In silico study of bioactive compounds in blue shark (Prionace glauca) cartilage and its extract as anti-inflammatory agents Studi in silico senyawa bioaktif tulang rawan hiu biru (<i>Prionace glauca</i>) dan ekstraknya sebagai agen antiinflamasi
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bioactive compounds, inflammation, LC-HRMS, molecular docking
Abstract
Blue shark (Prionace glauca) cartilage contains various bioactive compounds that may be beneficial to human health. This study aimed to identify bioactive compounds in shark cartilage and evaluate their potential as anti-inflammatory agents by targeting NF-kB p65 and TNF-α convertase. Shark cartilage powder and its extract were analyzed using Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), while ligand-protein interactions were evaluated in silico via molecular docking using Autodock on the NF-kB p65 (PDB ID: 2RAM) and TNF-α convertase (PDB ID: 3EWJ) targets. LC-HRMS analysis identified 64 bioactive compounds in the cartilage powder and 141 in the extract. A total of 20 powdered compounds (powder) and 37 compounds (extract) showed mzCloud Best Match values >80%. Thirteen compounds were successfully identified, including betaine, creatine, hypoxanthine, L-norleucine, choline, caprolactam, nicotinamide, L-phenylalanine, creatinine, guanine, trigonelline, trans-3-indoleacrylic acid, and D-(+)-proline, with isocytosine and lactamide specific to the powder, and 3,5-di-tert-butyl-4-hydroxybenzaldehyde, TEMPO, and piperine specific to the extract. Docking results indicated that l-phenylalanine and trans-3-indoleacrylic acid possess high binding affinities and stably interact with the active sites of NF-kB p65 and TNF-α convertase, potentially inhibiting the pro-inflammatory pathways mediated by these two proteins. These findings indicate that shark cartilage powder and its extract show promise as candidates for anti-inflammatory therapeutic agents with low toxicity potential, which requires further validation in vitro and in vivo studies.
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References
Agustin, T. I., Wahyu, S., & Yatmasari, E. (2016). Study on the bioactive compounds of shark (Prionace glauca) cartilage and its inflammatory activity. International Journal of PharmTech Research, 9(1), 171–178.
Agustin, T., Nursyam, H., Firdaus, M., Rifa’I, M., Ekaputri, I. D., & Mahmiah. (2025). The characterization of blue shark (Prionace glauca) cartilage potential as nature-derived drug material. In IOP Conference Series: Earth and Environmental Science (Vol. 1473). https://doi.org/10.1088/1755-1315/1473/1/012049
Alves, V. M., Muratov, E., Fourches, D., Strickland, J., Kleinstreuer, N., Andrade, C. H., & Tropsha, A. (2015). Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization. Toxicology and Applied Pharmacology, 284(2), 273–280. https://doi.org/10.1016/j.taap.2014.12.013
Banerjee, P., Dehnbostel, F. O., & Preissner, R. (2018). Prediction is a balancing act: Importance of sampling methods to balance sensitivity and specificity of predictive models based on imbalanced chemical data sets. Frontiers in Chemistry, 6(AUG). https://doi.org/10.3389/fchem.2018.00362
Bennion, B. J., Be, N. A., McNerney, M. W., Lao, V., Carlson, E. M., Valdez, C. A., Malfatti, M., Enright, H., Nguyen, T., Lightstone, F., & Carpenter, T. S. (2017). Predicting a drug’s membrane permeability: a computational model validated with in vitro permeability assay data. Journal of Physical Chemistry B, 121(20), 5228–5237. https://doi.org/10.1021/acs.jpcb.7b02914
Castaño-Ortiz, J. M., Gago-Ferrero, P., Barceló, D., Rodríguez-Mozaz, S., & Gil-Solsona, R. (2023). HRMS-based suspect screening of pharmaceuticals and their transformation products in multiple environmental compartments: An alternative to target analysis?. Journal of Hazardous Materials, 465, 132974. https://doi.org/10.1016/j.jhazmat.2023.132974
Chander, S., Tang, C. R., Al-Maqtari, H. M., Jamalis, J., Penta, A., Hadda, T. B., Sirat, H., Zheng, Y., & Sankaranarayanan, M. (2017). Synthesis and study of anti-HIV-1 RT activity of 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives. Bioorganic Chemistry, 72, 74–79. https://doi.org/10.1016/j.bioorg.2017.03.013
Coumar, M. S. (2021). Molecular docking for computer-aided drug design: fundamentals, techniques, resources and applications. Elsevier, pp. 1–503. Academic Press. https://doi.org/10.1016/B978-0-12-822312-3.01001-8
da Silva, C. P. M., das Neves, G. M., Poser, G. L. von, Eifler-Lima, V. L., & Rates, S. M. K. (2023). In silico prediction of ADMET/Drug-likeness properties of bioactive phloroglucinols from Hypericum genus. Medicinal Chemistry, 19(10), 1002–1017. https://doi.org/10.2174/1573406419666230601092358
Damaiyanti, D.W. (2015). Karakterisasi esktrak air teripang emas (Stichopus hermanii). Jurnal Kedokteran Gigi, 9(1), 74–81.
