Models for skin and brain penetration of major components from essential oils used in aromatherapy for dementia patients

Aromatherapy with essential oils (EOs) has been linked to improvement of cognitive function in patients with dementia. In order to act systemically, active EO components must be absorbed through the skin, enter the systemic circulation, and cross the blood brain barrier (BBB). Thus, the aim of this work was to develop quantitative structure activity relationships (QSARs), to predict skin and blood barrier penetrative abilities of 119 terpenoids from EOs used in aromatherapy. The first model was based on experimentally measured skin permeability for 162 molecules, and the second model on BBB permeability for 138 molecules. Each molecule was encoded with 63 calculated molecular descriptors and an artificial neural network was used to correlate molecular descriptors to permeabilities. Developed QSAR models confirm that EOs components penetrate through the skin and across the BBB. Some well-known descriptors, such as log P (lipophilicity), molecular size and shape, dominated the QSAR model for BBB permeability. Compounds with the highest predicted BBB penetration were hydrocarbon terpenes with the smallest molecular size and highest lipophilicity. Thus, molecular size is a limiting factor for penetration. Compounds with the highest skin permeability have slightly higher molecular size, high lipophilicity and low polarity. Our work shows that a major disadvantage of novel multitarget compounds developed for the treatment of Alzheimer's disease is the size of molecules, which cause problems in their delivery to the brain. Therefore, there is a need for smaller compounds, which possess more desirable physicochemical properties and pharmacokinetics, in addition to targeted biological effects.Communicated by Ramaswamy H. Sarma.