Abstract
Psoriasis is a chronic autoimmune human skin disorder that is characterized by excessive proliferation of keratinocytes, scaly plaques, severe inflammation and erythema. The pathophysiology of psoriasis involves interplay between epidermal keratinocytes, T lymphocytes, leukocytes and vascular endothelium. Increased leukocyte recruitment and elevated levels of cytokines, growth factors and genetic factors like interleukin (IL)-1β, IL-6, IL-17, IL-22, IL-23, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, toll-like receptor (TLR)-2, signal transducer and activator of transcription (STAT-3), 15-lipoxygenase (LOX)-2, coiled-coil alpha-helical rod protein 1 (CCHCR1), steroidogenic acute regulatory protein (StAR) and vitamin D receptor (VDR) are the most critical factors governing the exacerbation of psoriasis. In the present study, an attempt was made to elucidate the preventive role of herbal extracts of four dermo-protective Ayurvedic plants, Tinospora cordifolia (TC), Curcuma longa (CL), Celastrus paniculatus (CP) and Aloe vera (AV), against psoriasis-like dermatitis. Parkes (P) strain mice were initially induced with psoriasis-like dermatitis using topical application of imiquimod (IMQ, 5 %), followed by subsequent treatment with the herbal extracts to examine their curative effect on the psoriasis-like dermatitis-induced mice. The extracts were orally/topically administered to mice according to their ED/LD50 doses. Phenotypical observations, histological examinations, and semi-quantitative reverse transcription PCR (RT-PCR) analyses of the skin and blood samples of the control, IMQ-treated and herbal extract-treated psoriasis-like dermatitis-induced mice lead to the conclusion that the combination extract from all the plants was instrumental in downregulating the overexpressed cytokines, which was followed by the CL extract. Moreover, lesser yet positive response was evident from CP and TC extracts. The results suggest that these plants can prove to have tremendous preventive potential against the disease and can open the way to new therapeutic strategies for psoriasis treatment.
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Abbreviations
- IMQ:
-
Imiquimod
- IL:
-
Interleukin
- TNF:
-
Tumour necrosis factor
- IFN:
-
Interferon
- TGF:
-
Transforming growth factor
- TLR:
-
Toll-like receptor
- LOX:
-
Lipoxygenase
- STAT:
-
Signal transducer and activator of transcription
- CCHCR1:
-
Coiled-coil alpha-helical rod protein 1
- StAR:
-
Steroidogenic acute regulatory protein
- VDR:
-
Vitamin D receptor
References
Abe Y, Hashimoto S, Horie T (1999) Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res 39:411–17
Aggarwal BB, Prasad S, Reuter S et al (2011) Identification of novel anti-inflammatory agents from ayurvedic medicine for prevention of chronic diseases: “reverse pharmacology” and “bedside to bench” approach. Curr Drug Targets 12(11):1595–1653
Albanesi C, Scarponi C, Giustizieri ML, Girolomoni G (2005) Keratinocytes in inflammatory skin diseases. Curr Drug Targets Inflamm Allergy 4:329–34
Alexandrow MG, Song LJ, Altiok S et al (2012) Curcumin: a novel Stat3 pathway inhibitor for chemoprevention of lung cancer. Eur J Cancer Prev 21(5):407–412
Aliahmadi E, Gramlich R, Grützkau A et al (2009) TLR2-activated human langerhans cells promote Th17 polarization via IL-1beta, TGF-beta and IL-23. Eur J Immunol 39(5):1221–30
Arora N, Rai SP (2012) Celastrus paniculatus, an endangered Indian medicinal plant with miraculous cognitive and other therapeutic properties: an overview. Int J Pharm Bio Sci 3(3):290–303
