Preview
In silico analysis of Bruguiera gymnorhiza leaf extracts using ethyl acetate as an anti-inflammatory agent Analisis in silico ekstrak daun Bruguiera gymnorhiza menggunakan etil asetat sebagai agen antiinflamasi
Abstract
Bruguiera gymnorhiza is a mangrove plant that contains many bioactive compounds, which exhibit anti-inflammatoryproperties. This study aims to evaluate the anti-inflammatory potential of bioactive compounds extracted from B. gymnorhiza leaves using ethyl acetate, through in silico analysis. A literature review was conducted using internationally recognized electronic databases to identify the chemical profiles of these compounds. In silico analyses were performed using PASS Server to predict biological activity, SwissADME for drug discovery potential, and ProTox III for toxicity assessment. Molecular docking was performed using the IKKβ receptor. A literature review identified 15 compounds present in the leaves of B. gymnorhiza. PASS Server analysis revealed that all identified compounds exhibited anti-inflammatory properties. Further evaluation using SwissADME and ProTox III indicated favorable drug-likeness and absorption, distribution, metabolism, and excretion potential, with varying levels of toxicity; four compounds were classified as Class 3, five as Class 4, four as Class 5, and two as Class 6. Molecular docking results demonstrated that elemicin and lauric acid formed hydrogen bonds with IKKβ, with binding energies of -4.4 kcal/mol and -6.6 kcal/mol, respectively, suggesting significant anti-inflammatory activity. These findings provide a foundation for the development of anti-inflammatory drugs based on B. gymnorhiza leaf extracts.
References
Almeida, I. T. D., Cortez-Pinto, H., Fidalgo, G., Rodrigues, D., & Camilo, M. E. (2002). Plasma total and free fatty acids composition in human non-alcoholic steatohepatitis. Clinical nutrition (Edinburgh, Scotland), 21(3), 219–223. https://doi.org/10.1054/clnu.2001.0529.
Amaya, M., Keck, F., Bailey, C., & Narayanan, A. (2014). The role of the IKK complex in viral infections. Pathogens and disease, 72(1), 32–44. 10.1111/2049-632X.12210.
Amirah, S., Kosman, R., & Novianti, Y. R. (2014). uji efek anti-inflamasi ekstrak n-butanol dan etil asetat daun petai cina (Leucaena leucocephala (Lamk.) De Wit) pada mencit jantan (Mus musculus) yang diinduksi dengan karagen. Jurnal Bionature, 15(2): 123-126. https://doi.org/10.35580/bionature.v15i2.1559.
Ano, Y., Ozawa, M., Kutsukake, T., Sugiyama, S., Uchida, K., Yoshida, A., & Nakayama, H. (2015). Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity. PloS one, 10(3). 10.1371/journal.pone.0118512.
Artini, P. E. U. D., Astuti, K. W., & Warditiani, N. K. (2013). Uji fitokimia ekstrak etil asetat rimpang bangle (Zingiber purpureum Roxb). Jurnal Farmasi Udayana 2(4), 6-12. https://ojs.unud.ac.id/index.php/jfu/article/view/7396.
Arulanandam, C. D., Hwang, J. S., Rathinam, A. J., & Dahms, H. U. (2022). Evaluating different web applications to assess the toxicity of plasticizers. Scientific reports, 12(1), 19684. https://doi.org/10.1038/s41598-022-18327-0.
Aswad, M., Christine, L., Nursamsiar, N., & Hardianti, B. (2020). Studi penambatan molekul senyawa-senyawa bioaktif dari kulit akar murbei (Morus sp.) terhadap reseptor TNF-α. Majalah Farmasi dan Farmakologi, 23(3), 85-100. https://doi.org/10.20956/mff.v23i3.9399.
Banerjee P., Eckert A. O., Schrey A. K., & Preissner R. (2018). Protox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(1), 257-263. 10.1093/nar/gky31.
Basson A. R., Chen, C., Sag F., Trotter A., Bederman I., Nguyen A. G., Sundrud M. S., Ilic S., Cominelli F., & Palacios A. R. (2021). Regulation of intestinal inflammation by dietary fats. Frontiers in Immunology, 11, 604989. 10.3389/fimmu.2020.604989.
Benet L.Z., Hosey C. M., Ursu O., & Oprea T. I. (2016). BDDCS, the rule of 5 and drugability. Adv Drug Deliv Rev, 101, 89-98. 10.1016/j.addr.2016.05.007.
Bhardwaj M., Sali V. K., Mani S., & Vasanthi H. R. (2020). Correction to: neophytadiene from Turbinaria ornata suppresses lps-induced inflammatory response in raw 264.7 macrophages and sprague dawley rats. Inflammation, 43(3), 1-2. https://doi.org/10.1007/s10753-020-01179-z.
Boden G. (2011). Obesity, insulin resistance and free fatty acids. Current opinion in endocrinology, diabetes, and obesity, 18(2), 139–143. https://doi.org/10.1097/MED.0b013e3283444b09.
Bouyahya, J., Abrini, A., Et-Touys, Y., Bakri, N., & Dakka. (2017). Indigenous knowledge of the use of medicinal plants in the North-West of Morocco and their biological activities. European Journal of Integrative Medicine, 13, 9-25. https://doi.org/10.1016/J.EUJIM.2017.06.004.
Burdock, G. A., & Carabin, I. G. (2007). Safety assessment of myristic acid as a food ingredient. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 45(4), 517–529. 10.1016/j.fct.2006.10.009.
Calder P. C. (2013). Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology?. British journal of clinical pharmacology, 75(3), 645–662. https://doi.org/10.1111/j.1365-2125.2012.04374.x.
