Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary Fibrosis.
Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary Fibrosis.
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DOI：
10.2147/dddt.s404710
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发表时间：
2023
影响因子：
4.8
通讯作者：
Cao, Wen-Fu
中科院分区：
文献类型：
--
作者：
Yuan, Su;Zuo, Biao;Zhou, Si-Cong;Wang, Meng;Tan, Kai-Yue;Chen, Zhi-Wei;Cao, Wen-Fu
关键词：
本研究旨在通过网络药理学和实验验证，揭示黄芪甲苷治疗肺纤维化的药理机制。我们首先通过HE染色、MASSON染色和肺系数测定黄芪甲苷体内抗肺纤维化作用，然后利用网络药理学预测信号通路和分子对接的关键通路蛋白，最后通过体内外实验验证结果。在体实验中，黄芪甲苷能显著改善肺纤维化小鼠的体重（P < 0.05），增加肺系数（P < 0.05），减轻肺组织炎症反应和胶原沉积。网络药理学结果显示黄芪甲苷与特发性肺纤维化有104个交叉靶点，KEGG富集分析结果表明细胞衰老可能是黄芪甲苷治疗肺纤维化的重要途径。根据分子对接结果，黄芪甲苷也与衰老相关蛋白结合良好。体内外实验结果表明，黄芪甲苷能显著抑制衰老蛋白标志物P53、P21、P16的表达，延缓细胞衰老（P < 0.05）。在体内实验中，黄芪甲苷还能降低SASPs的产生（P < 0.05），在体外实验中，黄芪甲苷还能降低ROS的产生。此外，通过检测上皮间质转化（EMT）相关标志蛋白的表达，我们还发现黄芪甲苷在体内外实验中均能显著抑制EMT的发生（P < 0.05）。我们的研究发现黄芪甲苷可以通过防止细胞衰老和EMT来减轻博莱霉素诱导的PF。
Our study aims to reveal the pharmacological mechanism of Astragaloside IV in the treatment of pulmonary fibrosis(PF) through network pharmacology and experimental validation. We first determined the in vivo anti-pulmonary fibrosis effect of Astragaloside IV by HE, MASSON staining, and lung coefficients, then used network pharmacology to predict the signaling pathways and molecularly docked key pathway proteins, and finally validated the results by in vivo and in vitro experiments. In in vivo experiments, we found that Astragaloside IV improved body weight (P < 0.05), increased lung coefficients (P < 0.05), and reduced lung inflammation and collagen deposition in mice with pulmonary fibrosis. The network pharmacology results showed that Astragaloside IV had 104 cross-targets with idiopathic pulmonary fibrosis, and the results of KEGG enrichment analysis indicated that cellular senescence could be an important pathway for Astragaloside IV in the treatment of pulmonary fibrosis. Astragaloside IV also bound well to senescence-associated proteins, according to molecular docking results. The results of both in vivo and in vitro experiments showed that Astragaloside IV significantly inhibited senescence protein markers such as P53, P21, and P16 and delayed cellular senescence (P < 0.05). In in vivo experiments, we also found that Astragaloside IV reduced the production of SASPs (P < 0.05), and in in vitro experiments, Astragaloside IV also reduced the production of ROS. In addition, by detecting epithelial-mesenchymal transition(EMT)-related marker protein expression, we also found that Astragaloside IV significantly inhibited the development of EMT in both in vivo and in vitro experiments (P < 0.05). Our research found that Astragaloside IV could alleviate bleomycin-induced PF by preventing cellular senescence and EMT.