Atal CK, Sharma ML, Kaul A, Khajuria A (1986) Immunomodulating agents of plant origin. I: preliminary screening. J Ethnopharmacol 18(2):133–41
Brash AR, Boeglin WE, Chang MS (1997) Discovery of a second 15S-lipoxygenase in humans. Proc Natl Acad Sci U S A 94:6148–52
Brash AR, Jisaka M, Boeglin WE, Chang MS (1999) Molecular cloning of a second human 15S-lipoxygenase and its murine homologue, an 8S-lipoxygenase. Their relationship to other mammalian lipoxygenases. Adv Exp Med Biol 447:29–36
Camp RD, Mallet AI, Woollard PM et al (1983) The identification of hydroxy fatty acids in psoriatic skin. Prostaglandins 26(3):431–47
Carrasco S, Neves FS, Fonseca MH et al (2011) Toll-like receptor (TLR) 2 is upregulated on peripheral blood monocytes of patients with psoriatic arthritis: a role for a gram-positive inflammatory trigger? Clin Exp Rheumatol 29(6):958–62
Da Rocha MD, Viegas FP, Campos HC et al (2011) The role of natural products in the discovery of new drug candidates for the treatment of neurodegenerative disorders II: Alzheimer’s disease. CNS Neurol Disord Drug Targets 10(2):251–270
Debets R, Hegmans JP, Croughs P et al (1997) The IL-1 system in psoriatic skin: IL-1 antagonist sphere of influence in lesional psoriatic epidermis. J Immunol 158:2955–63
Di Cesare A, Di Meglio P, Nestle FO (2009) The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol 129(6):1339–50
Fitch E, Harper E, Skorcheva I et al (2007) Pathophysiology of psoriasis: recent advances on IL-23 and Th17 cytokines. Curr Rheumatol Rep 9:461–67
Flisiak I, Chodynicka B, Porebski P, Flisiak R (2002) Association between psoriasis severity and transforming growth factor beta (1) and beta (2) in plasma and scales from psoriatic lesions. Cytokine 19:121–5
Gheorghe KR, Korotkova M, Catrina AI et al (2009) Expression of 5-lipoxygenase and 15-lipoxygenase in rheumatoid arthritis synovium and effects of intraarticular glucocorticoids. Arthritis Res Ther 11(3):R83
Ghoreschi K, Weigert C, Röcken M (2007) Immunopathogenesis and role of T cells in psoriasis. Clin Dermatol 25(6):574–580
Giannopoulos PF, Joshi YB, Chu J, Praticò D (2013) The 12-15-lipoxygenase is a modulator of Alzheimer’s-related tau pathology in vivo. Aging Cell 12(6):1082–90
Grossman RM, Krueger J, Yourish F et al (1989) Interleukin-6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes. Proc Natl Acad Sci U S A 86:6367–71
Hagan SN, Murphy EW, Shelley LM (1967) Extraction of lipids from raw beef lean by using various solvent systems. J Assoc Off Anal Chem 50:250–55
Heidenreich R, Röcken M, Ghoreschi K (2009) Angiogenesis drives psoriasis pathogenesis. Int J Exp Pathol 90(3):232–48
Heidt M, Furstenberger G, Vogel S et al (2000) Diversity of murine lipoxygenases: identification of a subfamily of epidermal isoenzymes exhibiting a differentiation-dependent mRNA expression pattern. Lipids 35:701–7
Honma M, Minami-Hori M, Takahashi H, Iizuka H (2012) Podoplanin expression in wound and hyperproliferative psoriatic epidermis: regulation by TGF-β and STAT-3 activating cytokines, IFN-γ, IL-6, and IL-22. J Dermatol Sci 65(2):134–140
Huang MT, Ma W, Yen P et al (1997) Inhibitory effects of topical application of low doses of curcumin on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion and oxidized DNA bases in mouse epidermis. Carcinogenesis 18(1):83–88
Jain BN, Jain VK, Shete A (2010) Antipsychotic activity of aqueous ethanolic extract of tinospora cordifolia in amphetamine challenged mice model. J Adv Pharm Technol Res 1(1):30–33
Kastelein RA, Hunter CA, Cua DJ (2007) Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol 25:221–42
