Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

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

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3713-3724
Number of pages12
JournalJournal of Clinical Investigation
Volume124
Issue number9
DOIs
Publication statusPublished - Sep 2 2014

Fingerprint

Cannabidiol
Anti-Inflammatory Agents
TRPV Cation Channels
Physiological Phenomena
Sebaceous Glands
Endocannabinoids
Skin
Lipogenesis
Purinergic P1 Receptors
MAP Kinase Signaling System
Organ Culture Techniques
Acne Vulgaris
Linoleic Acid
Cannabis
Ion Channels
Lipid Metabolism
Arachidonic Acid
Testosterone
Cell Differentiation
Up-Regulation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Oláh, A., Tóth, B. I., Borbíró, I., Sugawara, K., Szöllõsi, A. G., Czifra, G., ... Bíró, T. (2014). Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. Journal of Clinical Investigation, 124(9), 3713-3724. https://doi.org/10.1172/JCI64628

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. / Oláh, Attila; Tóth, Balázs I.; Borbíró, István; Sugawara, Koji; Szöllõsi, Attila G.; Czifra, Gabriella; Pál, Balázs; Ambrus, Lídia; Kloepper, Jennifer; Camera, Emanuela; Ludovici, Matteo; Picardo, Mauro; Voets, Thomas; Zouboulis, Christos C.; Paus, Ralf; Bíró, Tamás.

In: Journal of Clinical Investigation, Vol. 124, No. 9, 02.09.2014, p. 3713-3724.

Research output: Contribution to journalArticle

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 2014, 'Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes', Journal of Clinical Investigation, vol. 124, no. 9, pp. 3713-3724. https://doi.org/10.1172/JCI64628
Oláh A, Tóth BI, Borbíró I, Sugawara K, Szöllõsi AG, Czifra G et al. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. Journal of Clinical Investigation. 2014 Sep 2;124(9):3713-3724. https://doi.org/10.1172/JCI64628
Oláh, Attila ; Tóth, Balázs I. ; Borbíró, István ; Sugawara, Koji ; Szöllõsi, Attila G. ; Czifra, Gabriella ; Pál, Balázs ; Ambrus, Lídia ; Kloepper, Jennifer ; Camera, Emanuela ; Ludovici, Matteo ; Picardo, Mauro ; Voets, Thomas ; Zouboulis, Christos C. ; Paus, Ralf ; Bíró, Tamás. / Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. In: Journal of Clinical Investigation. 2014 ; Vol. 124, No. 9. pp. 3713-3724.
@article{f9089c4f10fe425cbdd6449a0bd37b19,
title = "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.",
author = "Attila Ol{\'a}h and T{\'o}th, {Bal{\'a}zs I.} and Istv{\'a}n Borb{\'i}r{\'o} and Koji Sugawara and Sz{\"o}ll{\~o}si, {Attila G.} and Gabriella Czifra and Bal{\'a}zs P{\'a}l and L{\'i}dia Ambrus and Jennifer Kloepper and Emanuela Camera and Matteo Ludovici and Mauro Picardo and Thomas Voets and Zouboulis, {Christos C.} and Ralf Paus and Tam{\'a}s B{\'i}r{\'o}",
year = "2014",
month = "9",
day = "2",
doi = "10.1172/JCI64628",
language = "English",
volume = "124",
pages = "3713--3724",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "9",

}

TY - JOUR

T1 - Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

AU - Oláh, Attila

AU - Tóth, Balázs I.

AU - Borbíró, István

AU - Sugawara, Koji

AU - Szöllõsi, Attila G.

AU - Czifra, Gabriella

AU - Pál, Balázs

AU - Ambrus, Lídia

AU - Kloepper, Jennifer

AU - Camera, Emanuela

AU - Ludovici, Matteo

AU - Picardo, Mauro

AU - Voets, Thomas

AU - Zouboulis, Christos C.

AU - Paus, Ralf

AU - Bíró, Tamás

PY - 2014/9/2

Y1 - 2014/9/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84907010601&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907010601&partnerID=8YFLogxK

U2 - 10.1172/JCI64628

DO - 10.1172/JCI64628

M3 - Article

VL - 124

SP - 3713

EP - 3724

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 9

ER -