Potential Activity Of Secondary Metabolites Of Kawista (Limonia Acidissima) As Neurodegenerative Diseases : A Network Pharmacology Approaches
Keywords:
Kawita, Limonia acidissima, Neurodegenerative, Network pharmacologyAbstract
Kawista (Limonia acidissima) is a tropical plant traditionally used in South and Southeast Asian medicine, and its known for its rich nutritional profile and bioactive compounds. This study explores the therapeutic potential of kawista for neurodegenerative diseases. This study aims to investigate the potential of kawista in managing neurodegenerative through a pharmacological network approach. Proteins that can interact with secondary metabolites of kawista were predicted using SwissTargetPrediction, proteins related to neurodegenerative were obtained from GeneCards. The intersecting results were analyzed using STRING with GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment methods. From 47 secondary metabolites of kawista, 218 neuro-related proteins was identified potentially interacting with kawista's secondary metabolites. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and disease-gene association analyses highlighted key biological processes, molecular functions, cellular components, and pathways relevant to neurodegenerative disease mechanisms. The findings suggest that kawista's bioactive compounds could modulate critical pathways and receptor activities, offering insights into developing novel, effective therapies for neurodegenerative disorders. This research providing a scientific basis for kawista-based therapeutic strategies aimed at improving neurodegenerative disease outcomes.
References
Adamu, A., Li, S., Gao, F., & Xue, G. (2024). The role of neuroinflammation in neurodegenerative diseases : current understanding and future therapeutic targets. Frontiers in Aging Neuroscience, 16(1347987). https://doi.org/10.3389/fnagi.2024.1347987
Aleksander, S. A., Balhoff, J., Carbon, S., Cherry, J. M., Drabkin, H. J., Ebert, D., Feuermann, M., Gaudet, P., Harris, N. L., Hill, D. P., Lee, R., Mi, H., Moxon, S., Mungall, C. J., Muruganugan, A., Mushayahama, T., Sternberg, P. W., Thomas, P. D., Van Auken, K., … Westerfield, M. (2023). The Gene Ontology knowledgebase in 2023. Genetics, 224(1), 1–14. https://doi.org/10.1093/genetics/iyad031
Arnsten, A. F. T., & Pliszka, S. R. (2011). Pharmacology , Biochemistry and Behavior Catecholamine in fl uences on prefrontal cortical function : Relevance to treatment of attention de fi cit / hyperactivity disorder and related disorders ☆. Pharmacology, Biochemistry and Behavior, 99(2), 211–216. https://doi.org/10.1016/j.pbb.2011.01.020
Azam, S., Haque, E., Jakaria, Jo, S.-H., Kim, I.-S., & Choi, D.-K. (2020). G-Protein-Coupled Receptors in CNS : A Potential Neurodegenerative Disorders and Associated. Cells, 9(506). https://doi.org/10.3390/cells9020506
Boczek, T., Mackiewicz, J., Sobolczyk, M., Wawrzyniak, J., Lisek, M., Ferenc, B., Guo, F., & Zylinska, L. (2021). Calcium Signaling in Schizophrenia . Focus on GPCRs Activated by Neurotransmitters and Chemokines. Cells, 10(1228).
