Antiatherosclerotic Effect of Korean Red Ginseng Extract Involves Regulator of G-Protein Signaling 5

Eun Ju Im,Sung Dae Kim,Taddesse Yayeh,Seung-Bok Hong,Young Min Son,Youn-Kyoung Goo,Sang-Joon Park,Seung-Hyung Kim,Man Hee Rhee

doi:10.1155/2014/985174

Abstract

Regulator of G-protein signaling 5 (RGS5), an inhibitor of Gα(q) and Gα(i) activation, has been reported to have antiatherosclerosis. Previous studies showed antiatherosclerotic effect of Korean red ginseng water extract (KRGE) via multiple signaling pathways. However, potential protective effect of KRGE through RGS5 expression has not been elucidated. Here, we investigated the antiatherosclerotic effect of KRGE in vivo and in vitro and its role on RGS5 mRNA expression. Elevated levels of total cholesterol, lactate dehydrogenase (LDH), and triglyceride (TG) in western diet groups of low-density lipoprotein receptor deficient LDLr−/− mice were reversed by oral administration of KRGE. KRGE suppressed transcriptional activity of tumor necrotic factor alpha (TNF-α), interleukin-6 (IL-6), and leptin in adipose tissue. It also potently repressed western diet-induced atheroma formation in aortic sinus. While KRGE showed reduced mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, IL-6, and TNF-α in LPS-stimulated RAW264.7 cells, it enhanced mRNA expression of RGS5. Moreover, RGS5 siRNA transfection of microglia cells pretreated with KRGE reversed its inhibitory effect on the expression of iNOS, COX-2, and IL-1β mRNA. In conclusion, KRGE showed antiatherosclerotic and anti-inflammatory effects in western diet fed LDLr−/− mice and this effect could partly be mediated by RGS5 expression.

Highlights

Cardiovascular diseases (CVD) have reached epidemic proportion in Western and Asian societies due to urbanization, economic growth, and irregular timing of meals
We investigated that Korean red ginseng water extract (KRGE) impaired the development of atherosclerosis in low-density lipoprotein (LDL) receptor deficient (LDLr−/−) mice fed with western diet (WD), and this event was involved by Regulator of G-protein signaling 5 (RGS5) mRNA expression
The levels of total cholesterol (T-CHOL), LDL, and TG were increased dramatically in LDLr−/− mice fed with WD; KRGE treatments at 50 and 200 mg/kg/day showed a significant reduction in the level of lipid profiles and lactate dehydrogenase (LDH) after 13 weeks compared to the WD group (Figures 1(a)–1(c))

Summary

Introduction

Cardiovascular diseases (CVD) have reached epidemic proportion in Western and Asian societies due to urbanization, economic growth, and irregular timing of meals. Atherosclerosis initiated when cholesterolcontaining low-density lipoproteins activate the endothelium to express leukocyte adhesion molecules (intracellular adhesion molecule-1 (ICAM-1) [2] and vascular adhesion molecule-1 (VAM-1) [3] and chemokines like macrophage chemoattractant protein-1 (MCP-1) [4]) that promote the Evidence-Based Complementary and Alternative Medicine recruitment of monocytes and T cells into atherosclerotic prone sites in aortic and carotid arteries [5]. While low-density lipoprotein (LDL) is associated with the formation of fatty streaks and subsequent plaque formation, high-density lipoprotein (HDL) removes excess cholesterol from peripheral tissues and prevents oxidation of LDL. It is the imbalance of these two lipoproteins in the serum that leads to the development of atherosclerotic lesions at the predilection sites in large arteries [9]. Adipokines and cytokines are critically involved in the initiation and perpetuation of atherosclerosis [10]

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