Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes
Attila Oláh, … , Ralf Paus, Tamás Bíró
Attila Oláh, … , Ralf Paus, Tamás Bíró
Published July 25, 2014
Citation Information: J Clin Invest. 2014;124(9):3713-3724. https://doi.org/10.1172/JCI64628.
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Research Article Dermatology

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

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.

Authors

Attila Oláh, Balázs I. Tóth, István Borbíró, Koji Sugawara, Attila G. Szöllõsi, Gabriella Czifra, Balázs Pál, Lídia Ambrus, Jennifer Kloepper, Emanuela Camera, Matteo Ludovici, Mauro Picardo, Thomas Voets, Christos C. Zouboulis, Ralf Paus, Tamás Bíró

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Figure 5

Lipostatic activity of CBD is mediated by TRPV4.

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Lipostatic activity of CBD is mediated by TRPV4. (A) Fluorescent Ca2+ im...
(A) Fluorescent Ca2+ imaging. Compounds were applied as indicated by the arrow. Fluorescence (measured in relative fluorescence units [RF]) was normalized to the baseline. “Low [Ca2+]EC” indicates the use of nominally Ca2+-free Hank’s solution. Two additional experiments yielded similar results. (B) Statistical analysis of the fluorescent Ca2+-imaging data. Fluorescence (expressed in RF) was normalized to the baseline. Measured peak values were expressed as the percentage of the baseline (mean ± SEM of 3 independent determinations). The solid line indicates 100%. Two additional experiments yielded similar results. ***P < 0.001 compared with the CBD-treated group. (C) Neutral lipid synthesis (Nile Red staining). Data are expressed as the percentage of the vehicle control (mean ± SEM of 4 independent determinations). The solid line indicates 100%. Two additional experiments yielded similar results. “Low [Ca2+]EC” indicates the use of low-Ca2+ Sebomed medium. *P < 0.05, **P < 0.01, ***P < 0.001. (D and E) Neutral lipid synthesis (Nile Red staining) following selective gene silencing of TRPV4 channel (24-hour treatments, started at day 3 after the transfection). Data are expressed as the percentage of the untransfected vehicle control (mean ± SEM of 4 independent determinations). The solid line indicates 100%. Two additional experiments yielded similar results. *P < 0.05, ***P < 0.001 compared with the SCR cells. “siV4a” and “siV4b” mark 2 different siRNA constructs against TRPV4. SCR, scrambled control; UC, untransfected vehicle control.