Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
1.
J Agric Food Chem ; 68(7): 1763-1779, 2020 Feb 19.
Article in English | MEDLINE | ID: mdl-30907588

ABSTRACT

Multidrug resistance (MDR) is a major challenge for the 21th century in both cancer chemotherapy and antibiotic treatment of bacterial infections. Efflux pumps and transport proteins play an important role in MDR. Compounds displaying inhibitory activity toward these proteins are prospective for adjuvant treatment of such conditions. Natural low-cost and nontoxic flavonoids, thanks to their vast structural diversity, offer a great pool of lead structures with broad possibility of chemical derivatizations. Various flavonoids were found to reverse both antineoplastic and bacterial multidrug resistance by inhibiting Adenosine triphosphate Binding Cassette (ABC)-transporters (human P-glycoprotein, multidrug resistance-associated protein MRP-1, breast cancer resistance protein, and bacterial ABC transporters), as well as other bacterial drug efflux pumps: major facilitator superfamily (MFS), multidrug and toxic compound extrusion (MATE), small multidrug resistance (SMR) and resistance-nodulation-cell-division (RND) transporters, and glucose transporters. Flavonoids and particularly flavonolignans are therefore highly prospective compounds for defying multidrug resistance.


Subject(s)
ATP-Binding Cassette Transporters/antagonists & inhibitors , Bacterial Proteins/antagonists & inhibitors , Drug Resistance, Bacterial , Drug Resistance, Neoplasm , Flavonoids/administration & dosage , Flavonolignans/administration & dosage , Neoplasms/metabolism , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Animals , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/therapeutic use , Bacteria/genetics , Bacteria/metabolism , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Humans , Neoplasms/drug therapy , Neoplasms/genetics
2.
Molecules ; 22(1)2017 Jan 15.
Article in English | MEDLINE | ID: mdl-28098838

ABSTRACT

Silymarin is the most commonly used herbal medicine by patients with chronic liver disease. Silymarin flavonolignans undergo rapid first-pass metabolism primarily by glucuronidation. The aims of this investigation were: (1) to determine the association of UGT1A1*28 polymorphism with the area under the plasma concentration-time curves (AUCs) for silybin A (SA) and silybin B (SB); (2) to evaluate the effect of UGT1A1*28 polymorphism on the profile of flavonolignan glucuronide conjugates found in the plasma; and (3) to investigate the role of UGT1A1 enzyme kinetics on the pharmacokinetics of SA and SB. AUCs and metabolic ratios for thirty-three patients with chronic liver disease administered oral doses of silymarin were compared between different UGT1A1*28 genotypes. The AUCs, metabolic ratios, and the profiles of major SA and SB glucuronides did not differ significantly among the three UGT1A1 genotypes. In contrast, an increase in the proportion of sulfated flavonolignan conjugates in plasma was observed in subjects with UGT1A1*28/*28 genotype compared to subjects carrying wild type alleles. Differences in SA and SB in vitro intrinsic clearance estimates for UGTIA1 correlated inversely with SA and SB exposures observed in vivo indicating a major role for UGT1A1 in silymarin metabolism. In addition, a significant difference in the metabolic ratio observed between patients with NAFLD and HCV suggests that any effect of UGT1A1 polymorphism may be obscured by a greater effect of liver disease on the pharmacokinetics of silymarin. Taken together, these results suggest the presence of the UGT1A1*28 allele does not contribute significantly to a large inter-subject variability in the pharmacokinetics of silybin A and silybin B which may obscure the ability to detect beneficial effects of silymarin in patients with liver disease.


Subject(s)
Flavonolignans/metabolism , Glucuronosyltransferase/genetics , Hepatitis C/drug therapy , Non-alcoholic Fatty Liver Disease/drug therapy , Silymarin/metabolism , Adult , Alleles , Female , Flavonolignans/administration & dosage , Flavonolignans/pharmacokinetics , Genotype , Hepatitis C/blood , Hepatitis C/genetics , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/genetics , Pharmacogenomic Testing , Polymorphism, Genetic , Silymarin/administration & dosage , Silymarin/pharmacokinetics
3.
Rev Diabet Stud ; 11(2): 167-74, 2014.
Article in English | MEDLINE | ID: mdl-25396404

ABSTRACT

Milk thistle has been known for more than 2.000 years as a herbal remedy for a variety of disorders. It has mainly been used to treat liver and gallbladder diseases. Silibum marianum, the Latin term for the plant, and its seeds contain a whole family of natural compounds, called flavonolignans. Silimarin is a dry mixture of these compounds; it is extracted after processing with ethanol, methanol, and acetone. Silimarin contains mainly silibin A, silibin B, taxifolin, isosilibin A, isosilibin B, silichristin A, silidianin, and other compounds in smaller concentrations. Apart from its use in liver and gallbladder disorders, milk thistle has recently gained attention due to its hypoglycemic and hypolipidemic properties. Recently, a substance from milk thistle has been shown to possess peroxisome proliferator-activated receptor γ (PPARγ) agonist properties. PPARγ is the molecular target of thiazolidinediones, which are used clinically as insulin sensitizers to lower blood glucose levels in diabetes type 2 patients. The thiazolidinedione type of PPARγ ligands is an agonist with a very high binding affinity. However, this ligand type demonstrates a range of undesirable side effects, thus necessitating the search for new effective PPARγ agonists. Interestingly, studies indicate that partial agonism of PPARγ induces promising activity patterns by retaining the positive effects attributed to the full agonists, with reduced side effects. In this review, the therapeutic potential of milk thistle in the management of diabetes and its complications are discussed.


