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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.

PurposeSebum is an important shunt pathway for transdermal permeation and targeted delivery, but there have been limited studies on its permeation properties. Here we report a measurement and modelling study of solute partition to artificial sebum.MethodsEquilibrium experiments were carried out for the sebum-water partition coefficients of 23 neutral, cationic and anionic compounds at different pH.ResultsSebum-water partition coefficients not only depend on the hydrophobicity of the chemical but also on pH. As pH increases from 4.2 to 7.4, the partition of cationic chemicals to sebum increased rapidly. This appears to be due to increased electrostatic attraction between the cationic chemical and the fatty acids in sebum. Whereas for anionic chemicals, their sebum partition coefficients are negligibly small, which might result from their electrostatic repulsion to fatty acids. Increase in pH also resulted in a slight decrease of sebum partition of neutral chemicals.ConclusionsBased on the observed pH impact on the sebum-water partition of neutral, cationic and anionic compounds, a new quantitative structure-property relationship (QSPR) model has been proposed. This mathematical model considers the hydrophobic interaction and electrostatic interaction as the main mechanisms for the partition of neutral, cationic and anionic chemicals to sebum.

Propionibacterium acnes is considered to be involved in the aggravation of acne vulgaris, but it remains unclear whether P. acnes directly influences lipogenesis in sebaceous glands. In this study, we showed that a culture medium of P. acnes (acnes-CM) and formalin-killed P. acnes (F-acnes) prepared from P. acnes strains, JCM6473 and JCM6425, intracellularly augmented lipid droplet formation and triacylglycerol (TG) synthesis in undifferentiated and insulin-differentiated hamster sebocytes. Acnes-CM and F-acnes prepared from four clinical P. acnes strains elicited the same lipogenesis augmentation. The augmented TG production resulted from an increase in the diacylglycerol acyltransferase activity. Topical application of acnes-CM to the skin of hamster auricles every day for 4 weeks revealed that sebum accumulation was augmented in sebaceous glands and ducts. Furthermore, both acnes-CM and F-acnes increased the production of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a cytochrome P450 (CYP)-linked sebaceous lipogenic factor, in differentiated sebocytes. A CYP inhibitor, SKF-525A, decreased the acnes-CM- and F-acnes-augmented production of TG and 15d-PGJ2. Thus, to our knowledge these results provide previously unreported evidence that P. acnes directly participates in the augmentation of sebaceous lipogenesis through a proposed mechanism in which an increase of 15d-PGJ2 production through the CYP pathway is closely associated with the enhancement of TG production.

The pilosebaceous unit of the human skin consists of the hair follicle and the sebaceous gland. Within this “mini-organ”, the sebaceous gland has been neglected by the researchers of the field for several decades. Actually, it was labeled as a reminiscence of human development (“a living fossil with a past but no future”), and was thought to solely act as a producer of sebum, a lipid-enriched oily substance which protects our skin (and hence the body) against various insults. However, due to emerging research activities of the past two decades, it has now become evident that the sebaceous gland is not only a “passive” cutaneous “relic” to establish the physico-chemical barrier function of the skin against constant environmental challenges, but it rather functions as an “active” neuro-immuno-endocrine cutaneous organ. This review summarizes recent findings of sebaceous gland research by mainly focusing on newly discovered physiological functions, novel regulatory mechanisms, key events in the pathology of the gland, and future directions in both experimental and clinical dermatology.

Background: Zinc pyrithione (ZnPT) is deposited on the skin as a fine particulate and must reach microorganisms localized in the stratum corneum and hair follicles in molecular form to exert its broad-spectrum antimicrobial/antifungal activity. Dissolution of ZnPT particles followed by molecular speciation results in the organic portion, i.e. pyrithione, being more susceptible to skin penetration than the inorganic component, i.e. zinc, or the chelate itself, i.e. ZnPT. Objectives: To further test the hypothesis that ZnPT skin penetration is rate-limited by dissolution and molecular speciation, the effect of different formulations and artificial sebum on the in vitro percutaneous absorption of radiolabel associated with Zn[ 14 C]PT was investigated. Method: In vitro penetration of [ 14 C]PT into and through excised human skin was measured following application of Zn[ 14 C]PT prepared as suspensions in distinct vehicles including water-based carboxymethylcellulose (CMC), diluted body wash comprised of surfactants, and castor oil, in the presence and absence of artificial sebum. Results: The steady-state flux and cumulative absorption of Zn[ 14 C]PT increased 4- to 5-fold when deposited from a body wash or castor oil compared to a water-based CMC suspension. Tritiated water flux measured before and after treatment showed that neither the surfactant vehicle nor castor oil significantly altered barrier function versus water alone. An artificial sebum layer on the skin potentiated Zn[ 14 C]PT and 3 H 2 O absorption when dosed from both aqueous formulations, but not from castor oil. Conclusion: These data are consistent with the hypothesis that ZnPT percutaneous absorption, as measured by [ 14 C]PT kinetics, is controlled by particle dissolution and molecular speciation.

