Psoriasis-like Dermatitis In Mice Research Articles

Forsythoside A Alleviates Imiquimod-Induced Psoriasis-like Dermatitis in Mice by Regulating Th17 Cells and IL-17A Expression.

Psoriasis is a recurrent inflammatory skin disease characterized by redness and scaly skin lesions with itchy or painful sensations. Forsythoside A, one of the main active compounds isolated from the fruit of Forsythia suspensa, has been widely applied to treat inflammatory diseases in the clinical use of traditional oriental medicine. However, the effect of forsythoside A on psoriasis remains unclear. This study aimed to explore the therapeutic effects and immune regulation of forsythoside A on psoriasis. C57BL/6 mice were divided into six groups and treated with imiquimod cream on their shaved back skin to induce psoriasis-like dermatitis. Different doses of forsythoside A (5 mg/kg, 10 mg/kg, or 20 mg/kg) were administered to the respective treatment groups. Skin redness, scaling, and ear thickness were measured; keratinocyte proliferation and inflammatory cytokine expression were detected by hematoxylin–eosin and immunohistochemical staining. Th17 cells in the inguinal lymph nodes were detected by flow cytometric analysis. IL-17A levels were measured using ELISA. The results showed that forsythoside A relieved psoriatic skin symptoms such as skin redness, thickness, scaling, and reduced epidermal thickening. The expression of IL-6, IL-17, and Ki-67 was downregulated in the forsythoside-A-treated groups. Th17 cell expression in inguinal lymph nodes and IL-17A secretion was suppressed by forsythoside A. In conclusion, forsythoside A was found to alleviate imiquimod-induced psoriasis-like dermatitis in mice by suppressing Th17 development and IL-17A secretion. These findings demonstrate the feasibility of forsythoside A in treating human psoriasis.

Sphingosine-1-Phosphate and Its Signal Modulators Alleviate Psoriasis-Like Dermatitis: Preclinical and Clinical Evidence and Possible Mechanisms.

BackgroundPsoriasis is an autoimmune skin disease associated with lipid metabolism. Sphingosine-1-phosphate (S1P) is a bioactive lipid that plays a key role in the development of autoimmune diseases. However, there is currently a lack of comprehensive evidence of the effectiveness of S1P on psoriasis.ObjectiveTo assess the efficacy and possible mechanism of S1P and its signal modulators in the treatment of psoriasis-like dermatitis.MethodsSix databases were searched through May 8, 2021, for studies reporting S1P and its signal modulators. Two reviewers independently extracted information from the enrolled studies. Methodological quality was assessed using SYRCLE’s risk of bias tool. RevMan 5.3 software was used to analyze the data. For clinical studies, the Psoriasis Area and Severity Index score were the main outcomes. For preclinical studies, we clarified the role of S1P and its regulators in psoriasis in terms of phenotype and mechanism.ResultsOne randomized double-blind placebo-controlled trial and nine animal studies were included in this study. The pooled results showed that compared with control treatment, S1P receptor agonists [mean difference (MD): −6.80; 95% confidence interval (CI): −8.23 to −5.38; p<0.00001], and sphingosine kinase 2 inhibitors (MD: −0.95; 95% CI: −1.26 to −0.65; p<0.00001) alleviated psoriasis-like dermatitis in mice. The mechanism of S1P receptor agonists in treating psoriasis might be related to a decrease in the number of white blood cells, topical lymph node weight, interleukin-23 mRNA levels, and percentage of CD3+ T cells (p<0.05). Sphingosine kinase 2 inhibitors ameliorated psoriasis in mice, possibly by reducing spleen weight and cell numbers (p<0.05).ConclusionsS1P receptor agonists and sphingosine kinase 2 inhibitors could be potential methods for treating psoriasis by decreasing immune responses and inflammatory factors.

