The Beneficial Additive Effect of Silymarin in Metformin Therapy of Liver Steatosis in a Pre-Diabetic Model

The combination of plant-derived compounds with anti-diabetic agents to manage hepatic steatosis closely associated with diabetes mellitus may be a new therapeutic approach. Silymarin, a complex of bioactive substances extracted from , evinces an antioxidative, anti-inflammatory, and hepatoprotectiv...

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Published in:Pharmaceutics 2021-12, Vol.14 (1), p.45
Main Authors: Hüttl, Martina, Markova, Irena, Miklankova, Denisa, Zapletalova, Iveta, Poruba, Martin, Racova, Zuzana, Vecera, Rostislav, Malinska, Hana
Format: Article
Language:English
Subjects:
Cholesterol
combination therapy
Diabetes
Drug dosages
Glucose
Heavy metal content
Hyperglycemia
Insulin resistance
Laboratory animals
Lipids
Liver
liver steatosis
Metabolic syndrome
metformin
Obesity
Overweight
Oxidative stress
Phytochemicals
pre-diabetes
silymarin
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Summary:The combination of plant-derived compounds with anti-diabetic agents to manage hepatic steatosis closely associated with diabetes mellitus may be a new therapeutic approach. Silymarin, a complex of bioactive substances extracted from , evinces an antioxidative, anti-inflammatory, and hepatoprotective activity. In this study, we investigated whether metformin (300 mg/kg/day for four weeks) supplemented with micronized silymarin (600 mg/kg/day) would be effective in mitigating fatty liver disturbances in a pre-diabetic model with dyslipidemia. Compared with metformin monotherapy, the metformin-silymarin combination reduced the content of neutral lipids (TAGs) and lipotoxic intermediates (DAGs). Hepatic gene expression of enzymes and transcription factors involved in lipogenesis ( , , , and ) and fatty acid oxidation ( ) were positively affected, with hepatic lipid accumulation reducing as a result. Combination therapy also positively influenced arachidonic acid metabolism, including its metabolites (14,15-EET and 20-HETE), mitigating inflammation and oxidative stress. Changes in the gene expression of cytochrome P450 enzymes, particularly Cyp4A, can improve hepatic lipid metabolism and moderate inflammation. All these effects play a significant role in ameliorating insulin resistance, a principal background of liver steatosis closely linked to T2DM. The additive effect of silymarin in metformin therapy can mitigate fatty liver development in the pre-diabetic state and before the onset of diabetes.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14010045