Combination of hormones and nutrients for the development of hybrid nutraceuticals.

The role of diet is crucial in the prevention and management of several pathologies, mostly metabolic imbalances and cardiovascular diseases. For example, it has been now well established that an altered blood lipid profile is strongly correlated to the risk of coronary artery failure or occlusion and heart attack. A diet rich in saturated fatty acids and cholesterol unavoidably leads to an altered plasma level of these constituents. Animal food generally contains plenty of saturated fats and cholesterol, whereas trans fatty acids are present in hydrogenated vegetable oils and are equally bad for health. On the other hand, unsaturated and polyunsaturated fatty acids of fish and particular vegetable food result of great benefit. The essential ω-3 and ω-6 long-chain acids require to be introduced by the diet, since they are not produced by human metabolism. In particular, two essential unsaturated fatty acids, ω-3 α-linoleic acid (ALA) and ω-6 linoleic acid (LA), need to be introduced with diet, as they can undergo metabolic conversion into several beneficial analogs. However, the amount introduced by the diet in not always enough and then an integration by the use of nutraceutical formulations is often recommended, particularly during diseases due to dyslipidemia associated to an altered hormonal balance. Such chronic diseases are often accompanied by inflammatory and degenerative processes. Estrogens were repeatedly found to be involved in these functions, while the administration of Testosterone (T), the main precursor of estrogens in the brain, has been proposed in the therapy of chronic diseases, such as X-linked adrenoleukodystrophy.[1] Herein we present the preliminary results of a research focused on the development of esters of androgens with specific unsaturated fatty acids, as a new potential therapeutic approach for the treatment of chronic pathologies with altered lipid homeostasis. The esters of the testosterone, along with those of other androgen derivatives, with selected unsaturated fatty acids were obtained under mild conditions in order to avoid concomitant isomerization reactions. A first series of compounds has been tested in mouse NIH3T3 and human astrocyte cell lines with the aim to exclude any cytotoxic activity.[2] All substances were also tested on rats subjected to the formalin test. Preliminary results strongly indicate the possibility for estrogen receptor to be modulated by T-esters in brain areas involved in endocrine and cognitive functions. References [1] De Maddalena C., Vodo S., Petroni A., Aloisi A.M. Impact of testosterone on body fat composition. J. Cell Physiol. 2012, 227, 3744-3748. [2] Aiello F., Garofalo A. et al. Synthesis of esters of androgens with unsaturated fatty acids for androgen requiring therapy. J. Endocrinol. Invest., 2013, 36, 390-395.