Analisis In Silico Interaksi antara Interferon Beta dengan Senyawa Turunan Flavonoid dan Terpenoid dari Bunga Carthamus tinctorius

Lismayana Hansur; Nurmasita; Paisal; Sandy Vitria Kurniawan

doi:10.56951/nej0dw97

Analisis In Silico Interaksi antara Interferon Beta dengan Senyawa Turunan Flavonoid dan Terpenoid dari Bunga Carthamus tinctorius

Penulis

Lismayana Hansur Departemen Mikrobiologi, Fakultas Kedokteran dan Ilmu Kesehatan, Universitas Muhammadiyah Makassar, Sulawesi Selatan
Nurmasita Akademi Keperawatan Yapenas 21 Maros, Sulawesi Selatan
Paisal Pusat Penelitian Obat Praklinis dan Klinik, Badan Riset dan Inovasi Nasional, Jakarta
Sandy Vitria Kurniawan Departemen Farmakologi dan Farmasi, Fakultas Kedokteran dan Ilmu Kesehatan, Universitas Katolik Indonesia Atma Jaya, Jakarta

DOI:

https://doi.org/10.56951/nej0dw97

Kata Kunci:

Carthamus tinctorius, in silico, interferon beta, molecular docking, carthamon, imunomodulator

Abstrak

Latar belakang: Kasumba turatea (Carthamus tinctorius) telah lama digunakan secara empiris oleh masyarakat Sulawesi
Selatan sebagai obat tradisional untuk mengatasi penyakit yang disebabkan oleh infeksi virus. Tanaman ini diketahui mengandung senyawa thymol, carvacrol, carthamon, chalcone, dan linalool yang berpotensi sebagai imunomodulator, termasuk dalam kaitannya dengan penyakit multiple sclerosis. Salah satu mekanisme imun yang berperan adalah interferon beta (IFN-β), yang kemampuannya dipengaruhi oleh β-glucan yang dapat meningkatkan ekspresi IFN-β. Tujuan: Penelitian ini bertujuan untuk mengeksplorasi interaksi thymol, carvacrol, carthamon, chalcone, dan linalool (senyawa yang memiliki efek imunomodulasi) dengan IFN-β melalui pendekatan komputasional (in silico). Metode: Metode yang digunakan dalam penelitian ini yaitu molecular docking menggunakan aplikasi AutoDock Tools, AutoDock Vina, dan Discovery Studio. Struktur 3D IFN-β diperoleh dari Protein Data Bank (PDB) dengan PDB ID 1AU1. Senyawa kontrol yang digunakan adalah beta-D-glucan (BDG). Ligan yang digunakan adalah carthamon, carvacrol, chalcone, linalool, dan thymol. Hasil: Hasil docking menunjukkan bahwa carthamon memiliki nilai binding affinity tertinggi di antara ligan lainnya. Residu-residu yang paling berperan dalam interaksi ligan pada situs aktif IFN-β adalah glutamic acid 43, arginine 28, serine 13, asparagine 90, dan leucine 9, yang berinteraksi melalui ikatan hidrogen. Kesimpulan: Penelitian ini memberikan bukti awal bahwa senyawa aktif dari kasumba turatea, khususnya carthamon, memiliki potensi untuk berinteraksi dengan IFN-β. Hasil ini dapat menjadi dasar untuk penelitian lanjutan untuk menguji senyawa interaksi carthamon bersama IFN-β yang dapat meningkatkan kemampuan imunomodulator.

Unduhan

Baca Selengkapnya

Referensi

1. Agasing A, Quinn JL, Kumar G, Axtell RC. Interferon-β intensifies interleukin-23-driven pathogenicity of T helper cells in neuroinflammatory disease. Cells. 2021;10(8):2139. doi: 10.3390/cells10082139.

