ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Unravelling the anti-diabetic mechanism of action of L. leonurus at adipose, liver, muscle and pancreatic level. AIMS: To investigate the mechanism of action of an organic extract of L. leonurus and marrubiin at the gene level in adipose, liver and muscle tissues of an obese rat model and in a co-culture model. MATERIALS AND METHODS: Obese Wistar rats were fed a cafeteria diet for eight weeks, treated with an extract of L. Leonurus, marrubiin, sulfonylurea and aspirin for two weeks and the level of gene expression of selected markers were investigated across different tissues. The effects mediated by the different treatments were investigated in co-culture cell models involving 3T3-L1 (fat), Chang (liver), C2C12 (muscle) and INS-1 (pancreatic) cells under both normal and hyperglycemic conditions. RESULTS: L. leonurus extract mediated a significant increase in PPAR gamma, glucokinase, FAS and UCP2 gene expression in adipose tissue, whilst the opposite was observed in the liver. At the muscle level, a significant increase in FAS gene expression was observed relative to the obese control rats. Furthermore, the extract as well as marrubiin, modulated improvements in the adipokine profile. The co-culture models showed that the effect mediated by the extract was dependent on, the tissue type as well as the glycemic conditions. CONCLUSIONS: L. Leonurus extract as well as marrubiin exhibit anti-diabetic properties where the mechanism of action is mainly at the adipose tissue level. The increase in expression of the genes of interest mentioned above potentially play a protective role towards the liver and possibly towards the muscle tissues as well.
Subject(s)
Adipose Tissue/drug effects , Cell Communication/drug effects , Hypoglycemic Agents/pharmacology , Lamiaceae , Obesity/drug therapy , Plant Extracts/pharmacology , 3T3 Cells , Adipokines/genetics , Adipokines/metabolism , Adipose Tissue/metabolism , Animals , Coculture Techniques , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Gene Expression Regulation , Hypoglycemic Agents/isolation & purification , Lamiaceae/chemistry , Liver/drug effects , Liver/metabolism , Mice , Muscle, Skeletal/drug effects , Obesity/genetics , Obesity/metabolism , Pancreas/drug effects , Pancreas/metabolism , Plant Extracts/isolation & purification , Rats, Wistar , Signal TransductionABSTRACT
The objectives of this paper is to investigate, demonstrate, and compare the mechanism of action of phytocannabinoids as antidiabetic and anti-obesity agents in preadipocytes and adipocytes, relative to rosiglitazone and metformin. Briefly, cannabis extract, Δ9 -tetrahydrocannabinol and cannabidiol (in very low dosages) were shown to promote glucose uptake higher or to equivalent levels, reduce fat accumulation, and reverse the insulin-resistant state of 3T3-L1 cells more effectively, relative to rosiglitazone and metformin. The phytocannabinoids had a more pronounced effect in preadipocytes undifferentiated model rather than the differentiated model. They induced a protective effect at the mitochondrial level by preventing overactivity of the succinate dehydrogenase pathway (p < .01), unlike rosiglitazone, through activation of the glycerol-3-phosphate dehydrogenase shuttling system. An increase in oxygen consumption and an increased expression of beta to alpha adrenoceptors (p < .05) in treated cells were noted. These findings contribute toward understanding the mechanism of action of phytocannabinoids in fat cells and highlight the antidiabetic and anti-obesity properties of various phytocannabinoids that could potentially support the treatment of obesity-related insulin resistance.