Chander S., Tang C. R., Al-Maqtari H. M., Jamalis J., Penta A., Hadda T. B., Sirat H. M., Zheng Y. T., & Sankaranarayanan M. (2017). Synthesis and study of antiHIV-1 RT activity of 5-benzoyl 4-methyl 1,3,4,5-tetrahydro 2h-1,5-benzodiazepin-2-one derivatives. Bioorga-nic Chemistry, 72, 74-9. 10.1016/j.bioorg.2017.03.013.
Chen, M., Suzuki, A., Thakkar, S., Yu, K., Hu, C., & Tong, W. (2016). DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug discovery today, 21(4), 648–653. https://doi.org/10.1016/j.drudis.2016.02.015.
Cook, M., Lin, H., Mishra, S. K., & Wang, G. Y. (2022). BAY 11-7082 inhibits the secretion of interleukin-6 by senescent human microglia. Biochemical and biophysical research communications, 617(Pt 1), 30–35. 10.1016/j.bbrc.2022.05.090.
Daggupati, T., Chitrala, K., Pamanji, R., & Yeguvapalli, S. (20170. Molecular screening and analysis of novel therapeutic inhibitors against c-Jun N-terminal kinase. Med Chem Res 26, 2112–2118. 10.1007/s00044-017-1919-5.
Dahibhate N. L., Dwivedib P., & Kumara K. (2022). GC-MS and UHPLC-HRMS based metabolite profiling of Bruguiera gymnorhiza reveals key bioactive compounds. South African Journal of Botany, 149, 1044-1048. 10.1016/j.sajb.2022.02.004
Daina A., Michielin O., & Zoete V. (2017). Swissadme: a free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules. Scientific Reports 7, 42717. 10.1038/srep42717.
Dia S. P. S., Nurjanah, & Jacoeb A. M. (2015). Komposisi kimia dan aktivitas antioksidan akar, kulit batang dan daun lindur. JPHPI, 18(2), 205-219. 10.17844/jphpi.2015.18.2.205.
European Chemicals Agency. https://echa.europa.eu/.
Di Marzo V. (2008). Endocannabinoids: synthesis and degradation. Reviews of physiology, biochemistry and pharmacology, 160, 1–24. https://doi.org/10.1007/112_0505.
Filimonov, D.A., Lagunin, A.A., Gloriozova, T., Rudik, A.V., Druzhilovskii, D.S., Pogodin, P.V., Pogodin, P.V., Poroikov, V.V., & Poroikov, V.V. (2014). Prediction of the Biological Activity Spectra of Organic Compounds Using the Pass Online Web Resource. Chemistry of Heterocyclic Compounds, 50(3), 444-457. 10.1007/s10593-014-1496-1.
Finch, A. J., & Pillans, P. I. (2014). P-glycoprotein and its role in drug-drug interactions. Australian Prescriber, 37(4), 137-139. 10.18773/austprescr.2014.050.
Gadaleta, D., Vuković, K., Toma, C.,. Lavado, G. J., Karmaus, A. L., Mansouri, K., Kleinstreuer, N. C., Benfenati, E., & Roncaglioni, A. (2019). SAR and QSAR modeling of a large collection of LD50 rat acute oral toxicity data. Journal of Cheminformatics, 11, 5. https://doi.org/10.1186/s13321-019-0383-2.
Gamble, C., McIntosh, K., Scott, R., Ho, K. H., Plevin, R., & Paul, A. (2012). Inhibitory kappa B Kinases as targets for pharmacological regulation. British journal of pharmacology, 165(4), 802–819. 10.1111/j.1476-5381.2011.01608.x.
Gan, J., Guo, L., Zhang, X., Yu, Q., Yang, Q., Zhang, Y., Zeng, W., Jiang, X., & Guo, M. (2023). Anti-inflammatory therapy of atherosclerosis: focusing on IKKβ. Journal of inflammation (London, England), 20(1), 8. https://doi.org/10.1186/s12950-023-00330-5.
Geldenhuys W. J., Mohammad A. S., Adkins C. E., & Lockman P. R. (2015). Molecular determinants of blood– brain barrier permeation. Ther Deliv, 6, 961-971. https://doi.org/10.4155%2Ftde.15.32.
Gil, J. A., Magro, A. S., Garcia J. A. M., Cristobal M. S., Gil S. A., Canteli M. C., Santano M. N., Chacón G. M., Fuentes J. M., Santos A., & Castilo A. P. (2022). Neuroprotective and anti-inflammatory effects of linoleic acid in models of parkinson’s disease: the implication of lipid droplets and lipophagy. Cells, 2297(11), 1-24. https://doi.org/10.3390/cells11152297.
Giorgini, M., Taroncher, M., Ruiz, M. J., Rodríguez-Carrasco, Y., & Tolosa, J. (2023). In Vitro and Predictive Computational Toxicology Methods for the Neurotoxic Pesticide Amitraz and Its Metabolites. Brain sciences, 13(2), 252. 10.3390/brainsci13020252.
Hähnke, V. D., Kim, S., & Bolton, E. E. (2018). PubChem chemical structure standardization. Journal of cheminformatics, 10(1), 36. 10.1186/s13321-018-0293-8.
Hayden, M. S., & Ghosh, S. (2008). Shared principles in NF-kappaB signaling. Cell, 132(3), 344–362. 10.1016/j.cell.2008.01.020
Huang, H. J., Lee, Y. H., Hsu, Y. H., Liao, C. T., Lin, Y. F., & Chiu, H. W. (2021). Current Strategies in Assessment of Nanotoxicity: Alternatives to In Vivo Animal Testing. International journal of molecular sciences, 22(8), 4216. https://doi.org/10.3390/ijms22084216.
Huxford, T., Hoffmann, A., & Ghosh, G. (2011). Understanding the logic of IκB:NF-κB regulation in structural terms. Current topics in microbiology and immunology, 349, 1–24. 10.1007/82_2010_99.
