Network pharmacology and experimental validation of inflammation inhibition by ChuanKeZhi Injection in treating asthma

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-05-21 DOI:10.1016/j.phymed.2025.156891

Jiaying Yuan , Yuhan Wang , Bingxian Sha , Yunfeng Zhang , Ondo Osie Eloina Margarita Mokuy , Mingming Jin , Li Yu , Xianghuai Xu

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引用次数: 0

Abstract

Background

Chuankezhi injection (CKZ), derived from the traditional Chinese herbs Ying-Yang-Huo (Epimedium brevicornu Maxim) and Ba-Ji-Tian (Morinda officinalis F.C. How), has demonstrated remarkable clinical effects in the treatment of asthma. However, the underlying mechanisms remain unclear.

Purpose

This study aims to explore the mechanisms and molecular targets of CKZ in the treatment of asthma, utilizing network pharmacology and molecular biology experiments.

Study Design

A combination of network pharmacology and experimental validation was used to identify the specific targets and pathways through which CKZ exerts its effects on asthma. In vitro and in vivo experiments were conducted to further verify the findings.

Methods

Liquid chromatography-mass spectrometry (LC/MS) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were employed to identify the components of CKZ. GeneCards was used to gather asthma-related targets, and the STRING online database was utilized to construct protein-protein interaction (PPI) networks. Hub genes were identified from the PPI network and analyzed through Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In vitro and in vivo experiments were conducted to validate the network pharmacology predictions.

Results

LC/MS and MALDI-TOF analysis revealed that CKZ is rich in flavonoid compounds. Network pharmacological analysis identified TNF, AKT1, IL-6, GAPDH, and SRC as the top five hub genes. GO and KEGG pathway analyses suggested that CKZ’s effect on asthma is closely associated with mitochondrial function and the mitogen-activated protein kinase (MAPK) signaling pathway. In vivo and in vitro experiments showed that CKZ treatment alleviated airway inflammation and collagen deposition in asthma mouse models, as demonstrated by HE, PAS, and Masson staining. CKZ also reduced the levels of inflammatory cytokines (IL-4, IL-5, IL-13, and TNF-α) in bronchoalveolar lavage fluid (BALF) and serum. Furthermore, CKZ improved mitochondrial damage and inhibited the activation of the MAPK signaling pathway, as confirmed by Western blotting analysis.

Conclusion

CKZ effectively alleviates airway inflammation and improves airway damage in asthma by inhibiting the MAPK signaling pathway. These findings suggest that CKZ is a promising therapeutic option for asthma treatment.

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喘可治注射液治疗哮喘的网络药理学及实验验证

喘可治注射液（CKZ）是由中药阴阳火（淫羊藿）和巴吉天（巴戟天）衍生而来，具有显著的治疗哮喘的临床疗效。然而，潜在的机制仍不清楚。目的利用网络药理学和分子生物学实验，探讨CKZ治疗哮喘的作用机制和分子靶点。研究设计采用网络药理学和实验验证相结合的方法，确定CKZ对哮喘作用的具体靶点和途径。通过体外和体内实验进一步验证研究结果。方法采用液相色谱-质谱联用（LC/MS）和基质辅助激光解吸/电离飞行时间（MALDI-TOF）质谱联用技术对其成分进行鉴定。利用GeneCards收集哮喘相关靶点，利用STRING在线数据库构建蛋白-蛋白相互作用（PPI）网络。从PPI网络中鉴定出枢纽基因，并通过基因本体（GO）富集和京都基因与基因组百科全书（KEGG）通路分析进行分析。体外和体内实验验证了网络药理学预测。结果slc /MS和MALDI-TOF分析显示，黄酮类化合物含量丰富。网络药理学分析发现TNF、AKT1、IL-6、GAPDH和SRC是前五大枢纽基因。GO和KEGG通路分析表明，CKZ对哮喘的作用与线粒体功能和丝裂原活化蛋白激酶（MAPK）信号通路密切相关。HE、PAS和Masson染色显示，体内和体外实验表明，CKZ治疗可以减轻哮喘小鼠模型的气道炎症和胶原沉积。CKZ还能降低支气管肺泡灌洗液（BALF）和血清中炎症因子（IL-4、IL-5、IL-13和TNF-α）的水平。此外，Western blotting分析证实，CKZ改善了线粒体损伤，抑制了MAPK信号通路的激活。结论ckz通过抑制MAPK信号通路，有效缓解哮喘气道炎症，改善气道损伤。这些发现表明，CKZ是一种很有前途的治疗哮喘的选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.