基于网络药理学探讨复方苦参注射液治疗黑色素瘤的作用机制

doi:10.5246/jcps.2024.05.034

中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (5): 448-457.DOI: 10.5246/jcps.2024.05.034

基于网络药理学探讨复方苦参注射液治疗黑色素瘤的作用机制

崔旭阳¹^,^#, 姬中杰²^,^#, 时潘扬¹, 魏晓岑³, 马玉宁³, 邢梦真³^,^*()

^1. 山东中医药大学医学院, 山东济南 250355
^2. 山东中医药大学针灸推拿学院, 山东济南 250355
^3. 山东中医药大学药物研究院, 山东济南 250355

收稿日期:2023-11-18 修回日期:2023-12-05 接受日期:2024-03-19 出版日期:2024-05-31 发布日期:2024-05-31
通讯作者: 邢梦真

Unraveling the mechanisms of compound Sophora flavescens injection in melanoma treatment: A network pharmacology

Xuyang Cui¹^,^#, Zhongjie Ji²^,^#, Panyang Shi¹, Xiaocen Wei³, Yuning Ma³, Mengzhen Xing³^,^*()

¹ Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China
² College of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China
³ Institute of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China

Received:2023-11-18 Revised:2023-12-05 Accepted:2024-03-19 Online:2024-05-31 Published:2024-05-31
Contact: Mengzhen Xing
About author:
^# Xuyang Cui and Zhongjie Ji contributed equally to this work.
Supported by:
Shandong Province Postdoctoral Innovation Talent Support Program Project (Grant No. SDBX2022018); Open Project of Key Laboratory of Photochemical Conversion and Functional Materials, Chinese Academy of Sciences (Grant No. PCOM202317).

摘要/Abstract

摘要：

本文通过网络药理学研究复方苦参注射液对防治黑色素瘤的作用机理。运用TCMSP数据库探索复方苦参注射液中苦参和土茯苓的活性成分, 通过Pubchem和SwissTargetPrediction数据库检测苦参和土茯苓的药物靶点, 经GeneCards、OMIM、TTD和CTD数据库检索与黑色素瘤相关的疾病靶点, 并运用Cytoscape 3.9.1建立中药-成分-疾病-靶点网络, 使用String与Cytoscape建立交集靶点蛋白的相互作用网络, 经Cyto-Hubba插件根据MCC算法进行拓扑分析, 筛选关键靶点。最后, 使用Metascape数据库对相关靶点进行GO和KEGG分析。最终在复方苦参注射液中共筛选出60个活性成分, 包括槲皮素、去甲果肉皮素、白军恩等; 与黑色素肿瘤相关的靶点有916个, 包括AKT1、EGFR、ESR1等。此外, 复方苦参注射液的抗黑色素瘤功能包括对磷酸化效应的调节和影响氧化应激反应等生物学过程, 并通过调节癌症通道、内分泌通路、Th17细胞分化通道等信息通路发挥抗肿瘤效果。本研究首次报道了复方苦参注射液治疗黑色素瘤疾病的潜在作用机制, 为后续实验研究提供了思路与依据。

关键词: 复方苦参注射液, 黑色素瘤, 网络药理学, 作用机制

Abstract:

In this paper, the mechanism of effect of compound Sophora flavescens injection on the prevention and treatment of melanoma was studied through network pharmacology. TCMSP database was used to explore the active ingredients of Sophora flavescens and Poria cocos in compound Sophora flavescens injection, the drug targets of Sophora flavescens and Poria cocos were detected by Pubchem and Swiss Target Prediction databases, the disease targets related to melanoma were retrieved through GeneCards, OMIM, TTD and CTD databases, and Cytoscape 3.9.1 was used to establish a TCM-component-disease-target network. The interaction network of intersecting target proteins was established by String and Cytoscape, and the topological analysis was performed according to the MCC algorithm by the Cyto-Hubba plug-in to screen the key targets. Finally, GO and KEGG analyses of the relevant targets were performed using the Metascape database. Finally, a total of 60 active ingredients were screened in the compound Sophora flavescens injection, including quercetin, norcetin and white junen. There are 916 targets related to melanoma tumors, including AKT1, EGFR, ESR1, etc. In addition, the anti-melanoma functions of Sophora flavescens injection include the regulation of phosphorylation effects and the effects of oxidative stress responses, and exert anti-tumor effects by regulating cancer pathways, endocrine pathways, Th17 cell differentiation channels and other information pathways. This study reported for the first time the potential mechanism of compound Sophora flavescens injection in the treatment of melanoma disease, and provided ideas and basis for follow-up experimental research.

