Dai Shuying, Zhang Gaochenxi, Zhao Fangmin, Shu Qijin
Department of First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Department of Oncology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou 310006, China.
Evid Based Complement Alternat Med. 2021 Jun 18;2021:6664489. doi: 10.1155/2021/6664489. eCollection 2021.
Lung cancer has a poor prognosis and a high mortality rate, and patients may develop multidrug resistance. Sparganii Rhizoma-Curcumae Rhizoma (HCSC), the classic herbal drug combination of traditional Chinese medicine (TCM), is commonly used in treating tumors, but its molecular mechanism is still unclear.
We explored the possible mechanisms underlying the antitumor effect of HCSC using network pharmacology. The bioactive components of HCSC and their targets were collected from the TCM Systems Pharmacology (TCMSP) database and PharmMapper. Gene Ontology (GO) and KEGG enrichment analyses were performed; the GeneMANIA platform was used for the functional enrichment analysis of the core targets and their neighboring genes. Molecular docking was performed between the bioactive components and core targets. HCSC freeze-dried powder was prepared, and the bioactive components were verified by liquid chromatography- (LC-) mass spectrometry (MS). Human lung adenocarcinoma H1975 cells were cultured to verify the molecular mechanism of action of HCSC in treating lung cancer, as predicted by network pharmacology. Finally, we used the Symmap database to predict the relationship between the herb and TCM syndrome.
A total of seven bioactive components were identified by network pharmacological analysis. Through enrichment analyses, it was found that the mechanism of action mainly involved mitochondrial-mediated caspase-dependent cell apoptosis signaling pathways. The results of molecular docking showed that the bioactive components in HCSC have a good affinity with the target proteins (ALB, BCL2L1, ESR1, HRAS, MAP2K1, MAPK14, and SIRT1). LC-MS confirmed that formononetin and bisdemethoxycurcumin were present in the HCSC freeze-dried powder, consistent with the prediction. The results of experiments on NCI-H1975 cells confirmed that HCSC can upregulate the mitochondrial-mediated caspase-dependent apoptosis signaling pathway by inducing the cleavage of caspase-3, caspase-9, and PARP, consistent with the network pharmacology prediction. Further, the qi deficiency and blood stasis associated with TCM syndrome can be treated with HCSC.
肺癌预后较差，死亡率高，患者可能会产生多药耐药性。三棱莪术（HCSC）是传统中药中的经典草药组合，常用于治疗肿瘤，但其分子机制仍不清楚。
我们运用网络药理学探索HCSC抗肿瘤作用的潜在机制。从中药系统药理学（TCMSP）数据库和PharmMapper中收集HCSC的生物活性成分及其靶点。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析；利用GeneMANIA平台对核心靶点及其邻近基因进行功能富集分析。对生物活性成分与核心靶点进行分子对接。制备HCSC冻干粉，并通过液相色谱 - 质谱联用（LC - MS）对生物活性成分进行验证。培养人肺腺癌H1975细胞，以验证网络药理学预测的HCSC治疗肺癌的分子作用机制。最后，我们使用Symmap数据库预测草药与中医证候之间的关系。
通过网络药理学分析共鉴定出7种生物活性成分。通过富集分析发现，其作用机制主要涉及线粒体介导的半胱天冬酶依赖性细胞凋亡信号通路。分子对接结果表明，HCSC中的生物活性成分与靶蛋白（ALB、BCL2L1、ESR1、HRAS、MAP2K1、MAPK14和SIRT1）具有良好的亲和力。LC - MS证实HCSC冻干粉中存在芒柄花黄素和双去甲氧基姜黄素，与预测结果一致。对NCI - H1975细胞的实验结果证实，HCSC可通过诱导半胱天冬酶 - 3、半胱天冬酶 - 9和聚（ADP - 核糖）聚合酶（PARP）的裂解来上调线粒体介导的半胱天冬酶依赖性凋亡信号通路，与网络药理学预测结果一致。此外，HCSC可治疗与中医证候相关的气虚血瘀。
