2-2--azino-di-(3-ethylbenzothiazoline)-6-sulfonic-acid and Cardiovascular-Diseases

Myeloperoxidase (MPO) is known to cause oxidative stress and inflammation leading to cardiovascular disease (CVD) complications. MPO-mediated oxidation of lipoproteins leads to dysfunctional entities altering the landscape of lipoprotein functionality. The specificity of guaiacol derivatives toward preventing MPO-mediated oxidation to limit MPO's harmful effects is unknown. Diligent in silico studies were accomplished for a portfolio of compounds with guaiacol as a building block. The compounds' activity toward MPO inhibition was also validated. The role of these chemical entities in controlling MPO-mediated oxidation of lipoproteins (LDL and HDL) was shown to agree with our approach of developing powerful MPO inhibitors. The mechanism of MPO inhibition was demonstrated to be reversible in nature. This study reveals that there is great potential for guaiacol derivatives as therapeutics for CVD by modulating lipid profiles, reducing atherosclerotic plaque burden, and subsequently optimizing cardiovascular functions.

Topics: Animals; Antioxidants; Atherosclerosis; Benzothiazoles; Biphenyl Compounds; Cardiovascular Diseases; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme Inhibitors; Guaiacol; Humans; Interleukin-1beta; Lipopolysaccharides; Mice; Molecular Docking Simulation; Molecular Structure; Peroxidase; Picrates; RAW 264.7 Cells; Structure-Activity Relationship; Sulfonic Acids; Tumor Necrosis Factor-alpha

Three extraction methods were sequentially combined to obtain fractions from Lentinula edodes (shiitake mushrooms) containing bioactive compounds against cardiovascular diseases (CVDs). Fruiting bodies were first extracted with plain water, obtained residue was then submitted to supercritical fluid extraction (SFE) and remaining residue submitted to hot water extraction. Sequential design allowed reutilization of the nonextracted material as raw material for the successive extractions increasing extraction yields and separating interesting compounds. Obtained fractions contained different amounts of ß-glucans, chitins, eritadenine, lenthionine, ergosterol, proteins/peptides and phenolic compounds conferring them different bioactivities. Water soluble fractions showed high antioxidant activities (ABTS

Topics: Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Benzothiazoles; Biphenyl Compounds; Cardiovascular Diseases; Chemical Fractionation; Humans; Picrates; Shiitake Mushrooms; Sulfonic Acids