Hwangbo, Ji H. S. Y., Kim M. Y., Kim S. Y., Lee H., Kim G., Kim S., Cheong J., & Choi Y. H. (2021). Anti‐Inflammatory effect of auranofin on palmitic acid and lps‐induced inflammatory response by modulating tlr4 and nox4‐mediated Nf‐Kb signaling pathway in raw264.7 macrophages. International Journal of Molecular Sciences, 22, 5920. https://doi.org/10.3390/ ijms22115920.
Jacoeb A. M., Suptijah P., & Zahidah. (2013). Komposisi kimia, komponen bioaktif dan aktivitas antioksidan buah lindur (Bruguiera gymnorrhiza). Jurnal Pengolahan Hasil Perikanan Indonesia, 16(1), 86-94. https://doi.org/10.17844/jphpi.v16i1.7772.
Khongthong, P., Roseweir, A. K., & Edwards, J. (2019). The NF-KB pathway and endocrine therapy resistance in breast cancer. Endocrine-related cancer, 26(6), R369–R380. https://doi.org/10.1530/ERC-19-0087.
Klos, A., Tenner, A. J., Johswich, K. O., Ager, R. R., Reis, E. S., & Köhl, J. (2009). The role of the anaphylatoxins in health and disease. Molecular immunology, 46(14), 2753–2766, doi: 10.1016/j.molimm.2009.04.027.
Korbecki, J. & Bajdak-Rusine, K. (2019). The efect of palmitic acid on infammatory response in macrophages: an overview of molecular mechanisms. Infammation Research. 68: 915–932. https://doi.org/10.1007/s00011-019-01273-5.
Lagunin, A., Stepanchikova, A., Filimonov, D., & Poroikov, V. (2000). PASS: prediction of activity spectra for biologically active substances , Bioinformatics, 1698):747–748. https://doi.org/10.1093/bioinformatics/16.8.747.
Leiba, J., Özbilgiç, R., Hernández, L., Demou, M., Lutfalla, G., Yatime, L., & Nguyen-Chi, M. (2023). Molecular Actors of Inflammation and Their Signaling Pathways: Mechanistic Insights from Zebrafish. Biology, 12(2), 153. 10.3390/biology12020153.
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46(3), 3-26. 10.1016/s0169-409x(00)00129-0.
Mahla, R. S., Reddy, M. C., Prasad, D. V., & Kumar, H. (2013). Sweeten PAMPs: role of sugar complexed pamps in innate immunity and vaccine biology. Frontiers in immunology, 4, 248. 10.3389/fimmu.2013.00248.
Makin, F. M. P. R., Tnunay, I. M. Y., & Wiguna, G. A. (2023). GC-MS (Gas Chromatography-Mass Spectrometry) metabolit sekunder ekstrak etanol dan metanol daun kirinyuh (Chromolaena odorata L.). Bioscientist : Jurnal Ilmiah Biologi. 11(1): 194-202. 10.33394/bioscientist.v11i1.6519.
Martiny, Virginie Y., Miteva, & Maria A. (2013). Advances in molecular modeling of human cytochrome P450 polymorphism. J. Mol. Biol. 425, 3978-3992. https://doi.org/ b.10.1016/j.jmB2013.07.010.
Meng, X. Y., Zhang, H. X., Mezei, M., & Cui, M. (2011). Molecular docking: a powerful approach for structure-based drug discovery. Current computer-aided drug design, 7(2), 146–157. https://doi.org/10.2174/157340911795677602.
Mondello, L., Tranchida, P. Q., Dugo, P., & Dugo, G. (2008). Comprehensive two-dimensional gas chromatography-mass spectrometry: a review. Mass spectrometry reviews, 27(2), 101–124. https://doi.org/10.1002/mas.20158.
Mulero, M. C., Huxford, T., & Ghosh, G. (2019). NF-κB, IκB, and IKK: Integral components of immune system signaling. Advances in experimental medicine and biology, 1172, 207–226. 10.1007/978-981-13-9367-9_10.
Ononamadu, C. J., & Ibrahim, A. (2021). Molecular docking and prediction of ADME/drug-likeness properties of potentially active antidiabetic compounds isolated from aqueous-methanol extracts of Gymnema sylvestre and Combretum micranthum. Biotechnologia, 102(1), 85–99. 10.5114/bta.2021.103765.
Pan P., Lin S., Ou Y., Chen W., Chuang Y., Yen Y., Liao S., Raung S., & Chen C. (2010). Stearic acid attenuates cholestasis-induced liver injury. Biochemical and Biophysical Research Communications, 391, 1537-1542. 10.1016/j.bbrc.2009.12.119.
Pinzi, L., & Rastelli, G. (2019). Molecular Docking: Shifting Paradigms in Drug Discovery. International journal of molecular sciences, 20(18), 4331. https://doi.org/10.3390/ijms20184331.
Pires D. E. V., Blundell T. L., & Ascher D. B. (2015). pkCSM: predicting smallmolecule pharmacokinetic and toxicity properties using graphbased signatures. J Med Chem, 58, 4066-4072. https://doi.org/10.1021/acs.jmedchem.5b00104.
Pratama, A. A., Rifai, Y., & Marzuki, A. (2017). Docking molekuler senyawa 5,5’-dibromometilsesamin. Majalah Farmasi dan Farmakologi, 21(3), 67-69. https://doi.org/10.20956/mff.v21i3.6857.
Pu, L., Govindaraj, R. G., Lemoine, J. M., Wu, H. C., & Brylinski, M. (2019). DeepDrug3D: Classification of ligand-binding pockets in proteins with a convolutional neural network. PLoS computational biology, 15(2), e1006718. https://doi.org/10.1371/journal.pcbi.1006718.
Riyadi P. H., Dewi E. N., Anggo A. D., & Damayanti A. (2023). In silico analysis of the potential of Sargassum sp brewed and Syzygium polyanthum leaf as nutraceuticals. AIP Conference Proceedings, 2586, 060015. https://doi.org/10.1063/5.0112747.
