Analisis Network Pharmacology Senyawa Metabolit Sekunder Tanaman Lengkuas (Alpinia galanga) pada Penyakit Kanker

Dwi Hanif Muluqul Fath, Muhammad Artabah Muchlisin, Ahmad Shobrun Jamil

Abstract


Kanker masih menjadi tantangan kesehatan yang berat di seluruh dunia, dengan mekanisme molekuler kompleks yang mendorong inisiasi, perkembangan, dan resistensi terapi. Penelitian ini bertujuan untuk menganalisis lebih lanjut senyawa metabolit sekunder Alpinia galanga (A. galanga) yang berpotensi sebagai antikanker. Analisis network pharmacology digunakan untuk mendapatkan gambaran bagaimana senyawa metabolit sekunder A. galanga berhubungan dengan penyakit kanker. Skrining senyawa A. galanga dilakukan dengan menggunakan aturan Lipinski Rules of Five untuk mendapatkan senyawa metabolit sekunder yang memenuhi kriteria, prediksi protein target dilakukan dengan SwissTargetPrediction, identifikasi protein yang berhubungan dengan kanker dilakukan dengan GeneCards, dan irisannya dilakukan dengan menggunakan Venny. Network pharmacology dianalisis menggunakan String-DB, hasilnya dilakukan pengayaan menggunakan Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, dan analisis prediksi protein yang paling berpengaruh dilakukan dengan menggunakan algoritma Maximal Clique Centrality (MCC). Berdasarkan hasil skrining diperoleh 30 senyawa yang memenuhi persyaratan Lipinski Rules of Five. Hasil analisa menggunakan GeneCards menunjukkan teridentifikasi sejumlah 24.513 protein terkait kanker. Protein yang diprediksi mampu berinteraksi dengan metabolit sekunder A. galanga sejumlah 489 protein dengan sejumlah 487 protein merupakan irisan dari keduanya. Analisis KEGG menunjukkan bahwa senyawa metabolit sekunder A. galanga berkaitan dengan beberapa jalur penyakit kanker dengan keterkaitan tertinggi pada kanker prostat yang memiliki nilai False Discovery Rate (FDR) 26,31876. Analisis dengan algoritma MCC menunjukkan terdapat sepuluh protein target utama yang berkaitan dengan penyakit kanker. Hasil dari penelitian ini dapat disimpulkan bahwa senyawa metabolit sekunder A. galanga memiliki potensi sebagai antikanker terutama pada kanker prostat dengan nilai FDR tertinggi.


