Coumarin (2H-1-benzopyran-2-one) is a phenolic compound derived from the shikimate pathway and synthesized by various medicinal and aromatic plants as parent molecule of a large group of secondary metabolites, namely coumarins. Its main utilization is as fixative in perfumes and flavour enhancer. Given its role as phytoalexin and phagodepression activity, herein we evaluated for the first time its efficacy against several insect species: the green peach aphid, Myzus persicae, the moth Spodoptera littoralis, the housefly, Musca domestica and the filariasis vector Culex quinquefasciatus. Two non-target species were also included in our toxicity evaluation experiments: the ladybug Harmonia axyridis and the earthworm Eisenia fetida. Results highlighted remarkable selectivity of coumarin, being highly toxic to M. persicae aphids (LC50(90) values of 1.3(1.9) mg L-1) and friendly to natural enemies of aphids as well as soil invertebrates.
- MeSH
- Culex drug effects MeSH
- Inhibitory Concentration 50 MeSH
- Insecticides toxicity MeSH
- Coumarins toxicity MeSH
- Larva drug effects MeSH
- Houseflies drug effects MeSH
- Aphids drug effects MeSH
- Moths drug effects MeSH
- Plant Extracts chemistry MeSH
- Seeds chemistry MeSH
- Spodoptera drug effects MeSH
- Toxicity Tests MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
The hepatic cytochrome p450 enzymes 1 A, 2A19 and 2E1 is very important for the elimination of skatole from the body of pigs. Impaired skatole metabolism, results in skatole accumulation, which give rise to off flavor of the meat. Several metabolites of skatole has been identified, however the role of these metabolites in the inhibition of the skatole metabolizing enzymes are not documented. Using microsomes from pigs and fish, we determined the ability of several skatole metabolites to inhibit CYP1 A, CYP2A19 and CYP2E1 dependent activity. Our results show that 2-aminoacetophenone is an inhibitor of porcine CYP2A19 and CYP2E1 activity, but not the piscine orthologues. In conclusion, there is species specific differences in the inhibition of CYP1 A and CYP2A19 dependent metabolism of probe substrates. This is relevant to the evaluation of different model systems and to the reduction of off flavor of meat.
- MeSH
- Acetophenones toxicity MeSH
- Red Meat analysis MeSH
- Cytochrome P-450 CYP1A1 antagonists & inhibitors metabolism MeSH
- Cytochrome P-450 CYP2E1 metabolism MeSH
- Species Specificity MeSH
- Cytochrome P-450 CYP2E1 Inhibitors toxicity MeSH
- Microsomes, Liver drug effects metabolism MeSH
- Liver drug effects metabolism MeSH
- Coumarins toxicity MeSH
- Nitrophenols toxicity MeSH
- Oxazines toxicity MeSH
- Seafood analysis MeSH
- Swine MeSH
- Fishes MeSH
- Skatole toxicity MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Wedelolactone is a multi-target natural plant coumestan exhibiting cytotoxicity towards cancer cells. Although several molecular targets of wedelolactone have been recognized, the molecular mechanism of its cytotoxicity has not yet been elucidated. In this study, we show that wedelolactone acts as an inhibitor of chymotrypsin-like, trypsin-like, and caspase-like activities of proteasome in breast cancer cells. The proteasome inhibitory effect of wedelolactone was documented by (i) reduced cleavage of fluorogenic proteasome substrates; (ii) accumulation of polyubiquitinated proteins and proteins with rapid turnover in tumor cells; and (iii) molecular docking of wedelolactone into the active sites of proteasome catalytic subunits. Inhibition of proteasome by wedelolactone was independent on its ability to induce reactive oxygen species production by redox cycling with copper ions, suggesting that wedelolactone acts as copper-independent proteasome inhibitor. We conclude that the cytotoxicity of wedelolactone to breast cancer cells is partially mediated by targeting proteasomal protein degradation pathway. Understanding the structural basis for inhibitory mode of wedelolactone might help to open up new avenues for design of novel compounds efficiently inhibiting cancer cells.
- MeSH
- Proteasome Inhibitors chemistry pharmacology toxicity MeSH
- Coumarins chemistry pharmacology toxicity MeSH
- Humans MeSH
- Copper metabolism MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms metabolism MeSH
- Proteasome Endopeptidase Complex chemistry metabolism MeSH
- Proteolysis MeSH
- Reactive Oxygen Species metabolism MeSH
- Molecular Docking Simulation MeSH
- Ubiquitination MeSH
- Protein Binding MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Coumarins are a large group of substances, primarily of plant origin. Like their more intensively examined congeners flavonoids, many of them are antioxidants. Although such properties may be advantageous in cardiovascular diseases, it has been shown that coumarins exhibit direct effects on the cardiovascular system which are not based on antioxidant activity. The most common example is the well-known drug warfarin, a synthetic compound derived from natural dicoumarol. Moreover, other coumarins have been shown to possess antiplatelet and vasodilatory potential. Interestingly, the former effect may be mediated by the inhibition of various pathways leading to platelet aggregation, their differing effects on those pathways being due to structural differences between the various coumarins. Conversely, their vasodilatory potential is linked in the majority of cases to the inhibition of increases in intracellular calcium concentration in vascular smooth muscle cells, and in several coumarins also to NO-mediated vasodilatation. Available data on both activities are summarized in this review. At the end of this review, relevant data are provided from a few studies testing the in vivo effects of coumarins on major cardiovascular diseases; the clinical use of warfarin and other coumarin anticoagulants, as well as the limited data on the clinical use of coumarins in chronic venous insufficiency and the possible toxicological effects of coumarins.
- MeSH
- Antioxidants pharmacokinetics pharmacology therapeutic use toxicity MeSH
- Platelet Aggregation Inhibitors pharmacokinetics pharmacology therapeutic use toxicity MeSH
- Cardiovascular Diseases blood drug therapy metabolism physiopathology MeSH
- Clinical Trials as Topic MeSH
- Coumarins pharmacokinetics pharmacology therapeutic use toxicity MeSH
- Humans MeSH
- Molecular Structure MeSH
- Drug Discovery MeSH
- Vasodilator Agents pharmacokinetics pharmacology therapeutic use toxicity MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- MeSH
- Cinnamates pharmacokinetics pharmacology toxicity MeSH
- Cynara * chemistry MeSH
- Hypolipidemic Agents therapeutic use MeSH
- Coumarins pharmacokinetics pharmacology toxicity MeSH
- Plants, Medicinal chemistry growth & development MeSH
- Humans MeSH
- Liver Diseases * drug therapy prevention & control MeSH
- Gallbladder Diseases * drug therapy prevention & control MeSH
- Polyphenols pharmacokinetics pharmacology toxicity MeSH
- Sesquiterpenes pharmacokinetics pharmacology toxicity MeSH
- Sterols pharmacokinetics pharmacology toxicity MeSH
- Check Tag
- Humans MeSH
- MeSH
- Anticoagulants adverse effects toxicity MeSH
- Skin Diseases etiology therapy MeSH
- Coumarins adverse effects toxicity MeSH
- Middle Aged MeSH
- Humans MeSH
- Necrosis etiology therapy MeSH
- Thrombophlebitis drug therapy complications MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