Camandola, S., & Mattson, M. P. (2011). Biochimica et Biophysica Acta Aberrant subcellular neuronal calcium regulation in aging and Alzheimer ’ s disease ☆. BBA - Molecular Cell Research, 1813(5), 965–973. https://doi.org/10.1016/j.bbamcr.2010.10.005
Chandran, U., Mehendale, N., Patil, S., Chaguturu, R., & Patwardhan, B. (2017). Network Pharmacology. Innovative Approaches in Drug Discovery: Ethnopharmacology, Systems Biology and Holistic Targeting, 25(10), 127–164. https://doi.org/10.1016/B978-0-12-801814-9.00005-2
Chmielarz, P., & Saarma, M. (2020). Neurotrophic factors for disease ‑ modifying treatments of Parkinson ’ s disease : gaps between basic science and clinical studies. Pharmacological Reports, 72(5), 1195–1217. https://doi.org/10.1007/s43440-020-00120-3
Cho, W., Yoon, S., & Chung, T. D. (2023). Chemical Science Streamlining the interface between electronics and neural systems for bidirectional electrochemical. Chemical Science, 14, 4463–4479. https://doi.org/10.1039/d3sc00338h
Daina, A., Michielin, O., & Zoete, V. (2019). SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Research, 47(W1), W357–W3664. https://doi.org/10.1093/nar/gkz382
Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021). The cGAS–STING pathway as a therapeutic target in inflammatory diseases. Nature Reviews Immunology, 21(9), 548–569. https://doi.org/10.1038/s41577-021-00524-z
Dhakar, A., Chorotiya, P., Meena, M., Singh, C., Purvia, R. P., & Adlakha, M. K. (2019). Pharmacological properties and phytochemical of Limonia acidissima: a review. World Journal Of Pharmaceutical Research, 8(10), 637–645. https://doi.org/10.20959/wjpr201910-15730.
Franco, R., & Cedazo-Minguez, A. (2014). Successful therapies for Alzheimer’s disease: Why so many in animal models and none in humans? Frontiers in Pharmacology, 5(146). https://doi.org/10.3389/fphar.2014.00146
Hampel, H., Hardy, J., Blennow, K., Chen, C., George, P., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., Masters, C. L., Cho, M., Lannfelt, L., Cummings, J. L., & Vergallo, A. (2021). The Amyloid- β Pathway in Alzheimer ’ s Disease. Molecular Psychiatry, 26, 5481–5503. https://doi.org/10.1038/s41380-021-01249-0
Hentu, D. S. R. M., Muchlisin, M. A., Jamil, A. S., Astuti, E. J., & Rafikayanti, A. (2024). Pemanfaatan Senyawa Metabolit Sekunder Kawista (Limonia acidissima) Untuk Pengelolaan Dabetes : Tinjauan Analisis Jejaring Farmakologi. Pharma Xplore : Jurnal Sains Dan Ilmu Farmasi, 9(1), 51–63.
Ihya, Z., Irfandi, R., Rijal, S., Yani, A., Arafah, M., & Rompegading, A. B. (2024). Literature Review : Network Pharmacology as a New Approach and Trend in Medicine. Hayyan Journal, 1(1), 1–8.
Jha, S. K., Jha, N. K., Kumar, D., Sharma, R., Shrivastava, A., Ambasta, R. K., & Kumar, P. (2016). Un rre cte d Au tho r P Stress-Induced Synaptic Dysfunction Neurotransmitters and Neuromodulators roo f cte d Au tho r P roo f Un. Journal of Alzheimer’s Disease, 57(4), 1017–1039. https://doi.org/10.3233/JAD-160623
Johnson, W. M., Wilson-delfosse, A. L., & Mieyal, J. J. (2012). Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases. Nutrients, 4, 1399–1440. https://doi.org/10.3390/nu4101399
Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M., & Ishiguro-Watanabe, M. (2023). KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Research, 51(D1), D587–D592. https://doi.org/10.1093/nar/gkac963
Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J., & Bolton, E. E. (2023). PubChem 2023 update. Nucleic Acids Research, 51(D1), D1373–D1380. https://doi.org/10.1093/nar/gkac956