Demarque, D. P., Crotti, A. E. M., Vessecchi, R., Lopes, J. L. C., & Lopes, N. P. (2016). Fragmentation reactions using electrospray ionization mass spectrometry: an important tool for the structural elucidation and characterization of synthetic and natural products. Natural Product Reports, 33(3), 432–455. https://doi.org/10.1039/c5np00073d
Dwi Krihariyani Dwi, Retno Sasongkowati, & Edy Haryanto. (2020). Studi in silico sifat farmakokinetik, toksisitas, dan aktivitas imunomodulator brazilein kayu secang terhadap enzim 3-Chymotrypsin-Like cysteine protease coronavirus. Journal of Indonesian Medical Laboratory and Science (JoIMedLabS), 1(1), 76–85. https://doi.org/10.53699/joimedlabs.v1i1.14
Enni, M. A., & Maraj, M. A. A. (2022). In silico drug repurposing for inflammatory diseases: a systematic review of molecular docking and virtual screening studies. American Journal of Advanced Technology and Engineering Solutions, 02(04), 35–64. https://doi.org/10.63125/j1hbts51
Fahmi & Darmadi. (2013). Tinjauan status perikanan hiu dan upaya konservasinya di indonesia. Edisi pertama. Direktorat konservasi kawasan dan jenis ikan. Direktorat jendral kelautan, pesisir dan pulau pulau kecil. Kementrian kelautan dan perikanan. ISBN : 978-602-913- 09-7.
Fitrial, Y., & Khotimah, I. K. (2017). Antibacterial activity of melanin from cuttlefish and squid ink. Jurnal Pengolahan Hasil Perikanan Indonesia, 20(2), 266. https://doi.org/10.17844/jphpi.v20i2.17907
Frallicciardi, J., Melcr, J., Siginou, P., Marrink, S. J., & Poolman, B. (2022). Membrane thickness, lipid phase and sterol type are determining factors in the permeability of membranes to small solutes. Nature Communications, 13(1), 1605. https://doi.org/10.1038/s41467-022-29272-x
Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., Ferrucci, L., Gilroy, D. W., Fasano, A., Miller, G. W., Miller, A. H., Mantovani, A., Weyand, C. M., Barzilai, N., Goronzy, J. J., Rando, T. A., Effros, R. B., Lucia, A., Kleinstreuer, N., & Slavich, G. M. (2019). Chronic inflammation in the etiology of disease across the life span. Nature Medicine, 25(12), 1822–1832. https://doi.org/10.1038/s41591-019-0675-0
Gao, S., Jennings, E. K., Han, L., Koch, B. P., Herzsprung, P., & Lechtenfeld, O. J. (2024). Detection and exclusion of false-positive molecular formula assignments via mass error distributions in UHR mass spectra of natural organic matter. Analytical Chemistry, 96(25), 10210–10218. https://doi.org/10.1021/acs.analchem.4c00489
Gao, X., Wang, N., Jia, J., Wang, P., Zhang, A., & Qin, X. (2020). Chemical profliling of Dingkun Dan by ultra High performance liquid chromatography Q exactive orbitrap high resolution mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 177, 112732. https://doi.org/10.1016/j.jpba.2019.06.029
Gerriets, V., Goyal, A., & Karam Khaddour. (2023, July 3). Tumor Necrosis Factor Inhibitors. Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK482425
Giridharan, S., & Srinivasan, M. (2018). Mechanisms of NF-κB p65 and strategies for therapeutic manipulation. Journal of Inflammation Research, 11, 407–419. https://doi.org/10.2147/jir.s140188
Hannoodee, S., & Nasuruddin, D. N. (2021). Acute Inflammatory Response. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK556083
Huang, E. T. C., Yang, J.-S., Liao, K. Y. K., Tseng, W. C. W., Lee, C. K., Gill, M., Compas, C., See, S., & Tsai, F.-J. (2024). Predicting blood–brain barrier permeability of molecules with a large language model and machine learning. Scientific Reports, 14(1), 15844. https://doi.org/10.1038/s41598-024-66897-y
Kumar, R., Sharma, A., Alexiou, A., Bilgrami, A. L., Kamal, M. A., & Ashraf, G. M. (2022). DeePred-BBB: A blood brain barrier permeability prediction model with improved accuracy. Frontiers in Neuroscience, 16, 858126. https://doi.org/10.3389/fnins.2022.858126
Lei, M., Xue, C.-H. ., Wang, Y.-M. ., Li, Z.-J. ., Xue, Y., & Wang, J.-F. (2008). Effect of squid ink melanin-fe on iron deficiency anemia remission. Journal of Food Science, 73(8), H207–H211. https://doi.org/10.1111/j.1750-3841.2008.00930.x
Ma’arif, N., Sari, A. N., Nafisah, W., Krama, A., Isfaeni, H., Rusdi, R., & Gholam, G. M. (2025). In silico studies of stylissa carteri-compounds against EGFR and RAF proteins in triple-negative breast cancer. Tropical Journal of Natural Product Research, 9(6), 2922–2932. https://doi.org/10.26538/tjnpr/v9i6.77
Mukesh, B., & Rakesh, K. (2011). Molecular docking : a review. International Journal of Research in Ayurveda & Pharmacy, 2(6), 1746–1751.
