Moupinamide from Polygonatum odoratum predicted to target CCR1, a key monocyte chemotaxis receptor upregulated in Primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by inflammation of exocrine glands, leading to symptoms like dry eyes and mouth. Despite its prevalence, there is currently no specific etiological treatment for pSS, leaving a significant unmet medical need. Traditional remedies like Polygonatum odoratum are used, but their molecular mechanisms are poorly understood. Identifying specific therapeutic targets and understanding how natural compounds interact with them could pave the way for novel, targeted pSS therapies.

Researchers integrated transcriptomic datasets (GSE51092, GSE66795, GSE84844) and single-cell RNA sequencing data (GSE253568) from GEO. Network pharmacology screened active component targets of Polygonatum odoratum. A 'three-dimensional intersection' strategy identified candidate therapeutic targets. Single-cell analyses included monocyte subtyping, pseudotime trajectory, SCENIC transcription factor network, and CellChat cell communication analyses. Molecular docking predicted drug-target binding, and RT-qPCR validated CCR1 expression in peripheral blood mononuclear cells (PBMCs) from 65 pSS patients and 48 healthy controls.