Kono T, Kondo S, Pastore S et al (1994) Effects of a novel topical immunomodulator, imiquimod, on keratinocyte cytokine gene expression. Lymphokine Cytokine Res 13:71–76
Kupper TS, Min K, Sehgal PB et al (1989) Production of IL-6 by keratinocytes: implications for epidermal inflammation and immunity. Ann NY Acad Sci 557:454–64
Lee E, Trepicchio WL, Oestreicher JL et al (2004) Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med 199:125–30
Lekha G, Mohan K, Samy IA (2010) Effect of Celastrus paniculatus seed oil (Jyothismati oil) on acute and chronic immobilization stress induced in swiss albino mice. Pharmacognosy Res 2(3):169–74
Li AG, Wang D, Feng XH, Wang XJ (2004) Latent TGFbeta1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder. EMBO J 23:1770–81
Lowes MA, Bowcock AM, Krueger JG (2007) Pathogenesis and therapy of psoriasis. Nature 445:866–73
Lu J, Xiao WP, Geng ZL, Liu D, Wang YF (2012) Effect of aloe polysaccharides pretreatment on the cerebral inflammatory response and lipid peroxidation in severe hemorrhagic shock rats first entering high altitude. Zhonghua Wai Ke Za Zhi 50(7):655–8
Lukita-Atmadja W, Ito Y, Baker GL, McCuskey RS (2002) Effect of curcuminoids as anti-inflammatory agents on the hepatic microvascular response to endotoxin. Shock 17:399–403
Nair PK, Rodriguez S, Ramachandran R et al (2004) Immune stimulating properties of a novel polysaccharide from the medicinal plant Tinospora cordifolia. Int Immunopharmacol 4(13):1645–59
Nickoloff BJ, Nestle FO (2004) Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest 113(12):1664–75
Niu G, Wright KL, Huang M et al (2002) Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 21(13):2000–8
Palamara F, Meindl S, Holcmann M et al (2004) Identification and characterization of pDC-like cells in normal mouse skin and melanomas treated with imiquimod. J Immunol 173:3051–61
Palfreeman AC, McNamee KE, McCann FE (2013) New developments in the management of psoriasis and psoriatic arthritis: a focus on apremilast. Drug Des Devel Ther 7:201–10
Piskin G, Sylva-Steenland RM, Bos JD, Teunissen MB (2006) In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin. J Immunol 176(3):1908–15
Popuri AK, Pagala B (2013) Extraction of curcumin from turmeric roots. Int J Innov Res Studies 2(5):289–99
Rajan N, Langtry JA (2006) Generalized exacerbation of psoriasis associated with imiquimod cream treatment of superficial basal cell carcinomas. Clin Exp Dermatol 31:140–41
Rojas Anaya E, Loza-Rubio E, Banda Ruiz VM, Hernández Baumgarten E (2006) Use of reverse transcription-polymerase chain reaction to determine the stability of rabies virus genome in brains kept at room temperature. J Vet Diagn Invest 18(1):98–101
Sano S, Chan KS, Carbajal S et al (2005) Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med 11:43–49
Schneider C, Strayhorn WD, Brantley DM et al (2004) Upregulation of 8-lipoxygenase in the dermatitis of IkappaB-alpha-deficient mice. J Invest Dermatol 122:691–98
Schön M, Behmenburg C, Denzer D, Schön MP (2001) Pathogenic function of IL-1 beta in psoriasiform skin lesions of flaky skin (fsn/fsn) mice. Clin Exp Immunol 123(3):505–10
Sengupta M, Sharma GD, Chakraborty B (2011) Effect of aqueous extract of Tinospora cordifolia on functions of peritoneal macrophages isolated from CCl4 intoxicated male albino mice. BMC Complement Altern Med 11:102
Setsu N, Matsuura H, Hirakawa et al (2006) Interferon-gamma-induced 15-lipoxygenase-2 expression in normal human epidermal keratinocytes and a pathogenic link to psoriasis vulgaris. Eur J Dermatol 16(2):141–5
