Authors:
Oláh A, Tóth BI, Borbíró I, Sugawara K, Szöllõsi AG, Czifra G, Pál B, Ambrus L, Kloepper J, Camera E, Ludovici M, Picardo M, Voets T, Zouboulis CC, Paus R, Bíró T.
Abstract:
The endocannabinoid system (ECS) regulates multiple physiological
processes, including cutaneous cell growth and differentiation. Here, we
explored the effects of the major nonpsychotropic phytocannabinoid of
Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland
function and determined that CBD behaves as a highly effective
sebostatic agent. Administration of CBD to cultured human sebocytes and
human skin organ culture inhibited the lipogenic actions of various
compounds, including arachidonic acid and a combination of linoleic acid
and testosterone, and suppressed sebocyte proliferation via the
activation of transient receptor potential vanilloid-4 (TRPV4) ion
channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2
MAPK pathway and resulted in the downregulation of nuclear receptor
interacting protein-1 (NRIP1), which influences glucose and lipid
metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted
complex antiinflammatory actions that were coupled to A2a adenosine
receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and
inhibition of the NF-κB signaling. Collectively, our findings suggest
that, due to the combined lipostatic, antiproliferative, and
antiinflammatory effects, CBD has potential as a promising therapeutic
agent for the treatment of acne vulgaris.