Topically Used Herbal Products for the Treatment of Psoriasis – Mechanism of Action, Drug Delivery, Clinical Studies

Abstract

Psoriasis is a chronic inflammatory skin disease characterized histologically by hyperproliferation and aberrant differentiation of epidermal keratinocytes. A wide range of conventional medical therapies to treat psoriasis is established, from topical therapies and systemic medications through to phototherapy or combinations of those. However, most of these therapies have a limited efficacy and may cause a number of side effects, including cutaneous atrophy, organ toxicity, carcinogenicity, and broadband immunosuppression, which are restricting their long-term use. Therefore, it would be desirable to use herbal products as an alternative treatment for psoriasis that causes fewer side effects. For this purpose, several electronic databases and literature references were used to summarize the current knowledge acquired on the basis of animal studies and clinical trials regarding herbal products used to treat psoriasis topically. This review discusses the mechanisms of herbal products activities through (1) inhibition of the keratinocyte hyperproliferation and inducing apoptosis, (2) inhibition of immune-inflammatory reaction, (3) suppression of phosphorylase kinase (PhK) activity, and (4) inhibition of the hedgehog (Hh) signaling pathway. Moreover, the penetration of herbal products through the psoriatic skin barrier, novel herbal drug delivery systems in psoriasis treatment, and possible adverse effects of herbal therapy are discussed.

Key words

Psoriasis - herbal products - keratinocyte hyperproliferation - inflammatory reaction - skin barrier - herbal drug delivery systems

• References

• 1 Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007; 445: 866-873
• 2 Rahman M, Alam K, Ahmad MZ, Gupta G, Afzal M, Akhter S, Kazmi I, Ahmad FJ, Anwar F. Classical to current approach for treatment of psoriasis: a review. Endocr Metab Immune Disord Drug Targets 2012; 12: 287-302
• 3 Yuqi TT. Review of a treatment for psoriasis using herose, a botanical formula. J Dermatol 2005; 32: 940-945
• 4 Traub M, Marshall K. Psoriasis-pathophysiology, conventional, and alternative approaches to treatment. Altern Med Rev 2007; 12: 319-330
• 5 Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet 2007; 370: 263-271
• 6 Keseroglu HO, Gönül M. Traditional topical herbal therapies in psoriasis. TANG 2014; 4: 13-20
• 7 Johnson-Huang LM, Lowes MA, Krueger JG. Putting together the psoriasis puzzle: an update on developing targeted therapies. Dis Model Mech 2012; 5: 423-433
• 8 Bruch-Gerharz D, Schnorr O, Suschek C, Beck KF, Pfeilschifter J, Ruzicka T, Kolb-Bachofen V. Arginase 1 overexpression in psoriasis: limitation of inducible nitric oxide synthase activity as a molecular mechanism for keratinocyte hyperproliferation. Am J Pathol 2003; 162: 203-211
• 9 Ghadially R, Reed JT, Elias PM. Stratum corneum structure and function correlates with phenotype in psoriasis. J Invest Dermatol 1996; 107: 558-564
• 10 Katare OP, Raza K, Singh B, Dogra S. Novel drug delivery systems in topical treatment of psoriasis: Rigors and vigors. Indian J Dermatol Venereol Leprol 2010; 76: 612-621
• 11 Gudjonsson JE, Johnston A, Sigmundsdottir H, Valdimarsson H. Immunopathogenic mechanisms in psoriasis. Clin Exp Immunol 2004; 135: 1-8
