Takahiro Hirabayashi

Lavender essential oil (LEO) is commonly used in aromatherapy for stress reduction, relaxation and recovery from (muscle) fatigue. However, molecular mechanisms underlying its potential physiological effects on the skeletal muscle remain unclear. This study investigates whether LEO affects the intracellular signaling pathways in skeletal muscle cells that respond to physical activity. Prior to the experiment, GC-MS analysis confirmed linalyl acetate and linalool as the main components of LEO used in this study. Transdermal permeability was assessed using a reconstructed human epidermis model, which showed that linalool permeated the epidermal layer, while linalyl acetate showed minimal permeation. Following this confirmation, the differentiated C2C12 myotubes were treated with LEO in an in vitro muscle contraction model using electrical pulse stimulation (EPS). LEO significantly increased Interleukin 6 (IL-6) mRNA expression under EPS, and DNA whole-genome microarray analysis showed that LEO induced different gene expression profiles depending on the contraction state of the muscle cells. These results provide the first molecular evidence that LEO modulates skeletal muscle gene networks in a stimulation-dependent manner and may indicate its potential use as an aid to recovery (from fatigue) after exercise. Notably, the skin permeation of LEO components showed a saturation trend at concentrations above 5%, suggesting the presence of an optimal concentration range for topical application in sports aromatherapy.

Sweat plays a critical role in human body, including thermoregulation and the maintenance of the skin environment and health. Hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion, resulting in severe skin conditions (pruritus and erythema). Bioactive peptide and pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated and identified to activate adenylate cyclase in pituitary cells. Recently, it was reported that PACAP increases sweat secretion via PAC1R in mice and promotes the translocation of AQP5 to the cell membrane through increasing intracellular [Ca²⁺] via PAC1R in NCL-SG3 cells. However, intracellular signaling mechanisms by PACAP are poorly clarified. Here, we used PAC1R knockout (KO) mice and wild-type (WT) mice to observe changes in AQP5 localization and gene expression in sweat glands by PACAP treatment. Immunohistochemistry revealed that PACAP promoted the translocation of AQP5 to the lumen side in the eccrine gland via PAC1R. Furthermore, PACAP up-regulated the expression of genes (Ptgs2, Kcnn2, Cacna1s) involved in sweat secretion in WT mice. Moreover, PACAP treatment was found to down-regulate the Chrna1 gene expression in PAC1R KO mice. These genes were found to be involved in multiple pathways related to sweating. Our data provide a solid basis for future research initiatives in order to develop new therapies to treat sweating disorders.