IL-6R/Signal Transducer and Activator of Transcription 3 Signaling in Keratinocytes rather than in T Cells Induces Psoriasis-Like Dermatitis in Mice

Signal transducer and activator of transcription 3 (STAT3) is important for psoriasis pathogenesis because STAT3 signaling downstream of IL-6, IL-21, IL-22, and IL-23 contributes to T helper type 17 cell development and because transgenic mice with keratinocyte (KC) STAT3 expression (K14-Stat3C mice) develop psoriasis-like dermatitis. In this study, the relative contribution of STAT3 signaling in KCs versus in T cells was evaluated in the imiquimod model of psoriasis-like dermatitis. Mice with STAT3-inducible deletion in KCs (K5-Stat3-/- mice) had decreased psoriasis-like dermatitis and epidermal STAT3 phosphorylation compared with wild-type mice, whereas mice with constitutive deletion of STAT3 in all T cells were similar to wild-type mice. Interestingly, mice with KC-inducible deletion of IL-6Rα had similar findings to those of K5-Stat3-/- mice, identifying IL-6/IL-6R as a predominant upstream signal for KC STAT3-induced psoriasis-like dermatitis. Moreover, psoriasis-like dermatitis inversely associated with type 1 immune gene products, especially CXCL10, whereas CXCL10 limited psoriasis-like dermatitis, suggesting that KC STAT3 signaling promoted psoriasis-like dermatitis by restricting downstream CXCL10 expression. Finally, treatment of mice with the pan-Jak inhibitor, tofacitinib, reduced psoriasis-like dermatitis and epidermal STAT3 phosphorylation. Taken together, STAT3 signaling in KCs rather than in T cells was a more important determinant for psoriasis-like dermatitis in a mechanism that involved upstream KC IL-6R signaling and downstream inhibition of type 1 immunity‒associated CXCL10 responses.

Positive Allosteric Modulation of A2AR Alters Immune Cell Responses and Ameliorates Psoriasis-Like Dermatitis in Mice

Psoriasis is an immune cell‒mediated inflammatory disease of the skin with a mixed T helper type 1/T helper type17 cytokine environment combined with an innate immune response engaging toll-like receptors. Inflammatory diseases are characterized by dysregulated immune cell responses and elevated levels of adenosine at disease sites. Adenosine, acting through the A2AR, regulates inflammation, immune response, T-cell homeostasis, and tissue repair. We have identified a unique means to enhance A2AR function using a positive allosteric modulator. We show that oral administration of the A2AR-positive allosteric modulator AEA061 reduced ear swelling, skin thickness, erythema, scale formation, and inflammatory cytokine expression in A2Ar+/+ but not in A2Ar-/- mice with imiquimod-induced psoriasis-like dermatitis. Similar clinical and mRNA improvements were observed with topical administration. AEA061 also reduced clinical scores and cytokine expression in a mouse model of IL-23‒induced psoriasis-like dermatitis. In addition, AEA061 attenuated imiquimod-induced expression of IFN-α in plasmacytoid dendritic cells invivo and IL-23 and IL-36α in conventional dendritic cells. TCR-mediated IL-17 expression in γδT cells invivo and IL-17 production by CD4+ T cells enriched for γδT cells invitro were also inhibited. Thus, the enhancement of A2AR responsiveness to the endogenous agonist adenosine through positive allosteric modulation is sufficient to enhance intrinsic homeostatic mechanisms attenuating disease progression.