Kim, Y., Park, J., & Cho, Y. (2022). Network-Based Approaches for Disease-Gene Association Prediction Using Protein-Protein Interaction Networks. International Journal of Molecular Sciences, 23(7411). https://doi.org/10.3390/ijms23137411
Lepeta, K., Lourenco, M. V., Schweitzer, B. C., Adami, P. V. M., Banerjee, P., Catuara-Solarz, S., Revenga, M. de L. F., Guillem, A. M., Haidar, M., Ijomone, O. M., Nadorp, B., Qi, L., Perepa, N. D., RefsGaard, L. K., Reid, K. M., Sabbar, M., Sahoo, A., Schafer, N., Sheean, R. K., … Seidenbecher, C. (2016). Synaptopathies: synaptic dysfunction in neurological disorders A review from students to students. Journal of Neurochemistry, 138, 785–805. https://doi.org/10.1111/jnc.13713
Maiti, P., Manna, J., & Dunbar, G. L. (2017). Current understanding of the molecular mechanisms in Parkinson ’ s disease : Targets for potential treatments. Translational Neurodegeneration, 6(28). https://doi.org/10.1186/s40035-017-0099-z
Muddapu, V. R., Dharshini, S. A. P., Chakravarthy, V. S., & Gromiha, M. M. (2020). Neurodegenerative Diseases – Is Metabolic Deficiency the Root Cause ? Frontiers in Neuroscience, 14(213). https://doi.org/10.3389/fnins.2020.00213
Mukta, M. M., Hossain, J., Akter, M., Banik, B., Mithun, M. M. Z., Sarwar, S., Arefin, S., Islam, M. R., & Islam, S. N. (2023). Cardioprotection of Water Spinach (Ipomoea aquatica), Wood Apple (Limonia acidissima) and Linseed (Linum usitatissimum L.) on Doxorubicin-Induced Cardiotoxicity and Oxidative Stress in Rat Model. Nutrition and Metabolic Insights, 16. https://doi.org/10.1177/11786388231212116
Murthy, H. N., & Dalawai, D. (2020). Bioactive Compounds of Wood Apple (Limonia acidissima L.). In H. N. Murthy & V. A. Bapat (Eds.), Bioactive Compounds in Underutilized Fruits and Nuts (pp. 543–569). Springer Nature Switzerland. https://doi.org/10.1007/978-3-030-06120-3_12-1
Oleari, R., Massa, V., & Cariboni, A. (2021). The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency. International Journal of Molecular Science, 22(9425).
Oliveros, J. C. (2015). Venny. An interactive tool for comparing lists with Venn’s diagrams. https://bioinfogp.cnb.csic.es/tools/venny/index.html
Parvez, G. M. M., & Sarker, R. K. (2021). Pharmacological potential of wood apple (Limonia acidissima): A Review. International Journal of Minor Fruits, Medicinal and Aromatic Plants, 7(2), 40–47. https://doi.org/10.53552/ijmfmap.2021.v07ii02.003
Rakhunde, P. B., Saher, S., & Ali, S. A. (2014). Neuroprotective effect of Feronia limonia on ischemia reperfusion induced brain injury in rats. Indian Journal of Pharmacology, 46(6), 617–621. https://doi.org/10.4103/0253-7613.144920
Rekatsina, M., Paladini, A., Piroli, A., & Zis, P. (2020). Pathophysiology and Therapeutic Perspectives of Oxidative Stress and Neurodegenerative Diseases : A Narrative Review. Advances in Therapy, 37(1), 113–139. https://doi.org/10.1007/s12325-019-01148-5
Safran, M., Rosen, N., Twik, M., BarShir, R., Stein, T. I., Dahary, D., Fishilevich, S., & Lancet, D. (2022). The GeneCards Suite. Practical Guide to Life Science Databases, 27–56. https://doi.org/10.1007/978-981-16-5812-9_2
Salari, N., Ghasemi, H., Fatahian, R., Mansouri, K., & Dokaneheifard, S. (2023). The global prevalence of primary central nervous system tumors : a systematic review and meta ‑ analysis. European Journal of Medical Research, 28(39), 1–16. https://doi.org/10.1186/s40001-023-01011-y
