Topical cannabinoid receptor 1 agonist attenuates the cutaneous inflammatory responses in oxazolone‐induced atopic dermatitis model

Kim, Hyun Jong; Kim, BongWoo; Park, Bu Man; Jeon, Jeong Eun; Lee, Sin Hee; Mann, Shivtaj; Ahn, Sung Ku; Hong, Seung‐Phil; Jeong, Se Kyoo

doi:10.1111/ijd.12841

Cited by 52 publications

(36 citation statements)

References 28 publications

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“…Two major CBRs are CB1 and CB2, and recently another G protein-coupled cannabinoid receptor, GPR55, has emerged as a type 3 CBR [58]. Several studies have shown that CB1 agonists relieve inflammatory symptoms [59] by downregulating mast cell activation [60] and decreasing keratinocyte-derived proinflammatory mediators [61]. In addition, CB2 agonists suppress skin inflammation by inhibiting inflammatory cell migration [62], and GPR55, which is found in mast cells, has anti-inflammatory effects by inhibiting mast cell-mediated release of nerve growth factor and reducing angiogenesis [63].…”

Section: Discussionmentioning

confidence: 99%

Effect of Hataedock Treatment on Epidermal Structure Maintenance through Intervention in the Endocannabinoid System

Ahn

Yang

Park

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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The aim of this study was to investigate the efficacy of Hataedock (HTD) on skin barrier maintenance through the endocannabinoid system (ECS) intervention in Dermatophagoides farinae-induced atopic dermatitis (AD) NC/Nga mice. Douchi (fermented Glycine max Merr.) extracts prepared for HTD were orally administered to NC/Nga mice at a 20 mg/kg dose. Then, Dermatophagoides farinae extract (DfE) was applied to induce AD-like skin lesions during the 4th–6th and 8th–10th weeks. Changes in the epidermal structure of the mice were observed by histochemistry, immunohistochemistry, and TUNEL assay. The results showed that HTD significantly reduced the clinical scores (p<0.01) and effectively alleviated the histological features. In the experimental groups, increased expression of cannabinoid receptor type (CB) 1, CB2, and G protein-coupled receptor 55 (GPR55) and distribution of filaggrin, involucrin, loricrin, and longevity assurance homolog 2 (Lass2) indicated that HTD maintained the epidermal barrier through intervening in the ECS. The expression of E-cadherin and glutathione peroxidase 4 (GPx4) was increased, and the levels of cluster of differentiation 1a (CD1A) were low. Moreover, the apoptosis of inflammatory cells was elevated. The production of phosphorylated extracellular signal-related kinase (p-ERK), phosphorylated c-Jun amino-terminal kinase (p-JNK), and phosphorylated mammalian target of rapamycin (p-mTOR) was low, and epidermal thickness was decreased. Besides, the expression levels of involucrin were measured by treating genistein, an active ingredient of Douchi extract, and palmitoylethanolamide (PEA), one of the ECS agonists. The results showed that genistein had a better lipid barrier formation effect than PEA. In conclusion, HTD alleviates the symptoms of AD by maintaining skin homeostasis, improving skin barrier formation, and downregulating inflammation, through ECS intervention.

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Section: Discussionmentioning

confidence: 99%

Effect of Hataedock Treatment on Epidermal Structure Maintenance through Intervention in the Endocannabinoid System

Ahn

Yang

Park

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…Therefore, in an in vivo experimental model using phorbol ester-induced acute inflammation developed in mice and atopic dermatitis-like symptoms induced with oxazolone, CB1 agonists proved their anti-inflammatory action through several proposed mechanisms. Mast-cells downregulation, peroxisome-proliferator activated receptors (PPARs) activation, and the decrease of epidermal production of IFN-γ and several chemokines, such as CCL2, CCL8, and CXL10 were the possible anti-inflammatory involved pathways [115,116].…”

Section: Allergic Contact Dermatitismentioning

confidence: 99%

Cannabinoids in the Pathophysiology of Skin Inflammation

et al. 2020

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Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component. However, various studies cite conflicting results concerning the cellular mechanisms involved, while others suggest that cannabinoids may even exert pro-inflammatory behaviors. This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer. In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances. Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.

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“…Mice with CB1 -/keratinocytes presented higher skin inflammation, eosinophil infiltration, and expression levels of IL-4, TSLP, and CCL8 when challenged with fluorescein isothiocyanate [138]. Topical administration of AEA and α-oleoyl oleylamine serinol (α-OOS), a synthetic CB1 agonist, accelerated barrier recovery and reduced chemokines in both oxazolone-and tetradecanoylphorbol acetate-induced AD models [140,141]. CB1 activation also showed anti-inflammatory functions, reduced mast cell recruitment, proliferation, and degranulation, and decreased Th2 cytokines [73,141,142].…”

Section: Cannabinoids In Allergy 575mentioning

confidence: 99%

The Role of Cannabinoids in Allergic Diseases: Collegium Internationale Allergologicum (CIA) Update 2020

Angelina

Pérez‐Diego

López‐Abente

et al. 2020

Int Arch Allergy Immunol

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The human endocannabinoid system (ECS) is a complex signalling network involved in many key physiological processes. The ECS includes the cannabinoid receptors, the endocannabinoid ligands, and the enzymes related to their synthesis and degradation. Other cannabinoids encompass the phytocannabinoids from Cannabis sativa L. (marijuana) and the synthetic cannabinoids. Alterations in the ECS are associated with different diseases, including inflammatory and immune-mediated disorders such as allergy. Allergy is a global health problem of increasing prevalence with high socioeconomic impact. Different studies have convincingly demonstrated that cannabinoids play a role in allergy, but their actual contribution is still controversial. It has been shown that cannabinoids exert anti-inflammatory properties in the airways and the skin of allergic patients. Other studies reported that cannabinoids might exacerbate asthma and atopic dermatitis mainly depending on CB2-mediated signalling pathways. A better understanding of the molecular mechanisms involved in the mode of action of specific cannabinoids and cannabinoid receptors on relevant immune cells under different biological contexts might well contribute to the design of novel strategies for the prevention and treatment of allergic diseases. Future research in this promising emerging field in the context of allergy is warranted for the upcoming years.

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Topical cannabinoid receptor 1 agonist attenuates the cutaneous inflammatory responses in oxazolone‐induced atopic dermatitis model

Abstract: All of the results suggest that topical application of CB1R-specific agonist can be beneficial for alleviating the inflammatory symptoms in chronic skin diseases, including atopic dermatitis.

Cited by 52 publications

References 28 publications

Effect of Hataedock Treatment on Epidermal Structure Maintenance through Intervention in the Endocannabinoid System

Effect of Hataedock Treatment on Epidermal Structure Maintenance through Intervention in the Endocannabinoid System

Cannabinoids in the Pathophysiology of Skin Inflammation

The Role of Cannabinoids in Allergic Diseases: Collegium Internationale Allergologicum (CIA) Update 2020

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