1-1-diphenyl-2-picrylhydrazyl 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

Our aim was to determine whether vascular deposition of advanced glycation end-products (AGEs) is associated with arterial calcification and cardiovascular mortality in chronic kidney disease (CKD) patients and to assess the relationships between vascular content of AGEs and selected clinical and biochemical parameters.. The study comprised 54 CKD patients (33 hemodialyzed, 21 predialyzed). Examined parameters included BMI, incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, serum C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and fetuin-A. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using alizarin red. AGEs deposits were identified immunohistochemically and their relative content was quantified.. Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI-1, and DPPH scavenging in simple regression; only fetuin-A was an independent predictor in multiple regression. There was a significant positive trend in the intensity of AGEs immunostaining among patients with grades 1, 2, and 3 calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular mortality irrespective of patient's age.. The present study demonstrates an involvement of AGEs in the development of medial arterial calcification and the impact of arterial AGE deposition on cardiovascular mortality in CKD patients.

Topics: Aged; alpha-2-HS-Glycoprotein; Biomarkers; Biphenyl Compounds; C-Reactive Protein; Calcinosis; Cardiovascular Diseases; Female; Glycation End Products, Advanced; Humans; Male; Middle Aged; Picrates; Plasminogen Activator Inhibitor 1; Radial Artery; Renal Insufficiency, Chronic

Epidemiological studies have verified the protective role of fish lipids in cardiovascular diseases. However, the effects of fish lipids on health boost remain undefined. Large amounts of by-products, such as fish brain which contains high level of lipids, are produced with silver carp processing. Fish brain is rich in bioactive lipids which are overwhelmingly effective in preventing cardiovascular diseases. The aim of this study was to elucidate the pharmacological activities of silver carp brain lipids against diseases by inhibiting platelet-activating factor (PAF), suppressing bacterial growth and scavenging free radicals.. Total lipids (TL) were extracted from silver carp brain and separated into polar lipids (PL) and neutral lipids (NL). The capabilities of the lipid fractions in aggregating washed rabbit platelet or in inhibiting PAF-induced platelet aggregation were tested. Their antibacterial and antiradical activities were studied as well.. The lipid fractions exhibited strong inhibitory activities, and the activity of TL was mainly attributed to NL. TL exhibited antibacterial activity towards Staphylococcus aureus, while NL managed to fight against S. aureus and Escherichia coli. PL excelled TL and NL in simultaneously suppressing the growths of Shigella dysenteriae and Salmonella typhi besides those of S. aureus and E. coli. The scavenging effect of PL on 2,2-diphenyl-1-picrylhydrazyl radical was considerably higher than those of TL and NL.. The present study may help to explain the protective role of fish lipids against diseases and may be responsible for the effectiveness of fish brain in benefiting health.

Topics: Animals; Anti-Bacterial Agents; Biphenyl Compounds; Blood Platelets; Brain Chemistry; Cardiovascular Diseases; Carps; Escherichia coli; Free Radical Scavengers; Lipids; Picrates; Platelet Activating Factor; Rabbits; Staphylococcus aureus; Tissue Extracts

This study demonstrated that the aqueous extracts of plants employed in Mexican traditional medicine for the treatment of cardiovascular diseases are able to modify the tone of arterial smooth muscle. Agastache mexicana (Kunth) Lint & Epling (Labiatae), Chenopodium murale L. (Chenopodiaceae), Chirantodendron pentadactylon Larreat (Sterculiaceae), Dracocephalum moldavica L. (Labiatae), Psittacanthus calyculatus G. Don (Loranthaceae), Prunus serotina ssp. capuli (Cav. ex Spreng) McVaugh (Rosaceae), and Sechium edule Sw. (Cucurbitaceae) contain secondary metabolites that promote vascular relaxation and display antioxidant activities. As expected, their antioxidant effects showed a significant correlation with the polyphenolics content. However, a lower correlation was found between the antioxidant activity and the maximum vasodilatory effect, suggesting that the vasodilatation elicited by the plant extracts could be only partly attributed to their antioxidant properties. The extract of P. calyculatus, which displayed a maximum vasorelaxant effect that was higher than that of acetylcholine, induced endothelium-dependent vasodilatation. Futhermore, the vasorelaxant response to the P. calyculatus extract was reduced after adding an inhibitor of soluble guanylate cyclase activity, providing evidence that the NO/cGMP pathway is involved. On the other hand, the extracts of Bocconia frutescens L. (Papaveraceae), Magnolia grandiflora L. (Magnoliaceae), and Solanum rostratum Dunal (Solanaceae) induced concentration-dependent contraction of rat aortic rings, suggesting that these plants have potential health benefits for the treatment of ailments such as venous insufficiency. The pharmacological activities of the extracts studied provide scientific support for their ethnomedical use.