The mRNA expression patterns of the androgen receptor and the androgen metabolizing enzymes 3β-hydroxysteroid dehydrogenase/Δ5-4-isomerase, 17β-hydroxysteroid dehydrogenase, 5α-reductase, and 3α-hydroxysteroid dehydrogenase were investigated in three different cell populations originating from human skin, SZ95 sebocytes, HaCaT keratinocytes, and MeWo melanoma cells, by means of reverse transcription polymerase chain reaction. Restriction analysis of cDNA fragments was performed to identify isozymes of 3β-hydroxysteroid dehydrogenase/Δ5-4-isomerase and 3α-hydroxysteroid dehydrogenase. In addition, 3H-dihydroepiandrosterone and 3H-testosterone were used as substrates to determine the metabolic activity of these enzymes in SZ95 sebocytes, primary sebocyte cultures, and HaCaT keratinocytes. Furthermore, the effects of the selective 5α-reductase type 1 and 2 inhibitors, 4,7β-dimethyl-4-aza-5α-cholestan-3-one and dihydrofinasteride, respectively, and of the 3β-hydroxysteroid dehydrogenase/Δ5-4-isomerase inhibitor cyproterone acetate on androgen metabolism were investigated. Androgen receptor mRNA was detected in SZ95 sebocytes and HaCaT keratinocytes but not in MeWo melanoma cells, whereas 3β-hydroxysteroid dehydrogenase/Δ5-4-isomerase isotype 1 mRNA and metabolic activity were only found in SZ95 sebocytes. The enzyme activity could be inhibited by cyproterone acetate. Type 2 17β-hydroxysteroid dehydrogenase, type 1 5α-reductase, and 3α-hydroxysteroid dehydrogenase mRNA were expressed in all three cell populations tested, whereas type 3 17β-hydroxysteroid dehydrogenase mRNA could only be detected in SZ95 sebocytes. The major metabolic steps of testosterone in SZ95 sebocytes, primary sebocyte cultures, and HaCaT keratinocytes were its conversion to androstenedione by 17β-hydroxysteroid dehydrogenase and further to 5α-androstanedione by 5α-reductase. The type 1 5α-reductase selective inhibitor 4,7β-dimethyl-4-aza-5α-cholestan-3-one, but not the type 2 selective inhibitor dihydrofinasteride, inhibited 5α-reductase at low concentrations in SZ95 sebocytes and HaCaT keratinocytes. 5α-androstanedione was degraded to androsterone by 3α-hydroxysteroid dehydrogenase, which exhibited a stronger activity in HaCaT keratinocytes than in SZ95 sebocytes and in primary sebocyte cultures. Lower levels of 5α-dihydrotestosterone and 5α-androstanediol were also detected in all cells tested. Our investigations show that specific enzyme expression and activity in cultured sebocytes and keratinocytes seem to allocate different duties to these cells in vitro. Sebocytes are able to synthesize testosterone from adrenal precursors and to inactivate it in order to maintain androgen homeostasis, whereas keratinocytes are responsible for androgen degradation.

Acne is the most common skin disease which affects millions of people worldwide. Seborrhea and sebostasis are major cosmetic problems but also lead occasionally to diseases. This article summarizes the data of newest research of sebostasis, seborrhoea and acne made possible through the development of human and animal sebocyte culture models.

α-Tocopherol, the major biologically active form of vitamin E, represents a frequently added lipophilic compound of skin care products. Despite its emerging use in rinse-off formulations, little is known on its efficacy with respect to its deposition or its antioxidant potential in human skin. The objective of this study was to investigate whether the single use of an α-tocopherol-enriched rinse-off product provides effective deposition of α-tocopherol on human stratum corneum. To test this, forearm skin of 13 volunteers was washed either with an α-tocopherol-enriched rinse-off product (test product, TP) or with an α-tocopherol-free vehicle control (control product, CP) (contralateral arm) using a standardized wash protocol. Thereafter, skin surface lipids were extracted with pure ethanol after the wash procedure as well as after 24 h. Additionally, one group of volunteers was subjected to irradiation of their forearms with low-dose UVA (8 J/cm 2 ) prior to lipid extraction. Skin lipid extracts were analyzed by high performance liquid chromatography using electrochemical detection for vitamin E and UV detection for squalene (SQ) and squalene monohydroperoxide. The results of this in vivo study demonstrated that (1) while CP treatment lowers, TP treatment strongly increases α-tocopherol levels of skin barrier lipids; (2) increased vitamin E deposition levels were maintained for a period of at least 24 h, and (3) TP treatment significantly inhibited photooxidation of SQ. In conclusion, the use of α-tocopherol-enriched rinse-off products may help to maintain the integrity of the skin barrier by providing protection against photooxidative stress at the level of skin surface lipids.

Summary The secretions of sebaceous and apocrine glands fulfil an important thermoregulatory role in cold-stressed and heat-stressed hunter-gatherers. In hot conditions the secretions emulsify eccrine sweat and thus encourage the formation of a sweat sheet and discourage the formation and loss of sweat drops from the skin. In colder conditions sebum changes its nature and repels rain from skin and hair.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, which is characterised by degeneration of distinct neuronal populations, including dopaminergic neurons of the substantia nigra. Here, we use a metabolomics profiling approach to identify changes to lipids in PD observed in sebum, a non-invasively available biofluid. We used liquid chromatography-mass spectrometry (LC-MS) to analyse 274 samples from participants (80 drug naïve PD, 138 medicated PD and 56 well matched control subjects) and detected metabolites that could predict PD phenotype. Pathway enrichment analysis shows alterations in lipid metabolism related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis. This study shows sebum can be used to identify potential biomarkers for PD. Studies of metabolites in neurodegeneration have not yet used sebum as a source fluid. Here the authors demonstrate the potential of metabolomics of sebum samples from individuals with Parkinson’s disease and controls.