Carnosic Acid and Carnosol, Phenolic Diterpene Compounds of the Labiate Herbs Rosemary and Sage, are Activators of the Human Peroxisome Proliferator-Activated Receptor Gamma

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand activated transcription factor, belonging to the metazoan family of nuclear hormone receptors. Activation of PPARγ increases the transcription of enzymes involved in primary metabolism, leading to lower blood levels of fatty acids and glucose. Hence, PPARγ represents the major target for the glitazone type of drugs currently being used clinically for the treatment of type 2 diabetes. Furthermore, activators of PPARγ show beneficial anti-inflammatory and anti-tumour effects. Utilizing a fusion receptor of the yeast Gal4-DNA binding domain joined to the hinge region and ligand binding domain of the human PPARγ in combination with a Gal4-driven luciferase reporter gene, cotransfected into Cos7 cells, we tested sage and rosemary extracts prepared with 80 % aqueous ethanol for possible PPARγ activation. This revealed that both extracts are capable of selectively activating Gal4-PPARγ fusion receptor, in a concentration-dependent manner, with EC₅₀ values of 22.8 ± 8.4 mg/L and 33.7 ± 7.3 mg/L for rosemary and sage, respectively. Subsequent analysis of the characteristic constituents revealed the phenolic diterpene compounds carnosol, present in both herbs, and carnosic acid to be active principles of these extracts, showing EC₅₀ values of 41.2 ± 5.9 μM and 19.6 ± 2.0 μM, respectively. Thus it can be concluded that the glucose lowering effect reported recently for rosemary may be attributed to PPARγ activation. Moreover, our observations may also explain the anti-inflammatory and antiproliferative effects of both compounds published previously.

PPARγ - carnosic acid - carnosol - Salvia officinalis L. - sage - Rosmarinus officinalis L. - rosemary - Lamiaceae

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