基于网络药理学与实验验证探讨喘可治注射液治疗哮喘的抗炎机制
2025/06/27
摘要
背景：喘可治注射液（CKZ）由传统中药淫羊藿（Epimedium brevicornu Maxim）和巴戟天（Morinda officinalis F.C. How）提取而成，已在临床上表现出治疗哮喘的显著疗效。然而，其潜在作用机制尚不清晰。本研究旨在通过网络药理学结合分子生物学实验，探讨CKZ治疗哮喘的作用机制及分子靶点。
方法：本研究采用网络药理学结合体内外实验验证的方法，识别CKZ治疗哮喘的特异性靶点及信号通路。通过液相色谱-质谱联用技术（LC/MS）与基质辅助激光解吸电离飞行时间质谱（MALDI-TOF）对CKZ的化学成分进行分析；利用GeneCards数据库筛选与哮喘相关的靶点，并通过STRING数据库构建蛋白-蛋白相互作用（PPI）网络，识别核心基因。随后对核心基因进行Gene Ontology（GO）功能富集分析及京都基因与基因组百科全书（KEGG）通路分析。通过体外细胞实验及体内小鼠模型进一步验证网络药理学预测结果。
结果：LC/MS与MALDI-TOF分析结果显示，CKZ富含黄酮类化合物。网络药理学分析识别出TNF、AKT1、IL-6、GAPDH和SRC为前五位核心基因。GO和KEGG分析表明，CKZ的抗哮喘作用与线粒体功能调节及丝裂原活化蛋白激酶（MAPK）信号通路密切相关。动物实验和细胞实验结果显示，CKZ能显著缓解哮喘小鼠气道炎症及胶原沉积（经HE、PAS和Masson染色证实），并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及TNF-α）水平。此外，CKZ还能改善线粒体损伤并抑制MAPK信号通路的激活（通过Western blot分析验证）。
结论：喘可治注射液通过抑制MAPK信号通路，有效缓解哮喘相关气道炎症并改善气道损伤。研究结果表明，CKZ是一种具有潜力的哮喘治疗新方案。
Network pharmacology and experimental validation of inflammation inhibition by ChuanKeZhi Injection in treating asthma
Yuan, J., Wang, Y., Sha, B., Zhang, Y., Mokuy, O. O. E. M., Jin, M., Yu, L., & Xu, X.
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. This study aims to explore the mechanisms and molecular targets of CKZ in the treatment of asthma, utilizing network pharmacology and molecular biology experiments.
METHODS:
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. 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.
背景：喘可治注射液（CKZ）由传统中药淫羊藿（Epimedium brevicornu Maxim）和巴戟天（Morinda officinalis F.C. How）提取而成，已在临床上表现出治疗哮喘的显著疗效。然而，其潜在作用机制尚不清晰。本研究旨在通过网络药理学结合分子生物学实验，探讨CKZ治疗哮喘的作用机制及分子靶点。
方法：本研究采用网络药理学结合体内外实验验证的方法，识别CKZ治疗哮喘的特异性靶点及信号通路。通过液相色谱-质谱联用技术（LC/MS）与基质辅助激光解吸电离飞行时间质谱（MALDI-TOF）对CKZ的化学成分进行分析；利用GeneCards数据库筛选与哮喘相关的靶点，并通过STRING数据库构建蛋白-蛋白相互作用（PPI）网络，识别核心基因。随后对核心基因进行Gene Ontology（GO）功能富集分析及京都基因与基因组百科全书（KEGG）通路分析。通过体外细胞实验及体内小鼠模型进一步验证网络药理学预测结果。
结果：LC/MS与MALDI-TOF分析结果显示，CKZ富含黄酮类化合物。网络药理学分析识别出TNF、AKT1、IL-6、GAPDH和SRC为前五位核心基因。GO和KEGG分析表明，CKZ的抗哮喘作用与线粒体功能调节及丝裂原活化蛋白激酶（MAPK）信号通路密切相关。动物实验和细胞实验结果显示，CKZ能显著缓解哮喘小鼠气道炎症及胶原沉积（经HE、PAS和Masson染色证实），并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及TNF-α）水平。此外，CKZ还能改善线粒体损伤并抑制MAPK信号通路的激活（通过Western blot分析验证）。
结论：喘可治注射液通过抑制MAPK信号通路，有效缓解哮喘相关气道炎症并改善气道损伤。研究结果表明，CKZ是一种具有潜力的哮喘治疗新方案。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
（Phytomedicine. 2025 Jul 25; DOI: 10.1016/j.phymed.2025.156891）
Network pharmacology and experimental validation of inflammation inhibition by ChuanKeZhi Injection in treating asthma
Yuan, J., Wang, Y., Sha, B., Zhang, Y., Mokuy, O. O. E. M., Jin, M., Yu, L., & Xu, X.
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. This study aims to explore the mechanisms and molecular targets of CKZ in the treatment of asthma, utilizing network pharmacology and molecular biology experiments.
METHODS:
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. 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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