Skrzypczak-Jankun E, McCabe NP, Selman SH, Jankun J (2000) Curcumin inhibits lipoxygenase by binding to its central cavity: theoretical and X-ray evidence. Int J Mol Med 6:521–6
Spelman K, Burns J, Nichols D et al (2006) Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators. Altern Med Rev 11(2):128–50
Sugawara T, Shimizu H, Hoshi N et al (2003) Steroidogenic acute regulatory protein-binding protein cloned by a yeast two-hybrid system. J Biol Chem 278:42487–94
Sun J, Zhao Y, Hu J (2013) Curcumin inhibits imiquimod-induced psoriasis-like inflammation by inhibiting IL-1beta and IL-6 production in mice. PLoS One 8(6), e67078
Syed TA, Cheeman KM, Ahmad SA, Holt AH (1996) Aloe vera extract 0.5% in hydrophilic cream versus Aloe vera gel for the management of genital herpes in males. A placebo-controlled, double blind, comparative study. J Eur Acad Dermatol Venereol 7:294–95
Szeimies RM, Gerritsen MJ, Gupta G et al (2004) Imiquimod 5% cream for the treatment of actinic keratosis: results from a phase III, randomized, double-blind, vehicle-controlled, clinical trial with histology. J Am Acad Dermatol 51:547–55
Tervaniemi MH, Siitonen HA, Soderhall C et al (2012) Centrosomal localization of the psoriasis candidate gene product, CCHCR1, supports a role in cytoskeletal organization. PLoS One 7(11), e49920
Teunissen MBM, Koomen CW, de Waal MR et al (1998) Interleukin-17 and interferon-γ synergize in the enhancement of proinflammatory cytokine production by human keratinocytes. J Invest Dermatol 111(4):645–49
Tiala I, Suomela S, Huuhtanen J et al (2007) The CCHCR1 (HCR) gene is relevant for skin steroidogenesis and downregulated in cultured psoriatic keratinocytes. J Mol Med (Berl) 85(6):589–601
Tiala I, Wakkinen J, Suomela S et al (2008) The PSORS1 locus gene CCHCR1 affects keratinocyte proliferation in transgenic mice. Hum Mol Genet 17(7):1043–51
Van der Fits L, Mourits S, Voerman JS et al (2009) Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol 182(9):5836–45
Vanderhoek JY, Bailey JM (1984) Activation of a 15-lipoxygenase/leukotriene pathway in human polymorphonuclear leukocytes by the anti-inflammatory agent ibuprofen. J Biol Chem 259(11):6752–6
Wilson NJ, Boniface K, Chan JR et al (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8:950–57
Wolk K, Kunz S, Witte E et al (2004) IL-22 increases the innate immunity of tissues. Immunity 21:241
Wu JK, Siller G, Strutton G (2004) Psoriasis induced by topical imiquimod. Australas J Dermatol 45:47–50
Zaba LC, Fuentes-Duculan J, Eungdamrong NJ et al (2009) Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. J Invest Dermatol 129(1):79–88
Zheng Y, Danilenko DM, Valdez P et al (2007) Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445:648–51
Zhu JW, Wu XJ, Lu ZF et al (2013) Role of VEGF receptors in normal and psoriatic human keratinocytes: evidence from irradiation with different UV sources. PLoS One 8(1), e55463
Acknowledgments
The authors are thankful to DBT (Department of Biotechnology), Govt. of India, for financial support (Grant No. BT/PR13597/GBD/27/274/201). Authors sincerely acknowledge Prof. Rajiva Raman, Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, for providing mice and animal house facility for conducting in vivo studies. NA is sponsored by UGC (University Grants Commission), India, in the form of a fellowship.
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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 253, 503–515 (2016). https://doi.org/10.1007/s00709-015-0829-y
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DOI: https://doi.org/10.1007/s00709-015-0829-y