Xing Qichang, Liu Xiang, Liu Zheng, Yan Qingzi, Hu Yixiang, Li Wencan, Peng Ke
Department of Clinical Pharmacy, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, China.
Zhou Honghao Research Institute Xiangtan, Xiangtan, Hunan, 411100, China.
Comb Chem High Throughput Screen. 2024;27(7):1046-1055. doi: 10.2174/1386207326666230823093958.
Buyanghuanwu Decoction (BYHWD) is a clinically proven prescription effective in treating pulmonary fibrosis (PF), but the molecular mechanism underlying its action remains unclear. The network pharmacology analysis was performed to elucidate the acting substances and related pathways of BYHWD in treating bleomycin (BLM) induced PF mouse.
First, the pharmacologically active components and corresponding targets in BYHWD were identified through the TCMSP database and literature review. Second, PF-related targets were identified through the DisGeNet database. Then, the components-targets network of BYHWD in PF treatment was constructed using Cytoscape. The DAVID database was used for the enrichment analysis of GO terms and KEGG pathways. At last, the therapeutic effect of BYHWD on BLMinduced PF mice were verified, and the mRNA and protein expression of related targets was determined through RT-PCR and western blotting, respectively.
The core component-target network contained 58 active components and 147 targets. Thirty-nine core targets were mainly involved in the regulation of biological functions and KEGG pathways, such as the positive regulation of nitric oxide biosynthesis and the TNF signaling pathway. These core targets were obtained through enrichment analysis. Moreover, animal studies revealed that BYHWD down-regulated the mRNA expression levels of TNF, IL-6, IL-1β, and NOS2 and inhibited NF-κB and p38 phosphorylation.
The effects of BYHWD on PF mice are therapeutic, and its anti-PF mechanism mainly involves the effects on inflammatory factors and the NF-κB/p38 pathway.
补阳还五汤（BYHWD）是一种经临床验证对治疗肺纤维化（PF）有效的方剂，但其作用的分子机制尚不清楚。进行网络药理学分析以阐明补阳还五汤治疗博来霉素（BLM）诱导的PF小鼠的作用物质及相关途径。
首先，通过中药系统药理学数据库与分析平台（TCMSP）数据库和文献检索确定补阳还五汤中的药理活性成分及相应靶点。其次，通过疾病基因数据库（DisGeNet）确定PF相关靶点。然后，使用Cytoscape构建补阳还五汤治疗PF的成分-靶点网络。利用DAVID数据库进行基因本体（GO）术语和京都基因与基因组百科全书（KEGG）通路的富集分析。最后，验证补阳还五汤对BLM诱导的PF小鼠的治疗效果，并分别通过逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法测定相关靶点的mRNA和蛋白表达。
核心成分-靶点网络包含58种活性成分和147个靶点。39个核心靶点主要参与生物功能和KEGG通路的调节，如一氧化氮生物合成的正调控和肿瘤坏死因子（TNF）信号通路。这些核心靶点通过富集分析获得。此外，动物研究表明，补阳还五汤下调TNF、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和一氧化氮合酶2（NOS2）的mRNA表达水平，并抑制核因子κB（NF-κB）和p38磷酸化。
补阳还五汤对PF小鼠具有治疗作用，其抗PF机制主要涉及对炎症因子和NF-κB/p38通路的影响。
