Integration of Bioinformatics and Pharmacological Network for Exploring the Potential of Curcumin as a Herbal Medicine for Adenomyosis
Main Article Content
Abstract
Adenomyosis is a benign gynecological disorder characterized by abnormal uterine bleeding, infertility, and dysmenorrhea, affecting approximately 10% of women worldwide during their reproductive years. The high morbidity and postoperative complications associated with surgical treatments have generated interest in conservative therapies. Natural medicine, particularly plant-based compounds, is increasingly recognized in the field of reproductive health. Curcumin, a bioactive component found in Indonesian medicinal plants, demonstrates potential as a therapeutic candidate for adenomyosis. This study aimed to explore the physicochemical characteristics, suitable targets, and pharmacological mechanisms of curcumin’s action as a potential therapeutic alternative for adenomyosis. Pharmacological networks integrated with bioinformatics databases was used to explore curcumin’s potential pharmacological targets and mechanisms as an alternative therapy for adenomyosis. Data integration identified shared therapeutic targets, with protein-protein interaction (PPI) networks constructed via the STRING database. CytoHubba analysis identified key hub genes based on connectivity, highlighting EPHA5, EPHB2, and EPHA4 as the top nodes of interest within the PPI network. Compound-target-disease interactions analysis highlighted the therapeutic relevance of curcumin and its impact on adenomyosis-related molecular pathways. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified axon guidance as a significantly implicated pathway in adenomyosis. Molecular docking confirmed curcumin’s stable binding affinities with target proteins. This study presents theoretical and experimental evidence supporting curcumin’s potential as a therapeutic agent for adenomyosis. Key molecular targets and pathways are highlighted for further exploration, contributing to a broader understanding of curcumin’s pharmacological profile and its potential as a non-surgical therapy in adenomyosis.
Downloads
Article Details
Section

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
References
Rossi M, Vannuccini S, Capezzuoli T, Fambrini M, Vannuzzi V, Donati C, Petraglia F. Mechanisms and Pathogenesis of Adenomyosis. Curr Obstet Gynecol Rep. 2022; 11(2):95-102. doi:10.1007/s13669-022-00326-7 DOI: https://doi.org/10.1007/s13669-022-00326-7
Penariol LBC, Thomé CH, Tozetti PA, Paier CRK, Buono FO, Peronni KC, Orellana MD, Covas DT, Moraes MEA, Silva WA, Rosa-e-Silva JC, Ferriani RA, Faça VM, Poli-Neto OB, Tiezzi DG, Meola J. What do the Transcriptome and Proteome of Menstrual Blood-Derived Mesenchymal Stem Cells Tell Us About Endometriosis? Int J Mol Sci. 2022; 23(19):1-17. doi:10.3390/ijms231911515 DOI: https://doi.org/10.3390/ijms231911515
