Ginsenoside Compound K Reduces Psoriasis-related Inflammation by Activation of the Glucocorticoid Receptor in Keratinocytes.

Wu Wang, Xiujin Xu, Mei Yang, Mengya Jiang, Dandan Wang, Caihong Tang, Wei Wei, Jingyu Chen
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Abstract

Aim: To investigate the effects and mechanism of Ginsenoside Compound K (GCK) on psoriasis, focusing on the glucocorticoid receptor (GR) in keratinocytes.

Methods: An imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model was generated to evaluate the anti-inflammatory effect of GCK. Hematoxylin and eosin (H&E) staining was used to assess skin pathological changes. Protein expression of K17 and p-p65 in mice skin was assayed by immunohistochemical. Protein expression and phosphorylation of p65 IκB were assayed by Western blot. Protein expression of K1, K6, K10, K16, K17, and GR were assayed by Western blot and immunofluorescence. Enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine levels of TNF-α, IL-6, CXCL-8, and ICAM-1. Real-time polymerase chain reaction (RT-PCR) was used to quantify TNF-α, IL-6, IL-8, and ICAM-1 mRNA expression. Cell viability was determined by Cell Counting Kit-8(CCK-8) assay. A high-content cell-imaging system was used to assay cell proliferation. Nuclear translocation of p65 and GR was assayed by imaging flow cytometry and immunofluorescence microscopy. Small interfering RNA was used to confirm the role of GR in the anti-inflammatory and immunoregulatory effect of GCK in normal human epidermal keratinecytes (NHEKs).

Results: GCK reduced the psoriasis area, severity index, and epidermal thickening in IMQ-induced mice. GCK significantly attenuated the mRNA levels of IL-6, IL-8, TNF-α, and ICAM-1 and reduced epidermal hyperproliferation in the skin of IMQ-induced mice. GCK inhibited in vitro activation of NF-κB, leading to attenuated release of inflammatory mediators (IL-6, IL-8, TNF-α, and ICAM-1) and suppression of NHEK hyperproliferation and abnormal differentiation. These inhibitory effects of GCK were diminished by GR silencing in NHEKs.

Conclusion: GCK suppressed psoriasis-related inflammation by suppressing keratinocyte activation, which may be related to promoting GR nuclear translocation and inhibiting NF-κB activation. In summary, GCK appears to be a GR activator and a promising therapeutic candidate for antipsoriatic agents.

人参皂苷化合物 K 通过激活角朊细胞中的糖皮质激素受体减轻与牛皮癣相关的炎症反应
目的:研究人参皂苷化合物K(GCK)对银屑病的作用和机制,重点是角质形成细胞中的糖皮质激素受体(GR):方法:为了评估人参皂苷化合物 K(GCK)的抗炎作用,我们制作了一种咪喹莫特(IMQ)诱导的银屑病样皮炎小鼠模型。血红素和伊红(H&E)染色用于评估皮肤病理变化。用免疫组化方法检测小鼠皮肤中 K17 和 p-p65 的蛋白表达。通过 Western 印迹检测 p65 IκB 的蛋白表达和磷酸化。通过 Western 印迹和免疫荧光检测 K1、K6、K10、K16、K17 和 GR 的蛋白表达。酶联免疫吸附试验(ELISA)用于检测 TNF-α、IL-6、CXCL-8 和 ICAM-1 的细胞因子水平。实时聚合酶链反应(RT-PCR)用于量化 TNF-α、IL-6、IL-8 和 ICAM-1 mRNA 的表达。细胞活力由细胞计数试剂盒-8(CCK-8)测定。高含量细胞成像系统用于检测细胞增殖。通过成像流式细胞仪和免疫荧光显微镜检测 p65 和 GR 的核转运。用小干扰 RNA 证实了 GR 在正常人表皮角质细胞(NHEKs)中 GCK 的抗炎和免疫调节作用:结果:GCK减少了IMQ诱导小鼠的银屑病面积、严重程度指数和表皮增厚。GCK 能明显降低 IL-6、IL-8、TNF-α 和 ICAM-1 的 mRNA 水平,并减少 IMQ 诱导的小鼠皮肤表皮的过度增殖。GCK 可抑制 NF-κB 的体外激活,从而减少炎症介质(IL-6、IL-8、TNF-α 和 ICAM-1)的释放,抑制 NHEK 的过度增殖和异常分化。GCK的这些抑制作用在NHEKs中被GR沉默后减弱:结论:GCK通过抑制角质形成细胞的活化来抑制银屑病相关炎症,这可能与促进GR核转位和抑制NF-κB活化有关。总之,GCK似乎是一种GR激活剂,是一种很有希望的候选抗银屑病治疗药物。
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