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网络药理学揭示复方斑蝥胶囊治疗不可切除原发性肝癌的作用机制及临床数据验证。

Network Pharmacology to Reveal the Mechanism of Fufang Banmao Capsule for Treating Unresectable Primary Liver Cancer and Clinical Data Validation.

机构信息

Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.

Department of Gerontology, Jiangxi University of Traditional Chinese Medicine Affiliated Hospital, Nanchang, Jiangxi Province, China.

出版信息

Curr Pharm Des. 2024;30(35):2785-2796. doi: 10.2174/0113816128322791240722064234.

Abstract

INTRODUCTION

Fufang Banmao capsule (FFBM), a traditional Chinese medicine, has been used to treat primary liver cancer (PLC) for several years. However, the bioactive ingredients, and mechanism of FFBM for treating PLC remains unclear. Our objective is to utilize network pharmacology to investigate these aspects and subsequently validate their effectiveness through clinical data.

MATERIALS AND METHODS

The FFBM ingredients were obtained from the HERB database and screened for bioactive ingredients using the SwissTargetPrediction database. The PharmMapper and GEO database were used to acquire targets and differentially expressed genes (DEGs) for FFBM and PLC, respectively. Common targets were identified using Venn diagrams, followed by enrichment and protein-protein interaction (PPI) analysis. Furthermore, the Cytoscape software was utilized to identify Hub genes and construct the ingredienttarget- pathway network. Subsequently, patients diagnosed with unresectable PLC who underwent transcatheter arterial chemoembolization (TACE) at our hospital between January 2008 and December 2019 were retrospectively collected. Finally, Cox analysis was conducted to reveal the role of FFBM in the treatment of unresectable PLC.

RESULTS

FFBM had 232 targets, and PLC had 1582 DEGs. HSP90AA1 and SRC were identified as crucial targets. Alpha-santalol, glycyrrhizin, and morroniside were identified as the top three bioactive ingredients. Enrichment analysis revealed a significant connection between FFBM utilization for treating PLC and multiple pathways, such as chemical carcinogenesis, PI3K-AKT, Rap1, FoxO, MAPK, and VEGF pathway. Clinical data revealed that consuming FFBM significantly improved the prognosis of unresectable PLC with a hazard ratio of 0.69.

CONCLUSION

Our study identified the bioactive ingredients of FFBM and its potential mechanisms for treating PLC. Additionally, we validated the effectiveness through clinical data.

摘要

简介

复方斑蝥胶囊(FFBM)是一种传统中药,已用于治疗原发性肝癌(PLC)多年。然而,FFBM 治疗 PLC 的生物活性成分和机制仍不清楚。我们的目标是利用网络药理学来研究这些方面,并随后通过临床数据验证其疗效。

材料和方法

FFBM 的成分从 HERB 数据库中获得,并使用 SwissTargetPrediction 数据库筛选出生物活性成分。PharmMapper 和 GEO 数据库分别用于获取 FFBM 和 PLC 的靶标和差异表达基因(DEG)。使用 Venn 图识别共同靶标,然后进行富集和蛋白质-蛋白质相互作用(PPI)分析。此外,使用 Cytoscape 软件识别 Hub 基因并构建成分-靶标-通路网络。随后,回顾性收集了 2008 年 1 月至 2019 年 12 月在我院接受经导管动脉化疗栓塞(TACE)治疗的不可切除 PLC 患者的临床资料。最后,通过 Cox 分析揭示 FFBM 在治疗不可切除 PLC 中的作用。

结果

FFBM 有 232 个靶标,PLC 有 1582 个 DEG。HSP90AA1 和 SRC 被鉴定为关键靶标。Alpha-santalol、甘草酸和莫诺糖苷被鉴定为前三种生物活性成分。富集分析表明,FFBM 用于治疗 PLC 与多种途径密切相关,如化学致癌作用、PI3K-AKT、Rap1、FoxO、MAPK 和 VEGF 途径。临床数据表明,服用 FFBM 可显著改善不可切除 PLC 的预后,风险比为 0.69。

结论

本研究鉴定了 FFBM 的生物活性成分及其治疗 PLC 的潜在机制,并通过临床数据验证了其疗效。

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