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1.
Exp Dermatol ; 27(3): 280-284, 2018 03.
Article in English | MEDLINE | ID: mdl-29520873

ABSTRACT

Polyols (e.g. glycerol, xylitol) are implicated as moisturizers of the skin and other epithelial tissues. However, we lack information about their exact cellular mechanisms and their effects on the gene expression profiles. Therefore, in this study, we aimed at investigating the effects of glycerol and xylitol on human epidermal keratinocytes. The polyols (identical osmolarities; xylitol: 0.0045%-0.45%; glycerol: 0.0027%-0.27%) did not alter cellular viability or intracellular calcium concentration. However, they exerted differential effects on the expression of certain genes and signalling pathways. Indeed, both polyols up-regulated the expression of filaggrin, loricrin, involucrin and occludin; yet, xylitol exerted somewhat more profound effects. Moreover, while both polyols stimulated the MAPK pathway, only xylitol induced the activation-dependent translocation of protein kinase Cδ, a key promoter of epidermal differentiation. Finally, in various keratinocyte inflammation models, both polyols (albeit with different efficacies) exerted anti-inflammatory effects. Taken together, these data strongly suggest that glycerol and xylitol differentially modulate expressions of multiple genes and activities of signalling pathways in epidermal keratinocytes. Thus, our findings invite clinical trials to explore the applicability and the impact of a combined glycerol-xylitol therapy in the management of various skin conditions.


Subject(s)
Gene Expression/drug effects , Glycerol/pharmacology , Keratinocytes , Signal Transduction/drug effects , Transcriptome/drug effects , Xylitol/pharmacology , Cell Survival , Filaggrin Proteins , HLA-DR Antigens/genetics , Humans , Interleukins/metabolism , MAP Kinase Signaling System/drug effects , Matrix Metalloproteinases/metabolism , Protein Kinase C-delta/metabolism , Protein Transport/drug effects , Skin Physiological Phenomena/drug effects , Toll-Like Receptors/metabolism , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation
2.
J Dermatol Sci ; 88(1): 67-77, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28610718

ABSTRACT

BACKGROUND: Atopic eczema (AE) is a chronic inflammatory and pruritic skin disease. There is still an unmet need for topical anti-inflammatory and anti-pruritic substances exhibiting an excellent safety profile. The endocannabinoid system is known to regulate various aspects of cutaneous barrier and immune functions, thus targeting it may be a valid approach for alleviating the symptoms of AE. OBJECTIVE: To assess the putative efficacy of Echinacea purpurea-derived alkylamides (Ec. extract) activating cannabinoid (CB)-2 receptors in exerting anti-inflammatory effects and alleviating symptoms of AE. METHODS: In vitro anti-inflammatory efficiency was investigated by monitoring the effects of Ec. extract on poly-(I:C)-induced pro-inflammatory cytokine expression (Q-PCR) and release (ELISA) of HaCaT keratinocytes. Irritancy and sensitization potential (assessed by Human Repeat Insult Patch Test; Clinical trial 1); clinical efficiency in alleviating symptoms of AE (Clinical trial 2) as well as effects on human skin structure and lipid content (Clinical trial 3 followed by transmission electron microscopy and HPTLC) were investigated in randomized double blind clinical trials. RESULTS: Ec. extract significantly reduced mRNA expression as well as release of poly-(I:C)-induced pro-inflammatory cytokines (IL-6 and IL-8) in keratinocytes. Thus, not surprisingly, the well-tolerated (Clinical trial 1) Ec. extract-based cream reduced local SCORAD statistically significantly, not only compared to baseline, but also compared to the comparator (Clinical trial 2). Of great importance, besides the in vitro anti-inflammatory effects, administration of the Ec. extract-based cream also resulted in significantly higher levels of overall epidermal lipids, ceramide EOS (ω-esterified fatty acid+sphingosine sphingoid base), and cholesterol at Day 15 compared to baseline as well as significantly greater numbers of intercellular lipid lamellae in the intercellular space (Clinical trial 3). CONCLUSION: The investigated Ec. extract shows great potential in alleviating cutaneous symptoms of AE, and by exerting remarkable anti-inflammatory actions and restoring the epidermal lipid barrier, it will be very likely a well-tolerated, powerful novel ingredient for the adjuvant therapy of AE.


Subject(s)
Antipruritics/therapeutic use , Dermatitis, Atopic/drug therapy , Echinacea/chemistry , Plant Extracts/therapeutic use , Polyunsaturated Alkamides/therapeutic use , Pruritus/drug therapy , Receptor, Cannabinoid, CB2/agonists , Adolescent , Adult , Aged , Aged, 80 and over , Antipruritics/pharmacology , Cell Line , Chemotherapy, Adjuvant/methods , Child , Cytokines/metabolism , Dermatitis, Atopic/pathology , Double-Blind Method , Enzyme-Linked Immunosorbent Assay , Extracellular Space/chemistry , Female , Healthy Volunteers , Humans , Keratinocytes , Lipids/analysis , Male , Microscopy, Electron, Transmission , Middle Aged , Patch Tests , Plant Extracts/pharmacology , Polyunsaturated Alkamides/pharmacology , Pruritus/pathology , Real-Time Polymerase Chain Reaction , Skin/cytology , Skin/drug effects , Skin/pathology , Skin/ultrastructure , Young Adult
4.
Exp Dermatol ; 25(9): 701-7, 2016 09.
Article in English | MEDLINE | ID: mdl-27094344

ABSTRACT

Acne is a common skin disease characterized by elevated sebum production and inflammation of the sebaceous glands. We have previously shown that a non-psychotropic phytocannabinoid ((-)-cannabidiol [CBD]) exerted complex anti-acne effects by normalizing 'pro-acne agents'-induced excessive sebaceous lipid production, reducing proliferation and alleviating inflammation in human SZ95 sebocytes. Therefore, in this study we aimed to explore the putative anti-acne effects of further non-psychotropic phytocannabinoids ((-)-cannabichromene [CBC], (-)-cannabidivarin [CBDV], (-)-cannabigerol [CBG], (-)-cannabigerovarin [CBGV] and (-)-Δ(9) -tetrahydrocannabivarin [THCV]). Viability and proliferation of human SZ95 sebocytes were investigated by MTT and CyQUANT assays; cell death and lipid synthesis were monitored by DilC1 (5)-SYTOX Green labelling and Nile Red staining, respectively. Inflammatory responses were investigated by monitoring expressions of selected cytokines upon lipopolysaccharide treatment (RT-qPCR, ELISA). Up to 10 µm, the phytocannabinoids only negligibly altered the viability of the sebocytes, whereas high doses (≥50 µm) induced apoptosis. Interestingly, basal sebaceous lipid synthesis was differentially modulated by the substances: CBC and THCV suppressed it, and CBDV had only minor effects, whereas CBG and CBGV increased it. Importantly, CBC, CBDV and THCV significantly reduced arachidonic acid (AA)-induced 'acne-like' lipogenesis. Moreover, THCV suppressed proliferation, and all phytocannabinoids exerted remarkable anti-inflammatory actions. Our data suggest that CBG and CBGV may have potential in the treatment of dry-skin syndrome, whereas CBC, CBDV and especially THCV show promise to become highly efficient, novel anti-acne agents. Moreover, based on their remarkable anti-inflammatory actions, phytocannabinoids could be efficient, yet safe novel tools in the management of cutaneous inflammations.


Subject(s)
Acne Vulgaris/drug therapy , Cannabinoids/therapeutic use , Cannabinoids/pharmacology , Cell Line , Drug Evaluation, Preclinical , Humans , Lipogenesis/drug effects
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