• 12 Nickoloff BJ, Nestle FO. Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest 2004; 113: 1664-1675
• 13 Chamian F, Lowes MA, Lin SL, Lee E, Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG. Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris. Proc Natl Acad Sci U S A 2005; 102: 2075-2080
• 14 Lowes MA, Chamian F, Abello MV, Fuentes-Duculan J, Lin SL, Nussbaum R, Novitskaya I, Carbonaro H, Cardinale I, Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Wittkowski KM, Papp K, Garovoy M, Dummer W, Steinman RM, Krueger JG. Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proc Natl Acad Sci U S A 2005; 102: 19057-19062
• 15 Quin JZ, Chaturvedi V, Denning MF, Choubey D, Diaz MO, Nickoloff BJ. Role of NF-kappaB in the apoptotic-resistant phenotype of keratinocytes. J Biol Chem 1999; 274: 37957-37964
• 16 Ruckert R, Asadullah K, Seifert M, Budagian VM, Arnold R, Trombotto C, Paus R, Bulfone-Paus S. Inhibition of keratinocyte apoptosis by IL-15: a new parameter in the pathogenesis of psoriasis?. J Immunol 2000; 165: 2240-2250
• 17 Arora N, Shah K, Pandey-Rai S. Inhibition of imiquimod-induced psoriasis-like dermatitis in mice by herbal extracts from some Indian medicinal plants. Protoplasma 2016; 253: 503-515
• 18 Lowes MA, Suárez-Fariñas M, Krueger JG. Immunology of psoriasis. Annu Rev Immunol 2014; 32: 227-255
• 19 Goldminz AM, Au SC, Kim N, Gottlieb AB, Lizzul PF. NF-κB: an essential transcription factor in psoriasis. J Dermatol Sci 2013; 69: 89-94
• 20 Johansen C, Flindt E, Kragballe K, Henningsen J, Westergaard M, Kristiansen K, Iversen L. Inverse regulation of the nuclear factor-kappaB binding to the p53 and interleukin-8 kappaB response elements in lesional psoriatic skin. J Invest Dermatol 2005; 124: 1284-1292
• 21 Singh KK, Tripathy S. Natural treatment alternative for psoriasis: a review on herbal resources. J App Pharm Sci 2014; 4: 114-121
• 22 Jarrett A, Spearman RIG. Psoriasis. In: Taverner D, Trounce J, eds. Histochemistry of the Skin. London: University Press; 1964
• 23 Dhanabal SP, Priyanka Dwarampudi L, Muruganantham N, Vadivelan R. Evaluation of the antipsoriatic activity of Aloe vera leaf extract using a mouse tail model of psoriasis. Phytother Res 2012; 26: 617-619
• 24 Dwarampudi LP, Palaniswamy D, Nithyanantham M, Raghu PS. Antipsoriatic activity and cytotoxicity of ethanolic extract of Nigella sativa seeds. Pharmacogn Mag 2012; 8: 268-272
• 25 Lin ZX, Jiao BW, Che CT, Zuo Z, Mok CF, Zhao M, Ho WK, Tse WP, Lam KY, Fan RQ, Yang ZJ, Cheng CH. Ethyl acetate fraction of the root of Rubia cordifolia L. inhibits keratinocyte proliferation in vitro and promotes keratinocyte differentiation in vivo: potential application for psoriasis treatment. Phytother Res 2010; 24: 1056-1064
• 26 Vijayalakshmi A, Ravichandiran V, Velraj M, Nirmala S, Jayakumari S. Screening of flavonoid “quercetin” from the rhizome of Smilax china Linn. for anti-psoriatic activity. Asian Pac J Trop Biomed 2012; 2: 269-275
• 27 Shrivastav S, Sindhu R, Kumar S, Kumar P. Anti-psoriatic and phytochemical evaluation of Thespesia populnea bark extracts. Int J Pharm Pharm Sci 2009; 1: 176-185
• 28 Raj BA, Muruganantham N, Praveen TK, Raghu PS. Screening of Wrightia tinctoria leaves for anti psoriatic activity. Hygeia J Drug Med 2012; 4: 73-78
