo and Vascular Smooth Muscle Cell Dedifferentiation, Proliferation, and Migration In Vitro via Activation of the Keap1-Nrf2-ARE Antioxidant System

“…Rosmarinic acid (RA) is a natural metabolite and phenolic acid compound mainly found in Lamiaceae and Boraginaceae medicinal plants, such as rosemary, spearmint, lemon balm, and salvia . RA exhibits a wide range of pharmacological effects such as protecting vascular endothelial cells, inhibiting platelet aggregation, anti-inflammatory, antioxidant, preventing ischemia reperfusion-induced myocardial damage, as well as related cardiovascular diseases. − In vivo studies have also confirmed that RA inhibits fibrinolysis and exhibits antithrombotic effects . Furthermore, it inhibits human umbilical vein endothelial cell proliferation, migration, adhesion; blood vessel formation; and other angiogenesis processes, while reducing intracellular reactive oxygen species (ROS) .…”