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探讨结梗汤对体内外肺纤维化的预防作用:一种网络药理学方法。

Exploring the preventive effects of Jie Geng Tang on pulmonary fibrosis induced in vitro and in vivo: a network pharmacology approach.

机构信息

School of Life Science, Huaibei Normal University, Dongshan Road 100, Huaibei, 235000, China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec;397(12):10005-10016. doi: 10.1007/s00210-024-03262-w. Epub 2024 Jul 3.

DOI:10.1007/s00210-024-03262-w
PMID:38961002
Abstract

Pulmonary fibrosis is a debilitating lung disease marked by excessive fibrotic tissue accumulation, which significantly impairs respiratory function. Given the limitations of current therapies, there is an increasing interest in exploring traditional herbal formulations like Jie Geng Tang (JGT) for treatment. This study examines the potential of JGT and its bioactive component, quercetin, in reversing bleomycin (BLM)-induced pulmonary fibrosis in mice. We employed a BLM-induced MLE-12 cell damage model for in vitro studies and a bleomycin-induced fibrosis model in C57BL/6 mice for in vivo experiments. In vitro assessments showed that JGT significantly enhanced cell viability and reduced apoptosis in MLE-12 cells treated with BLM. These findings underscore JGT's potential for cytoprotection against fibrotic agents. In vivo, JGT was effective in modulating the expression of E-cadherin and vimentin, key markers of the epithelial-mesenchymal transition (EMT) pathway, indicating its role in mitigating EMT-associated fibrotic changes in lung tissue. Quercetin, identified through network pharmacology analysis as a potential key bioactive component of JGT, was highlighted for its role in the regulatory mechanisms underlying fibrosis progression, particularly through the modulation of the IL-17 pathway and Il6 expression. By targeting inflammatory pathways and key processes like EMT, JGT and quercetin offer a potent alternative to conventional therapies, meriting further clinical exploration to harness their full therapeutic potential in fibrotic diseases.

摘要

肺纤维化是一种使人衰弱的肺部疾病,其特征是过多的纤维组织积聚,这会显著损害呼吸功能。鉴于当前疗法的局限性,人们越来越感兴趣地探索传统草药配方,如桔梗汤(JGT),以用于治疗。本研究考察了 JGT 及其生物活性成分槲皮素在逆转博莱霉素(BLM)诱导的小鼠肺纤维化中的潜力。我们使用博莱霉素诱导的 MLE-12 细胞损伤模型进行体外研究,并使用博莱霉素诱导的 C57BL/6 小鼠纤维化模型进行体内实验。体外评估表明,JGT 可显著提高 BLM 处理的 MLE-12 细胞的活力并减少细胞凋亡。这些发现强调了 JGT 对纤维形成剂的细胞保护潜力。在体内,JGT 可有效调节 E-钙粘蛋白和波形蛋白的表达,这是上皮-间充质转化(EMT)途径的关键标志物,表明其在减轻肺组织 EMT 相关纤维化变化中的作用。通过网络药理学分析确定的槲皮素是 JGT 的一种潜在关键生物活性成分,它在纤维化进展的调节机制中发挥作用,特别是通过调节 IL-17 途径和 Il6 表达。通过靶向炎症途径和 EMT 等关键过程,JGT 和槲皮素为传统疗法提供了一种有效的替代方法,值得进一步的临床探索,以充分发挥它们在纤维化疾病中的治疗潜力。

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