A Targetable, Noncanonical Signal Transducer and Activator of Transcription 3 Activation Induced by the Y-Less Region of IL-22 Receptor Orchestrates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice

Exacerbated IL-22 activity induces tissue inflammation and immune disorders such as psoriasis. However, because IL-22 is also essential for tissue repair and defense at barrier interfaces, targeting IL-22 activity to treat psoriasis bears the risk of deleterious effects at mucosal sites such as the gut. We previously showed invitro that IL-22 signaling relies on IL-22 receptor alpha (IL-22Rα) Y-dependent and -independent pathways. The second depends on the C-terminal Y-less region of IL-22Rα and leads to a massive signal transducer and activator of transcription 3 (STAT3) activation. Because STAT3 activation is associated with the development of psoriasis, we hypothesized that the specific inhibition of the noncanonical STAT3 activation by the Y-less region of IL-22Rα could reduce psoriasis-like disease while leaving intact its tissue defense functions in the gut. We show that mice expressing a C-terminally truncated version of IL-22Rα (ΔCtermut/mut mice) are protected from the development of psoriasis-like dermatitis lesions induced by imiquimod to a lesser extent than Il22ra-/- mice. In contrast, only Il22ra-/- mice lose weight after Citrobacter rodentium infection. Altogether, our data suggest that specific targeting of the noncanonical STAT3 activation by IL-22 could serve to treat psoriasis-like skin inflammation without affecting IL-22‒dependent tissue repair or barrier defense at other sites.

Suppression of neuropeptide by botulinum toxin improves imiquimod-induced psoriasis-like dermatitis via the regulation of neuroimmune system

BackgroundPsoriasis is a multifactorial disease arises from a complex interaction of genetics, immune system, and environmental aspects. IL-23/Th17 immune axis has been considered as a primary modulator in psoriasis. In addition, several findings imply that nervous system may take a part in the pathogenesis of psoriasis, suggesting that nervous system, through its neuropeptide, may interact with immune system and lead to the formation of psoriasis. ObjectiveWe aimed to ascertain the role of neuropeptides secreted from neurons in the pathogenesis of psoriasis in vivo. MethodsThe release of neuropeptide was inhibited by injecting Botulinum toxin B (BTX-B) on Imiquimod (IMQ)-induced psoriasis-like dermatitis mice model. Quantification of skin dermatitis, infiltrating inflammatory cells, and the production of cytokines at the lesional skin area were performed by PSI score, immunostaining, and real-time PCR. We also tested the effect of selective CGRP antagonist (CGRP8−37) on psoriasis-like dermatitis in IMQ-treated mice. ResultsBTX-B injection significantly suppressed PSI score and reduced the number of CD4+ T cells, CD11c+ dendritic cells, and the production of IL-17A/F in the lesional skin. The expressions of PGP9.5+ nerve fibers and neuropeptides (SP, CGRP) were also significantly reduced following BTX-B injection. Additionally, CGRP antagonist also suppressed the development of IMQ-induced psoriasis-like dermatitis in mice. ConclusionThe suppression of neuropeptide secretion in the skin by BTX injection might inhibit nerve elongation, the infiltration of immune cells, as well as IL-17 production, resulting in the improvement of psoriasis. Neuropeptide inhibitor could also be applied to the treatment of psoriasis.

RETRACTED: Amelioration of imiquimod-induced psoriasis-like dermatitis in mice by DSW therapy inspired hydrogel

Psoriasis is a long-lasting and recurrent autoimmune disease which is incurable so far. Dead Sea water (DSW) therapy is an effective approach to help control the symptoms of psoriasis due to the abundant mineral ions in DSW, which inspired the material formulation in this study. Rubidium–Sodium alginate/Polyacrylamide hydrogels (Rb-SA/PAAm gels) composed of sodium alginate and polyacrylamide interpenetrating network structure with different concentrations of rubidium and certain magnesium and zinc content were prepared for the treatment of psoriasis. The obtained results suggest the good mechanical properties of the Rb-SA/PAAm gels including toughness and swelling performance. In terms of in vitro tests, the Rb-SA/PAAm gels not only show nontoxicity to human keratinocyte cell line (Hacats) but also inhibits the activity against inflammatory NF-κβ signaling pathway. Meanwhile, they can release Rb+ which enable the Rb-SA/PAAm gels have better antibacterial ability to Streptococcus and Escherichia coli. The results obtained from in vivo tests indicate that these hydrogels could alleviate the symptoms of psoriasis caused by Imiquimod (IMQ) in mice by reducing the inflammatory factor in STAT3 pathway and therefore reduce the immune stimulation of the spleen. In conclusion, the 100Rb-SA/PAAm gel has demonstrated great potential to be a topical wettable dressing for psoriasis treatment.

