Korean Red Ginseng Water Extract Restores Impaired Endothelial Function by Inhibiting Arginase Activity in Aged Mice

Abstract

Cardiovascular disease is the prime cause of morbidity and mortality and the population ages that may contribute to increase in the occurrence of cardiovascular disease. Arginase upregulation is associated with impaired endothelial function in aged vascular system and thus may contribute to cardiovascular disease. According to recent research, Korean Red Ginseng water extract (KRGE) may reduce cardiovascular disease risk by improving vascular system health. The purpose of this study was to examine mechanisms contributing to age-related vascular endothelial dysfunction and to determine whether KRGE improves these functions in aged mice. Young (10±3 weeks) and aged (55±5 weeks) male mice (C57BL/6J) were orally administered 0, 10, or 20 mg/mouse/day of KRGE for 4 weeks. Animals were sacrificed and the aortas were removed. Endothelial arginase activity, nitric oxide (NO) generation and reactive oxygen species (ROS) production, endothelial nitric oxide synthase (eNOS) coupling, vascular tension, and plasma peroxynitrite production were measured. KRGE attenuated arginase activity, restored nitric oxide (NO) generation, reduced ROS production, and enhanced eNOS coupling in aged mice. KRGE also improved vascular tension in aged vessels, as indicated by increased acetylcholine-induced vasorelaxation and improved phenylephrine-stimulated vasoconstriction. Furthermore, KRGE prevented plasma peroxynitrite formation in aged mice, indicating reduced lipid peroxidation. These results suggest KRGE exerts vasoprotective effects by inhibiting arginase activity and augmenting NO signaling and may be a useful treatment for age-dependent vascular diseases.

Ginseng: An Nonnegligible Natural Remedy for Healthy Aging

“…In addition, KRG reduced plasma peroxynitrite production in aged mice, indicating decreased lipid peroxidation. These results suggest KRG exerts its vasoprotective effects by suppressing arginase activity and enhancing NO signaling [ 67 ]. However, cardiovascular remodeling due to age is by no means a uniform and generalized structural degeneration; rather, different components of the cardiovascular system may be affected heterogeneously [ 58 ].…”

Knockdown of transglutaminase-2 prevents early age-induced vascular changes in mice

“…In addition, elevated arterial pressure is known to relate to older ages in clinical and experimental settings 26 . Other aging studies, however, were performed on older animals when compared to our study, with ages ranging from 13 to 32 months [27][28][29][30] .…”

Phenolic Compounds as Arginase Inhibitors: New Insights Regarding Endothelial Dysfunction Treatment

“…A further two published studies that evaluated the use of the aqueous extract of Korean red ginseng [Panax ginseng C. A.Mey (Araliaceae)] to improve endothelial function impairment associated with age (in atherosclerosis models) reached similar conclusions; the extract (10-20 mg/mouse/day during 4-6 weeks) inhibited ARG activity in a nonselective manner, causing an increase in eNOS dimerisation and a consequent increase in NO levels, which strengthened the vasodilatation dependent on this mediator. Moreover, active components of Korean red ginseng (ginsenoside Rb1 and Rg3) have been linked to increased NO production in endothelial cells by the activation of the phosphoinositide 3-kinase (PI3K)/PKB intracellular pathway (also known as Akt, which is a serine/threonine-specific protein kinase) [91,92].…”