Zhai J, Vannuccini S, Petraglia F, Giudice LC, Sciences R, Francisco S, Francisco S, Hospital RJ, Tong SJ, Genetics R, Biomedical C, Medicine D. Adenomyosis: Mechanisms and Pathogenesis. Semin Reprod Med. 2021; 38:129-143. doi:10.1055/s-0040-1716687.Adenomyosis DOI: https://doi.org/10.1055/s-0040-1716687
Deraya IE, Hestiantoro A, Muharam R, Marwali ML, As’adi AS, Darmawi, Harzif AK, Pratama G, Ocktariyana, Zahrah A, Asmarinah. Analysis of mRNA Expression and DNA Methylation Level of RAC1 Gene Encoding Focal Adhesion Molecule in Endometrial and Peritoneal Endometriosis. Asia Pac J Mol Biol Biotechnol. 2020; 28(2):43-49. doi:10.35118/apjmbb.2020.028.2.05 DOI: https://doi.org/10.35118/apjmbb.2020.028.2.05
Annisa NG, Febri RR, Darmawi, Kinasih T, Muharam R, Asmarinah. Analysis of the Methylation Profiles of the Steroidogenic Factor-1 (SF-1) Gene in Peritoneal and Ovarian Endometriosis. J Phys Conf Ser. 2018; 1073(3):032080. doi:10.1088/1742-6596/1073/3/032080 DOI: https://doi.org/10.1088/1742-6596/1073/3/032080
Buggio L, Dridi D, Barbara G. Adenomyosis: Impact on Fertility and Obstetric Outcomes. Reprod Sci. 2021; 28(11):3081-3084. doi:10.1007/s43032-021-00679-z DOI: https://doi.org/10.1007/s43032-021-00679-z
Deraya IE, Hestiantoro A, Muharam R, Marwali MLS, Darmawi, Asmarinah. The mRNA Expression and DNA Methylation Level of Fibronectin 1 (FN1) Gene Encoding Focal Adhesion Molecule in Endometrial Endometriosis. IOP Conf Ser Earth Environ Sci. 2020; 457(1):012079. doi:10.1088/1755-1315/457/1/012079 DOI: https://doi.org/10.1088/1755-1315/457/1/012079
Darmawi, Marwali MLS, Febri RR, Muharam R, Hestiantoro A, Asmarinah. DNA Methylation of the Progesterone Receptor B (PR-B) Gene Promoter in Human Eutopic Endometrium, Ectopic Peritoneum, and Ovarian Endometriosis. J Phys Conf Ser. 2018; 1073(3):032079. doi:10.1088/1742-6596/1073/3/032079 DOI: https://doi.org/10.1088/1742-6596/1073/3/032079
Putra MFA and Anggraini MA. Adenomyosis: Diagnosis and Treatment. J Biol Trop. 2022; 22(4):1462-1473. doi:10.29303/jbt.v22i4.4315 DOI: https://doi.org/10.29303/jbt.v22i4.4315
Nirgianakis K, Kalaitzopoulos DR, Schwartz SK, Spaanderman M, Kramer BW, Mueller D, Mueller M. Fertility, Pregnancy and Neonatal Outcomes of Patients with Adenomyosis: A Systematic Review and Meta-Analysis. Reprod Biomed Online. 2021; 42(1):185-206. doi:10.1016/j.rbmo.2020.09.023 DOI: https://doi.org/10.1016/j.rbmo.2020.09.023
Sharara FI, Kheil MH, Feki A, Rahman S, Klebanoff JS, Ayoubi JM, Moawad GN. Current and Prospective Treatment of Adenomyosis. J Clin Med. 2021; 10(15):3410. doi:10.3390/jcm10153410 DOI: https://doi.org/10.3390/jcm10153410
Darmawi D, Adikusuma W, Irham LM, Suyanto S. Identification of Biomarker and Biological Risk Genes to Drive Drug Repurposing in Malaria Using Transcriptomics Database. Iran J Pharm Sci. 2023; 19(3):250-260. doi:10.22037/ijps.v19i3.43886
Setiawan A. Biodiversity in Indonesia: Issues and Conservation Strategies. Indones J Conserv. 2022; 11(1):13-21. doi:10.15294/ijc.v11i1.34532
