Liangxue Qushi Zhiyang Decoction Inhibits Atopic Dermatitis in Mice via FcγR-Mediated Phagocytosis

TL;DR

This study shows that Liangxue Qushi Zhiyang Decoction reduces atopic dermatitis in mice by inhibiting a key immune pathway involving phagocytosis.

Contribution

The study identifies the FcγR-mediated phagocytosis pathway as a novel mechanism for the therapeutic effects of LQZ in atopic dermatitis.

Findings

LQZ reduced skin damage and inflammation in AD mice and lowered IgE, IL-4, and IL-1β levels.

Proteomic analysis revealed 248 differentially expressed proteins, with FcγR-mediated phagocytosis being a key pathway.

LQZ treatment significantly reduced key proteins in the FcγR pathway, including Fcgr3, Lyn, Syk, and others.

Abstract

Background: Liangxue Qushi Zhiyang Decoction (LQZ) is a traditional formula known for its efficacy in treating Atopic Dermatitis (AD). However, the specific mechanisms through which LQZ alleviates AD symptoms remain largely unknown. The objective of this study is to investigate the protective effects of LQZ on AD and to uncover its potential mechanisms of action.

Methods: An AD model was established in mice using 2,4-dinitrochlorobenzene (DNCB). Mice were then orally administered LQZ or prednisolone (PDN). Throughout the treatment period, dermatitis scores and scratching frequencies of the mice were regularly monitored. Histopathological analyses were conducted using hematoxylin and eosin (H&E) staining and toluidine blue (TB) staining. Serum levels of inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Further, tandem mass tag (TMT) labeling quantitative proteomics was employed to identify differentially expressed proteins (DEPs). Enrichment analysis was conducted to pinpoint potential targets and pathways involved in LQZ's therapeutic action. Finally, validation experiments were performed to further explore the specific pathways and core targets of LQZ in AD treatment..

Results: LQZ treatment notably mitigated the skin barrier damage and inflammatory response induced by DNCB in AD mice, and reduced the serum levels of IgE, IL-4, and IL-1β. Proteomic analysis identified 248 proteins with differential expression, implicating multiple pathways in LQZ' therapeutic action. Among these, the Fc gamma R(FcγR)−mediated phagocytosis pathway emerged as a crucial factor in AD's inflammatory and immune responses. Key proteins associated with this pathway, including Fc-gamma RIII (Fcgr3), V-yes-1 Yamaguchi sarcoma viral related oncogene homolog (Lyn), Tyrosine-protein kinase (Syk), Phosphoinositide phospholipase C-gamma-2 (Plcg2), Neutrophil cytosol factor 1 (Ncf1), Ras-related C3 botulinum toxin substrate 2 (Rac2) and Actin-related protein 2/3 complex subunit 3 (Arpc3), exhibited significantly reduced expression levels following LQZ treatment.

Conclusion: LQZ is effective in treating AD by alleviating skin barrier damage and inflammatory reactions. Its anti-AD properties of LQZ may be attributed to the inhibition of the FcγR-mediated phagocytic pathway.

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