Integrating Network Pharmacology, Transcriptome and Artificial Intelligence for Investigating Into the Effect and Mechanism of Ning Fei Ping Xue Decoction Against the Acute Respiratory Distress Syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a high-mortality disease and lacks effective pharmacotherapy. A traditional Chinese medicine (TCM) formula, Ning Fei Ping Xue (NFPX) decoction, was demonstrated to play a critical role in alleviating inflammatory responses of the lung. However, its therapeutic effectiveness in ARDS and active compounds, targets, and molecular mechanisms remain to be elucidated. The present study investigates the effects of NFPX decoction on ARDS mice induced by lipopolysaccharides (LPS). The results revealed that NFPX alleviated lung edema evaluated by lung ultrasound, decreased lung wet/Dry ratio, the total cell numbers of bronchoalveolar lavage fluid (BALF), and IL-1β, IL-6, and TNF-α levels in BALF and serum, and ameliorated lung pathology in a dose-dependent manner. Subsequently, UPLC-HRMS was performed to establish the compounds of NFPX. A total of 150 compounds in NFPX were characterized. Moreover, integrating network pharmacology approach and transcriptional profiling of lung tissues were performed to predict the underlying mechanism. 37 active components and 77 targets were screened out, and a herbs-compounds-targets network was constructed. Differentially expressed genes (DEGs) were identified from LPS-treated mice compared with LPS combined with NFPX mice. GO, KEGG, and artificial intelligence analysis indicated that NFPX might act on various drug targets. At last, potential targets, HRAS, SMAD4, and AMPK, were validated by qRT-PCR in ARDS murine model. In conclusion, we prove the efficacy of NFPX decoction in the treatment of ARDS. Furthermore, integrating network pharmacology, transcriptome, and artificial intelligence analysis contributes to illustrating the molecular mechanism of NFPX decoction on ARDS.