Riyadi P. H., Romadhon, Sari I. D., Kurniasih R. A., Agustini T. W., Swastawati F., Herawati V. E., & Tanod W. A. (2021) SwissADME predictions of pharmacokinetics and druglikeness properties of small molecules present in Spirulina platensis. Earth and Environmental Science 890, 012021. 10.1088/1755-1315/890/1/012021.
Riyadi P. H., Tanod W. A., Wahyudi D., Susanto E., Fahmi A. S. &, Aisiah S. (2020). Potential of tilapia (Oreochromis niloticus) viscera bioactive peptides as antiviral for SARS-CoV-2 (COVID 19), in international conference on fisheries and marine, IOP Conference Series: Earth and Environmental Science, 58(19), 1-15. 10.1088/1755-1315/584/1/012004.
Rochmadi I., & Rohmah S. (2019). Pemanfaatan buah pandan laut sebagai pangan olahan pada masyarakat pesisir. Jurnal Riset Ekonomi Pembangunan, 4(2), 161-173. http://dx.doi.org/10.31002/rep.v4i2.1953.
Sakib S. A., Tareq A. M., Islam A., Rakib A., Islam M. N., Uddin M. A., Rahman M. M., Seidel V., & Emran T. B. (2021). Anti-Inflammatory, thrombolytic and hair-growth promoting activity of the n-hexane fraction of the methanol extract of Leea indica leaves. Plants, 10, 1081. https://doi.org/10.3390/ plants10061081.
Safa, A. N., Sheibani, A., Baei, M. T., Sayyed-Alangi, S. Z., & Tazikeh Lemeski, E. (2023). Theoretical and experimental studies on sulfasalazine interactions with poly (lactic acid): Impact of hydrogen bonding and charge transfer interactions on molecular structure, electronic and optical properties. Heliyon, 10(1), e23813. https://doi.org/10.1016/j.heliyon.2023.e23813
Sánchez-Quesada, C., López-Biedma, A., Toledo, E., & Gaforio J. J. (2018). Squalene stimulates a key innate immune cell to foster wound healing and tissue repair. Evidence-Based Complement Altern Med. 2018:1-9. doi:10.1155/2018/9473094.
Sergeant, S., Keith, B. A., Seeds, M. C., Legins, J. A., Young, C. B., Vitolins, M. Z., & Chilton, F. H. (2023). Impact of FADS gene variation and dietary fatty acid exposure on biochemical and anthropomorphic phenotypes in a Hispanic/Latino cohort. Frontiers in nutrition, 10, 1111624. https://doi.org/10.3389/fnut.2023.1111624
Setiawan F. F., & Istyastomo E. P. (2015). Uji in silico senyawa 2, 6- dihidroksi antrakuinon sebagai ligan pada reseptor estrogen alfa. Jurnal Farmasi Sains dan Komunitas, 12(2), 77-80. https://doi.org/10.24071/jpsc.00137.
Shariare, M. H., Noor, H. B., Khan, J. H., Uddin, J., Ahamad, S. R., Altamimi, M. A., Alanazi, F. K., & Kaz, M. (2021). Liposomal drug delivery of Corchorus olitorius leaf extract containing phytol using design of experiment (DoE): In-vitro anticancer and in-vivo anti-inflammatory studies. Colloids and Surfaces B: Biointerfaces, 199, 111543. https://doi.org/10.1016/j.colsurfb.2020.111543.
Sharom F. J. (2011). The P-glycoprotein multidrug transporter. Essays in biochemistry, 50(1), 161–178. https://doi.org/10.1042/bse0500161.
Shofa, A. F., Lestari, A. F., Soputri, H. A., & Safenti, K. (2022). Studi penambatan maya dan prediksi toksisitas turunan 5-fluorouridin monofosfat pada enzim orotidin-5-monofosfat dekarboksilase. Pharmaceutical and Biomedical Sciences Journal (PBSJ), 3(2), 91-98. https://doi.org/10.15408/pbsj.v3i2.24524.
Smith, C. A., Want, E. J., O'Maille, G., Abagyan, R., & Siuzdak, G. (2006). XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Analytical chemistry, 78(3), 779–787. https://doi.org/10.1021/ac051437y.
Spector, A. A., & Kim, H. Y. (2015). Discovery of essential fatty acids. Journal of lipid research, 56(1), 11–21. https://doi.org/10.1194/jlr.R055095.
Sun S. C. (2012). The noncanonical NF-κB pathway. Immunological reviews, 246(1), 125–140. 10.1111/j.1600-065X.2011.01088.x.
Takeuchi, O., & Akira, S. (2010). Pattern recognition receptors and inflammation. Cell, 140(6), 805–820. 10.1016/j.cell.2010.01.022.
Testa, B., & Krämer, S. D. (2007). The biochemistry of drug metabolism--an introduction: Part 2. Redox reactions and their enzymes. Chemistry & biodiversity, 4(3), 257-405. https://doi.org/10.1002/cbdv.200790032.
Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334.
Wang, Y., Zhu, L., Zeng, D., Long, W., & Zhu, S. (2016). Chemical composition and anti-inflammatory activities of essential oil from Trachydium roylei. Journal of Food and Drug Analysis, 24, 602-609. http://dx.doi.org/10.1016/j.jfda.2016.02.009.
Weber, C. K., Liptay, S., Wirth, T., Adler, G., & Schmid, R. M. (2000). Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology, 119(5), 1209–1218. 10.1053/gast.2000.19458.
Williams, P., Cosme, J., Ward, A., Angove, H. C., Matak, V. D., Jhoti, H. (2003). Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature, 424, 464–468. https://doi.org/10.1038/nature01862.