• 29 Wu J, Li H, Li M. Effects of baicalin cream in two mouse models: 2,4-dinitrofluorobenzene-induced contact hypersensitivity and mouse tail test for psoriasis. Int J Clin Exp Med 2015; 8: 2128-2137
• 30 Oyedeji FO, Bankole-Ojo OS. Quantitative evaluation of the antipsoriatic activity of sausage tree (Kigelia africana). Afr J Pure Appl Chem 2012; 6: 214-218
• 31 Singhal M, Kansara N. Cassia tora Linn cream inhibits ultraviolet-B-induced psoriasis in rats. ISRN Dermatol 2012; 2012: 346510
• 32 Nagakuma H, Kambara T, Yamamoto T. Rat ultraviolet ray B photodermatitis: an experimental model of psoriasis vulgaris. Int J Exp Pathol 1995; 76: 65-73
• 33 Divakara P, Nagaraju B, Buden RP, Sekhar HS, Ravi CM. Antipsoriatic activity of ayurvedic ointment containing aqueous extract of the bark of Pongamia pinnata using the rat ultraviolet ray photodermatitis model. Adv Med Plant Res 2013; 1: 8-16
• 34 Gulliver WP, Donsky HJ. A report on three recent clinical trials using Mahonia aquifolium 10 % topical cream and a review of the worldwide clinical experience with Mahonia aquifolium for the treatment of plaque psoriasis. Am J Ther 2005; 12: 398-406
• 35 Koo J, Arain S. Traditional Chinese medicine in dermatology. Clin Dermatol 1999; 17: 21-27
• 36 Choonhakarn C, Busaracome P, Sripanidkulchai B, Sarakarn P. A prospective, randomized clinical trial comparing topical aloe vera with 0.1 % triamcinolone acetonide in mild to moderate plaque psoriasis. J Eur Acad Dermatol Venereol 2010; 24: 168-172
• 37 Gelmini F, Beretta G, Anselmi C, Centini M, Magni P, Ruscica M, Cavalchini A, Facino RM. GC-MS profiling of the phytochemical constituents of the oleoresin from Copaifera langsdorffii Desf. and a preliminary in vivo evaluation of its antipsoriatic effect. Int J Pharm 2013; 440: 170-178
• 38 Stücker M, Memmel U, Hoffmann M, Hartung J, Altmeyer P. Vitamin B(12) cream containing avocado oil in the therapy of plaque psoriasis. Dermatology 2001; 203: 141-147
• 39 Syed TA, Ahmad SA, Holt AH, Ahmad SA, Ahmad SH, Afzal M. Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-controlled, double-blind study. Trop Med Int Health 1996; 1: 505-509
• 40 Lin YK, Wong WR, Chang YC, Chang CJ, Tsay PK, Chang SC, Pang JH. The efficacy and safety of topically applied Indigo naturalis ointment in patients with plaque-type psoriasis. Dermatology 2007; 214: 155-161
• 41 Wang A, Liu Z, Liu S. Treatment of psoriasis vulgaris with lacquer made of Camptotheca acuminata nuts. J Clin Dermatol 1998; 27: 243-244
• 42 Sarafian G, Afshar M, Mansouri P, Asgarpanah J, Raoufinejad K, Rajabi M. Topical turmeric microemulgel in the management of plaque psoriasis; A clinical evaluation. Iran J Pharm Res 2015; 14: 865-876
• 43 Najafizadeh P, Hashemian F, Mansouri P, Farshi S, Surmaghi MS, Chalangari R. The evaluation of the clinical effect of topical St Johns wort (Hypericum perforatum L.) in plaque type psoriasis vulgaris: a pilot study. Australas J Dermatol 2012; 53: 131-135
• 44 Lin YK, Yen HR, Wong WR, Yang SH, Pang JHS. Successful treatment of pediatric psoriasis with Indigo naturalis composite ointment. Pediatr Dermatol 2006; 23: 507-510
• 45 Lin YK, See LC, Huang YH, Chang YC, Tsou TC, Lin TY, Lin NL. Efficacy and safety of Indigo naturalis extract in oil (Lindioil) in treating nail psoriasis: a randomized, observer-blind, vehicle-controlled trial. Phytomedicine 2014; 21: 1015-1020