Permatasari GW, Atho’illah MF, Putra WE. Target Protein Prediction of Indonesian Jamu Kunyit Asam (Curcumin-Tamarind) for Dysmenorrhea Pain Reliever: A Network Analysis Approach. J Kedokt Kesehatan Indones. 2021; 3(12):238-242. doi:10.20885/JKKI.Vol12.Iss3.art7 DOI: https://doi.org/10.20885/JKKI.Vol12.Iss3.art7
Sutrisno S and Paramadina PN. The Role of Herbal Medicine as An Alternative Treatment Option for Endometriosis: A Literature Review. Asian J Health Res. 2023; 2(3):47-54. doi:10.55561/ajhr.v2i3.125 DOI: https://doi.org/10.55561/ajhr.v2i3.125
Wahyuni A, Mudigdo A, Soetrisno, Wasita B, Budi UR, Widyaningsih V, Sari IP. Beneficial Effects of Self-Nanoemulsifying Drug Delivery System Extract of Curcuma longa on Polycystic Ovary Syndrome Rats Model Through Insulin Sensitization Activity. Trop J Nat Prod Res. 2024; 8(3):6563-6569. doi:10.26538/tjnpr/v8i3.14 DOI: https://doi.org/10.26538/tjnpr/v8i3.14
Adikusuma W, Firdayani F, Irham LM, Darmawi D, Hamidy MY, Nopitasari BL, Soraya S, Azizah N. Integrated Genomic Network Analysis Revealed Potential of a Druggable Target for Hemorrhoid Treatment. Saudi Pharm J. 2023; 31(12):101831. doi:10.1016/j.jsps.2023.101831 DOI: https://doi.org/10.1016/j.jsps.2023.101831
Darmawi D, S D, Suhandri W, Winarto W, Adikusuma W, Irham LM, Fidiawati WA, Razali RR, Nathania A, Zahra LP. Repurposing Drugs in Endometrial Cancer Using Genomic Variants Database. Pharmaciana. 2023; 13(3):306. doi:10.12928/pharmaciana.v13i3.27201 DOI: https://doi.org/10.12928/pharmaciana.v13i3.27201
Nakamura K, Shimura N, Otabe Y, Hirai-Morita A, Nakamura Y, Ono N, Ul-Amin MA, Kanaya S. KNApSAcK-3D: A Three-Dimensional Structure Database of Plant Metabolites. Plant Cell Physiol. 2013; 54(2):1-8. doi:10.1093/pcp/pcs186 DOI: https://doi.org/10.1093/pcp/pcs186
Li Q, Cheng T, Wang Y, Bryant SH. PubChem as a Public Resource for Drug Discovery. Drug Discov Today. 2010; 15(23-24):1052-1057. doi:10.1016/j.drudis.2010.10.003 DOI: https://doi.org/10.1016/j.drudis.2010.10.003
Daina A, Michielin O, Zoete V. SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules. Sci Rep. 2017; 7:42717. doi:10.1038/srep42717 DOI: https://doi.org/10.1038/srep42717
Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: A Webserver for the Prediction of Toxicity of Chemicals. Nucleic Acids Res. 2018; 46(W1):W257-W263. doi:10.1093/nar/gky318 DOI: https://doi.org/10.1093/nar/gky318
Gfeller D, Grosdidier A, Wirth M, Daina A, Michielin O, Zoete V. SwissTargetPrediction: A Web Server for Target Prediction of Bioactive Small Molecules. Nucleic Acids Res. 2014; 42:W32-W38. doi:10.1093/nar/gku293 DOI: https://doi.org/10.1093/nar/gku293
Clough E and Barrett T. The Gene Expression Omnibus Database. Methods Mol Biol. 2016; 1418:93-110. doi:10.1007/978-1-4939-3578-9_5 DOI: https://doi.org/10.1007/978-1-4939-3578-9_5
Falah Alshehri F, Alzahrani FM, Alkhoshaiban A, Al Shehri ZS. Exploring the Multi-Gene Regulatory Molecular Mechanism of Saudi Arabian Flora Against Epilepsy Based on Data Mining, Network Pharmacology and Docking Analysis. Saudi Pharm J. 2023; 31(9):101732. doi:10.1016/j.jsps.2023.101732 DOI: https://doi.org/10.1016/j.jsps.2023.101732
Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, Gable AL, Fang T, Doncheva NT, Pyysalo S, Bork P, Jensen LJ, Von Mering C. The STRING Database in 2023: Protein-Protein Association Networks and Functional Enrichment Analyses for Any Sequenced Genome of Interest. Nucleic Acids Res. 2023; 51(1D):D638-D646. doi:10.1093/nar/gkac1000 DOI: https://doi.org/10.1093/nar/gkac1000
Ge SX, Jung D, Yao R. ShinyGO: A Graphical Gene-Set Enrichment Tool for Animals and Plants. Bioinformatics. 2020; 36(8):2628-2629. doi:10.1093/bioinformatics/btz931 DOI: https://doi.org/10.1093/bioinformatics/btz931
Dwira S, Tedjo A, Dharmawan MA, Erlina L, Fadilah F. Differentially Expressed Genes, and Molecular Docking and Dynamic Analysis Revealing the Potential of Compounds in Zingiber officinale Roscoe as Inhibitors of TP53-Regulating Kinase (TP53RK) That Influence the p53 Signaling Pathway Related to Apoptosis and Cell Cycle. Trop J Nat Prod Res. 2024; 8(8):8007-8013. doi:10.26538/tjnpr/v8i8.12 DOI: https://doi.org/10.26538/tjnpr/v8i8.12
C S, S DK, Ragunathan V, Tiwari P, A S, P BD. Molecular Docking, Validation, Dynamics Simulations, and Pharmacokinetic Prediction of Natural Compounds Against the SARS-CoV-2 Main-Protease. J Biomol Struct Dyn. 2022; 40(2):585-611. doi:10.1080/07391102.2020.1815584 DOI: https://doi.org/10.1080/07391102.2020.1815584
Jasril, Nurulita Y, Afriana N, Ikhtiarudin I, Frimayanti N. Synthesis, Docking, and Molecular Dynamic Study of Hydrazones Compounds to Search Potential Inhibitor for Breast Cancer MCF-7. Thai J Pharm Sci. 2021; 45(6):477-486. doi:10.56808/3027-7922.2529 DOI: https://doi.org/10.56808/3027-7922.2529
Frimayanti N, Nasution MR, Etavianti E. Molecular Docking and Molecular Dynamic Simulation of 1,5-Benzothiazepine Chalcone Derivative Compounds as Potential Inhibitors for Zika Virus Helicase. J Ris Kimia. 2021; 12(1):44-52. doi:10.25077/jrk.v12i1.365 DOI: https://doi.org/10.25077/jrk.v12i1.365
Islam MR, Awal MA, Khames A, Abourehab MAS, Samad A, Hassan WMI, Alam R, Osman OI, Nur SM, Molla MHR, Abdulrahman AO, Rajia S, Ahammad F, Hasan MN, Qadri I, Kim B. Computational Identification of Druggable Bioactive Compounds from Catharanthus roseus and Avicennia marina Against Colorectal Cancer by Targeting Thymidylate Synthase. Molecules. 2022; 27(7):2089. doi:10.3390/molecules27072089 DOI: https://doi.org/10.3390/molecules27072089
Frimayanti N, Ikhtiarudin I, Dona R, Oktarizal R, Nurfatimah AC. Exploring Substituted Tetrazoloquinazoline: Biological Activities, Molecular Docking Analysis, and Anti‐Breast Cancer MCF7/HER2 Effects. Adv Pharmacol Pharm Sci. 2024; 2024(1):1. doi:10.1155/2024/6952142 DOI: https://doi.org/10.1155/2024/6952142
Struble J, Reid S, Bedaiwy MA. Adenomyosis: A Clinical Review of a Challenging Gynecologic Condition. J Minim Invasive Gynecol. 2016; 23(2):164-185. doi:10.1016/j.jmig.2015.09.018 DOI: https://doi.org/10.1016/j.jmig.2015.09.018
