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Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes
Attila Oláh, … , Ralf Paus, Tamás Bíró
Attila Oláh, … , Ralf Paus, Tamás Bíró
Published September 2, 2014; First published July 25, 2014
Citation Information: J Clin Invest. 2014;124(9):3713-3724. https://doi.org/10.1172/JCI64628.
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Categories: Research Article Dermatology

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

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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 1

CBD prevents excessive lipogenesis induced by “pro-acne agents” in human SZ95 sebocytes.

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CBD prevents excessive lipogenesis induced by “pro-acne agents” in human...
(A, B, D, and E) Semiquantitative determination of lipid synthesis for (A) control, (B) 10 μM CBD, (D) 30 μM AEA, and (E) 30 μM AEA plus 10 μM CBD (sebum droplets: Oil Red O staining, red; nuclei: hematoxylin, blue). Scale bars: 10 μm. (C) Quantitative determination of lipid synthesis (Nile Red staining). **P < 0.01, ***P < 0.001 compared with the AEA-treated group. PL, polar lipids; NL, neutral lipids. (F) Neutral lipid synthesis (Nile Red staining). ***P < 0.001 compared with the respective AA- or LA-T–treated group. (C and F) 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. (G) Analysis of the sebaceous lipidome. Sebaceous lipid classes were analyzed by HPLC-ToF/MS in sebocytes. CH, free cholesterol; CE, cholesteryl esters; WE, wax esters; DG, diacylglycerols; TG, triacylglycerols; SQ, squalene; FFA, free fatty acids. Results are expressed as the percentage of the vehicle control (mean ± SD of 3 independent determinations). The solid line indicates 100%. Two additional experiments yielded similar results. *P < 0.05, **P < 0.01, ***P < 0.001.
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