• 46 Bernstein S, Donsky H, Gulliver W, Hamilton D, Nobel S, Norman R. Treatment of mild to moderate psoriasis with Relieva, a Mahonia aquifolium extract – a double-blind, placebo-controlled study. Am J Ther 2006; 13: 121-126
• 47 Wiesenauer M, Lüdtke R. Mahonia aquifolium in patients with psoriasis vulgaris – an intraindividual study. Phytomedicine 1996; 3: 231-235
• 48 Lin YK, Chang CJ, Chang YC, Wong WR, Chang SC, Pang JHS. Clinical assessment of patients with recalcitrant psoriasis in a randomized, observer-blind, vehicle-controlled trial using Indigo naturalis . Arch Dermatol 2008; 144: 1457-1464
• 49 Bernstein JE, Parish LC, Rapaport M, Rosenbaum MM, Roenigk Jr. HH. Effects of topically applied capsaicin on moderate and severe psoriasis vulgaris. J Am Acad Dermatol 1986; 15: 504-507
• 50 Augustin M, Andrees U, Grimme H, Schöpf E, Simon J. Effects of Mahonia aquifolium ointment on the expression of adhesion, proliferation, and activation markers in the skin of patients with psoriasis. Forsch Komplementarmed 1999; 6: 19-21
• 51 Brown AC, Koett J, Johnson DW, Semaskvich NM, Holck P, Lally D, Cruz L, Young R, Higa B, Lo S. Effectiveness of kukui nut oil as a topical treatment for psoriasis. Int J Dermatol 2005; 44: 684-687
• 52 Paulsen E, Korsholm L, Brandrup F. A double-blind, placebo-controlled study of a commercial Aloe vera gel in the treatment of slight to moderate psoriasis vulgaris. J Eur Acad Dermatol Venereol 2005; 19: 326-331
• 53 Thomas J, Narkowicz CK, Jacobson GA, Peterson GM. Safety and efficacy of kunzea oil-containing formulations for the management of psoriasis: a randomized, controlled trial. J Clin Pharm Ther 2015; 40: 566-572
• 54 Suresh PK, Singh P, Saraf S. Novel topical drug carriers as a tool for treatment of psoriasis: progress and advances. Afr J Pharm Pharmacol 2013; 7: 138-147
• 55 Pradhan M, Singh D, Singh MR. Novel colloidal carriers for psoriasis: current issues, mechanistic insight and novel delivery approaches. J Control Release 2013; 170: 380-395
• 56 Saraf S. Applications of novel drug delivery system for herbal formulations. Fitoterapia 2010; 81: 680-689
• 57 Singh MR, Nag MK, Patel S, Daharwal SJ, Singh D. Novel approaches for dermal and transdermal delivery of herbal drugs. Res J Pharmacog Phytochem 2013; 5: 271-279
• 58 Nagle A, Goyal AK, Kesarla R, Murthy RSR. Efficacy study of vesicular gel containing methotrexate and menthol combination on parakeratotic rat skin model. J Liposome Res 2011; 21: 134-140
• 59 Singh HP, Utreja P, Tiwary AK, Jain S. Elastic liposomal formulation for sustained delivery of colchicine: in vitro characterization and in vivo evaluation of anti-gout activity. AAPS J 2009; 11: 54-64
• 60 Gupta R, Gupta M, Mangal S, Agrawal U, Vyas SP. Capsaicin-loaded vesicular systems designed for enhancing localized delivery for psoriasis therapy. Artif Cells Nanomed Biotechnol 2016; 44: 825-834
• 61 Marianecci C, Rinaldi F, Mastriota M, Pieretti S, Trapasso E, Paolino D, Carafa M. Anti-inflammatory activity of novel ammonium glycyrrhizinate/niosomes delivery system: Human and murine models. J Control Release 2012; 164: 17-25
• 62 Zhang YT, Shen LIN, Zhao JH, Feng NP. Evaluation of psoralen ethosomes for topical delivery in rats by using in vivo microdialysis. Int J Nanomedicine 2014; 9: 669-678