Subject(s)
Diabetes Mellitus/drug therapy , Silybum marianum , Animals , Anti-Obesity Agents , Diabetes Mellitus, Type 2/drug therapy , Flavonolignans/administration & dosage , Flavonolignans/chemistry , Flavonolignans/therapeutic use , Humans , Hypoglycemic Agents , Silybum marianum/adverse effects , Silybum marianum/chemistry , PPAR gamma/agonists , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Rats , Seeds/chemistry , Silybin , Silymarin/administration & dosage , Silymarin/adverse effects , Silymarin/pharmacokinetics , Silymarin/therapeutic use
4.
Res Vet Sci ; 91(3): 426-33, 2011 Dec.
Article in English | MEDLINE | ID: mdl-20971486

ABSTRACT

Ivermectin, the antiparasitic drug from the macrocyclic lactones class raises attention due to its high efficiency against nematodes and arthropods and very specific toxic and side effects that it may produce in host. Dominant clinical symptoms of adverse effects and toxicity of ivermectin in animals are tremor, ataxia, CNS depression and coma which often results in mortality. In our study increasing intravenous doses of ivermectin, (6 or more times higher than therapeutic dose: 1.25, 2.5, 3.75, 5.0, 6.25 and 7.5 mg/kg), caused dose-dependent disturbance of motor coordination in treated rats. The median effective dose (ED50) that was able to impair the rota-rod performance in rats treated 3 min before testing was 2.52 mg/kg. This effect weakens over time, while in the rats treated 60 min before the rota-rod test, ED50 of ivermectin was 4.21 mg/kg. Whereas, all tested doses of ivermectin did not cause any other clinical symptoms of toxicity. Ivermectin has no effect on the contractions of isolated diaphragm caused by the EFS, which effectively blocked mecamylamine (100 µM) and pancuronium (1 and 2 µM). Effect on motor coordination is the first detectable clinical symptom of ivermectin toxicity and apparently is a result of its central effects.


Subject(s)
Diaphragm/drug effects , Flavonolignans/toxicity , Ivermectin/toxicity , Muscle Contraction/drug effects , Psychomotor Performance/drug effects , Animals , Dose-Response Relationship, Drug , Flavonolignans/administration & dosage , Ganglionic Blockers/pharmacology , Ivermectin/administration & dosage , Male , Mecamylamine/pharmacology , Neuromuscular Nondepolarizing Agents/pharmacology , Pancuronium/pharmacology , Rats , Rats, Wistar
5.
Phytother Res ; 18(2): 107-10, 2004 Feb.
Article in English | MEDLINE | ID: mdl-15022159

ABSTRACT

Silymarin, an extract of fl avonolignans from the dried fruits of milk thistle (Silybum marianum L. Gaertneri) and its constituents silibinin, dehydrosilibinin, silychristin and silydianin were tested for protective effects on rat cardiomyocytes exposed to doxorubicin. Silymarin and individual fl avonolignans did not exert cytotoxicity in the range 25-100 micro m (incubation 9 h). Dehydrosilibinin was tested only at 25 micro m concentration due to its low solubility. All substances increased the cell ATP level. Silymarin and fl avonolignans displayed a dose-dependent cytoprotection against doxorubicin (100 micro m, incubation 8 h). The protective effects of silymarin, silibinin, dehydrosilibinin and silychristin were comparable to that of dexrasoxane, while silydianin exerted the best protective effect. The ability of silymarin complex and its components to protect cardiomyocytes against doxorubicin-induced oxidative stress is due mainly to their cell membrane stabilization effect, radical scavenging and iron chelating potency.


Subject(s)
Antioxidants/pharmacology , Myocardium/metabolism , Phytotherapy , Protective Agents/pharmacology , Silybum marianum , Silymarin/pharmacology , Animals , Antioxidants/administration & dosage , Antioxidants/therapeutic use , Dose-Response Relationship, Drug , Flavonolignans/administration & dosage , Flavonolignans/pharmacology , Flavonolignans/therapeutic use , Fruit , Myocardium/cytology , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Protective Agents/administration & dosage , Protective Agents/therapeutic use , Rats , Silymarin/administration & dosage , Silymarin/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL
...