The Inhibitory Effect of Ojeoksan on Early and Advanced Atherosclerosis

• Published in: Nutrients 2018-09, Vol.10 (9), p.1256
• Main Authors: Han, Byung Hyuk, Seo, Chang Seob, Yoon, Jung Joo, Kim, Hye Yoom, Ahn, You Mee, Eun, So Young, Hong, Mi Hyeon, Lee, Jae Geon, Shin, Hyeun Kyoo, Lee, Ho Sub, Lee, Yun Jung, Kang, Dae Gill
• Format: Article
• Language: English
• Subjects: adhesion molecule; AKT protein; Animals; Aorta - drug effects; Aorta - metabolism; Aorta - pathology; Aortic Diseases - drug therapy; Aortic Diseases - genetics; Aortic Diseases - metabolism; Aortic Diseases - pathology; Apolipoprotein E; Apolipoproteins; Arteriosclerosis; Atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; Blood pressure; Cardiovascular disease; Cell adhesion & migration; Cell Adhesion Molecules - metabolism; Cells, Cultured; Chemical compounds; Cholesterol; Diet, Western; Disease Models, Animal; Disease Progression; E protein; Endothelial cells; Endothelium; Gene expression; GTP cyclohydrolase; Guanosine triphosphate; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hyperlipidemia; Hypertension; In vivo methods and tests; Inflammation; Kinases; Lesions; Male; Matrix metalloproteinases; Matrix Metalloproteinases - metabolism; Medicine; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - metabolism; Nitric-oxide synthase; Nutrient deficiency; Ojeoksan; Oxidative stress; Pharmacology; Phosphorylation; Plant Extracts - pharmacology; Plaque, Atherosclerotic; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; TNF inhibitors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Umbilical vein; vascular inflammation; vasodilation
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu10091256

Atherosclerosis is closely related to vascular dysfunction and hypertension. Ojeoksan (OJS), originally recorded in an ancient Korean medicinal book named "Donguibogam", is a well-known, blended herbal formula. This study was carried out to investigate the beneficial effects of OJS on atherosclerosis in vitro and in vivo. Western-diet-fed apolipoprotein-E gene-deficient mice (ApoE -/-) were used for this study for 16 weeks, and their vascular dysfunction and inflammation were analyzed. OJS-treated ApoE -/- mice showed lowered blood pressure and glucose levels. The levels of metabolic parameters with hyperlipidemia attenuated following OJS administration. Hematoxylin and eosin (H&E) staining revealed that treatment with OJS reduced atherosclerotic lesions. OJS also suppressed the expression of adhesion molecules and matrix metalloproteinases (MMPs) compared to Western-diet-fed ApoE -/- mice and tumor necrosis factor-alpha (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs). Expression levels of MicroRNAs (miRNA)-10a, -126 3p were increased in OJS-fed ApoE -/- mice. OJS significantly increased the phosphorylation of endothelial nitric oxide synthase (eNOS) and protein kinase B (Akt), which are involved in nitric oxide (NO) production. OJS also regulated eNOS coupling by increasing the expression of endothelial GTP Cyclohydrolase-1 (GTPCH). Taken together, OJS has a protective effect on vascular inflammation via eNOS coupling-mediated NO production and might be a potential therapeutic agent for both early and advanced atherosclerosis.