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

doi:10.5246/jcps.2024.05.034

Abstract

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:

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.

Figures/Tables 10

Table 1. Drug disease intersection targets.

Table 2. Top five active ingredients in Degree value.

References 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.