title: Ankaflavin and monascin regulate endothelial adhesion molecules and endothelial NO synthase (eNOS) expression induced by tumor necrosis factor-α (TNF-α) in human umbilical vein endothelial cells (HUVECs).
abstract: Previous studies have established that red mold rice can regulate blood pressure in spontaneously hypertensive rats (SHR) and that  Monascus -fermented products, including monacolin K, ankaflavin (AF), and monascin (MS), can inhibit expression of adhesion factors such as E-selectin and endothelin-1 to prevent human acute monocytic leukemia cell line THP-1 monocytes from adhering to human aortic endothelial cells. However, it remains unknown whether AF and MS act directly on human umbilical endothelial cells (HUVECs) to enhance nitric oxide (NO) synthesis through the stimulation of endothelial NO synthase (eNOS) expression. To address this knowledge gap, this study investigated whether AF and MS directly regulate NO synthesis and attenuate adhesion factor expression induced by treatment with tumor necrosis factor-α (TNF-α) in HUVECs. The results revealed that both AF and MS (20 μM) treatments promoted increases in eNOS expression and decreases in vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and endothelin-1 mRNA and protein expression resulting from 12 h of TNF-α treatment. These effects are attributed to the ability of AF and MS to inhibit extracellular signal-regulated protein kinase (ERK) phosphorylation and nuclear factor κB (NF-κB) translocation from the cytoplasm into the nucleus, thereby exerting antihypertensive activity.
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Wei-Hsuan
authors.initials: WH
authors.lastname: Hsu
authors.forename: Bao-Hong
authors.initials: BH
authors.lastname: Lee
authors.forename: I-Jen
authors.initials: IJ
authors.lastname: Lu
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Pan
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019040:E-Selectin / Q000235:genetics; D019332:Endothelin-1 / Q000235:genetics; D005415:Flavins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019332:Endothelin-1; D005415:Flavins; D006575:Heterocyclic Compounds, 3-Ring; D014409:Tumor Necrosis Factor-alpha; C499916:ankaflavin; D052250:Nitric Oxide Synthase Type III; C517880:monascin