Integrative analysis of network pharmacology and proteomics reveal the protective effect of Xiaoqinglong Decotion on neutrophilic asthma

Gang Liao; Qian Yan; Miaofen Zhang; Xinxin Zhang; Jing Yang; Huiting Huang; Xiaohong Liu; Yong Jiang; Jing Gong; Shaofeng Zhan; Detang Li; Xiufang Huang

doi:10.1016/j.jep.2024.118102

Integrative analysis of network pharmacology and proteomics reveal the protective effect of Xiaoqinglong Decotion on neutrophilic asthma

J Ethnopharmacol. 2024 Mar 30:330:118102. doi: 10.1016/j.jep.2024.118102. Online ahead of print.

Authors

Gang Liao¹, Qian Yan², Miaofen Zhang², Xinxin Zhang², Jing Yang², Huiting Huang³, Xiaohong Liu³, Yong Jiang¹, Jing Gong⁴, Shaofeng Zhan⁵, Detang Li⁶, Xiufang Huang⁷

Affiliations

¹ Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China.
² The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China; The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China; Guangdong Provincial Clinical Research Academy of Chinese Medicine, Guangzhou, China.
³ The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.
⁴ Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou, China.
⁵ The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: zsfstone@163.com.
⁶ The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China; Department of Pharmacy, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: lidetang2002@163.com.
⁷ The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China; Guangdong Provincial Clinical Research Academy of Chinese Medicine, Guangzhou, China. Electronic address: huangxiufang@gzzyydxdyfsyy.wecom.work.

PMID: 38561057
DOI: 10.1016/j.jep.2024.118102

Abstract

Ethnopharmacological relevance: Xiaoqinglong Decotion (XQLD) is a commonly used Chinese herbal formula in clinical practice, especially for allergic diseases such as asthma. However, its intrinsic mechanism for the treatment of neutrophilic asthma (NA) remains unclear.

Aim of the study: The aim of this study was to evaluate the efficacy and potential mechanisms of XQLD on NA using network pharmacology and in vivo experiments.

Materials and methods: First, the active compounds, potential targets and mechanisms of XQLD against NA were initially elucidated by network pharmacology. Then, OVA/CFA-induced NA mice were treated with XQLD to assess its efficacy. Proteins were then analyzed and quantified using a Tandem Mass Tags approach for differentially expressed proteins (DEPs) to further reveal the mechanisms of NA treatment by XQLD. Finally, the hub genes, critical DEPs and potential pathways were validated.

Results: 176 active compounds and 180 targets against NA were identified in XQLD. Protein-protein interaction (PPI) network revealed CXCL10, CX3CR1, TLR7, NCF1 and FABP4 as hub genes. In vivo experiments showed that XQLD attenuated inflammatory infiltrates, airway mucus secretion and remodeling in the lungs of NA mice. Moreover, XQLD significantly alleviated airway neutrophil inflammation in NA mice by decreasing the expression of IL-8, MPO and NE. XQLD also reduced the levels of CXCL10, CX3CR1, TLR7, NCF1 and FABP4, which are closely associated with neutrophil inflammation. Proteomics analysis identified 28 overlapping DEPs in the control, NA and XQLD groups, and we found that XQLD inhibited ferroptosis signal pathway (elevated GPX4 and decreased ASCL3) as well as the expression of ARG1, MMP12 and SPP1, while activating the Rap1 signaling pathway.

Conclusion: This study revealed that inhibition of ARG1, MMP12 and SPP1 expression as well as ferroptosis pathways, and activation of the Rap1 signaling pathway contribute to the therapeutic effect of XQLD on NA.

Keywords: Ferroptosis; Network pharmacology; Neutrophilic asthma; Proteomics; Xiaoqinglong decotion.