Modified Sanliangsan Improved Sjogren’s Syndrome Complicated with Interstitial Lung Disease by Suppressing Serum MUC1 Levels

Objectives: To clarify
if the mechanism of Sanliangsan in improving
Sjogren’s syndrome complicated with interstitial lung disease
(SS-ILD) involves MUC1 suppression, which is involved in SS-ILD pathogenesis.
Methods: Fifty-six patients were randomly divided into two groups
receiving Sanliangsan prescription (SP) therapy and conventional therapy
(western medicine). In-depth transcriptome profiles from a large database
of SS-ILD patients were collected and analyzed to identify candidate
genes involved in SS pathogenesis. Clinical symptom scores, metabolic
compositions, lung HRCT (high-resolution computed tomography) scores,
and serum MUC1 levels were compared between the two groups before
and after treatment. Network pharmacology, molecular docking, and
ITC assays were performed to identify bioactive compounds of SP in
improving SS. Metabolome analyzed the metabolic composition of serum
associated with SS-ILD before and after SP treatment. Results: Transcriptome
results identified the involvement of abnormal expression of genes
relevant to the immune system, inflammatory responses, and signaling
pathways. Numerous genes, including CD58, CD86, CTLA4, CXCL8, STAT1, and especially MUC1, were involved
in SS pathogenesis and could be used to diagnose SS-ILD early. Both
treatments improved the lung HRCT scores and clinical symptoms of
SS-ILD. The SP therapy improved SS-ILD more effectively than conventional
therapy. Moreover, Sanliangsan prescription therapy reduced serum
MUC1 levels and restored the abnormal metabolisms, improving the abnormal
inflammatory and immune responses of patients. Eugenol directly interacted
with MUC1, suppressed related genes, and was the bioactive compound
of SP. SP could partially restore the abnormal metabolisms associated
with SS-ILD pathogenesis. Conclusion: Based on conventional Western
medicine treatment, modified Sanliangsan can significantly improve
the clinical symptoms, signs, and lung function of patients; the mechanism
may be due to eugenol and related to MUC1 regulation.