Key words: Compound Sophora flavescens injection, Melanoma, Network pharmacology, Mechanism of action

Supporting:

崔旭阳, 姬中杰, 时潘扬, 魏晓岑, 马玉宁, 邢梦真. 基于网络药理学探讨复方苦参注射液治疗黑色素瘤的作用机制[J]. 中国药学(英文版), 2024, 33(5): 448-457.

Xuyang Cui, Zhongjie Ji, Panyang Shi, Xiaocen Wei, Yuning Ma, Mengzhen Xing. Unraveling the mechanisms of compound Sophora flavescens injection in melanoma treatment: A network pharmacology[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(5): 448-457.

图/表 10

Figure 1. Potential targets for MEL.

Table 1. Drug disease intersection targets.

Figure 2. Venn diagram of TCM and disease targets.

Figure 3. TCM component disease target network diagram.

Table 2. Top five active ingredients in Degree value.

Figure 4. PPI network diagram of drug-disease common targets.

Figure 5. Key node PPI network.

Figure 6. GO results of three ontologies.

Figure 7. GO enrichment analysis.

Figure 8. The top 30 enriched KEGG pathways.

参考文献 26

[1]	Ahmed, B.; Qadir, M.I.; Ghafoor, S. Malignant melanoma: skin cancer-diagnosis, prevention, and treatment. Crit. Rev. Eukaryot. Gene Expr. 2020, 30, 291–297.
[2]	An, M.; Blekher, L.; Liu, M.; Pitre, M.; Shaner, R.; Silva, D.; Vlahovic, T.C. Plantar melanoma. Clin. Podiatric Med. Surg. 2021, 38, 595–599.
[3]	Rastrelli, M.; Tropea, S.; Rossi, C.R.; Alaibac, M. Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. In Vivo. 2014, 28, 1005–1011.
[4]	Tao, L. Clinical efficacy of compound Sophora flavescens injection in the treatment of cancer induced pain in malignant tumors. Clin. Ration. Drug Use. 2023, 16, 85–87.
[5]	Xue, T.L.; Shi, G.F.; Feng, X.L. The effect of compound sophora flavescens injection combined with tigio and oxaliplatin in the treatment of advanced gastric cancer and its impact on immune function. J. Clin. Chin. Med. 2023, 35, 169–174.
[6]	Dai, Y. A study on the material basis of Kushen decoction pieces based on the classic processing method of "Lei Gong Pao Zhi Lun". Chin. Acad. Tradit. Chin. Med. 2022.
[7]	Yang, Y.; Sun, M.Y.; Yao, W.B.; Wang, F.; Li, X.G.; Wang, W.; Li, J.Q.; Gao, Z.H.; Qiu, L.; You, R.L.; Yang, C.H.; Ba, Q.; Wang, H. Compound Kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib. J. Immunother. Cancer. 2020, 8, e000317.
[8]	Wu, C.; Huang, Z.H.; Meng, Z.Q.; Fan, X.T.; Lu, S.; Tan, Y.Y.; You, L.M.; Huang, J.Q.; Stalin, A.; Ye, P.Z.; Wu, Z.S.; Zhang, J.Y.; Liu, X.K.; Zhou, W.; Zhang, X.M.; Wu, J.R. A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound Kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation. Chin. Med. 2021, 16, 121.
[9]	Liu, Z.H.; Sun, X.B. Network pharmacology: new opportunity for the modernization of traditional Chinese medicine. Acta Pharm. Sin. 2012, 47, 696–703.
[10]	Zhang, Y.Q.; Li, S. Progress in network pharmacology for modern research of traditional Chinese medicine. Chin. J. Pharmacol. Toxicol. 2015, 29, 883–892.
[11]	Ru, J.L.; Li, P.; Wang, J.N.; Zhou, W.; Li, B.H.; Huang, C.; Li, P.D.; Guo, Z.H.; Tao, W.Y.; Yang, Y.F.; Xu, X.; Li, Y.; Wang, Y.H.; Yang, L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J. Cheminf. 2014, 6, 13.
[12]	Davis, A.P.; Grondin, C.J.; Johnson, R.J.; Sciaky, D.; Wiegers, J.; Wiegers, T.C.; Mattingly, C.J. Comparative Toxicogenomics Database (CTD): update 2021. Nucleic Acids Res. 2021, 49, D1138–D1143.