Han L, Liu Y, Lao K, Jiang J, Zhang C, Wang Y. Individualized Conservative Therapeutic Strategies for Adenomyosis With the Aim of Preserving Fertility. Front Med (Lausanne). 2023; 10:1133042. doi:10.3389/fmed.2023.1133042 DOI: https://doi.org/10.3389/fmed.2023.1133042
Boyanapalli SSS, Kong ANT. “Curcumin, the King of Spices”: Epigenetic Regulatory Mechanisms in the Prevention of Cancer, Neurological, and Inflammatory Diseases. Curr Pharmacol Rep. 2015; 1(2):129-139. doi:10.1007/s40495-015-0018-x DOI: https://doi.org/10.1007/s40495-015-0018-x
Guan L, Yang H, Cai Y, Sun L, Di P, Li W, Liu G, Tang Y. ADMET-Score - a Comprehensive Scoring Function for Evaluation of Chemical Drug-Likeness. Medchemcomm. 2019; 10(1):148-157. doi:10.1039/c8md00472b DOI: https://doi.org/10.1039/C8MD00472B
Lisabeth EM, Falivelli G, Pasquale EB. Eph Receptor Signaling and Ephrins. Cold Spring Harb Perspect Biol. 2013; 5(9):a009159. doi:10.1101/cshperspect.a009159 DOI: https://doi.org/10.1101/cshperspect.a009159
Adu-Gyamfi EA, Czika A, Liu TH, Gorleku PN, Fondjo LA, Djankpa FT, Ding YB, Wang YX. Ephrin and Eph Receptor Signaling in Female Reproductive Physiology and Pathology. Biol Reprod. 2021; 104(1):71-82. doi:10.1093/biolre/ioaa171 DOI: https://doi.org/10.1093/biolre/ioaa171
Guo SW. The Pathogenesis of Adenomyosis Vis-a-Vis Endometriosis. J Clin Med. 2020; 9:485. doi:10.3390/jcm9020485 DOI: https://doi.org/10.3390/jcm9020485
Rajuddin R, Wiweko B, Nugroho L. The Effects of Curcumin Administration on Expression Patterns of VEGF and COX-2 in Fertile Endometrium: A Randomised Clinical Trial. Int J Appl Pharm. 2019; 11(Special Issue 6):149-152. doi:10.22159/ijap.2019.v11s6.33581 DOI: https://doi.org/10.22159/ijap.2019.v11s6.33581
Russell SA and Bashaw GJ. Axon Guidance Pathways and the Control of Gene Expression. Dev Dyn. 2018; 247(4):571-580. doi:10.1002/dvdy.24609 DOI: https://doi.org/10.1002/dvdy.24609
Morotti M, Vincent K, Brawn J, Zondervan KT, Becker CM. Peripheral Changes in Endometriosis-Associated Pain. Hum Reprod Update. 2014; 20(5):717-736. doi:10.1093/humupd/dmu021 DOI: https://doi.org/10.1093/humupd/dmu021
Zhang X, Lu B, Huang X, Xu H, Zhou C, Lin J. Endometrial Nerve Fibers in Women with Endometriosis, Adenomyosis, and Uterine Fibroids. Fertil Steril. 2009; 92(5):1799-1801. doi:10.1016/j.fertnstert.2009.05.016 DOI: https://doi.org/10.1016/j.fertnstert.2009.05.016
Elmezayen AD, Al-Obaidi A, Şahin AT, Yelekçi K. Drug Repurposing for Coronavirus (COVID-19): In Silico Screening of Known Drugs Against Coronavirus 3CL Hydrolase and Protease Enzymes. J Biomol Struct Dyn. 2021; 39(8):2980-2992. doi:10.1080/07391102.2020.1758791 DOI: https://doi.org/10.1080/07391102.2020.1758791
Gurung AB, Ali MA, Lee J, El-Zaidy M, Aljowaie RM, Almutairi SM. Potential of Antiviral Peptide-Based SARS-CoV-2 Inactivators to Combat COVID-19. PLoS One. 2022; 17(6):e0268919. doi:10.1371/journal.pone.0268919 DOI: https://doi.org/10.1371/journal.pone.0268919


