Abstract
Xuan-bai-cheng-qi decoction (XCD), a traditional Chinese medicine (TCM) prescription, has been widely used to treat a variety of respiratory diseases in China, especially to seriously infectious diseases such as acute lung injury (ALI). Due to the complexity of the chemical constituent, however, the underlying pharmacological mechanism of action of XCD is still unclear. To explore its protective mechanism on ALI, firstly, a network pharmacology experiment was conducted to construct a component-target network of XCD, which identified 46 active components and 280 predicted target genes. Then, RNA sequencing (RNA-seq) was used to screen differentially expressed genes (DEGs) between ALI model rats treated with and without XCD and 753 DEGs were found. By overlapping the target genes identified using network pharmacology and DEGs using RNA-seq, and subsequent protein–protein interaction (PPI) network analysis, 6 kernel targets such as vascular epidermal growth factor (VEGF), mammalian target of rapamycin (mTOR), AKT1, hypoxia-inducible factor-1α (HIF-1α), and phosphoinositide 3-kinase (PI3K) and gene of phosphate and tension homology deleted on chromsome ten (PTEN) were screened out to be closely relevant to ALI treatment. Verification experiments in the LPS-induced ALI model rats showed that XCD could alleviate lung tissue pathological injury through attenuating proinflammatory cytokines release such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Meanwhile, both the mRNA and protein expression levels of PI3K, mTOR, HIF-1α, and VEGF in the lung tissues were down-regulated with XCD treatment. Therefore, the regulations of XCD on PI3K/mTOR/HIF-1α/VEGF signaling pathway was probably a crucial mechanism involved in the protective mechanism of XCD on ALI treatment.
Highlights
Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) are the leading causes of acute respiratory failure in critically ill patients, with a mortality rate of 30–40% over the past 2 decades [1]
Candidate compounds of Xuan-bai-cheng-qi decoction (XCD) The chemical compounds from the four medicines of XCD were intensively searched from both traditional Chinese medicine (TCM) Systems Pharmacology Database (TCMSP) [20] and Integrative Pharmacology-based Research Platform of TCM (TCMIP) [21]
Candidate targets related to XCD and ALI The compound-related targets of XCD were collected from TCMSP with each candidate compound
Summary
Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) are the leading causes of acute respiratory failure in critically ill patients, with a mortality rate of 30–40% over the past 2 decades [1]. Xuan-bai-cheng-qi decoction (XCD) is a classic traditional Chinese medicine (TCM) prescription for the treatment of respiratory diseases in China [5, 6]. It contains four constituents, which are the mineral-based Gypsum Fibrosum and the herbs Rheum officinale Baill, Semen Armeniacae Amarum, and Trichosanthes kirilowii Maxim [7]. XCD is recommended by Chinese health authorities as an alternative therapy for severe infectious pulmonary diseases caused by influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [10, 11]
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