Reviews 1447 Topically Used Herbal Products for the Treatment of Psoriasis – Mechanism of Action, Drug Delivery, Clinical Studies Authors Anna Herman1, Andrzej P. Herman 2 Affiliations 1 Faculty of Cosmetology, The Academy of Cosmetics and Health Care, Warsaw, Poland 2 Laboratory of Molecular Biology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Jabłonna, Poland Key words Abstract several electronic databases and literature refer- l" Psoriasis ! ences were used to summarize the current l" herbal products Psoriasis is a chronic inflammatory skin disease knowledge acquired on the basis of animal stud- l" keratinocyte hyper- characterized histologically by hyperproliferation ies and clinical trials regarding herbal products proliferation and aberrant differentiation of epidermal kerati- used to treat psoriasis topically. This review dis- l" inflammatory reaction l" skin barrier nocytes. A wide range of conventional medical cusses the mechanisms of herbal products activ- l" herbal drug delivery systems therapies to treat psoriasis is established, from ities through (1) inhibition of the keratinocyte hy- topical therapies and systemic medications perproliferation and inducing apoptosis, (2) inhi- through to phototherapy or combinations of bition of immune-inflammatory reaction, (3) those. However, most of these therapies have a suppression of phosphorylase kinase (PhK) activ- limited efficacy and may cause a number of side ity, and (4) inhibition of the hedgehog (Hh) sig- effects, including cutaneous atrophy, organ toxic- naling pathway. Moreover, the penetration of ity, carcinogenicity, and broadband immunosup- herbal products through the psoriatic skin barrier, pression, which are restricting their long-term novel herbal drug delivery systems in psoriasis use. Therefore, it would be desirable to use herbal treatment, and possible adverse effects of herbal products as an alternative treatment for psoriasis therapy are discussed. that causes fewer side effects. For this purpose, Introduction treatment of psoriasis causes its remission after ! finishing the treatment or only relieves the pa- Psoriasis is a chronic autoimmune human skin tientʼs condition. Moreover, psoriasis is often ac- disorder that is characterized by excessive prolif- companied by other diseases, such as depressive received May 23, 2016 revised July 31, 2016 eration of keratinocytes, scaly plaques, severe in- illness, cardiovascular disease, and a seronegative accepted August 8, 2016 flammation, and erythema [1]. A wide range of arthritis known as psoriatic arthritis [5]. There- conventional medical therapies to treat psoriasis fore, the invention of new alternative treatments Bibliography This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. DOI http://dx.doi.org/ is established, from topical therapies [steroids, vi- for psoriasis causing fewer side effects would be 10.1055/s-0042-115177 tamin D analogues, psoralen, 5-aminolevulinic desirable. It seems that several herbal drugs can Published online August 30, acid, salicylates, fumaric acid esters, anthralins meet these requirements and have to be seen as 2016 (dithranol), tacrolimus, retinoids – e.g tazarotene] promising new agents for psoriasis treatment [6]. Planta Med 2016; 82: and systemic medications (methotrexate, cyclo- Herbal products are greatly accepted by patients 1447–1455 © Georg Thieme Verlag KG Stuttgart · New York · sporine, retinoids, 6-thioguanine, mycophenolate because they are believed to be safer than conven- ISSN 0032‑0943 mofetil, troglitazone and new biologic agents, tional therapeutics. Moreover, herbal products such as adalimumab, alefacept, efalizumab, eta- present a great structural diversity and multi- Correspondence Anna Herman, PhD, DSc, Prof. nercept, infliximab), through to phototherapy or directional mechanisms of action, which is not Faculty of Cosmetology combinations of those [2]. However, most of these commonly seen in synthetic compounds. Herbal The Academy of Cosmetics and therapies cause a number of side effects, and lim- drugs may become an effective treatment for Health Care Podwale 13 street ited in efficacy, inconvenience, cutaneous atro- psoriasis, causing lower costs and less side- or 00–252 Warsaw phy, organ toxicity (hepatotoxicity, nephrotoxic- toxic effects in comparison to other therapies. Poland ity, teratogenicity), carcinogenicity, and broad- Therefore, researchers are still looking for novel Phone: + 48226355009 Fax: + 482 26357362 band immunosuppression, which are limiting herbal products and/or their active constituents, [email protected] their long-term use [3,4]. In turn, a short-term Herman A, Herman AP. Topically Used Herbal… Planta Med 2016; 82: 1447–1455 1448 Reviews which