Hydroxysafflor yellow A suppresses oxidized low density lipoprotein induced proliferation of vascular smooth muscle cells

Abstract

To investigate the relationship between the suppression of hydroxysafflor yellow A (HSYA) on the oxidized low density lipoprotein (ox-LDL) induced proliferation of vascular smooth muscle cells (VSMCs) and the mRNA and protein expression of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and mitogen activated protein kinase phospholipase-1 (MAKP-1), VSMCs were treated with HSYA at 10 μmol/L and/or ox-LDL at 35 mg/L for 48 hours. MTT assay was done to measure cell survival rate, flow cytometry to detect cell cycle, reverse transcription PCR and Western blot to detect the expression of ERK1/2 and MAKP-1. When compared to cells treated with ox-LDL alone, the survival rate of cells treated with two reagents was reduced and the proportion of cells in G0/G1 phase significantly increased, with increased MKP-1 expression. The study suggests HSYA can inhibit VSMC proliferation via increasing MKP-1 expression, reducing p-ERK1/2 activity and suppressing cell cycle. Article Info

Therapeutic Potential of Hydroxysafflor Yellow A on Cardio-Cerebrovascular Diseases

“…In ox-LDL-induced foamy macrophages, HSYA displayed obvious repairing effects on the de novo fatty acid biosynthesis pathway, among which oleoyl-(acyl-carrier-protein) hydrolase was postulated to be a target of HSYA (Wei et al, 2018). HSYA also exerted protective effects against ox-LDL-induced VSMCs proliferation via increasing mitogen-activated protein kinase phospholipase-1 expression and the proportion of cells in the G0/ G1 phase, followed by reducing p-extracellular regulated protein kinases activity (Sheng et al, 2012). Moreover, HSYA has been shown to significantly improve ox-LDL-induced human endothelial injury, partially via the anti-apoptotic effect of the mitochondrial membranous voltage-dependent anion-selective channel protein 2 (Ye et al, 2017).…”

“…Induces relaxation in endothelium-intact/endotheliumprecontracted aortas precontracted by phenylephrine (Zhang et al, 2011) CaCl 2 -precontracted thoracic aorta rings of male Wistar rats 20 mmol•L -1 / Reduces Ca 2+ influx and inhibits inositol 1,4,5-triphosphate receptor (Zhang et al, 2011) U46619-induced mesenteric arteries of male Wistar rats 1-100 mmol•L -1 / Reverses the constriction, promotes Ca 2+ influx, eNOS phosphorylation and NO production (Yang et al, 2020) (Continued) Human THP-1 monocytes 400-800 mmol•L -1 / Induces an autophagic response via the PI3K/Akt/mTOR signaling pathway and inhibits inflammation by ROS (Jiang et al, 2017) Human coronary artery endothelial cells injury model 200-1600 mmol•L -1 / Up-regulates the eNOS gene and protein expression, increases NO release, inhibits lactate dehydrogenase release and down-regulates LDL receptor 1 expression (Miao et al, 2019) TNF-a-stimulated primary mouse kidney arterial endothelial cells and RAW264.7 macrophage cells 120 mmol•L -1 / Inhibits the TNF-a receptor type 1-mediated classical NF-kB pathway (Wang H. F. et al, 2016) Ox-LDL-induced foamy macrophages 65.30 mmol•L -1 / Up-regulates the abnormal metabolism of C12:0, C14:0, C18:1 (Wei et al, 2018) Ox-LDL-induced human endothelial cells 1, 5, 25 mmol•L -1 / Inhibits cell apoptosis by voltage-dependent anion-selective channel protein 2 (Ye et al, 2017) Ox-LDL-induced VSMCs 10 mmol•L -1 / Increases mitogen-activated protein kinase phospholipase-1 expression and the proportion of cells in G0/G1 phase, reduces p-extracellular signal-regulated protein kinase 1/2 activity, and suppresses cell cycle (Sheng et al, 2012) PAF-induced WRP suspension of male New Zealand white rabbits 250-1470 mmol•L -1 / Inhibits PAF binding to WRP receptors (Zang et al, 2002) PAF-induced WRP suspension of male New Zealand white rabbits IC 50 = 990 mmol•L -1 / Reduces PAF-mediated WRP aggregation (Zang et al, 2002) PAF-induced polymorphonuclear leukocytes suspension of male New Zealand white rabbits IC 50 = 700 mmol•L -1 / Reduces PAF-mediated polymorphonuclear leukocytes aggregation (Zang et al, 2002) Vascular Injury Diseases…”