• 63 Ali J, Akhtar N, Sultana Y, Baboota S, Ahuja A. Antipsoriatic microemulsion gel formulations for topical drug delivery of babchi oil (Psoralea corylifolia). Methods Find Exp Clin Pharmacol 2008; 30: 277-285
• 64 Behera J, Keservani RK, Yadav A, Tripathi M, Chadoker A. Methoxsalen loaded chitosan coated microemulsion for effective treatment of psoriasis. Int J Drug Deliv 2010; 2: 159-167
• 65 Khokhra S, Diwan A. Microemulsion based transdermal drug delivery of tea tree oil. Int J Drug Dev Res 2011; 3: 191-198
• 66 Ali MS, Alam MS, Imam FI, Siddiqui MR. Topical nanoemulsion of turmeric oil for psoriasis: characterization, ex vivo and in vivo assessment. Int J Drug Deliv 2012; 4: 184-197
• 67 Bernardi DS, Pereira TA, Maciel NR, Bortoloto J, Viera GS, Oliveira GC, Rocha-Filho PA. Formation and stability of oil-in-water nanoemulsions containing rice bran oil: In vitro and in vivo assessments. J Nanobiotechnology 2011; 9: 1-9
• 68 Puglia C, Rizza L, Drechsler M, Bonina F. Nanoemulsions as vehicles for topical administration of glycyrrhetic acid: characterization and in vitro and in vivo evaluation. Drug Deliv 2010; 17: 123-129
• 69 Agrawal U, Gupta M, Vyas SP. Capsaicin delivery into the skin with lipidic nanoparticles for the treatment of psoriasis. Artif Cells Nanomed Biotechnol 2013; 43: 33-39
• 70 Man MQ, Shi Y, Man M, Lee SH, Demerjian M, Chang S, Feingold KR, Elias PM. Elias Chinese herbal medicine (Tuhuai extract) exhibits topical anti-proliferative and anti-inflammatory activity in murine disease models. Exp Dermatol 2008; 17: 681-687
• 71 Lin YK, Leu YL, Yang SH, Chen HW, Wang CT, Pang JH. Anti-psoriatic effects of Indigo naturalis on the proliferation and differentiation of keratinocytes with indirubin as the active component. J Dermatol Sci 2009; 54: 168-174
• 72 Zhang H, Gu J. Progress of experimental study on treatment of psoriasis by Chinese medicinal monomer and single or compound recipe in Chinese materia medica. Chin J Integr Med 2007; 13: 312-316
• 73 Saelee C, Thongrakard V, Tencomnao T. Effects of Thai medicinal herb extracts with anti-psoriatic activity on the expression on NF-κB signaling biomarkers in HaCaT keratinocytes. Molecules 2011; 16: 3908-3932
• 74 Li XL, Wang ZH, Zhao YX, Luo SJ, Zhang DW, Xiao SX, Peng ZH. Purification of a polysaccharide from Gynostemma pentaphyllum Makino and its therapeutic advantages for psoriasis. Carbohydr Polym 2012; 89: 1232-1237
• 75 Bader A, Martini F, Schinella GR, Rios JL, Prieto JM. Modulation of Cox-1, 5-, 12- and 15-Lox by popular herbal remedies used in southern Italy against psoriasis and other skin diseases. Phytother Res 2015; 29: 108-113
• 76 Heng MCY, Song MK, Heng MK. Elevated phosphorylase kinase activity in psoriatic epidermis: correlation with increased phosphorylation and psoriatic activity. Br J Dermatol 1994; 130: 298-306
• 77 Heng MC, Song MK, Harker J, Heng MK. Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters. Br J Dermatol 2000; 143: 937-949
• 78 Hovhannisyan A, Matz M, Gebhardt R. From teratogens to potential therapeutics: natural inhibitors of the Hedgehog signaling network come of age. Planta Med 2009; 75: 1371-1380
• 79 Taş S, Avci O. Rapid clearance of psoriatic skin lesions induced by topical cyclopamine. A preliminary proof of concept study. Dermatology 2004; 209: 126-131