potentially could be used for the treatment of psoriasis in- Proinflammatory cytokines produced by these cells, including tu- stead of synthetic drugs. mor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin- The goal of this review is to summarize the knowledge based on 17 (IL-17), IL-20, IL-22, IL-23, IL-12, and IL-1b, have been linked animal studies and clinical trials regarding herbal products used to the pathogenesis of psoriasis through causing keratinocytes for the topical treatment of psoriasis and to characterize their hyperproliferation [7]. Moreover, IFN-γ and IL-15 seem to in- mechanisms of action. Penetration of herbal products through crease the apoptotic resistance of the keratinocytes [15,16]. Also the psoriatic skin barrier, novel herbal drug delivery systems in growth factors and genetic factors like transforming growth fac- psoriasis treatment, and possible adverse effects of herbal ther- tor (TGF)-β, toll-like receptor (TLR)-2, signal transducer and acti- apy are also discussed. vator of transcription (STAT-3), coiled-coil alpha-helical rod pro- tein 1 (CCHCR1), steroidogenic acute regulatory protein (StAR), and vitamin D receptor (VDR) are suggested to be the most crit- Methods ical factors governing the exacerbation of psoriasis [17,18]. The ! essential transcription factor in psoriasis, nuclear factor kappa B Search strategy (NF-κB), has been shown to be a key regulatory element occur- PubMed, Scopus and Google Scholar were searched for articles ring in a variety of immune and inflammatory pathways, in cellu- published from 1995 up to the present. Search terms included lar proliferation and differentiation, and in apoptosis [19]. An im- “herbal products and psoriasis”, “herbal treatments for psoriasis”, balance between the proapoptotic and antiapoptotic activities of “topical herbal medication for psoriasis”,and“herbal drug deliv- NF-κB proteins has been demonstrated to cause differentiation ery systems in psoriasis treatment”. References from reviews and hyperproliferation in psoriatic lesions rather than in normal about herbal products and psoriasis were examined for addition- cells [20]. al articles and case reports. A manual search was also conducted, based on citations in scientific literature. Topically Used Herbal Products for the Treatment of Psoriasis Inclusion and exclusion criteria Many herbal topical formulations have been marketed world- Selection criteria included articles which are examining herbal wide to prevent psoriasis [21]. There are many advantages of us- products used for the topical treatment of psoriasis by means of ing natural drugs, including patient compliance, less side-effects, animal studies and clinical trials, and are comparing herbal prod- easy availability, low-costs, and more than one mode of biochem- ucts treatment vs. control treatments (placebo or active therapy). ical action for psoriasis treatment. Therefore, researchers are Other forms of psoriasis treatment than topical administration of searching for new herbal products, which have the potential to herbal products (e.g. oral, systemic) were excluded from the be an alternative for synthetic drugs in psoriasis therapy. study. Also publications in languages other than English were ex- cluded. Animal-based studies Herbal products with an anti-psoriasis potential tested in animal- Pathology of Psoriasis based studies are summarized in l" Table 1. Most of the in vivo The pathophysiology of psoriasis involves both skin cells and im- studies performed in animals are based on a mouse tail model of mune cells. Psoriasis is typically characterized as inflamed skin psoriasis, introduced by Jarrett and Spearman [22]. The model is with surface scales, thickening of the epidermis (acanthosis; based on the induction of orthokeratosis in those parts of the granular layer is reduced or absent) caused by parakeratosis, adult mouse tail, which have normally a parakeratotic differenti- which is a consequence of nuclei retention in SC keratinocytes ation. Antipsoriatic drug activity is defined by the percentage in- caused by abnormal differentiation and hyperproliferation of epi- crease of orthokeratotic regions after topical drug treatment of a dermal keratinocytes [1,7]. Some scientific reports consider ni- mouse tail. Ethanolic extract of Aloe vera leaf gel [23], ethanolic tric oxide (NO), released from keratinocytes at high concentra- extract of Nigella sativa [24], ethanolic extract of Rubia cordifolia tions, as a key inhibitor of cellular proliferation and inducer of cell [25], methanol extract of Smilax china and the isolated flavonoid differentiation in vitro. Although a high-output NO synthesis is quercetin [26], Thespesia populne extract [27], hydro alcoholic ex-