Mechanism Investigation and Clinical Retrospective Evaluation of Qingyi Granules: Pancreas Cleaner About Ameliorating Severe Acute Pancreatitis with Acute Respiratory Distress Syndrome

Abstract

Background

Despite its extensive utilization in Chinese hospitals for treating acute pancreatitis (AP) and related acute respiratory distress syndrome (ARDS), the active components and mechanisms underlying the action of Qingyi Granule (QYKL) remain elusive.

Methods

This study consists of four parts. First, we used Mendelian randomization (MR) to investigate the causal relationship between AP, cytokine, and ARDS. Next, 321 patients were collected to evaluate the efficacy of QYKL combined with dexamethasone (DEX) in treating AP. In addition, we used UHPLC-QE-MS to determine the chemical constituents of QYKL extract and rat serum after the oral administration of QYKL. The weighted gene coexpression network analysis (WGCNA) method was used to find the main targets of AP-related ARDS using the GSE151572 dataset. At last, a AP model was established by retrograde injection of 5% sodium taurocholate.

Results

MR showed that AP may have a causal relationship with ARDS by mediating cytokine storms. Retrospective study results showed early administration of QYKL was associated with a lower incidence of ARDS, mortality, admissions to the intensive care unit, and length of stay in AP patients compared to the Control group. Furthermore, we identified 23 QYKL prototype components absorbed into rat serum. WGCNA and differential expression analysis identified 1558 APALI-related genes. The prototype components exhibited strong binding activity with critical targets. QYKL has a significant protective effect on pancreatic and lung injury in AP rats, and the effect is more effective after combined treatment with DEX, which may be related to the regulation of the IL-6/STAT3 signaling pathway.

Conclusion

By integrating MR, retrospective analysis, and systematic pharmacological methodologies, this study systematically elucidated the therapeutic efficacy of QYKL in treating AP-related ARDS, establishing a solid foundation for its medicinal use.

Graphical Abstract

Keywords:

• acute pancreatitis
• qingyi granule
• dexamethasone
• acute lung injury
• clinical efficacy
• Mendelian randomization
• rat

Data Sharing Statement

The manuscript and Supplementary Materials include all of the study’s data.

Ethics Approval and Consent to Participate

The studies involving human participants were reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University and were performed according to the Declaration of Helsinki’s ethical principles. The in vivo experiments were reviewed and approved by the Experimental Animal Ethics Committee of Dalian Medical University.

Acknowledgment

Peng Ge, Yalan Luo, and Jinquan Zhang are co-first authors for this study. We want to acknowledge the participants and investigators of the FinnGen consortium and MRC Integrative Epidemiology Unit.

Disclosure

We have no financial relationships to disclose.

Additional information

Funding

This study was supported by the National Key R&D Program of China (No. 2019YFE0119300) and the National Natural Science Foundation of China (NO. 82274311, 82074158, and 82104594).