• 80 Gudjonsson JE, Aphale A, Grachtchouk M, Ding J, Nair RP, Wang T, Voorhees JJ, Dlugosz AA, Elder JT. Lack of evidence for activation of the hedgehog pathway in psoriasis. J Invest Dermatol 2009; 129: 635-640
• 81 Welss T, Basketter DA, Schröder KR. In vitro skin irritation: facts and future. State of the art review of mechanisms and models. Toxicol In Vitro 2004; 18: 231-243
• 82 Ernst E. Adverse effects of herbal drugs in dermatology. Br J Dermatol 2000; 143: 923-929
• 83 De Smet PA. Health risks of herbal remedies: an update. Clin Pharmacol Ther 2004; 76: 1-17
• 84 Asif M. A brief study of toxic effects of some medicinal herbs on kidney. Adv Biomed Res 2012; 1: 44
• 85 Dwivedi S, Aggarwal A, Sharma V. Cardiotoxicity from ʼsafeʼ herbomineral formulations. Trop Doct 2011; 41: 113-115
• 86 Stedman C. Herbal hepatotoxicity. Semin Liver Dis 2001; 22: 195-206
• 87 Bode AM, Dong Z. Toxic phytochemicals and their potential risks for human cancer. Cancer Prev Res 2015; 8: 1-8
• 88 Niggemann B, Grüber C. Side-effects of complementary and alternative medicine. Allergy 2003; 58: 707-716
• 89 Huxtable RJ. The myth of beneficent nature: the risks of herbal preparations. Ann Intern Med 1992; 117: 165-166
• 90 Joshi BS, Kaul PN. Alternative medicine: herbal drugs and their critical appraisal – Part I. Prog Drug Res 2001; 56: 1-76
• 91 Zhou SF, Zhou ZW, Li CG, Chen X, Yu X, Xue CC, Herington A. Identification of drugs that interact with herbs in drug development. Drug Discov Today 2007; 12: 664-673
• 92 Bedi MK, Shenefelt PD. Herbal therapy in dermatology. Arch Dermatol 2002; 138: 232-242
• 93 Lebwohl M, Ting PT, Koo JYM. Psoriasis treatment: traditional therapy. Ann Rheum Dis 2005; 64: 83-86
• 94 Weger W. Current status and new developments in the treatment of psoriasis and psoriatic arthritis with biological agents. Br J Pharmacol 2010; 160: 810-820
• 95 Deng S, May BH, Zhang AL, Lu C, Xue CC. Topical herbal medicine combined with pharmacotherapy for psoriasis: a systematic review and meta-analysis. Arch Dermatol Res 2013; 305: 179-189
• 96 Tse WP, Cheng CHK, Che CT, Zhao M, Lin ZX. Induction of apoptosis underlies the Radix Rubiae-mediated anti-proliferative action on human epidermal keratinocytes: Implications for psoriasis treatment. Int J Mol Med 2007; 20: 663-672
• 97 Mok CF, Xie CM, Sham KWY, Lin ZX, Cheng CHK. 1,4-dihydroxy-2-naphthoic acid induces apoptosis in human keratinocyte: potential application for psoriasis treatment. Evid Based Complement Alternat Med 2013; 2013: 792840
• 98 Li FL, Xu R, Zeng QC, Li X, Chen J, Wang YF, Fan B, Geng L, Li B. Tanshinone IIA inhibits growth of keratinocytes through cell cycle arrest and apoptosis: underlying treatment mechanism of psoriasis. Evid Based Complement Alternat Med 2012; 2012: 927658
• 99 Zhou LL, Lin ZX, Fung KP, Cheng CH, Che CT, Zhao M, Wu SH, Zuo Z. Celastrol-induced apoptosis in human HaCaT keratinocytes involves the inhibition of NF-κB activity. Eur J Pharmacol 2011; 670: 399-408
• 100 Sampson JH, Raman A, Karlsen G, Navsaria H, Leigh IM. In vitro keratinocyte antiproliferant effect of Centella asiatica extract and triterpenoid saponins. Phytomedicine 2001; 8: 230-235
• 101 Wilkinson JD, Williamson EM. Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J Dermatol Sci 2007; 45: 87-92
• 102 Calixto JB. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents). Braz J Med Biol Res 2000; 33: 179-189