Analyzing how SiMiao Wan regulates ferroptosis to prevent RA-ILD using metabolomics and cyberpharmacology.

ABSTRACT

BACKGROUND: Interstitial lung disease (ILD) is a common complication of rheumatoid arthritis (RA) that plays a significant role in the morbidity and mortality of individuals with this condition. In clinical settings, Si Miao Wan (SMW), a traditional Chinese medicine, is often utilized for the management of RA, as it is believed to possess properties that aid in reducing inflammation, eliminating excess moisture, and alleviating joint pain. PURPOSE: The primary objective of this investigation was to elucidate the potential mechanism of RA-ILD prevention from the perspective of ferroptosis mediated by SMW. METHODS: UPLC-Q-TOF/MS and network pharmacology were employed to forecast the potential targets of SMW for the early prevention of RA-ILD. Following this, HE staining, metabolomics, and RT-PCR were utilized to investigate the mechanism by which SMW prevents RA-ILD at an early stage. RESULTS: Following six weeks of continuous administration of SMW extract at a dosage of 2.16 g/kg/day, it was observed that SMW exhibited early preventive effects against RA-ILD. Metabolomics analysis revealed seven potential biomarkers linked to the pharmacological efficacy of SMW in the early prevention of RA-ILD. Additionally, network pharmacology analysis suggested that SMW may exert its therapeutic effects on RA-ILD by modulating signaling pathways associated with lipid metabolism, atherosclerosis, TNF, and IL-17. Ultimately, through the integration of metabolomics and network pharmacology analysis, along with subsequent verification, it was determined that the early prevention of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) by Shenmai injection (SMW) is associated with the ferroptosis pathway. CONCLUSION: This research offers preliminary insights into the potential mechanism by which traditional Chinese medicine Shen Mai Wan (SMW) may mitigate the early onset of Rheumatoid Arthritis-Interstitial Lung Disease (RA-ILD) via the process of ferroptosis. Furthermore, it establishes a theoretical framework for the development of innovative SMW-based pharmaceuticals for the management of RA-ILD. The signal proteins implicated in this process are anticipated to emerge as crucial targets for the prevention of RA-ILD.