CTNNBIP1 modulates keratinocyte proliferation through promoting the transcription of β-catenin/TCF complex downstream genes.

During psoriasis initiation and development, deregulations in signalling pathways and gene expression are observed. Herein, we downloaded seven sets of microarray mRNA expression profiles showing differentially expressed genes in psoriasis lesion skin and non-lesion skin tissues and three sets of RNA-seq data and analysed these online data attempting to screen for crucial genes related to keratinocyte proliferation and psoriasis development. The expression of CTNNBIP1 in psoriasis patients and IMQ mouse model skin tissues were examined by RT-PCR, immunoblotting and IHC. The functions of CTNNBIP1 on HaCaT cell proliferation, apoptosis and β-catenin/TCF complex were measured by MTT, EdU, flow cytometry, IF, luciferase assays and immunoblotting. The expression of catenin beta interacting protein 1 (CTNNBIP1) was remarkably downregulated within psoriasis lesion skin tissue samples compared to that within non-lesion skin tissues based on both online data and experimental results. In response to a period of different therapies, respectively, CTNNBIP1 expression could be rescued in lesion skin tissues. Within IMQ-induced psoriasis-like dermatitis in mice, CTNNBIP1 silence further aggravated psoriatic phenotypes. In human immortalized keratinocytes, HaCaT cells, CTNNBIP1 silence significantly inhibited cell apoptosis and promoted cell proliferation. Regarding the molecular mechanism, CTNNBIP1 silence in HaCaT cells promoted β-catenin nucleus translocation, enhanced the transcriptional activity of TCF4 and increased β-catenin/TCF complex downstream c-Myc and cyclin D1 proteins, and also increased the expression of cell proliferation marker ki-67. In contrast to CTNNBIP1, the expression of c-Myc and cyclin D1 showed to be dramatically upregulated within psoriasis lesion tissue samples than that within non-lesion tissue samples. Within tissues, c-Myc and cyclin D1 showed to be negatively correlated with CTNNBIP1, respectively. We identify CTNNBIP1 as an abnormally downregulated gene in psoriasis. CTNNBIP1 silence significantly disturbs the proliferation of keratinocytes through promoting the transcription of β-catenin/TCF complex downstream genes.

Salvianolic Acid B in Microemulsion Formulation Provided Sufficient Hydration for Dry Skin and Ameliorated the Severity of Imiquimod-Induced Psoriasis-Like Dermatitis in Mice.

Psoriasis is a chronic inflammatory skin disorder with a pathogenesis involving the interleukin-23/interleukin-17 axis. Salvianolic acid B exerts several pharmacological effects, such as antioxidation, anti-inflammation, and antitumor effects. The anti-psoriatic effects of salvianolic acid B have not been reported. In this study, we aimed to determine the optimum vehicle for salvianolic acid B, investigate its therapeutic effect on psoriatic-like skin conditions, and explore its underlying mechanisms of action. BALB/c mice were administered topical imiquimod to induce psoriasis-like skin and were then randomly assigned to control, vehicle control, salvianolic acid B in vehicles, and 0.25% desoximetasone ointment treatment groups. Barrier function, cytokine expression, histology assessment, and disease severity were evaluated. The results showed that salvianolic acid B-containing microemulsion alleviated disease severity, reduced acanthosis, and inhibited interleukin-23/interleukin-17 (IL-23/IL-17) cytokines, epidermal proliferation, and increased skin hydration. Our study suggests that salvianolic acid B represents a possible new therapeutic drug for the treatment of psoriasis. In addition, such formulation could obtain high therapeutic efficacy in addition to providing sufficient hydration for dry skin.