Yang, H., Sun, L., Li, W., Liu G., & Tang, Y. (2018). In silico prediction of chemical toxicity for drug design using machine learning methods and structural alerts. Frontiers in Chemistry, 6, 1-12. 10.3389/fchem.2018.00030.
Zhang, Q. W., Lin, L. G., & Ye, W. C. (2018.) Techniques For Extraction and Isolation of Natural Products: A Comprehensive Review. Chinese Medicine, 13(1), 1-26. https://doi.org/10.1186/s13020-018-0177-x.
Zhu, Z., Chen, J., & Zheng, H. L. (2012). Physiological and proteomic characterization of salt tolerance in a mangrove plant, Bruguiera gymnorrhiza (L.) Lam. Tree Physiology, 32(11), 1378–1388. https:// doi.org/10.1093/treephys/tps097.
Amaya, M., Keck, F., Bailey, C., & Narayanan, A. (2014). The role of the IKK complex in viral infections. Pathogens and disease, 72(1), 32–44. 10.1111/2049-632X.12210.
Amirah, S., Kosman, R., & Novianti, Y. R. (2014). uji efek anti-inflamasi ekstrak n-butanol dan etil asetat daun petai cina (Leucaena leucocephala (Lamk.) De Wit) pada mencit jantan (Mus musculus) yang diinduksi dengan karagen. Jurnal Bionature, 15(2): 123-126. https://doi.org/10.35580/bionature.v15i2.1559.
Ano, Y., Ozawa, M., Kutsukake, T., Sugiyama, S., Uchida, K., Yoshida, A., & Nakayama, H. (2015). Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity. PloS one, 10(3). 10.1371/journal.pone.0118512.
Artini, P. E. U. D., Astuti, K. W., & Warditiani, N. K. (2013). Uji fitokimia ekstrak etil asetat rimpang bangle (Zingiber purpureum Roxb). Jurnal Farmasi Udayana 2(4), 6-12. https://ojs.unud.ac.id/index.php/jfu/article/view/7396.
Arulanandam, C. D., Hwang, J. S., Rathinam, A. J., & Dahms, H. U. (2022). Evaluating different web applications to assess the toxicity of plasticizers. Scientific reports, 12(1), 19684. https://doi.org/10.1038/s41598-022-18327-0.
Aswad, M., Christine, L., Nursamsiar, N., & Hardianti, B. (2020). Studi penambatan molekul senyawa-senyawa bioaktif dari kulit akar murbei (Morus sp.) terhadap reseptor TNF-α. Majalah Farmasi dan Farmakologi, 23(3), 85-100. https://doi.org/10.20956/mff.v23i3.9399.
Banerjee P., Eckert A. O., Schrey A. K., & Preissner R. (2018). Protox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(1), 257-263. 10.1093/nar/gky31.
Basson A. R., Chen, C., Sag F., Trotter A., Bederman I., Nguyen A. G., Sundrud M. S., Ilic S., Cominelli F., & Palacios A. R. (2021). Regulation of intestinal inflammation by dietary fats. Frontiers in Immunology, 11, 604989. 10.3389/fimmu.2020.604989.
Benet L.Z., Hosey C. M., Ursu O., & Oprea T. I. (2016). BDDCS, the rule of 5 and drugability. Adv Drug Deliv Rev, 101, 89-98. 10.1016/j.addr.2016.05.007.
Bhardwaj M., Sali V. K., Mani S., & Vasanthi H. R. (2020). Correction to: neophytadiene from Turbinaria ornata suppresses lps-induced inflammatory response in raw 264.7 macrophages and sprague dawley rats. Inflammation, 43(3), 1-2. https://doi.org/10.1007/s10753-020-01179-z.
Boden G. (2011). Obesity, insulin resistance and free fatty acids. Current opinion in endocrinology, diabetes, and obesity, 18(2), 139–143. https://doi.org/10.1097/MED.0b013e3283444b09.
Bouyahya, J., Abrini, A., Et-Touys, Y., Bakri, N., & Dakka. (2017). Indigenous knowledge of the use of medicinal plants in the North-West of Morocco and their biological activities. European Journal of Integrative Medicine, 13, 9-25. https://doi.org/10.1016/J.EUJIM.2017.06.004.
Burdock, G. A., & Carabin, I. G. (2007). Safety assessment of myristic acid as a food ingredient. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 45(4), 517–529. 10.1016/j.fct.2006.10.009.
Calder P. C. (2013). Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology?. British journal of clinical pharmacology, 75(3), 645–662. https://doi.org/10.1111/j.1365-2125.2012.04374.x.
Chander S., Tang C. R., Al-Maqtari H. M., Jamalis J., Penta A., Hadda T. B., Sirat H. M., Zheng Y. T., & Sankaranarayanan M. (2017). Synthesis and study of antiHIV-1 RT activity of 5-benzoyl 4-methyl 1,3,4,5-tetrahydro 2h-1,5-benzodiazepin-2-one derivatives. Bioorga-nic Chemistry, 72, 74-9. 10.1016/j.bioorg.2017.03.013.
Chen, M., Suzuki, A., Thakkar, S., Yu, K., Hu, C., & Tong, W. (2016). DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug discovery today, 21(4), 648–653. https://doi.org/10.1016/j.drudis.2016.02.015.
Cook, M., Lin, H., Mishra, S. K., & Wang, G. Y. (2022). BAY 11-7082 inhibits the secretion of interleukin-6 by senescent human microglia. Biochemical and biophysical research communications, 617(Pt 1), 30–35. 10.1016/j.bbrc.2022.05.090.
Daggupati, T., Chitrala, K., Pamanji, R., & Yeguvapalli, S. (20170. Molecular screening and analysis of novel therapeutic inhibitors against c-Jun N-terminal kinase. Med Chem Res 26, 2112–2118. 10.1007/s00044-017-1919-5.
