Effect and mechanism of longkui yinxiao soup in treating psoriasis in mice

Congcong Zhu; Ya Chen; Zongguang Tai; Huijun Pan; Min Shen; Zhongjian Chen; Quangang Zhu

doi:10.3389/fphar.2023.1136604

Effect and mechanism of longkui yinxiao soup in treating psoriasis in mice

Front Pharmacol. 2023 Mar 13:14:1136604. doi: 10.3389/fphar.2023.1136604. eCollection 2023.

Authors

Congcong Zhu^{1

2}, Ya Chen^{1

2}, Zongguang Tai^{1

2}, Huijun Pan^{1

2}, Min Shen^{1

2}, Zhongjian Chen^{1

2}, Quangang Zhu^{1

2}

Affiliations

¹ Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
² Shanghai Engineering Research Center for Topical Chinese Medicine, Shanghai, China.

Abstract

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Keywords: RAP1-MAPK signaling; RAP1-MAPK signaling inflammation; inflammation; keratinocyte proliferation; longkui yinxiao soup; psoriasis.

Grants and funding

This study was supported by the Traditional Chinese Medicine Research Project of the Shanghai Municipal Health Commission (Grant number: 2022QN039), the Clinical Transformation Incubation Project of the Shanghai Skin Disease Hospital (Grant number: lczh 2021-06), and the Science and Technology Commission of Shanghai Municipality (Grant number: 22S21902700 and 19401900700).