Combination Therapy of Acarbose and Cyclosporine a Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice.

Moderate to severe psoriasis, an immune-mediated inflammatory disease, adversely affects patients’ lives. Cyclosporin A (CsA), an effective immunomodulator, is used to treat psoriasis. CsA is ineffective at low doses and toxic at high doses. Acarbose (Acar), a common antidiabetic drug with anti-inflammatory and immunomodulatory effects, reduces imiquimod (IMQ)-induced psoriasis severity. Combinations of systemic drugs are generally more efficacious and safer than higher doses of single drugs. We observed that mice treated with a combination of Acar (250 mg/kg) and low-dose CsA (10 or 20 mg/kg) exhibited significantly milder IMQ-induced psoriasis-like dermatitis and smoother back skin than those treated with Acar (250 mg/kg), low-dose CsA (10 or 20 mg/kg), or IMQ alone. The combination therapy significantly reduced serum and skin levels of Th17-related cytokines (interleukin (IL)-17A, IL-22, and IL-23) and the Th1-related cytokine tumor necrosis factor-α (TNF-α) compared with Acar, low-dose CsA, and IMQ alone. Additionally, the combination therapy significantly reduced the percentages of IL-17- and IL-22-producing CD4+ T-cells (Th17 and Th22 cells, respectively) and increased that of Treg cells. Our data suggested that Acar and low-dose CsA in combination alleviates psoriatic skin lesions by inhibiting inflammation. The findings provide new insights into the effects of immunomodulatory drugs in psoriasis treatment.

Topical administration of nanocarrier miRNA-210 antisense ameliorates imiquimod-induced psoriasis-like dermatitis in mice.

Psoriasis is a chronic, recurrent inflammatory autoimmune skin disease. Although its etiology and pathogenesis are complex and multifarious, it has been proved to be closely related to dysregulation of immune cell function as well as keratinocyte proliferation/differentiation. Our previous study demonstrated that miRNA-210 (miR-210) plays an important role in the formation of skin lesions and immune imbalance in psoriasis. Here, we developed a biomimetic reconstituted high-density lipoprotein (rHDL) nanocarrier gel containing miR-210 antisense (NG-anti-miR-210) to investigate its effect on imiquimod (IMQ)-induced psoriasis-like dermatitis in mice. We found that topical treatment with NG-anti-miR-210 significantly decreased the expression of miR-210 in both the skin lesions and splenic CD4+ T cells from IMQ-induced psoriasis-like mouse models and ameliorated the dermatitis in terms of the erythema, scales, acanthosis and dermal inflammatory cell infiltration in IMQ-induced mice. In addition, the proportion of T-helper (Th)1 and Th17 cells in dermal and splenic cells of IMQ-treated mice were decreased by application of NG-anti-miR-210, accompanied by decreased interleukin-17A and γ-interferon mRNA levels. Therefore, our data demonstrate that topical inhibition of miR-210 delivered by rHDL nanocarrier effectively alleviates the psoriasis-like inflammation in mice and provides a potentially effective topical drug for psoriasis.

Observation on the efficacy and mechanism of Hirudoid in preventing psoriasis-like dermatitis in mice

