. 2022 Jan 11;2022:5782922.
doi: 10.1155/2022/5782922.
eCollection 2022.
Affiliations
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Mediators Inflamm.
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Abstract
Itch is one of the major clinical manifestations of psoriasis, which is closely related with neurogenic inflammation and difficult to control. Colquhounia Root (CR) is a Chinese herb exhibiting broad bioactivities on anti-inflammation. This study was designed to explore the antipsoriatic and anti-itch potential of CR and its underlying mechanisms. Mice in a model of imiquimod-induced psoriasiform dermatitis were treated topically with CR for 7 days, and the severity of skin lesions and itch was significantly ameliorated. CR reduced the inflammatory cell infiltration, as well as mast cells in skins. Particularly, the expression of inflammatory cytokines and chemokine including Il17a, Il22, and Ccl20 and itch-related molecules such as SP, CGRP, and NGF in lesions were decreased in diseased mice upon application with CR. The normal human epidermal keratinocytes were stimulated with the M5 cytokine cocktail, the mixture of IL-17A, IL-22, Oncostatin M, IL-1α, and TNF-α, and cell viability and mRNA expression levels of inflammatory factors and itch-related molecules were measured after being treated with CR. We found that CR inhibited both cell hyperproliferation and overexpression of inflammatory cytokines and itch-related molecules in vitro. Altogether, we conclude that CR relieves psoriatic lesions and itch via controlling immunological and neurogenic inflammation.
Copyright © 2022 Fei Li et al.
Conflict of interest statement
The authors declare no commercial or financial conflict of interest.
Figures
Figure 1
CR treatment attenuated the severity of IMQ-induced PsD in mice. (a) The scheme of IMQ-induced murine model and CR treatment. Clinical presentation of mice (b) and dermoscopic presentation (scale bar = 1 mm) (c) of the back skin of mice after 7 days of IMQ treatment with or without the topical application CR. (d) The daily scores of erythema, skin thickness, scaling of back skin, and PSI scores were compared among normal group (n = 11), IMQ group (n = 15), and IMQ + CR group (n = 15). Data are shown as the Mean mean ± SEM and were analyzed by using t-test. ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001, showing the difference between the IMQ group and IMQ+CR group.
Figure 2
CR treatment reduced the epidermal thickness and diminished neutrophil accumulation in IMQ-induced PsD in mice. (a) Representative microscopic images of H&E-stained skin sections from each group (scale bar = 145 μm). (b) Epidermal thickness was evaluated using Leica Microsystems software under a microscope. n = 11 in the normal group; n = 15 in IMQ group and IMQ+CR group. (c) Representative image of MM (scale bar = 145 μm). (d) Quantification of MM area. n = 15 in both the IMQ and IMQ+CR group. Epidermal thicknesses were compared by using one-way ANOVA and post hoc Tukey’s test, and MM areas were compared using a t-test. Data are shown as the Mean ± SEM. ∗∗P < 0.01 and∗∗∗P < 0.001.
Figure 3
CR treatment decreased immune cell infiltration and cytokine production in murine skins of IMQ-induced PsD. (a) Flow cytometry analysis of immune cells (CD45+ immune cells, neutrophils, macrophages, αβ T cells, and CD4+/CD8+αβ T cells) from skin tissues among groups. n = 5 in the normal group, n = 8 in the IMQ group, and n = 10 in the IMQ+CR group. (b) mRNA expression of Il17a, Il22, and Ccl20 in mouse skin was measured via RT-qPCR, and the relative mRNA expression was normalized to Gapdh expression. n = 6 in the normal group, n = 8 in the IMQ group, and n = 8 in the IMQ+CR group. Statistical analysis was performed using one-way ANOVA followed by post hoc Tukey’s test. Data are shown as the Mean ± SEM. ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001.
Figure 4
Pruritus was improved after CR treatment in IMQ-induced PsD in mice. (a) Spontaneous scratching was measured and compared among groups. n = 11 in the normal group and n = 15 in both the IMQ group and IMQ+CR group. (b) Mast cells were stained using Toluidine blue (scale bar = 73 μm). (c) Numbers of mast cells in each group were counted. n = 5 in the normal group and n = 6 in both the IMQ group and IMQ+CR group. Statistical analysis was performed using one-way ANOVA followed by post hoc Tukey’s test. Data are shown as the Mean ± SEM. ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001.
Figure 5
CR treatment reduced the expression of itch-related molecules in IMQ-induced PsD in mice. (a) mRNA expression of Sp, Cgrp, and Ngf in skins was detected by RT-qPCR. n = 6 mice in the control group and n = 8 mice in both the IMQ group and IMQ+CR group. Results of mRNA were normalized to Gapdh expression. (b) Representative immunohistochemical images of SP, CGRP, and NGF expression from the epidermis of back skins among groups (scale bar = 73 μm). (c) Mean of integrated optical density (IOD) of Sp, Cgrp, and Ngf in skins from each group. n = 5 mice in three groups. Statistical analysis was performed using one-way ANOVA followed by post hoc Tukey’s test. Mean ± SEM values are indicated, ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001.
Figure 6
CR treatment regulated cell viability and function of M5-induced keratinocytes in vitro. M5 (10 ng/ml) was used to stimulate NHEKs with or without CR treatment ((a): 0, 0.25 μg/ml, 0.5 μg/ml, 1 μg/ml, and 2 μg/ml; (b): 0.5 μg/ml). (a) Cell viability was measured by using CCK-8 (n = 4). (b) The mRNA expression of IL-6, CXCL8, IL-1β, CCL20, SP, CGRP, and NGF was detected by RT-qPCR (n = 3). The relative mRNA expression was normalized to GAPDH expression. Statistical analysis was performed using one-way ANOVA followed by post hoc Tukey’s test. Mean ± SEM values are indicated. ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001.
Figure 7
Characterization of the mechanism of CR for psoriasis pruritus improvement. CR treatment relieves the symptoms of psoriasis pruritus by inhibiting increased mast cells and neutrophils, as well as the upregulation of the inflammatory factors IL-17a, IL-22, IL-6, CXCL8, IL-1β, and CCL20 and itch-related molecules SP, CGRP, and NGF in psoriasis.
References
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