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Metabolic effects of silibinin in the rat liver.
- Source :
-
Chemico-biological interactions [Chem Biol Interact] 2012 Jan 25; Vol. 195 (2), pp. 119-32. Date of Electronic Publication: 2011 Nov 25. - Publication Year :
- 2012
-
Abstract
- The flavonolignan silibinin, which is a mixture of two diastereoisomers, silybin A and silybin B, is a component of the extract obtained from the fruit and seeds of the variegated milk thistle (Silybum marianum (L.) Gaertn. (Asteraceae)), known as silymarin. Among the therapeutic properties credited to silibinin, its antihyperglycaemic action has been extensively explored. Silibinin is structurally related to the flavonoids quercetin and fisetin, which have been previously demonstrated to be very active on liver metabolic processes related to glycaemic regulation. The aim of the present work was to investigate the effects of silibinin on metabolic pathways responsible for the maintenance of glycaemia, particularly glycogenolysis and gluconeogenesis, in the perfused rat liver. The activities of some key enzymes in these pathways and on parameters of energy metabolism in isolated mitochondria were also examined. At a concentration range of 50-300μM, silibinin inhibited gluconeogenesis in the fasted condition and inhibited glycogenolysis and glycolysis in the fed condition. The mechanisms by which silibinin exerted these actions were multiple and complex. It inhibited the activity of glucose 6-phosphatase, inhibited the pyruvate carrier, and reduced the efficiency of mitochondrial energy transduction. It can also act by reducing the supply of NADH for gluconeogenesis and mitochondria through its pro-oxidative actions. In general, the effects and the potency of silibinin were similar to those of quercetin and fisetin. However, silibinin exerted some distinct effects such as the inhibitory effect on oxygen consumption in the fed condition and a change in the energy status of the perfused livers. It can be concluded that the effects of silibinin on liver glucose metabolism may explain its antihyperglycaemic property. However, this effect was, in part, secondary to impairment in cellular energy metabolism, a finding that should be considered in its therapeutic usage.<br /> (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Blood Glucose metabolism
Flavonolignans metabolism
Gluconeogenesis drug effects
Glycolysis drug effects
Male
Metabolic Diseases metabolism
Metabolic Diseases pathology
Mitochondria, Liver enzymology
Mitochondria, Liver metabolism
Oxygen Consumption drug effects
Pyruvate Carboxylase metabolism
Rats
Rats, Wistar
Silybin
Antioxidants pharmacology
Hypoglycemic Agents pharmacology
Metabolic Diseases drug therapy
Mitochondria, Liver drug effects
Silymarin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7786
- Volume :
- 195
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 22137898
- Full Text :
- https://doi.org/10.1016/j.cbi.2011.11.006