Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083, China.
Comb Chem High Throughput Screen. 2021;24(2):306-318. doi: 10.2174/1386207323999200730210536.
As a well-known herb used in the treatment of colon adenocarcinoma (COAD), Spica Prunellae (SP) shows favorable clinical effect and safety in China for many years, but its active ingredients and therapeutic mechanisms against COAD remain poorly understood. Therefore, this study aims to uncover active ingredients and mechanisms of SP in the treatment of COAD using a combined approach of network pharmacology and bioinformatics.
A comprehensive approach mainly comprised of target prediction, network construction, pathway and functional enrichment analysis, and hub genes verification was adopted in the current study.
We collected 102 compounds-related genes and 3549 differently expressed genes (DEGs) following treatment with SP, and 64 disease-drug target genes between them were recognized. In addition, a total of 25 active ingredients in SP were identified. Pathway and functional enrichment analyses suggested that the mechanisms of SP against COAD might be to induce apoptosis of colon cancer cells by regulating PI3K-Akt and TNF signaling pathways. Recognition of hub genes and core functional modules was performed by constructing protein-protein interaction (PPI) network, from which TP53, MYC, MAPK8 and CASP3 were found as the hub target genes that might play an important part in therapy for COAD. Subsequently we further compared the differential expression level and assessed the prognostic value of these four hub genes. These result of verification suggested that SP exerted therapeutic effects against COAD via a PPI network involving TP53, MYC, MAPK8 and CASP3.
In this study, active ingredients and mechanisms of SP in the treatment of COAD were systematically discussed, which provided the foundation for further experimental studies and might act to promote its appropriate clinical application.
作为一种用于治疗结肠腺癌（COAD）的著名草药，夏枯草在中国多年来表现出良好的临床效果和安全性，但它对 COAD 的活性成分和治疗机制仍知之甚少。因此，本研究旨在采用网络药理学和生物信息学相结合的方法，揭示夏枯草治疗 COAD 的活性成分和机制。
本研究采用了一种综合方法，主要包括靶标预测、网络构建、通路和功能富集分析以及关键基因验证。
我们收集了夏枯草治疗后与 102 种化合物相关的基因和 3549 个差异表达基因（DEGs），并从中识别出 64 个疾病-药物靶标基因。此外，还鉴定了夏枯草中的 25 种活性成分。通路和功能富集分析表明，夏枯草治疗 COAD 的机制可能是通过调节 PI3K-Akt 和 TNF 信号通路诱导结肠癌细胞凋亡。通过构建蛋白质-蛋白质相互作用（PPI）网络，识别出夏枯草治疗 COAD 的关键基因和核心功能模块，其中 TP53、MYC、MAPK8 和 CASP3 被认为是在 COAD 治疗中可能发挥重要作用的关键靶基因。随后，我们进一步比较了这四个关键基因的差异表达水平和评估其预后价值。这些验证结果表明，夏枯草通过涉及 TP53、MYC、MAPK8 和 CASP3 的 PPI 网络发挥治疗 COAD 的作用。
本研究系统探讨了夏枯草治疗 COAD 的活性成分和机制，为进一步的实验研究提供了基础，并可能有助于促进其合理的临床应用。
