Investigation of the Mechanism of Huayu Xietu Formula (化瘀解毒方) in Regulating PPARγ/NF-κB Signaling Pathway for Lung Cancer Based on Molecular Docking of Integrative Pharmacology and Experimental Validation

Author：WU Aochun1, CAI Xiaoping2, WEI Zheng2, ZHANG Junping2, JU Jia1

Unit：1.The Second Clinical Medical College of He'nan University of Chinese Medicine, Zhengzhou He'nan 450000, China; 2.He'nan Provincial Hospital of Integrative Medicine, Zhengzhou He'nan 450000, China

Quote：引用：毋奥淳，蔡小平，魏征，张俊萍，巨佳.基于整合药理学分子对接及实验验证探讨化瘀解毒方调控PPARγ/NF-κB信号通路治疗肺癌的作用机制[J].中医药导报,2025,31(6):42-48.

DOI：10.13862/j.cn43-1446/r.2025.06.008

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Abstract：

Objective: To predict the potential targets and mechanisms of action of  Huayu Jiedu formula for the treatment of lung cancer with network pharmacology and molecular docking techniques, and to validate the findings through animal experiments. Methods: Potential action targets of the Huayu Jiedu formula and lung cancer-related disease targets were screened using the TCMIP database and GeneCards, OMIM, and TTD databases, respectively. The intersection targets between drugs and diseases were obtained with the Venny 2.1 visualization platform. The String database and Cytoscape 3.7.2 software were used to construct a protein-protein interaction network and screen for key targets, and the "Chinese medicine-component-core target" association network was constructed. The DAVID database was used to perform gene ontology (GO) functional enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis on key intersection targets. Autodock Vina software was used for molecular docking validation of important proteins and molecules. Tumor mass was analyzed in each group of mice. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of IL-6 and IFN-γ. The pathological morphology of tumor tissues, lungs, livers, and kidneys were observed with HE staining. The expression of PPARγ, VEGF, NF-κB, PCNA and Caspase-3 in tumor tissues were detected via immunohistochemistry. Results: The main active components of Huayu Jiedu formula for treating lung cancer include stigmasterol, eugenol, sitosterol, palmitic acid, etc. involving targets such as STAT3, PPARG, AKT1, NFKB1, IL6, and signaling pathways such as metabolic pathways, PPAR signaling pathways, and cAMP signaling pathway. Animal experiment results showed that the Huayu Jiedu formula could significantly inhibit tumor growth, downregulate IL-6 levels in rat serum, and upregulate IFN-γ levels, with no significant hepatotoxicity or nephrotoxicity. Conclusion: Huayu Jiedu formula can increase the expression of PPARγ and Caspase-3, inhibit the expression of VEGF, NF-κB, and PCNA, promote apoptosis in A549 lung cancer cells, and inhibit tumor cell proliferation and vascular growth. Its mechanism of action may be related to the regulation of the PPARγ/NF-κB signaling pathway.

Key words：lung cancer; Huayu Jiedu formula; network pharmacology; PPARγ；NF-κB; mouse

摘要：目的：采用网络药理学和分子对接技术预测化瘀解毒方治疗肺癌的潜在靶点和作用机制，并结合动物实验进行验证。方法：分别通过TCMIP数据库及GeneCards、OMIM、TTD数据库筛选化瘀解毒方的潜在作用靶点和肺癌相关疾病靶点，然后利用Venny 2.1可视化平台获得药物和疾病的交集靶标；通过String数据库和Cytoscape 3.7.2软件构建蛋白质-蛋白质互作网络并筛选关键靶点，构建“中药-成分-核心靶标”关联网络；利用DAVID数据库对关键交集靶标进行基因本体（GO）功能富集及京都基因与基因组百科全书（KEGG）通路富集分析；利用Autodock Vina软件对重要蛋白和分子进行分子对接验证；对各组小鼠瘤体质量进行分析；ELISA检测血清中IL-6、IFN-γ含量；HE染色观察肿瘤组织、肺脏、肝脏、肾脏病理形态；免疫组化法检测肿瘤组织中PPARγ、VEGF、NF-κB、PCNA、Caspase-3表达。结果：化瘀解毒方治疗肺癌的主要活性成分包括豆甾醇、丁香皂苷、谷甾醇、棕榈酸等，涉及STAT3、PPARG、AKT1、NFKB1、IL6等靶点及metabolic pathways、PPAR signaling pathways、cAMP signaling pathway等信号通路。动物实验结果显示化瘀解毒方能够明显抑制肿瘤增长，下调大鼠血清中IL-6含量，上调IFN-γ含量，且无明显肝肾毒性。结论：化瘀解毒方能够增加PPARγ、Caspase-3的表达，抑制VEGF、NF-κB、PCNA的表达，促进A549肺癌细胞发生凋亡，抑制肿瘤细胞增殖和血管生长，其作用机制可能与调控PPARγ/NF-κB信号通路有关。

关键词：肺癌；化瘀解毒方；网络药理学；PPARγ；NF-κB；小鼠

Release time：2026-01-03

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