Objective To observe the preventive effect of Hirudoid (MPS) ointment on psoriasis-like dermatitis in mice and explore its mechanism. Methods 21 Balb/C mice were randomly divided into three groups: blank control group, positive control group (imiquimod group) and treatment group (imiquimod+ Hirudoid group). The blank control group was treated with imiquimod matrix. The positive control group was treated with 5% imiquimod cream to induce psoriatic dermatitis in mice′s back. The treatment group was treated with 5% imiquimod cream in the morning and Hirudoid cream in the afternoon. The changes of skin erythema, scales , infiltration severity and skin histopathology in the experimental area of mice back and serum levels of interleukin (IL)-17A and protein expression of tumor necrosis factor-α (TNF-α) in the three groups of mice were observed. Results The clinical and pathological findings of skin lesions in the positive control group showed that 5% imiquimod cream successfully induced psoriasis-like dermatitis in mice. The appearance and pathological feature of skin lesions in the blank control group were almost close to normal skin. The degree of erythema, infiltration and scales in the back of the treatment group was significantly less than that in the positive control group, and the degree of microscopic inflammation in the treatment group was also lighter than that in the positive control group; The serum levels of IL-17A and TNF-α in the treatment group and the blank control group were significantly lower than that of the positive control group, with statistically significant difference (P<0.05). Conclusions Hirudoid can significantly reduce imiquimod-induced psoriasis-like dermatitis by inhibiting the expression of IL-17A and TNF-α. Key words: Psoriasis; Glycosaminoglycans; Mice

710 Tussilagonone ameliorates psoriatic features in an imiquimod-induced psoriasis-like dermatitis in mice

710 Tussilagonone ameliorates psoriatic features in an imiquimod-induced psoriasis-like dermatitis in mice

Quercitrin extracted from Tartary buckwheat alleviates imiquimod-induced psoriasis-like dermatitis in mice by inhibiting the Th17 cell response

Quercitrin (YDHH) is a natural dietary flavonoid extracted from Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.). Psoriasis is a chronic immune-mediated dermatosis. In this study, we report that YDHH had no obvious cytotoxicity and inhibited the proliferation of LPS-stimulated HaCaT keratinocytes. Furthermore, oral administration of YDHH alleviated imiquimod-induced psoriasis-like dermatitis in mice, significantly attenuating the excessive proliferation and abnormal differentiation of keratinocytes, and reducing inflammatory cell infiltrates. YDHH treatment lowered the expression of cytokines related to psoriasis, especially those on the IL-23/Th17 axis. Furthermore, it dramatically inhibited the Th17 cell response regulated by the JAK/STAT signalling pathway. In addition, it was less toxic to the liver and kidneys of mice than the classical immunosuppressant cyclosporine A. Taken together, these findings indicate that YDHH could be useful as a functional food supplement for protection against psoriasis.

690 Adenosine A2A receptor (A2AR) modulation attenuates innate and adaptive immune cell signaling during pathogenesis of psoriasis-like dermatitis in mice

690 Adenosine A2A receptor (A2AR) modulation attenuates innate and adaptive immune cell signaling during pathogenesis of psoriasis-like dermatitis in mice

Combinational effects of maxacalcitol and betamethasone butyrate propionate on imiquimod-induced psoriasis-like dermatitis in mice

Psoriasis is a chronic inflammatory skin disease, characterized by epidermal hyper-proliferation, abnormal differentiation and inflammatory cell infiltration. The combination therapy of vitamin D3 analogue (VD3) and glucocorticoid has been widely used for the topical treatment of psoriasis because of its better efficacy compared to each monotherapy. However, their underlying mechanisms on the combinational effects have not yet been fully elucidated. Therefore, we investigated the comparative effects of a novel VD3/glucocorticoid combination product, which contains maxacalcitol (MCT) and betamethasone butyrate propionate (BBP), with MCT or BBP single product on imiquimod (IMQ)-induced psoriasis-like dermatitis in mice. Mice were treated topically with IMQ cream for 4 consecutive days, and drugs were topically administrated for 3 days from the next day of the first IMQ treatment. MCT/BBP combination product strongly ameliorated the development of IMQ-induced psoriasis-like skin lesions. Histological findings also showed that it suppressed the thickening of epidermis and inflammatory cell infiltration in dermis. Moreover, it reduced an elevation in mRNA levels of Th17 cytokines (IL-17A, IL-17F, IL-22), inflammatory cytokines (TNF-α, IL-1β) and an antimicrobial peptide (S100A7), and increased those of epidermal differentiation markers (K1, Filaggrin, Loricrin) in dorsal skin. These effects were much stronger than the single products. In conclusion, our results demonstrated the remarkable improvement effect of MCT/BBP combination product to abnormal immune reaction and epidermal dysfunction, supporting the superior clinical efficacy of combination therapy compared to monotherapy in psoriasis.