[13]	Stelzer, G.; Rosen, N.; Plaschkes, I.; Zimmerman, S.; Twik, M.; Fishilevich, S.; Stein, T.I.; Nudel, R.; Lieder, I.; Mazor, Y.; Kaplan, S.; Dahary, D.; Warshawsky, D.; Guan-Golan, Y.; Kohn, A.; Rappaport, N.; Safran, M.; Lancet, D. The GeneCards suite: from gene data mining to disease genome sequence analyses. Curr. Protoc. Bioinformatics. 2016, 54, 1.30.1–1.30.33.
[14]	Amberger, J.S.; Hamosh, A. Searching online Mendelian inheritance in man (OMIM): a knowledgebase of human genes and genetic phenotypes. Curr. Protoc. Bioinformatics. 2017, 58, 1.2.1–1.2.12.
[15]	Su, W.; Liu, M.L.; Yang, Y.H.; Wang, J.S.; Li, S.H.; Lv, H.; Dao, F.Y.; Yang, H.; Lin, H. PPD: a manually curated database for experimentally verified prokaryotic promoters. J. Mol. Biol. 2021, 433, 166860.
[16]	Wang, Y.Q.; Zhou, J.L.; Bai, K.W. Research progress on the pathogenesis and treatment methods of melanoma. Pharm. Biotechnol. 2019, 26, 357–361
[17]	Liu, Q.; Hu, J.Y.; Wang, J. Clinical Overview of traditional Chinese medicine in the treatment of malignant melanoma. Hebei Tradit. Chin. Med. 2015, 37, 934–937.
[18]	Wei, Y.P.; Shi, S.J.; Zhang, R.X. Effects of quercetin on the proliferation and apoptosis of A375 human melanoma cells. J. Pract. Dermatol. 2016, 9, 171–174.
[19]	Jin, N.Z. Research on the preventive and therapeutic effects and mechanisms of quercetin on cancer. Nanjing Univ. Tradit. Chin. Med. 2005.
[20]	Ko, H.H.; Tsai, Y.T.; Yen, M.H.; Lin, C.C.; Liang, C.J.; Yang, T.H.; Lee, C.W.; Yen, F.L. Norartocarpetin from a folk medicine Artocarpus communis plays a melanogenesis inhibitor without cytotoxicity in B16F10 cell and skin irritation in mice. BMC Complement. Altern. Med. 2013, 13, 348.
[21]	Huang, D.S.; Wang, F.X.; Wu, W.Z.; Lian, C.H.; Liu, E.R. MicroRNA-429 inhibits cancer cell proliferation and migration by targeting the AKT1 in melanoma. Cancer Biomark. 2019, 26, 63–68.
[22]	Liu, Y.X.; Xu, B.W.; Niu, X.D.; Chen, Y.J.; Fu, X.Q.; Wang, X.Q.; Yin, C.L.; Chou, J.Y.; Li, J.K.; Wu, J.Y.; Bai, J.X.; Wu, Y.; Li, S.M.; Yu, Z.L. Inhibition of Src/STAT3 signaling-mediated angiogenesis is involved in the anti-melanoma effects of dioscin. Pharmacol. Res. 2022, 175, 105983.
[23]	Pastwińska, J.; Karaś, K.; Karwaciak, I.; Ratajewski, M. Targeting EGFR in melanoma – The Sea of possibilities to overcome drug resistance. Biochim. Biophys. Acta Rev. Cancer. 2022, 1877, 188754.
[24]	Glatthaar, H.; Katto, J.; Vogt, T.; Mahlknecht, U. Estrogen receptor alpha (ESR1) single-nucleotide polymorphisms (SNPs) affect malignant melanoma susceptibility and disease course. Genet. Epigenet. 2016, 8, 1–6.
[25]	He, G.H. The study on the effect of resveratrol on the proliferation of human melanoma A375 cell line by regulating the PI3K/Akt/mTOR signaling pathway. Southwest Med. Univ. 2018.
[26]	Radisavljevic, Z. AKT as locus of cancer positive loops conversion and chemotherapy. Crit. Rev. Eukaryot. Gene Expr. 2015, 25, 199–202.

基于网络药理学探讨复方苦参注射液治疗黑色素瘤的作用机制

Unraveling the mechanisms of compound Sophora flavescens injection in melanoma treatment: A network pharmacology

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