3-4-dihydroxyphenyllactic-acid and Atherosclerosis

The primary cause of acute cardiovascular events with high mortality is the rupture of atherosclerotic plaque followed by thrombosis. Sodium Danshensu (SDSS) has shown potential in inhibiting the inflammatory response in macrophages and preventing early plaque formation in atherosclerotic mice. However, the specific targets and detailed mechanism of action of SDSS are still unclear.. This study aims to investigate the efficacy and mechanism of SDSS in inhibiting inflammation in macrophages and stabilizing vulnerable plaques in atherosclerosis (AS).. The efficacy of SDSS in stabilizing vulnerable plaques was demonstrated using various techniques such as ultrasound, Oil Red O staining, HE staining, Masson staining, immunohistochemistry, and lipid analysis in ApoE. Initially, the administration of SDSS led to a decrease in the formation and area of aortic plaque, while also stabilizing vulnerable plaques in ApoE. SDSS stabilized vulnerable plaques and suppressed inflammatory responses by inhibiting the NF-κB pathway through its targeting of IKKβ.

Topics: Animals; Apolipoproteins E; Atherosclerosis; I-kappa B Kinase; Inflammation; Macrophages; Mice; Molecular Docking Simulation; NF-kappa B; Plaque, Atherosclerotic; Protein Serine-Threonine Kinases; Signal Transduction

Salvianic acid A (SAA) is an active water-soluble constituent derived from Salvia miltiorrhiza Bge that is used extensively in the treatment of angiocardiopathy in China. However, few reports have investigated the therapeutic effect and the underlying mechanisms of SAA on atherosclerosis (AS). This study examines the protective mechanisms of SAA on AS in vivo and in vitro. SAA treatment (3 and 10 mg/kg/d) prevented the progression of atherosclerotic lesions and decreased 58.2% and 72.8% of the lipid deposition in the aorta of high fat-diet-induced AS rat. Notably, SAA treatment ameliorated serum lipid abnormalities by decreasing 20.4% and 33.8% of triglyceride, 26.1% and 32.7% of total cholesterol, 36.0% and 57.3% of low-density lipoprotein-cholesterol levels and increasing 183.4% and 337.5% of high-density lipoprotein-cholesterol level in the serum of AS rat (all P <  0.05). SAA treatment lowered pro-inflammatory mediators including interleukin-1β, interleukin-6, tumor necrosis factor-α, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) (all P <  0.05) by inhibiting the toll-like receptor 4/nuclear factor kappa B pathway. In addition, SAA treatment significantly decreased oxidative stress by increasing antioxidant enzymes activity, upregulating nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway and downregulated expression of p47

Topics: Animals; Atherosclerosis; Drugs, Chinese Herbal; Endothelium, Vascular; Human Umbilical Vein Endothelial Cells; Humans; Inflammation Mediators; Lactates; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

To examine whether danshensu could protect vascular endothelia in a rat model of hyperhomocysteinemia.. The model was established by feeding rats with a methionine-rich diet (1 g·kg⁻¹·d⁻¹) for 3 months. Immediately following the discontinuation of methionine-rich diet, rats were treated with danshensu (67.5 mg·kg⁻¹·d⁻¹, po) or saline for 3 additional months. One group of rats receiving vitamin mixture (folic acid, vitamin B12 and vitamin B6) was included as a positive control. One group of rats not exposed to methionine-rich diet was also included as a blank control. The expression of tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) protein in the descending aorta was examined using immunohistochemistry and Western blot. Homocysteine and blood concentration of endothelin and nitric oxide (NO) was also examined.. Methionine-rich diet resulted in accumulation of "foam cells", up-regulated expression of TNF-alpha and ICAM-1 in the descending aorta, and significantly increased serum homocysteine. Plasma endothelin concentration was significantly increased; NO was decreased. Danshensu treatment, either simultaneous to methionine-rich diet or afterwards, attenuated the above mentioned changes.. Chronic treatment with danshensu could prevent/attenuate the formation of atherosclerosis. Potential mechanisms include inhibited expression of representative proinflammatory cytokines and adhesion molecules in arterial endothelia. Changes in homocysteine and circulating molecules that control vascular contraction/relaxation via endothelial cells (eg, endothelin and NO) were also implicated.

Topics: Animals; Aorta, Thoracic; Atherosclerosis; Cardiovascular Agents; Diet; Disease Models, Animal; Endothelins; Endothelium, Vascular; Female; Hyperhomocysteinemia; Intercellular Adhesion Molecule-1; Lactates; Male; Methionine; Nitric Oxide; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha