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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 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

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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 2

CBD exerts sebostatic effects in vitro and under “in vivo–like” circumstances.

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CBD exerts sebostatic effects in vitro and under “in vivo–like” circumst...
(A) CyQUANT proliferation assay after 72-hour treatments. *P < 0.05, ***P < 0.001 compared with the 72-hour vehicle control. The solid line indicates the level of the 24-hour vehicle control. (B) MTT assay. Viability of sebocytes following 48-hour treatments. (C) Cell death [DilC1(5) and SYTOX Green double labeling] assays after 24-hour treatments. (A–C) Results 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. (D–G) hSOC of (D) control, (E) 10 μM CBD, (F) 30 μM AEA, and (G) 30 μM AEA plus CBD 10 μM (14 days; sebum: Oil Red O staining, red; nuclei: hematoxylin, blue). Scale bars: 50 μm. (H) Statistical analysis of the lipid production on 4 histological sections per group. Results are expressed as mean ± SEM. **P < 0.01. (I) Statistical analysis of the number of MKI67+ cells as compared with the number of DAPI+ cells on 2 histological sections per group (hSOC; 48 hours). **P < 0.01 compared with the vehicle control. Results are expressed as mean ± SEM.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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