Ferroptosis in Rat Lung Tissue during Severe Acute Pancreatitis-Associated Acute Lung Injury: Protection of Qingyi Decoction

Abstract

Qingyi decoction (QYD) has anti-inflammatory pharmacological properties and substantial therapeutic benefits on severe acute pancreatitis (SAP) in clinical practice. However, its protective mechanism against SAP-associated acute lung injury (ALI) remains unclear. In this study, we screened the active ingredients of QYD from the perspective of network pharmacology to identify its core targets and signaling pathways against SAP-associated ALI. Rescue experiments were used to determine the relationship between QYD and ferroptosis. Then, metabolomics and 16s rDNA sequencing were used to identify differential metabolites and microbes in lung tissue. Correlation analysis was utilized to explore the relationship between core targets, signaling pathways, metabolic phenotypes, and microbial flora, sorting out the potential molecular network of QYD against SAP-associated lung ALI. Inflammatory damage was caused by SAP in the rat lung. QYD could effectively alleviate lung injury, improve respiratory function, and significantly reduce serum inflammatory factor levels in SAP rats. Network pharmacology and molecular docking identified three key targets: ALDH2, AnxA1, and ICAM-1. Mechanistically, QYD may inhibit ferroptosis by promoting the ALDH2 expression and suppress neutrophil infiltration by blocking the cleavage of intact AnxA1 and downregulating ICAM-1 expression. Ferroptosis activator counteracts the pulmonary protective effect of QYD in SAP rats. In addition, seven significant differential metabolites were identified in lung tissues. QYD relatively improved the lung microbiome’s abundance in SAP rats. Further correlation analysis determined the correlation between ferroptosis, differential metabolites, and differential microbes. In this work, the network pharmacology, metabolomics, and 16s rDNA sequencing were integrated to uncover the mechanism of QYD against SAP-associated ALI. This novel integrated method may play an important role in future research on traditional Chinese medicine.

Mechanisms of Qingyi Decoction in Severe Acute Pancreatitis-Associated Acute Lung Injury via Gut Microbiota: Targeting the Short-Chain Fatty Acids-Mediated AMPK/NF-κB/NLRP3 Pathway

“…QYD is a TCM commonly used after surgery for the treatment of SAP. In previous studies, our team has shown the potential for QYD to treat SAP-ALI or SAP-related multiple organ dysfunction by exerting antiinflammatory and enhancing the intestinal barrier while simultaneously maintaining immune homeostasis ( 47 , 48 ). Furthermore, QYD has been shown to mediate the recovery of intestinal dysbiosis in SAP, indicating its role in regulating intestinal bacteria ( 25 ).…”

An in-Depth Exploration of the Genetic Interaction Network Between Ferroptosis and Acute Pancreatitis

“… 11–15 Moreover, it is not only limited to pancreatic injury in AP but is also involved in the kidney injury and lung injury caused by AP. 16–18 These findings emphasize the important role of ferroptosis in the AP process. Ultimately, it was found that ferroptosis and AP are closely associated and jointly affect the AP disease process in several ways.…”

Recent advances in the potential effects of natural products from traditional Chinese medicine against respiratory diseases targeting ferroptosis

“…This suggests that QYD has potential therapeutic efficacy in treating lung injury related to severe acute pancreatitis (SAP). Originating from the formula in "Shanghan Lun," as a decoction made from Chinese herbal medicine, QYD is employed in the treatment of acute pancreatitis (AP) patients due to its laxative, heat-clearing, and detoxifying properties [134,135]. Uncoupling Protein-2 (UCP2) is crucial for managing ROS, maintaining redox balance, and modulating immune responses.…”