Saputro, D. V., Jamil, A. S., Muchlisin, M. A., & Almuhtarihan, I. F. (2023). A Network Pharmacology of Lemongrass (Cymbopogon citratus) on COVID-19 Cases. In T. J. D. Dewi, B. Ma’arif, M. Rahmayanti, F. F. Rahmadanita, & V. Vania (Eds.), Proceedings of International Pharmacy Ulul Albab Conference and Seminar (PLANAR) (Vol. 3, pp. 50–58). UIN Maliki Ibrahim. https://doi.org/10.18860/planar.v3i0.2471
Sarapultsev, A., Gusev, E., Komelkova, M., Utepova, I., Luo, S., & Hu, D. (2023). JAK ‑ STAT signaling in inflammation and stress ‑ related diseases : implications for therapeutic interventions. Molecular Biomedicine, 4(40). https://doi.org/10.1186/s43556-023-00151-1
Satpati, A., Neylan, T., & Grinberg, L. T. (2023). Histaminergic neurotransmission in aging and Alzheimer ’ s disease : A review of therapeutic opportunities and gaps. Alzheimer’s & Dementia, 9(e12379). https://doi.org/10.1002/trc2.12379
Savelieff, M. G., Nam, G., Kang, J., Lee, H. J., Lee, M., & Lim, M. H. (2019). Development of multifunctional molecules as potential therapeutic candidates for Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis in the last decade. Chemical Reviews, 119(2), 1221–1322. https://doi.org/10.1021/acs.chemrev.8b00138
Sullivan, P. F., & Geschwind, D. H. (2019). Review Defining the Genetic , Genomic , Cellular , and Diagnostic Architectures of Psychiatric Disorders. Cell, 177(1), 162–183. https://doi.org/10.1016/j.cell.2019.01.015
Susanto, A. F. F. S., Jamil, A. S., Muchlisin, M. A., & Almuhtarihan, I. F. (2023). A Network Pharmacology of Brotowali (Tinospora cordifolia) on Immunity Cases. In T. J. D. Dewi, B. Ma’arif, M. Rahmayanti, F. F. Rahmadanita, & V. Vania (Eds.), Proceedings of International Pharmacy Ulul Albab Conference and Seminar (PLANAR) (Vol. 3, pp. 29–37). UIN Maliki Ibrahim. https://doi.org/10.18860/planar.v3i0.2474
Szklarczyk, D., Kirsch, R., Koutrouli, M., Nastou, K., Mehryary, F., Hachilif, R., Gable, A. L., Fang, T., Doncheva, N. T., Pyysalo, S., Bork, P., Jensen, L. J., & Von Mering, C. (2023). The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Research, 51(1 D), D638–D646. https://doi.org/10.1093/nar/gkac1000
Thakur, N., Chugh, V., & Dwivedi, S. V. (2020). Wood apple: An underutilized miracle fruit of India. The Pharma Innovation Journal, 9(10), 198–202. http://www.thepharmajournal.com
Toader, C., Dobrin, N., Brehar, F., Popa, C., Glavan, L. A., Costin, H. P., Bratu, B., Corlatescu, A. D., Popa, A. A., & Ciurea, A. V. (2023). From Recognition to Remedy : The Significance of Biomarkers in Neurodegenerative Disease Pathology. International Journal of Molecular Science, 24(16119).
van Spronsen, M., & Hoogenraad, C. C. (2010). Synapse Pathology in Psychiatric and Neurologic Disease. Current Neulroogy and Neuroscience, 10, 207–214. https://doi.org/10.1007/s11910-010-0104-8
Wilson III, D. M., Cookson, M. R., Bosch, L. Van Den, Zetterberg, H., & Holtzman, D. M. (2023). ll Hallmarks of neurodegenerative diseases. Cell, 186(4), 693–714. https://doi.org/10.1016/j.cell.2022.12.032
Yu, X., Chen, K., Ma, Y., Bai, T., Zhu, S., Cai, D., Zhang, X., Wang, K., Tian, Y., & Wang, J. (2024). Molecular basis underlying changes of brain entropy and functional connectivity in major depressive disorders after electroconvulsive therapy. CNS Neuroscience & Therapeutics, 30(3), e14690. https://doi.org/10.1111/cns.14690
Zhong, S., Tian, L., Li, C., Storch, K. F., & Wong, W. H. (2004). Comparative analysis of gene sets in the gene ontology space under the multiple hypothesis testing framework. Proceedings - 2004 IEEE Computational Systems Bioinformatics Conference, 2004. CSB 2004., 425–435. https://doi.org/10.1109/csb.2004.1332455