Keywords


Alpinia galanga; GeneCards; kanker; KEGG pathway; network pharmacology

References


Hartini S, Winarsih BD, Nugroho EGZ. Peningkatan Pengetahuan Perawat Untuk Perawatan Anak Penderita Kanker. J Pengabdi Kesehat. 2020;3(2):141–9. https:/doi.org/10.31596/jpk.v3i2.87. [2] Suciati A, Maryati. Systematic Review: Anticancer Potential of Active Compounds from Galangal (Alpinia galanga) [Internet]. Vol. 3, Proceedings of the 4th International Conference Current Breakthrough in Pharmacy (ICB-Pharma 2022). Atlantis Press International BV; 2023. 269–282 p. Available from: http://dx.doi.org/10.2991/978-94-6463-050-3_23. [3] Nurhidayah I, Hendrawati S, S. Mediani H, Adistie F. Kualitas Hidup pada Anak dengan Kanker. J Keperawatan Padjadjaran. 2016;4(1):45–59. https:/doi.org/10.24198/jkp.v4n1.5. [4] Chaudhary S, Hisham H, Mohamed D. A Review on Phytochemical and Pharmacological Potential of Watercress Plant. Asian J Pharm Clin Res. 2018;11(12):102–7. https:/doi.org/10.22159/ajpcr.2018.v11i12.29422. [5] Eram S, Mujahid M, Bagga P, Ansari VA, Ahmad MA, Kumar A, et al. a Review on Phytopharmacological Activity of Alpinia Galanga. Int J Pharm Pharm Sci. 2019;11(3):6–11. https:/doi.org/10.22159/ijpps.2019v11i3.31352. [6] Makatita FA, Wardhani R, Nuraini. Riset In Silico dalam Pengembangan Sains di Bidang Pendidikan, Studi Kasus: Analisis Potensi Cendana Sebagai Agen Anti-Aging. J ABDI. 2020;2(1):59–67. [7] Adelina R. Mekanisme Katekin Sebagai Obat Antidislipidemia (Uji In Silico). Bul Penelit Kesehat. 2018;46(3):147–54. https:/doi.org/10.22435/bpk.v46i3.899. [8] Bare Y, Maulidi A, Ratih D, Sari T, Sulystyaningsih S, Daeng N. Studi in Silico Prediksi Potensi 6-Gingerol sebagai inhibitor c-Jun N-terminal kinases (JNK) Prediction Potential of 6-gingerol as c-Jun N-terminal kinases ( JNK ): In Silico approach. J Jejaring Mat dan Sains,. 2019;1(2):59–63. [9] Lena N, Jamil AS, Muchlisin MA, Almutahrihan IF. Analisis Jejaring Farmakologi Tanaman Jati Belanda (Guazuma ulmifolia Lamk.) Sebagai Imunomodulator. J Islam Pharm. 2023 Jun 30;8(1):1–6. https:/doi.org/10.18860/jip.v8i1.20782. [10] T MM, D R, Yaligar R, Jyothi R, G N, V RM. Swiss ADME Prediction of Phytochemicals Present in Butea monosperma (Lam.) Taub. ~ 1799 ~ J Pharmacogn Phytochem [Internet]. 2020;9(3):1799–809. Available from: www.phytojournal.com. [11] Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, et al. The GeneCards suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinforma. 2016;2016:1.30.1-1.30.33. https:/doi.org/10.1002/cpbi.5. [12] Safran M, Rosen N, Twik M, BarShir R, Stein TI, Dahary D, et al. The GeneCards Suite. Pract Guid to Life Sci Databases. 2022;27–56. https:/doi.org/10.1007/978-981-16-5812-9_2. [13] Hur B, Kang D, Lee S, Moon JH, Lee G, Kim S. Venn-diaNet: Venn Diagram Based Network Propagation Analysis Framework for Comparing Multiple Biological Experiments. BMC Bioinformatics [Internet]. 2019;20(Suppl 23):1–12. Available from: http://dx.doi.org/10.1186/s12859-019-3302-7. [14] Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, et al. The STRING database in 2021: Customizable Protein-protein Networks, and Functional Gharacterization of User-Uploaded Gene/Measurement sets. Nucleic Acids Res. 2021;49(D1):D605–12. https:/doi.org/10.1093/nar/gkaa1074. [15] Khoirunnisa A, Jamil AS, Muchlisin MA. Analisis Keterkaitan Network Pharmacology Senyawa Metabolit Sekunder Abrus precatorius L. Secara In Silico. J Penelit Farm Herb. 2024;6(2):15–22. https:/doi.org/10.36656/jpfh.v6i2.1686. [16] Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for Taxonomy-based Analysis of Pathways and Genomes. Nucleic Acids Res. 2023;51(D1):D587–92. https:/doi.org/10.1093/nar/gkac963. [17] Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, et al. The String Database in 2023: Protein-Protein Association Networks and Functional Enrichment Analyses for Any Sequenced Genome of Interest. Nucleic Acids Res. 2023;51(1 D):D638–46. https:/doi.org/10.1093/nar/gkac1000. [18] Doncheva NT, Morris JH, Gorodkin J, Jensen LJ. Cytoscape StringApp: Network Analysis and Visualization of Proteomics Data. J Proteome Res. 2019;18(2):623–32. https:/doi.org/10.1021/acs.jproteome.8b00702. [19] Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: Identifying Hub Objects and Sub-Networks from Complex Interactome. BMC Syst Biol. 2014;8(4). https:/doi.org/10.1186/1752-0509-8-S4-S11. [20] Tao Q, Du J, Li X, Zeng J, Tan B, Xu J, et al. Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Huashi Baidu Formula in The Treatment of COVID-19. Drug Dev Ind Pharm. 2020;46(13):1345–53. https:/doi.org/10.1080/03639045.2020.1788070. [21] Hartono Wijaya S, Tanaka Y, Altaf-Ul-Amin M, Hirai Morita A, Mochamad Afendi F, Batubara I, et al. Utilization of KNApSAcK Family Databases for Developing Herbal Medicine Systems. J Comput Aided Chem. 2016;17(0):1–7. https:/doi.org/10.2751/jcac.17.1. [22] Daina A, Michielin O, Zoete V. SwissTargetPrediction: Updated Data and New Features for Efficient Prediction of Protein Targets of Small Molecules. Nucleic Acids Res. 2019;47(W1):W357–3664. https:/doi.org/10.1093/nar/gkz382. [23] Giménez BG, Santos MS, Ferrarini M, Dos Santos Fernandes JP. Evaluation of Blockbuster Drugs Under The Rule-of-Five. Pharmazie. 2010;65(2):148–52. https:/doi.org/10.1691/ph.2010.9733. [24] Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings. Adv Drug Deliv Rev. 2001;46(1–3):3–26. [25] Rukmono, Rendra, Inarah Fajriaty, Hafrizal riza, Mitra Handini. Virtual Screening Metabolit Aktif Senyawa Asam dari Pacar Air (Impatients balsamina L.) terhadap Reseptor Sulfonilurea. J Mhs Farm Fak Kedokt UNTAN. 2019;4(1):1–9. [26] Alghifari MR, Jamil AS. Insight into Jasminum sambac Molecular Docking Interaction with GCK related to Diabetes Mellitus. Indones J Comput Biol. 2023;2(1):40. https://doi.org/10.24198/ijcb.v2i1.45616. [27] Fauzi MA, Muchlisin MA, Jamil AS, Almutahrihan IF. A Network Pharmacology of Beluntas (Pluchea indica) on Immunity Cases. In: Proceedings of International Pharmacy Ulul Albab Conference and Seminar (PLANAR). Malang; 2023. p. 77–92. [28] Siti D, Hentu RM, Muchlisin MA, Jamil AS, Juni E, Rafikayanti A. Potential Activity Of Secondary Metabolites Of Kawista (Limonia Acidissima) As Neurodegenerative Diseases : A Network Pharmacology Approaches. J Eduhealth. 2024;15(02):1246–58. https://doi.org/10.54209/eduhealth.v15i02. [29] Pistritto G, Trisciuoglio D, Ceci C, Alessia Garufi, D’Orazi G. Apoptosis as Anticancer Mechanism: Function and Dysfunction of Its Modulators and Targeted Therapeutic Strategies. Aging (Albany NY). 2016;8(4):603–19. https://doi.org/10.18632/aging.100934. [30] Qian S, Wei Z, Yang W, Huang J, Yang Y, Wang J. The Role of BCL-2 Family Proteins in Regulating Apoptosis and Cancer Therapy. Front Oncol. 2022;12:1–6. https://doi.org/10.3389/fonc.2022.985363. [31] Cui D, Qu R, Liu D, Xiong X, Liang T, Zhao Y. The Cross Talk Between p53 and mTOR Pathways in Response to Physiological and Genotoxic Stresses. Front Cell Dev Biol. 2021;9:1–11. https://doi.org/10.3389/fcell.2021.775507. [32] Song Y, Song W, Li Z, Song W, Wen Y, Li J, et al. CDC27 Promotes Tumor Progression and Affects PD-L1 Expression in T-Cell Lymphoblastic Lymphoma. Front Oncol. 2020;10(488):13. https://doi.org/10.3389/fonc.2020.00488. [33] Xiao X, Wang W, Li Y, Yang D, Li X, Shen C, et al. HSP90AA1-Mediated Autophagy Promotes Drug Resistance in Osteosarcoma. J Exp Clin Cancer Res. 2018;37(201):13. https://doi.org/10.1186/s13046-018-0880-6. [34] Zhang H, Yin X, Zhang X, Zhou M, Xu W, Wei Z, et al. HSP90AB1 Promotes the Proliferation, Migration, and Glycolysis of Head and Neck Squamous Cell Carcinoma. Technol Cancer Res Treat. 2022;21:1–4. https://doi.org/10.1177/15330338221118202.




DOI: https://doi.org/10.18860/jip.v9i1.27094

Refbacks

  • There are currently no refbacks.


Copyright (c) 2024 Journal of Islamic Pharmacy

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

© 2023 Journal of Islamic Pharmacy