Topical thioredoxin inhibits IL-6 and IL-1beta production from keratinocytes and is effective for psoriasis-like dermatitis in mice

Topical thioredoxin inhibits IL-6 and IL-1beta production from keratinocytes and is effective for psoriasis-like dermatitis in mice

Protective effects of agonistic anti-4-1BB antibody on the development of imiquimod-induced psoriasis-like dermatitis in mice

Agonistic anti-4-1BB antibodies (Abs) play a central role in immunomodulatory conditions that control the pathogenesis of immune-mediated autoimmune and allergic diseases. However, the effects of agonistic anti-4-1BB Abs have not been examined in an experimental mouse model of psoriasis. Therefore, we investigated the protective effects of agonistic anti-4-1BB Abs, using imiquimod (IMQ)-induced psoriasis-like dermatitis in mice, a condition histologically and clinically similar to human psoriasis. We found that administration of agonistic anti-4-1BB Abs (10mg/kg) significantly alleviated the severity of IMQ-induced psoriasis-like skin inflammation in mice, with reduced histologic symptoms, including inflammatory infiltration, parakeratosis, and hyperkeratosis. Subsequent analyses revealed that the production of Th17 cytokines (IL-17A and IL-23) in the serum and skin of IMQ-induced mice was significantly inhibited by agonistic anti-4-1BB Abs (10mg/kg), although Th1 cytokines (TNF-α and IFN-γ) were not. Moreover, administration of agonistic anti-4-1BB Abs (10mg/kg) induced a relative increase of CD4+FoxP3+ regulatory T (Treg) cells in the spleen and draining lymph node (DLN). Taken together, our data provide evidence that agonistic anti-4-1BB Abs possesses immunosuppressive properties in IMQ-induced psoriasis-like skin inflammation, providing insight into the immunomodulatory effect of agonistic anti-4-1BB Abs for psoriasis immunotherapy.

Inhibition of imiquimod-induced psoriasis-like dermatitis in mice by herbal extracts from some Indian medicinal plants.

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.

Therapeutic and immunomodulatory effects of glucosamine in combination with low-dose cyclosporine A in a murine model of imiquimod-induced psoriasis

Although cyclosporine A (CsA) is a potent immunomodulating agent and is commonly used as a systemic agent for the management of psoriasis patients, current clinical treatments are not always effective due to the clinical inefficacy of low-doses and numerous harmful effects of higher doses. Currently, the combined use of two other systemic drugs often has better therapeutic efficacy and is safer than low or high dose of a single drug. Glucosamine (Glu) also has immunomodulatory properties for autoimmune diseases. The aims of our study were to investigate the therapeutic efficacy of Glu in combination with low-dose CsA on imiquimod (IMQ)-induced psoriasis-like dermatitis in mice and to determine its immunomodulatory mechanism. We found that combined treatment with Glu (300mg/kg) and low-dose (10 or 20mg/kg) CsA strongly ameliorated the development of psoriasis-like skin lesions and reduced the levels of Th1 cytokine (TNF-α) and Th17 cytokines (IL-17, IL-22, and IL-23) in the serum and dorsal skin. Histological findings also showed that the thickening of epidermis, stratum corneum, and inflammatory cell infiltration. Particularly, these combined treatments increased the number of CD4+CD25+ regulatory T (Treg) cells in splenic. These results suggest that use of a combination of each drug might be used as an efficacious and safe alternative therapeutic strategy, as well as may provide an immunomodulatory approach for T cell-mediated autoimmune diseases, including psoriasis.