Dahibhate N. L., Dwivedib P., & Kumara K. (2022). GC-MS and UHPLC-HRMS based metabolite profiling of Bruguiera gymnorhiza reveals key bioactive compounds. South African Journal of Botany, 149, 1044-1048. 10.1016/j.sajb.2022.02.004
Daina A., Michielin O., & Zoete V. (2017). Swissadme: a free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules. Scientific Reports 7, 42717. 10.1038/srep42717.
Dia S. P. S., Nurjanah, & Jacoeb A. M. (2015). Komposisi kimia dan aktivitas antioksidan akar, kulit batang dan daun lindur. JPHPI, 18(2), 205-219. 10.17844/jphpi.2015.18.2.205.
European Chemicals Agency. https://echa.europa.eu/.
Di Marzo V. (2008). Endocannabinoids: synthesis and degradation. Reviews of physiology, biochemistry and pharmacology, 160, 1–24. https://doi.org/10.1007/112_0505.
Filimonov, D.A., Lagunin, A.A., Gloriozova, T., Rudik, A.V., Druzhilovskii, D.S., Pogodin, P.V., Pogodin, P.V., Poroikov, V.V., & Poroikov, V.V. (2014). Prediction of the Biological Activity Spectra of Organic Compounds Using the Pass Online Web Resource. Chemistry of Heterocyclic Compounds, 50(3), 444-457. 10.1007/s10593-014-1496-1.
Finch, A. J., & Pillans, P. I. (2014). P-glycoprotein and its role in drug-drug interactions. Australian Prescriber, 37(4), 137-139. 10.18773/austprescr.2014.050.
Gadaleta, D., Vuković, K., Toma, C.,. Lavado, G. J., Karmaus, A. L., Mansouri, K., Kleinstreuer, N. C., Benfenati, E., & Roncaglioni, A. (2019). SAR and QSAR modeling of a large collection of LD50 rat acute oral toxicity data. Journal of Cheminformatics, 11, 5. https://doi.org/10.1186/s13321-019-0383-2.
Gamble, C., McIntosh, K., Scott, R., Ho, K. H., Plevin, R., & Paul, A. (2012). Inhibitory kappa B Kinases as targets for pharmacological regulation. British journal of pharmacology, 165(4), 802–819. 10.1111/j.1476-5381.2011.01608.x.
Gan, J., Guo, L., Zhang, X., Yu, Q., Yang, Q., Zhang, Y., Zeng, W., Jiang, X., & Guo, M. (2023). Anti-inflammatory therapy of atherosclerosis: focusing on IKKβ. Journal of inflammation (London, England), 20(1), 8. https://doi.org/10.1186/s12950-023-00330-5.
Geldenhuys W. J., Mohammad A. S., Adkins C. E., & Lockman P. R. (2015). Molecular determinants of blood– brain barrier permeation. Ther Deliv, 6, 961-971. https://doi.org/10.4155%2Ftde.15.32.
Gil, J. A., Magro, A. S., Garcia J. A. M., Cristobal M. S., Gil S. A., Canteli M. C., Santano M. N., Chacón G. M., Fuentes J. M., Santos A., & Castilo A. P. (2022). Neuroprotective and anti-inflammatory effects of linoleic acid in models of parkinson’s disease: the implication of lipid droplets and lipophagy. Cells, 2297(11), 1-24. https://doi.org/10.3390/cells11152297.
Giorgini, M., Taroncher, M., Ruiz, M. J., Rodríguez-Carrasco, Y., & Tolosa, J. (2023). In Vitro and Predictive Computational Toxicology Methods for the Neurotoxic Pesticide Amitraz and Its Metabolites. Brain sciences, 13(2), 252. 10.3390/brainsci13020252.
Hähnke, V. D., Kim, S., & Bolton, E. E. (2018). PubChem chemical structure standardization. Journal of cheminformatics, 10(1), 36. 10.1186/s13321-018-0293-8.
Hayden, M. S., & Ghosh, S. (2008). Shared principles in NF-kappaB signaling. Cell, 132(3), 344–362. 10.1016/j.cell.2008.01.020
Huang, H. J., Lee, Y. H., Hsu, Y. H., Liao, C. T., Lin, Y. F., & Chiu, H. W. (2021). Current Strategies in Assessment of Nanotoxicity: Alternatives to In Vivo Animal Testing. International journal of molecular sciences, 22(8), 4216. https://doi.org/10.3390/ijms22084216.
Huxford, T., Hoffmann, A., & Ghosh, G. (2011). Understanding the logic of IκB:NF-κB regulation in structural terms. Current topics in microbiology and immunology, 349, 1–24. 10.1007/82_2010_99.
Hwangbo, Ji H. S. Y., Kim M. Y., Kim S. Y., Lee H., Kim G., Kim S., Cheong J., & Choi Y. H. (2021). Anti‐Inflammatory effect of auranofin on palmitic acid and lps‐induced inflammatory response by modulating tlr4 and nox4‐mediated Nf‐Kb signaling pathway in raw264.7 macrophages. International Journal of Molecular Sciences, 22, 5920. https://doi.org/10.3390/ ijms22115920.
Jacoeb A. M., Suptijah P., & Zahidah. (2013). Komposisi kimia, komponen bioaktif dan aktivitas antioksidan buah lindur (Bruguiera gymnorrhiza). Jurnal Pengolahan Hasil Perikanan Indonesia, 16(1), 86-94. https://doi.org/10.17844/jphpi.v16i1.7772.
Khongthong, P., Roseweir, A. K., & Edwards, J. (2019). The NF-KB pathway and endocrine therapy resistance in breast cancer. Endocrine-related cancer, 26(6), R369–R380. https://doi.org/10.1530/ERC-19-0087.
Klos, A., Tenner, A. J., Johswich, K. O., Ager, R. R., Reis, E. S., & Köhl, J. (2009). The role of the anaphylatoxins in health and disease. Molecular immunology, 46(14), 2753–2766, doi: 10.1016/j.molimm.2009.04.027.
