apigenin and myricetin

Random Forest screening of the phytochemical constituents of 240 herbs used in traditional Chinese medicine identified a number of compounds as potential inhibitors of the human aromatase enzyme (CYP19). Molecular modelling/docking studies indicated that three of these compounds (myricetin, liquiritigenin and gossypetin) would be likely to form stable complexes with the enzyme. The results of the virtual screening studies were subsequently confirmed experimentally, by in vitro (fluorimetric) assay of the compounds' inhibitory activity. The IC-50s for the flavones, myricetin and gossypetin were determined as 10 and 11 microM, respectively, whilst the flavanone, liquiritigenin, gave an IC-50 of 0.34 microM--showing about a 10-fold increase in potency, therefore, over the first generation aromatase inhibitor, aminoglutethimide.

Topics: Algorithms; Aminoglutethimide; Aromatase Inhibitors; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Flavanones; Flavonoids; Fluorometry; Humans; Inhibitory Concentration 50; Models, Molecular; Structure-Activity Relationship

Topics: Anticarcinogenic Agents; Antioxidants; Chamomile; Copper; Diet; Flavonoids; Humans; Kaempferols; Kinetics; Lipoproteins, LDL; Male; Oils, Volatile; Oxidation-Reduction; Plants, Medicinal; Quercetin; Rutin

Some flavonoids induce phase II enzymes both in vivo and in vitro. We have determined the structural requirements for this activity by examining the ability of naturally-occurring flavonoids to induce the phase II enzyme, quinone reductase (NAD(P)H:quinone oxidoreductase; EC 1.6.99.2), in murine Hepalclc7 cells. Hydroxylation of the B ring is not essential for induction, since galangin and kaempferol (with 0 and 1 hydroxyl in the B ring, respectively) are better inducers than quercetin (2 B ring hydroxyls). A 2,3 double bond in the C ring is essential for induction, since taxifolin, which has the same substitution pattern as quercetin but lacks the 2,3 double bond, is not an inducer. This is supported by catechin and epicatechin, which do not possess the 2,3 double bond and are also not inducers. A 3-hydroxyl group increases the activity but is not essential for induction, since apigenin is an inducer but kaempferol (which has the same structure as apigenin but possesses a 3-hydroxyl group) is more effective. The data show that, of the flavonoids, the flavonols are the most effective inducers of quinone reductase activity in Hepa1c1c7 cells (kaempferol approximately galangin > quercetin > myricetin approximately apigenin (a flavone)) and that flavanols and flavans are ineffective.

Topics: Animals; Catechin; Chamomile; Enzyme Induction; Enzyme Inhibitors; Flavonoids; Flavonols; Kaempferols; Liver Neoplasms, Experimental; Mice; NAD(P)H Dehydrogenase (Quinone); Oils, Volatile; Plants, Medicinal; Quercetin; Tumor Cells, Cultured

Flavonoids are polyphenolic antioxidants naturally present in vegetables, fruits, and beverages such as tea and wine. In vitro, flavonoids inhibit oxidation of low-density lipoprotein and reduce thrombotic tendency, but their effects on atherosclerotic complications in human beings are unknown. We measured the content in various foods of the flavonoids quercetin, kaempferol, myricetin, apigenin, and luteolin. We then assessed the flavonoid intake of 805 men aged 65-84 years in 1985 by a cross-check dietary history; the men were then followed up for 5 years. Mean baseline flavonoid intake was 25.9 mg daily. The major sources of intake were tea (61%), onions (13%), and apples (10%). Between 1985 and 1990, 43 men died of coronary heart disease. Fatal or non-fatal myocardial infarction occurred in 38 of 693 men with no history of myocardial infarction at baseline. Flavonoid intake (analysed in tertiles) was significantly inversely associated with mortality from coronary heart disease (p for trend = 0.015) and showed an inverse relation with incidence of myocardial infarction, which was of borderline significance (p for trend = 0.08). The relative risk of coronary heart disease mortality in the highest versus the lowest tertile of flavonoid intake was 0.42 (95% CI 0.20-0.88). After adjustment for age, body-mass index, smoking, serum total and high-density-lipoprotein cholesterol, blood pressure, physical activity, coffee consumption, and intake of energy, vitamin C, vitamin E, beta-carotene, and dietary fibre, the risk was still significant (0.32 [0.15-0.71]). Intakes of tea, onions, and apples were also inversely related to coronary heart disease mortality, but these associations were weaker. Flavonoids in regularly consumed foods may reduce the risk of death from coronary heart disease in elderly men.

Topics: Aged; Aged, 80 and over; Antioxidants; Beverages; Chamomile; Coffee; Cohort Studies; Coronary Disease; Diet; Flavonoids; Follow-Up Studies; Fruit; Humans; Kaempferols; Longitudinal Studies; Luteolin; Male; Myocardial Infarction; Netherlands; Oils, Volatile; Plants, Medicinal; Quercetin; Risk Factors; Smoking; Tea; Vegetables