Effects of Arachis hypogaea extract on TRPV4 activation and epidermal barrier function

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable non-selective cation channel and its activating stimuli include anandamide, bisandrographolide, citric acid, arachidonic acid metabolic products by epoxygenases, hypo-osmotic cell swelling, and warm temperature. TRPV4 is involved in Ca2+-dependent signal transduction in several tissues. Since the activation of TRPV4 facilitates adherens junction formation in the skin epithelium, compounds that activate TRPV4 are expected to maintain or improve the barrier function of epidermal cells. In this study, we found that the extract of Arachis hypogaea (A. hypogaea) activate human TRPV4 (hTRPV4). In the Ca2+-imaging experiment, the application of A. hypogaea extract exhibited an increase in intracellular Ca2+ concentration ([Ca2+]i) in HEK293T cells expressing hTRPV4. The [Ca2+]i increases by application of A. hypogaea extract were not observed in HEK293T cells expressing hTRPV1, mouse TRPV2, hTRPV3, hTRPM8, or hTRPA1. We then examined the physicochemical properties of the components responsible for TRPV4 activation. Ethanol extracts of A. hypogaea caused an increase in [Ca2+]i in hTRPV4-expressing HEK293JN cells, whereas water, chloroform, and hexane extracts showed no activity. Moreover, the application of A. hypogaea extract enhanced transepithelial electrical resistance in the keratinocyte monolayer. These results suggest that A. hypogaea extract may contribute to the maintenance and improvement of the epidermal barrier function.