Nursanto, R. M., Mustofa, A., & Widanti, Y. A. (2019). Nugget ikan hiu (Carcharhinus amblyrhynchos) dengan variasi penambahan jamur tiram (Pleurotus Sp.). Jurnal Teknologi dan Industri Pangan, 4(1), 15-21. https://doi.org/10.33061/jitipari.v4i1.3014
Pagadala, N. S., Syed, K., & Tuszynski, J. (2017). Software for molecular docking: a review. Biophysical Reviews, 9(2), 91–102. https://doi.org/10.1007/s12551-016-0247-1
Pires, D. E. V., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
Praditapuspa, E. N., Siswandono S, S., & Widiandani, T. (2021). In Silico analysis of pinostrobin derivatives from Boesenbergia pandurata on ErbB4 kinase target and QSPR linear models to predict drug clearance for searching anti-breast cancer drug candidates. Pharmacognosy Journal, 13(5), 1143–1149. https://doi.org/10.5530/pj.2021.13.147
Putranto, H. F., Asikin, A. N., & Kusumaningrum, D. I. (2015). Karakterisasi tepung tulang ikan belida (Chitala sp.) sebagai sumber kalsium dengan metode hidrolisis protein. Journal ZIRAA’AH, 40(1), 11–20.
Rai, M., Singh, A., Namuna Paudel, Anurag Kanase, Faletta, E., Pranali Kerkar, Heyda, J., Barghash, R. F., Singh, S., & Miroslav Šoóš. (2023). Herbal concoction Unveiled: A computational analysis of phytochemicals’ pharmacokinetic and toxicological profiles using novel approach methodologies (NAMs). Current Research in Toxicology, 5, 100118–100118. https://doi.org/10.1016/j.crtox.2023.100118
Rochman, F., Wujdi, A., Levi Arnenda, G., & Kurniawan, R. (2021). Blue sharks (Prionace glauca) by-catch in the Indonesian industrial tuna longline fishery in the eastern Indian Ocean. IOP Conference Series: Earth and Environmental Science, 860(1), 012115. https://doi.org/10.1088/1755-1315/860/1/012115
Sharma, M., Mohapatra, J., Wagh, A., Patel, H. M., Pandey, D., Kadam, S., Argade, A., Deshpande, S. S., Shah, G. B., Chatterjee, A., & Jain, M. R. (2014). Involvement of TACE in colon inflammation: A novel mechanism of regulation via SIRT-1 activation. Cytokine, 66(1), 30–39. https://doi.org/10.1016/j.cyto.2013.12.010
Solihah, H., Agustin, T. I., & Sulistyowati, W. (2019). Pengaruh prosentase absorben yang berbeda terhadap karakteristik hasil ekstrak tulang hiu (Prionace glauca). Fisheries: Jurnal Perikanan dan Ilmu Kelautan, 1(1), 12. https://doi.org/10.30649/fisheries.v1i1.12
Sulityowati, W., Titiek Indhira, A., Arsiniati, A., & Erina, Y. (2015). Glucosamine and chondroitin sulphate content of shark cartilage (Prionace glauca) and its potential as anti-aging supplements. International Journal of ChemTech Research, 8(10), 163–168.
Tambunan, U. S. F., & Alamudi, S. (2010). Designing cyclic peptide inhibitor of dengue virus NS3-NS2B protease by using molecular docking approach. Bioinformation, 5(6), 250–254. https://doi.org/10.6026/97320630005250
Tan, L. Y., Komarasamy, T. V., & RMT Balasubramaniam, V. (2021). Hyperinflammatory immune response and COVID-19: A double edged sword. Frontiers in Immunology, 12, 742941. https://doi.org/10.3389/fimmu.2021.742941
Ursu, O., Rayan, A., Goldblum, A., & Oprea, T. I. (2011). Understanding drug-likeness. Wiley Interdisciplinary Reviews: Computational Molecular Science, 1(5), 760–781. https://doi.org/10.1002/wcms.52
Wijaya, A., & Satriawan, B. (2023). Pengaruh perbedaan jenis pelarut terhadap nilai rendemen ekstrak daun pepaya (Carica papaya. L). Jurnal Ilmiah JOPHUS: Journal Of Pharmacy UMUS, 5(1), 10-17.
Windarsih, A., Nor, Rohman, A., Yuliana, N. D., & Dachriyanus. (2024). Untargeted metabolomics using liquid chromatography-high resolution mass spectrometry and chemometrics for analysis of non-halal meats adulteration in beef meat. Animal Bioscience. https://doi.org/10.5713/ab.23.0238
Zheng, C., Yin, Q., & Wu, H. (2010). Structural studies of NF-κB signaling. Cell Research, 21(1), 183–195. https://doi.org/10.1038/cr.2010.171
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Copyright (c) 2026 Titiek Indhira Agustin, Happy Nursyam, Muhamad Firdaus, Muhaimin Rifa’i, Maria Dolorosa Sare, Ersanda Nurma Praditapuspa
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