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International Journal of Dermatology Oct 2014Anthralin (1,8-dihydroxy-9anthrone, dithranol) was first synthesized as a derivative of chrysarobin, prepared from the araroba tree in Brazil over a century ago.... (Review)
Review
Anthralin (1,8-dihydroxy-9anthrone, dithranol) was first synthesized as a derivative of chrysarobin, prepared from the araroba tree in Brazil over a century ago. Drawbacks to the use of anthralin include irritation and discoloration of the skin. This property of the molecule prompted workers to investigate details of its pharmacology, mode of action, and indications. The major point of this article is to highlight and revisit these aspects for pertinent future use. Therefore, it is worthwhile to consider that the drug is relatively innocuous, yet effective, and is devoid of any systemic side effects in contrast to a wide variety of systemic and topical therapies available for psoriasis and other dermatoses.
Topics: Anthralin; Humans; Skin Diseases
PubMed: 25208745
DOI: 10.1111/j.1365-4632.2012.05611.x -
Dermatologica 1986
Topics: Anthralin; DNA Replication; Humans; Mitochondria; Psoriasis; Skin Pigmentation; Time Factors
PubMed: 3817237
DOI: 10.1159/000249268 -
Journal of the American Academy of... Aug 1983Anthralin was first synthesized in 1916. Earlier, a natural product, chrysarobin, originally derived from the South American araroba tree, had been used to treat... (Review)
Review
Anthralin was first synthesized in 1916. Earlier, a natural product, chrysarobin, originally derived from the South American araroba tree, had been used to treat psoriasis. Anthralin was first used in Germany, and later in the Ingram regimen in Britain, but it has never been popular with American dermatologists. This is probably due to the side effects of staining and irritation of the skin. Attempts to reduce these using low concentration, short contact therapy, and concomitant steroid therapy, have been only partially successful. It may be that better instruction of patients and physicians will lead to wider use of this effective topical agent for the treatment of psoriasis. The mode of action of anthralin is thought to be either through its effect on deoxyribonucleic acid (DNA), probably mitochondrial DNA, which reduces cell turnover, or through its effects on various enzyme systems, including those of polyamine synthesis and respiration. The aims of this review are to discuss historical aspects of anthralin and to update its chemistry, pharmacology, and clinical usage.
Topics: Anthracenes; Anthralin; Cell Division; Chemistry; Cyclic AMP; Cyclic GMP; DNA Replication; Drug Administration Schedule; England; Erythema; Glucosephosphate Dehydrogenase; History, 19th Century; History, 20th Century; Humans; Mitochondria; Oxidation-Reduction; Polyamines; Psoriasis; Skin Absorption; Skin Neoplasms; Structure-Activity Relationship
PubMed: 6309924
DOI: 10.1016/s0190-9622(83)70125-8 -
The British Journal of Dermatology Aug 1981
Topics: Anthracenes; Anthralin; Cell Line; Cell Survival; Fibroblasts; Humans; Skin
PubMed: 7284263
DOI: 10.1111/j.1365-2133.1981.tb00999.x -
Antipsoriatic and proinflammatory action of anthralin. Implications for the role of oxygen radicals.Biochemical Pharmacology May 1997Anthralin is among the most effective agents for the topical treatment of psoriasis. However, this drug causes unpleasant side-effects such as inflammation and staining... (Review)
Review
Anthralin is among the most effective agents for the topical treatment of psoriasis. However, this drug causes unpleasant side-effects such as inflammation and staining of the nonaffected skin surrounding a psoriatic lesion. The biochemical basis for the induction of an inflammatory response in the skin and the antipsoriatic effectiveness are uncertain, although several cellular targets of anthralin action have been identified. Because no single mechanism is operative, the view was taken that all the effects exerted by anthralin are caused by its redox activity leading to the generation of anthralin free radicals and oxygen radicals. Clear relationships between oxygen-radical production by anthralin and biological response are evident with respect to chemical lesions in cellular macromolecules such as DNA, lipid membranes, and enzymes, indicating that these species account for the antipsoriatic and proinflammatory effects elicited by anthralin. This poses new challenges for the medicinal chemist and provides impetus for identifying novel compounds having potential for an improved therapeutic index.
Topics: Anthralin; Free Radicals; Humans; Inflammation Mediators; Psoriasis; Reactive Oxygen Species; Skin
PubMed: 9214681
DOI: 10.1016/s0006-2952(96)00732-0 -
Der Hautarzt; Zeitschrift Fur... May 2017
Topics: Anthralin; Cell Proliferation; Dermatologic Agents; Drug Combinations; Humans; Psoriasis
PubMed: 28401270
DOI: 10.1007/s00105-017-3977-5 -
Acta Dermato-venereologica. Supplementum 1994Anthralin is still the most effective and safest therapeutic agent for treatment of psoriasis. Our data may assist toward an understanding of its mode of action and...
