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静方颗粒通过体外和体内靶向 MAPK 介导的树突状细胞成熟和 PPARγ 介导的角质形成细胞细胞周期进程发挥抗银屑病作用。

Jingfang granules exert anti-psoriasis effect by targeting MAPK-mediated dendritic cell maturation and PPARγ-mediated keratinocytes cell cycle progression in vitro and in vivo.

机构信息

Department of Dermato-Venereology, The Second Hospital of Shandong University, Jinan 250033, China; State Key laboratory of Generic Manufacture Technology of Chines Traditional Medicine, Lunan Pharmaceutical Co., Ltd., Linyi 276005, China; Shandong University of Traditional Chinese Medicine, Jinan 250355, China.

State Key laboratory of Generic Manufacture Technology of Chines Traditional Medicine, Lunan Pharmaceutical Co., Ltd., Linyi 276005, China; Advanced Medical Research Institute, Shandong University, Jinan 250012, China.

出版信息

Phytomedicine. 2023 Aug;117:154925. doi: 10.1016/j.phymed.2023.154925. Epub 2023 Jun 8.

DOI:10.1016/j.phymed.2023.154925
PMID:37321079
Abstract

BACKGROUND

Jingfang granules (JFG), derived from JingFangBaiDu San (JFBDS), are a traditional herbal formulas used for the treatment of respiratory tract infections. They were initially prescribed to treat skin disease, such as psoriasis in Chinese Taiwan, but are not widely used for psoriasis treatment in mainland China because of the lack of anti-psoriasis mechanism research.

PURPOSES

The present study was designed to evaluate the anti-psoriasis effect of JFG and reveal the correlated mechanisms of JFG in vivo and in vitro using network pharmacology, UPLC-Q-TOF-MS technology and molecular biotechnology methods.

RESULTS

An imiquimod-induced psoriasis-like murine model was used to verify the anti-psoriasis effect in vivo, with inhibition of lymphocytosis and CD3+CD19+B cell proliferation in the peripheral blood and prevention of the activation of CD4+IL17+T cells and CD11c+ MHC Ⅱ+ dendritic cells (DCs) in the spleen. Network pharmacology analysis demonstrated that the targets of the active components were significantly enriched in pathways involved in cancer, inflammatory bowel disease and rheumatoid arthritis, which were closely related to cell proliferation and immune regulation. The drug-component-target networks and molecular docking analysis demonstrated the active ingredients to be luteolin, naringin and 6'-feruloylnodakenin, which had a good binding affinity to PPARγ, p38a MAPK and TNF-a. Finally, UPLC-Q-TOF-MS analysis to validate the active ingredients in drug-containing serum and in vitro experiments showed that JFG inhibited the maturation and activation of BMDCs via the p38a MAPK signaling pathway and translocation of the agonist PPARγ into the nuclei to reduce the activity of NF-κB/STAT3 inflammatory signaling pathway in keratinocytes.

CONCLUSIONS

Our study demonstrated that JFG improved psoriasis by inhibiting the maturation and activation of BMDCs and proliferation and inflammation of keratinocytes, which may facilitate the applications of JFG in anti-psoriasis therapy in clinical settings.

摘要

背景

京方颗粒(JFG)源自京防败毒散(JFBDS),是一种用于治疗呼吸道感染的传统草药配方。它最初被开给台湾地区的银屑病患者使用,但由于缺乏抗银屑病机制的研究,在中国内地并不广泛用于银屑病的治疗。

目的

本研究旨在通过网络药理学、UPLC-Q-TOF-MS 技术和分子生物技术方法,评估 JFG 的抗银屑病作用,并揭示其在体内和体外的相关机制。

结果

采用咪喹莫特诱导的银屑病样小鼠模型验证其体内抗银屑病作用,抑制外周血淋巴细胞和 CD3+CD19+B 细胞增殖,预防脾内 CD4+IL17+T 细胞和 CD11c+MHCⅡ+树突状细胞(DC)的活化。网络药理学分析表明,活性成分的靶点显著富集在癌症、炎症性肠病和类风湿关节炎相关通路中,这些通路与细胞增殖和免疫调节密切相关。药物-成分-靶点网络和分子对接分析表明,活性成分包括木犀草素、柚皮苷和 6'-阿魏酰基柴胡皂苷元,它们与 PPARγ、p38a MAPK 和 TNF-α具有良好的结合亲和力。最后,UPLC-Q-TOF-MS 分析验证含药血清中的活性成分和体外实验表明,JFG 通过 p38a MAPK 信号通路抑制 BMDC 的成熟和激活,并通过激动剂 PPARγ转位入核减少角质形成细胞中 NF-κB/STAT3 炎症信号通路的活性,从而抑制角质形成细胞的增殖和炎症。

结论

本研究表明,JFG 通过抑制 BMDC 的成熟和激活以及角质形成细胞的增殖和炎症改善银屑病,这可能有助于 JFG 在临床抗银屑病治疗中的应用。

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