Korbecki, J. & Bajdak-Rusine, K. (2019). The efect of palmitic acid on infammatory response in macrophages: an overview of molecular mechanisms. Infammation Research. 68: 915–932. https://doi.org/10.1007/s00011-019-01273-5.
Lagunin, A., Stepanchikova, A., Filimonov, D., & Poroikov, V. (2000). PASS: prediction of activity spectra for biologically active substances , Bioinformatics, 1698):747–748. https://doi.org/10.1093/bioinformatics/16.8.747.
Leiba, J., Özbilgiç, R., Hernández, L., Demou, M., Lutfalla, G., Yatime, L., & Nguyen-Chi, M. (2023). Molecular Actors of Inflammation and Their Signaling Pathways: Mechanistic Insights from Zebrafish. Biology, 12(2), 153. 10.3390/biology12020153.
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46(3), 3-26. 10.1016/s0169-409x(00)00129-0.
Mahla, R. S., Reddy, M. C., Prasad, D. V., & Kumar, H. (2013). Sweeten PAMPs: role of sugar complexed pamps in innate immunity and vaccine biology. Frontiers in immunology, 4, 248. 10.3389/fimmu.2013.00248.
Makin, F. M. P. R., Tnunay, I. M. Y., & Wiguna, G. A. (2023). GC-MS (Gas Chromatography-Mass Spectrometry) metabolit sekunder ekstrak etanol dan metanol daun kirinyuh (Chromolaena odorata L.). Bioscientist : Jurnal Ilmiah Biologi. 11(1): 194-202. 10.33394/bioscientist.v11i1.6519.
Martiny, Virginie Y., Miteva, & Maria A. (2013). Advances in molecular modeling of human cytochrome P450 polymorphism. J. Mol. Biol. 425, 3978-3992. https://doi.org/ b.10.1016/j.jmB2013.07.010.
Meng, X. Y., Zhang, H. X., Mezei, M., & Cui, M. (2011). Molecular docking: a powerful approach for structure-based drug discovery. Current computer-aided drug design, 7(2), 146–157. https://doi.org/10.2174/157340911795677602.
Mondello, L., Tranchida, P. Q., Dugo, P., & Dugo, G. (2008). Comprehensive two-dimensional gas chromatography-mass spectrometry: a review. Mass spectrometry reviews, 27(2), 101–124. https://doi.org/10.1002/mas.20158.
Mulero, M. C., Huxford, T., & Ghosh, G. (2019). NF-κB, IκB, and IKK: Integral components of immune system signaling. Advances in experimental medicine and biology, 1172, 207–226. 10.1007/978-981-13-9367-9_10.
Ononamadu, C. J., & Ibrahim, A. (2021). Molecular docking and prediction of ADME/drug-likeness properties of potentially active antidiabetic compounds isolated from aqueous-methanol extracts of Gymnema sylvestre and Combretum micranthum. Biotechnologia, 102(1), 85–99. 10.5114/bta.2021.103765.
Pan P., Lin S., Ou Y., Chen W., Chuang Y., Yen Y., Liao S., Raung S., & Chen C. (2010). Stearic acid attenuates cholestasis-induced liver injury. Biochemical and Biophysical Research Communications, 391, 1537-1542. 10.1016/j.bbrc.2009.12.119.
Pinzi, L., & Rastelli, G. (2019). Molecular Docking: Shifting Paradigms in Drug Discovery. International journal of molecular sciences, 20(18), 4331. https://doi.org/10.3390/ijms20184331.
Pires D. E. V., Blundell T. L., & Ascher D. B. (2015). pkCSM: predicting smallmolecule pharmacokinetic and toxicity properties using graphbased signatures. J Med Chem, 58, 4066-4072. https://doi.org/10.1021/acs.jmedchem.5b00104.
Pratama, A. A., Rifai, Y., & Marzuki, A. (2017). Docking molekuler senyawa 5,5’-dibromometilsesamin. Majalah Farmasi dan Farmakologi, 21(3), 67-69. https://doi.org/10.20956/mff.v21i3.6857.
Pu, L., Govindaraj, R. G., Lemoine, J. M., Wu, H. C., & Brylinski, M. (2019). DeepDrug3D: Classification of ligand-binding pockets in proteins with a convolutional neural network. PLoS computational biology, 15(2), e1006718. https://doi.org/10.1371/journal.pcbi.1006718.
Riyadi P. H., Dewi E. N., Anggo A. D., & Damayanti A. (2023). In silico analysis of the potential of Sargassum sp brewed and Syzygium polyanthum leaf as nutraceuticals. AIP Conference Proceedings, 2586, 060015. https://doi.org/10.1063/5.0112747.
Riyadi P. H., Romadhon, Sari I. D., Kurniasih R. A., Agustini T. W., Swastawati F., Herawati V. E., & Tanod W. A. (2021) SwissADME predictions of pharmacokinetics and druglikeness properties of small molecules present in Spirulina platensis. Earth and Environmental Science 890, 012021. 10.1088/1755-1315/890/1/012021.
Riyadi P. H., Tanod W. A., Wahyudi D., Susanto E., Fahmi A. S. &, Aisiah S. (2020). Potential of tilapia (Oreochromis niloticus) viscera bioactive peptides as antiviral for SARS-CoV-2 (COVID 19), in international conference on fisheries and marine, IOP Conference Series: Earth and Environmental Science, 58(19), 1-15. 10.1088/1755-1315/584/1/012004.
Rochmadi I., & Rohmah S. (2019). Pemanfaatan buah pandan laut sebagai pangan olahan pada masyarakat pesisir. Jurnal Riset Ekonomi Pembangunan, 4(2), 161-173. http://dx.doi.org/10.31002/rep.v4i2.1953.