Anthralin is still the most effective and safest therapeutic agent for treatment of psoriasis. Our data may assist toward an understanding of its mode of action and introduce new derivatives, more antiproliferative and less toxic than anthralin in vitro. Anthralin exerts a direct effect on keratinocytes and leukocytes. In time-lapse studies it significantly prolonged the prophase of mitotic keratinocytes in subtoxic doses and suppressed the expression of keratin 6 mRNA in the immediately suprabasal layer of psoriatic epidermis in vivo. Anthralin inhibits the transformation of lymphocytes and the release of reactive oxygen species from activated leukocytes, in vitro. We provide evidence that these effects of anthralin are mediated by protein kinase C. Twelve new hydrophilic derivatives of anthralin, including a 1,8-dimethoxy compound, as well as C-2 and C-10 substituted anthrones were tested on human keratinocytes. The antiproliferative effect of those derivatives bearing lacton rings at a C-10, consisting of 4, 5, or 6 C atoms, exceeded that of anthralin and were equally or less cytotoxic than the parent drug. These compounds had no pro-drug character in vitro, since they did not metabolize via anthralin, as shown by HPLC. These data indicate that there may be anthralin derivatives with more favourable properties for topical therapy than anthralin itself.
Topics: Anthralin; Humans; Psoriasis
PubMed: 8073848
DOI: No ID Found -
Journal of Dermatological Science Sep 2017Psoriasis is an inflammatory skin disease with aberrant keratinocyte proliferation, presumably as a result of immune cell activation. Th17 cytokines like IL-17A and...
BACKGROUND
Psoriasis is an inflammatory skin disease with aberrant keratinocyte proliferation, presumably as a result of immune cell activation. Th17 cytokines like IL-17A and IL-22 are critically implicated in epidermal thickening, altered keratinocyte differentiation and production of innate factors such as antimicrobial peptides. Psoriasis treatment options include modern targeted therapies using anti-cytokine antibodies and traditional non-targeted treatments like anthralin (dithranol). While the mode of action of anti-cytokine antibodies is defined, the effects of topical anthralin on psoriatic skin are not fully understood.
OBJECTIVE
This study aims to unravel the direct effects of anthralin on keratinocyte proliferation, differentiation and production of psoriasis-associated factors.
METHODS
We tested the effects of anthralin on cell proliferation, cytokeratin expression and changes in the expression of antimicrobial peptides using primary keratinocytes and 3D psoriasis tissue models with and without stimulation of the psoriasis-promoting cytokines IL-17A and IL-22. Moreover, we compared the findings derived from monolayer and multilayer cultures to data derived from lesional skin of patients with psoriasis before and under treatment with anthralin.
RESULTS
Our study shows that anthralin directly induces cell apoptosis in vitro in monolayer cultures but not in 3D psoriasis tissue models treated with IL-17A and IL-22. Yet, keratinocyte proliferation as determined by Ki-67 staining is impaired by anthralin in vivo. In lesional skin but not in 3D psoriasis tissue models anthralin rapidly normalizes cytokeratin (CK)16 expression. Furthermore, anthralin directly inhibits DEFB4 expression in vitro and in vivo, while other antimicrobial peptides and cytokines studied like IL-6 and IL-8 are regulated differently in vitro and in vivo.
CONCLUSIONS
Our results show that anthralin directly regulates DEFB4A expression. However, its beneficial effects on psoriasis cannot be explained by direct effects on keratinocyte differentiation or cytokine expression.
Topics: Administration, Cutaneous; Anthralin; Apoptosis; Biopsy; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dermatologic Agents; Fluorescent Antibody Technique; Humans; Interleukin-17; Interleukin-6; Interleukin-8; Interleukins; Keratin-10; Keratin-16; Keratin-5; Keratinocytes; Ki-67 Antigen; Psoriasis; Skin; Tissue Culture Techniques; beta-Defensins; Interleukin-22
PubMed: 28673488
DOI: 10.1016/j.jdermsci.2017.06.007 -
International Journal of Dermatology Nov 1985Topical anthralin application producing a brisk irritant contact dermatitis has been reported to have therapeutic benefit in alopecia areata. A pilot clinical study was... (Clinical Trial)
Clinical Trial
Topical anthralin application producing a brisk irritant contact dermatitis has been reported to have therapeutic benefit in alopecia areata. A pilot clinical study was undertaken to determine whether topical anthralin application in doses low enough to produce only minimal contact dermatitis would produce a similar therapeutic response. None of the patients in the study received any benefit from this low-dose regimen. If anthralin is of benefit in the therapy of alopecia areata, a significant irritant contact dermatitis is apparently required.
Topics: Administration, Topical; Alopecia Areata; Anthracenes; Anthralin; Clinical Trials as Topic; Humans
PubMed: 3905640
DOI: 10.1111/j.1365-4362.1985.tb05863.x -
Annales de Dermatologie Et de... 1987
Topics: Animals; Anthralin; Chemical Phenomena; Chemistry; Humans; Psoriasis; Structure-Activity Relationship
PubMed: 3445989
DOI: No ID Found