Glabridin attenuates endothelial dysfunction and permeability, possibly via the MLCK/p‑MLC signaling pathway

Abstract

Atherosclerosis is caused by various factors, and Glabridin may have protective effects on the cardiovascular system. The purpose of the present study was to evaluate the effects of Glabridin on atherosclerosis and evaluate whether Glabridin attenuates arteriosclerosis and endothelial permeability by suppressing the myosin light chain (MLC) kinase (MLCK)/phosphorylated (p)-MLC system via the mitogen activated protein kinase (MAPK) signaling pathway. Male New Zealand rabbits were randomly divided into 3 groups: The control group was administered an ordinary diet, whereas the high fat group and the Glabridin (2 mg/kg/d) intervention group were administered a high fat diet. Following 12 weeks, the blood lipid levels of rabbits, the morphological structure of the arterial wall, the arterial intimal permeability, the endothelial function and the mRNA levels of MLCK were measured. Western blot analysis was used to detect the levels of MLCK, p-c-Jun N-terminal kinase (JNK), p-extracellular signal regulated kinase (ERK), and p-p38. The high-fat diet group exhibited significantly increased total cholesterol and triglycerides, and endothelial dysfunction, which were attenuated by Glabridin treatment. Notably, the aortic endothelial permeability was increased in the high-fat diet group but was ameliorated in the Glabridin treatment group. Hyperlipidemia enhanced the expression of p-MLC and MLCK, which were associated with the increased phosphorylation of ERK, p38 and JNK. These changes were also ameliorated by Glabridin. In conclusion, the results of the present study suggested that atherosclerosis may be associated with upregulated MLCK expression and activity, which was downregulated by Glabridin. The mechanism of action of Glabridin was thought to proceed through modulating MAPK pathway signal transduction. However, further studies are required to adequately illuminate the exact regulatory mechanisms involved.

Mechanism of Baoyuan Decoction in the Treatment of Chronic Heart Failure Based on Network Pharmacology

“…NLR family pyrin domain containing 3 (NLRP3) pathway inhibits the activation of NLRP3 protein, thereby exerting anti-inflammatory and improving heart function [16,17] ; Glaxo down-regulates the expression and activity of Myosin Light Chain Kinase (MLCK) through the MAPK pathway, reduces arterial intimal permeability, improves vascular endothelial function and then exerts a protective effect on the cardiovascular system [18] . It can also inhibit Low-Density Lipoprotein (LDL) oxidation and Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase, increase the expression of antioxidant enzymes in macrophages, stimulate DNA synthesis in endothelial cells, inhibit the proliferation of vascular smooth muscle and exert antioxidant effects to improve heart function [19] . It shows that the material basis of Baoyuan decoction for treating CHF is mainly flavonoids such as quercetin and naringenin.…”

Preventive Effects of Thinned Apple Extracts on TNF-α-Induced Intestinal Tight Junction Dysfunction in Caco-2 Cells through Myosin Light Chain Kinase Suppression

“…Previous studies have reported that MLC phosphorylation, which is activated by MLCK, generates TJ deterioration, and MLCK pathway activation is involved in NF-κB activation [ 13 , 37 ]. The translocation of the NF-κB subunit from the cytosol to the nucleus accelerates the synthesis of MLCK at the transcriptional level [ 13 , 19 , 37 , 38 ]. Therefore, we concluded that TNF-α disrupted TJ integrity by increasing MLCK expression through NF-κB activation; however, TAE inhibited TNF-α’s action, thus maintaining TJ integrity [ 5 ].…”

Inhibition of microRNA‐103 attenuates inflammation and endoplasmic reticulum stress in atherosclerosis through disrupting the PTEN‐mediated MAPK signaling

“…Although there are many studies on PTEN and AS or MAPK and AS alone (Q. Chen et al, ; F. P. Li et al, ; J. Li et al, ; Ma et al, ; Reustle & Torzewski, ; Wang et al, ), there is no systematic study on the relationship among miR‐103, PTEN and MAPK signaling. Our research explained the relationship between miR‐103, PTEN, MAPK, and ER stress more comprehensively.…”