Sakib S. A., Tareq A. M., Islam A., Rakib A., Islam M. N., Uddin M. A., Rahman M. M., Seidel V., & Emran T. B. (2021). Anti-Inflammatory, thrombolytic and hair-growth promoting activity of the n-hexane fraction of the methanol extract of Leea indica leaves. Plants, 10, 1081. https://doi.org/10.3390/ plants10061081.
Safa, A. N., Sheibani, A., Baei, M. T., Sayyed-Alangi, S. Z., & Tazikeh Lemeski, E. (2023). Theoretical and experimental studies on sulfasalazine interactions with poly (lactic acid): Impact of hydrogen bonding and charge transfer interactions on molecular structure, electronic and optical properties. Heliyon, 10(1), e23813. https://doi.org/10.1016/j.heliyon.2023.e23813
Sánchez-Quesada, C., López-Biedma, A., Toledo, E., & Gaforio J. J. (2018). Squalene stimulates a key innate immune cell to foster wound healing and tissue repair. Evidence-Based Complement Altern Med. 2018:1-9. doi:10.1155/2018/9473094.
Sergeant, S., Keith, B. A., Seeds, M. C., Legins, J. A., Young, C. B., Vitolins, M. Z., & Chilton, F. H. (2023). Impact of FADS gene variation and dietary fatty acid exposure on biochemical and anthropomorphic phenotypes in a Hispanic/Latino cohort. Frontiers in nutrition, 10, 1111624. https://doi.org/10.3389/fnut.2023.1111624
Setiawan F. F., & Istyastomo E. P. (2015). Uji in silico senyawa 2, 6- dihidroksi antrakuinon sebagai ligan pada reseptor estrogen alfa. Jurnal Farmasi Sains dan Komunitas, 12(2), 77-80. https://doi.org/10.24071/jpsc.00137.
Shariare, M. H., Noor, H. B., Khan, J. H., Uddin, J., Ahamad, S. R., Altamimi, M. A., Alanazi, F. K., & Kaz, M. (2021). Liposomal drug delivery of Corchorus olitorius leaf extract containing phytol using design of experiment (DoE): In-vitro anticancer and in-vivo anti-inflammatory studies. Colloids and Surfaces B: Biointerfaces, 199, 111543. https://doi.org/10.1016/j.colsurfb.2020.111543.
Sharom F. J. (2011). The P-glycoprotein multidrug transporter. Essays in biochemistry, 50(1), 161–178. https://doi.org/10.1042/bse0500161.
Shofa, A. F., Lestari, A. F., Soputri, H. A., & Safenti, K. (2022). Studi penambatan maya dan prediksi toksisitas turunan 5-fluorouridin monofosfat pada enzim orotidin-5-monofosfat dekarboksilase. Pharmaceutical and Biomedical Sciences Journal (PBSJ), 3(2), 91-98. https://doi.org/10.15408/pbsj.v3i2.24524.
Smith, C. A., Want, E. J., O'Maille, G., Abagyan, R., & Siuzdak, G. (2006). XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Analytical chemistry, 78(3), 779–787. https://doi.org/10.1021/ac051437y.
Spector, A. A., & Kim, H. Y. (2015). Discovery of essential fatty acids. Journal of lipid research, 56(1), 11–21. https://doi.org/10.1194/jlr.R055095.
Sun S. C. (2012). The noncanonical NF-κB pathway. Immunological reviews, 246(1), 125–140. 10.1111/j.1600-065X.2011.01088.x.
Takeuchi, O., & Akira, S. (2010). Pattern recognition receptors and inflammation. Cell, 140(6), 805–820. 10.1016/j.cell.2010.01.022.
Testa, B., & Krämer, S. D. (2007). The biochemistry of drug metabolism--an introduction: Part 2. Redox reactions and their enzymes. Chemistry & biodiversity, 4(3), 257-405. https://doi.org/10.1002/cbdv.200790032.
Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334.
Wang, Y., Zhu, L., Zeng, D., Long, W., & Zhu, S. (2016). Chemical composition and anti-inflammatory activities of essential oil from Trachydium roylei. Journal of Food and Drug Analysis, 24, 602-609. http://dx.doi.org/10.1016/j.jfda.2016.02.009.
Weber, C. K., Liptay, S., Wirth, T., Adler, G., & Schmid, R. M. (2000). Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology, 119(5), 1209–1218. 10.1053/gast.2000.19458.
Williams, P., Cosme, J., Ward, A., Angove, H. C., Matak, V. D., Jhoti, H. (2003). Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature, 424, 464–468. https://doi.org/10.1038/nature01862.
Yang, H., Sun, L., Li, W., Liu G., & Tang, Y. (2018). In silico prediction of chemical toxicity for drug design using machine learning methods and structural alerts. Frontiers in Chemistry, 6, 1-12. 10.3389/fchem.2018.00030.
Zhang, Q. W., Lin, L. G., & Ye, W. C. (2018.) Techniques For Extraction and Isolation of Natural Products: A Comprehensive Review. Chinese Medicine, 13(1), 1-26. https://doi.org/10.1186/s13020-018-0177-x.
Zhu, Z., Chen, J., & Zheng, H. L. (2012). Physiological and proteomic characterization of salt tolerance in a mangrove plant, Bruguiera gymnorrhiza (L.) Lam. Tree Physiology, 32(11), 1378–1388. https:// doi.org/10.1093/treephys/tps097.
Authors
Diana F. A. N., Riyadi P. H., & Susanto E. (2024). In silico analysis of Bruguiera gymnorhiza leaf extracts using ethyl acetate as an anti-inflammatory agent: Analisis in silico ekstrak daun Bruguiera gymnorhiza menggunakan etil asetat sebagai agen antiinflamasi. Jurnal Pengolahan Hasil Perikanan Indonesia, 27(9). https://doi.org/10.17844/jphpi.v27i9.54255
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Article Details
