August 2014
Christos E. Kazazis, Angelos A. Evangelopoulos, Aris Kollas, and Natalia G. Vallianou
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.
Keywords: type 2 diabetes, HbA1c, milk thistle, silibin, anti-diabetic, bioavailability, PPAR gamma
Introduction
A considerable number of herbs have been studied extensively regarding their hypoglycemic properties which may be useful in the control of diabetes mellitus. Among them is milk thistle (Silibum marianum), which was first considered as a therapeutic agent for liver disorders. S. marianum and its seeds contain a whole family of natural compounds, called flavonolignans. Milk thistle is regarded as a potent agent against insulin resistance and diabetes-induced hyperglycemia (Figure Figure11) [1-3].
In organs that do not depend on insulin for glucose transport, intracellular accumulation of sorbitol takes place under conditions of high glucose concentration. This is aided by the enzyme aldose reductase, with subsequent intracellular water accumulation and tissue damage. Silibin (aka silybin or silibinin) acts as an inhibitor of aldose reductase. Therefore, it is suggested as an attractive candidate for the prevention and treatment of diabetes and its complications. For the preparation of this review, we have searched the Pubmed database using the keywords "thistle" and "diabetes", and we considered articles dating from 1997 to 2014.
Conclusions
Milk thistle contains flavonolignans like silibin A. An isoform of silibin, isoform 3, has been demonstrated to possess partial PPARγ agonist effects. Being a newly discovered PPARγ activator, isoform 3 may serve as a prototype for future development of new PPARγ agonists. It cannot be terminally answered, whether PPARγ activation by milk thistle compounds is clinically relevant and suggests the use of silimarin as an herbal remedy. The answer needs further investigation.
Silibin has also demonstrated beneficial effects on several diabetic complications, including diabetic neuropathy, diabetic nephropathy, and non-alcoholic steatohepatitis, mainly by means of its anti-oxidant properties. Future research should focus on the potential of this component of milk thistle to control diabetes and its complications, and on improving the bioavailability of the plants compounds.
Disclosures: The authors report no conflict of interests.
