Deciphering potential pharmacological mechanism of Sha-Shen-Mai-Dong decoction on primary Sjogren's syndrome

Background: Sha-Shen-Mai-Dong decoction (SSMD) is a classical prescription widely used in primary Sjogren's Syndrome (pSS) therapy. This study aims to explore the potential pharmacological mechanism of SSMD on pSS.

Methods: Active components of SSMD were obtained from Traditional Chinese Medicine Integrative Database and Traditional Chinese Medicine Systems Pharmacology databases and targets of SSMD were predicted by Pharmmapper and STITCH database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out to explore the function characteristics of SSMD. The expression matrix of microarray of pSS was obtained from Gene Expression Omnibus and we obtained 162 differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks were constructed to identify the hub targets. Principal component analysis (PCA) and molecular docking were conducted to further elucidate the possibility of SSMD for pSS.

Results: SSMD contained a total of 1056 active components, corresponding to 88 targets, among which peripheral myelin protein 2(PMP2), androgen receptor (AR) and glutamic acid decarboxylase 1(GAD1) are associated with multiple active components in SSMD and may be the core targets. Moreover, these targets were closely related to tissue pathological injury in SS, such as lacrimal gland, salivary gland and nervous system injury. GO and KEGG analysis showed that 88 targets enriched in REDOX process, transcriptional regulation and negative regulation of apoptosis process. Besides, SSMD may influence the cell proliferation, gene transcription through regulating Ras and cAMP-related signaling pathways. In addition, SSMD may show effects on immune regulation, such as macrophage differentiation, Toll-like receptor 4 signaling pathway and T-helper 1 in SS. Moreover, PPI network suggested that FN1, MMP-9 may be the hub targets in SSMD. Result of PCA and molecular docking analysis further determined the feasibility of SSMD in treating pSS.

Conclusion: SSMD can regulate multiple biological processes by virtue of its multiple active components, thus showing prominent advantage in the treatment of pSS. The discovery of active ingredients and targets in SSMD provides valuable resources for drug research and development for pSS.