Topics: Animals; Antioxidants; Aorta; Biphenyl Compounds; Cardiovascular Diseases; Drug Evaluation, Preclinical; Flavonoids; In Vitro Techniques; Male; Medicine, Traditional; Mexico; Phenols; Phytotherapy; Picrates; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Vasoconstrictor Agents; Vasodilator Agents

The oxidative modification of LDL may play an important role in the early events of atherogenesis. Thus the identification of antioxidative compounds may be of therapeutic and prophylactic importance regarding cardiovascular disease. Copper-chlorophyllin (Cu-CHL), a Cu(2+)-protoporphyrin IX complex, has been reported to inhibit lipid oxidation in biological membranes and liposomes. Hemin (Fe(3+)-protoporphyrin IX) has been shown to bind to LDL thereby inducing lipid peroxidation. As Cu-CHL has a similar structure as hemin, one may assume that Cu-CHL may compete with the hemin action on LDL. Therefore, in the present study Cu-CHL and the related compound magnesium-chlorophyllin (Mg-CHL) were examined in their ability to inhibit LDL oxidation initiated by hemin and other LDL oxidizing systems. LDL oxidation by hemin in presence of H(2)O(2) was strongly inhibited by both CHLs. Both chlorophyllins were also capable of effectively inhibiting LDL oxidation initiated by transition metal ions (Cu(2+)), human umbilical vein endothelial cells (HUVEC) and tyrosyl radicals generated by myeloperoxidase (MPO) in presence of H(2)O(2) and tyrosine. Cu- and Mg-CHL showed radical scavenging ability as demonstrated by the diphenylpicrylhydracylradical (DPPH)-radical assay and estimation of phenoxyl radical generated diphenyl (dityrosine) formation. As assessed by ultracentrifugation the chlorophyllins were found to bind to LDL (and HDL) in serum. The present study shows that copper chlorophyllin (Cu-CHL) and its magnesium analog could act as potent antagonists of atherogenic LDL modification induced by various oxidative stimuli. As inhibitory effects of the CHLs were found at concentrations as low as 1 mumol/l, which can be achieved in humans, the results may be physiologically/therapeutically relevant.

Topics: Atherosclerosis; Biphenyl Compounds; Cardiovascular Diseases; Catalysis; Cells, Cultured; Chlorophyll; Chlorophyllides; Copper; Dose-Response Relationship, Drug; Endothelium, Vascular; Free Radical Scavengers; Free Radicals; Hemin; Humans; Hydrazines; Hydrogen Peroxide; Ions; Iron; Lipid Peroxidation; Lipids; Lipoproteins; Lipoproteins, LDL; Magnesium; Malondialdehyde; Models, Chemical; Octanols; Oxygen; Picrates; Protoporphyrins; Pyrazoles; Pyrimidines; Thiobarbituric Acid Reactive Substances; Thromboplastin; Time Factors; Tyrosine; Umbilical Veins; Water

Reactive oxygen species (ROS) are implicated in many pathogenic processes including the cardiovascular system. Detoxification of ROS by antioxidants (AO) therefore affords protection against such diseases. There is a growing body of evidence suggesting that antioxidants contribute to cardioprotection. Therefore, nine plants that are components of Ayurvedic formulations used for the therapy of cardiovascular diseases were investigated to determine whether antioxidant activity is one of the mechanisms by which these plants exert cardioprotection. Initially aqueous freeze dried extracts of the plants were prepared and the antioxidant activity was measured (a) in vitro, by DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging and deoxyribose damage protection assays, and (b) in vivo, by effects on lipid peroxidation. Terminalia arjuna showed significant DPPH radical scavenging activity with EC(50) 8.3 +/- 0.3 microg/mL (similar to L-ascorbic acid). The potency of this activity was much lower in Cassia fistula (EC(50) = 59.0 +/- 2.7 microg/mL). The other seven extracts demonstrated no such activity in the concentration range tested. In the deoxyribose damage protection assay, T. arjuna> demonstrated no significant effect in the concentration range 0-20 microg/mL, but above -20 microg/mL concentration (20-125 microg/mL), a pro-oxidant activity was observed (although markedly less than demonstrated by L-ascorbic acid). A similar trend was observed with Vitex negundo. In contrast, C. fistula afforded a 30% protection against such damage at 125 microg/mL concentration. Other plant extracts did not show any activity in this assay. At a dose of 90 mg/kg (single dose) T. arjuna, cardiac lipid peroxidation in male Wistar rats was reduced by 38.8% +/- 2.6% (p<0.05) whereas the reduction was only 11.6% +/- 3.5% in the case of C. fistula even at a dose of 120 mg/kg. Of all the plants tested, T. arjuna demonstrated the highest antioxidant activity. Overall results show that only some plants used in the therapy of cardiovascular disease exert their beneficial effects via antioxidant activity.

Topics: Animals; Antioxidants; Bepridil; Biphenyl Compounds; Cardiotonic Agents; Cardiovascular Diseases; Deoxyribose; Free Radical Scavengers; Free Radicals; Herbal Medicine; Lipid Peroxidation; Magnoliopsida; Male; Medicine, Ayurvedic; Phytotherapy; Picrates; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Reactive Oxygen Species; Sri Lanka; Thiobarbituric Acid Reactive Substances