Zhu Congcong, Chen Ya, Tai Zongguang, Pan Huijun, Shen Min, Chen Zhongjian, Zhu Quangang
Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
Shanghai Engineering Research Center for Topical Chinese Medicine, Shanghai, China.
Front Pharmacol. 2023 Mar 13;14:1136604. doi: 10.3389/fphar.2023.1136604. eCollection 2023.
Longkui Yinxiao Soup is a traditional Chinese medicine formula used to treat psoriasis for decades. Although Longkui Yinxiao Soup showed promising efficacy in clinical practice, the regulatory mechanisms of Longkui Yinxiao Soup remain elusive. This study aimed to explore the underlying mechanisms of Longkui Yinxiao Soup in a psoriasis-like mouse model. Longkui Yinxiao Soup was quality controlled by determining the contents of imperatorin and rhoifolin using high-performance liquid chromatography. The imiquimod-induced psoriasis-like mouse model was used to study the therapeutic effect and mechanism of Longkui Yinxiao Soup. The histopathological skin changes were observed by hematoxylin and eosin staining; the infiltration of proliferating proteins, proliferating cell nuclear antigen and Ki67, in skin tissues were observed by immunohistochemical analysis; and the inflammatory factors such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-23, and IL-17 in serum were detected using enzyme-linked immunosorbent assay. RNA sequencing and bioinformatic analysis were used to predict the mechanism of LYS against psoriasis. mRNA expressions of p38, extracellular regulated protein kinases (ERK), mitogen-activated protein kinase 3 (MEK3), mitogen-activated protein kinase 6 (MEK6), RAP1 GTPase activating protein (Rap1gap), and Rap1 were determined using real-time quantitative polymerase chain reaction. The expression levels of proteins related to Rap1-mitogen-activated protein kinase signaling pathways were measured by Western blotting. A quality-control method for Longkui Yinxiao Soup was successfully established using imperatorin and rhoifolin as content determination indexes. Longkui Yinxiao Soup significantly ameliorated the psoriatic symptoms in mice. The serum levels of inflammatory cytokines such as IL-6, TNF-α, IL-23, and IL-17 were decreased, and the expression levels of antigen identified by monoclonal antibody Ki67 (Ki67) and PCNA in skin tissues were downregulated. Moreover, the inhibition of Rap1-MAPK signaling pathways by Longkui Yinxiao Soup was detected. This study confirmed the antipsoriatic activity of Longkui Yinxiao Soup in psoriasis-like mice. This might be due to the inhibition of inflammatory factor secretion, keratinocyte proliferation, and the Rap1-MAPK signal pathway.
龙葵银屑汤是一种用于治疗银屑病数十年的中药方剂。尽管龙葵银屑汤在临床实践中显示出有前景的疗效,但其调控机制仍不清楚。本研究旨在探讨龙葵银屑汤在银屑病样小鼠模型中的潜在机制。通过高效液相色谱法测定欧前胡素和异鼠李素的含量来对龙葵银屑汤进行质量控制。采用咪喹莫特诱导的银屑病样小鼠模型来研究龙葵银屑汤的治疗效果和机制。通过苏木精和伊红染色观察皮肤组织病理学变化;通过免疫组织化学分析观察皮肤组织中增殖蛋白、增殖细胞核抗原和Ki67的浸润情况;使用酶联免疫吸附测定法检测血清中的炎症因子如白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、IL-23和IL-17。采用RNA测序和生物信息学分析来预测龙葵银屑汤治疗银屑病的机制。使用实时定量聚合酶链反应测定p38、细胞外调节蛋白激酶(ERK)、丝裂原活化蛋白激酶3(MEK3)、丝裂原活化蛋白激酶6(MEK6)、RAP1 GTP酶激活蛋白(Rap1gap)和Rap1的mRNA表达。通过蛋白质印迹法测量与Rap1-丝裂原活化蛋白激酶信号通路相关的蛋白质表达水平。以欧前胡素和异鼠李素为含量测定指标,成功建立了龙葵银屑汤的质量控制方法。龙葵银屑汤显著改善了小鼠的银屑病症状。血清中IL-6、TNF-α、IL-23和IL-17等炎症细胞因子水平降低,皮肤组织中由单克隆抗体Ki67(Ki67)和PCNA鉴定的抗原表达水平下调。此外,检测到龙葵银屑汤对Rap1-MAPK信号通路的抑制作用。本研究证实了龙葵银屑汤在银屑病样小鼠中的抗银屑病活性。这可能是由于其抑制了炎症因子分泌、角质形成细胞增殖以及Rap1-MAPK信号通路。