2. Jabbari S, Hosseinpourfeizi M, Safaralizadeh R, Baradaran B. Interferon signature’s members: a novel altered correlation upon interferon-β treatment in multiple sclerosis patients. Curr Mol Med. 2024;24(10):1301–6. doi: 10.2174/0115665240251182231008040710.

3. Dumitrescu L, Papathanasiou A, Coclitu C, Constantinescu CS, Popescu BO, Tanasescu R. Beta interferons as immunotherapy in multiple sclerosis: a new outlook on a classic drug during the COVID-19 pandemic. QJM. 2021;114(10):691–7. doi: 10.1093/qjmed/hcaa348.

4. Rasouli J, Casella G, Ishikawa LLW, Thome R, Boehm A, Ertel A, et al. IFN-β acts on monocytes to ameliorate CNS autoimmunity by inhibiting proinflammatory cross-talk between monocytes and Th cells. Front Immunol. 2021;12:679498. doi: 10.3389/fimmu.2021.679498.

5. Bellucci G, Albanese A, Rizzi C, Rinaldi V, Salvetti M, Ristori G. The value of interferon-β in multiple sclerosis and novel opportunities for its antiviral activity: a narrative literature review. Front Immunol.

2023;14. doi: 10.3389/fimmu.2023.1161849.

6. Myftiu B, Komoni E, Malazogu E, Jashari F, Rashiti SB, Pushka M, et al. Adherence to interferon-β treatment in Kosovan multiple sclerosis registry. Ital J Med. 2024;18(1). doi: 10.4081/itjm.2024.1672.

7. Kazakov AS, Sofin AD, Avkhacheva NV, Denesyuk AI, Deryusheva EI, Rastrygina VA, et al. Interferon beta activity is modulated via binding of specific S100 proteins. Int J Mol Sci. 2020;21(24):9473. doi:10.3390/ijms21249473.

8. Wang G, Li Z, Tian M, Cui X. β-Glucan induces trained immunity to promote antiviral activity by activating TBK1. Viruses. 2023;15(5). doi: 10.3390/v15051204.

9. Chang JM, Hung LM, Chyan YJ, Cheng CM, Wu RY. Carthamus tinctorius enhances the antitumor activity of dendritic cell vaccines via polarization toward Th1 cytokines and increase of cytotoxic T lymphocytes.

Evid Based Complement Alternat Med. 2011;2011:274858. doi: 10.1093/ecam/nen068.

10. Delshad E, Yousefi M, Sasannezhad P, Rakhshandeh H, Ayati Z. Medical uses of Carthamus tinctorius L. (safflower): a comprehensive review from traditional medicine to modern medicine. Electron Physician. 2018;10(4):6672–81. doi:10.19082/6672.

11. Lee H, Cho H, Son M, Sung GH, Lee T, Lee SW, Jung YW, Shin YS, Kang H. Dysregulation of KSHV replication by extracts from Carthamus tinctorius L. Journal of microbiology (Seoul, Korea). 2013;51(4):490–8. doi: 10.1007/s12275-013-3282-7.

12. Gholijani N, Amirghofran Z. Effects of thymol and carvacrol on T-helper cell subset cytokines and their main transcription factors in ovalbumin-immunized mice. Journal of immunotoxicology. 2016;13(5):729–37. doi: 10.3109/1547691X.2016.1173134.

13. Zhang LL, Tian K, Tang ZH, Chen XJ, Bian ZX, Wang YT, Lu JJ. Phytochemistry and pharmacology of Carthamus tinctorius L. American Journal of Chinese Medicine. 2016;44(2):197–226. doi: 10.1142/S0192415X16500130.

14. Firmino JP, , Fernández-Alacid L, Vallejos-Vidal E, Salomón R, Sanahuja I, Tort L, et al. Carvacrol, thymol, and garlic essential oil promote skin innate immunity in gilthead seabream (Sparus aurata) through the multifactorial modulation of the secretory pathway and enhancement of mucus protective capacity. Frontiers in immunology. 2021;12: 633621. doi: 10.3389/fimmu.2021.633621.

15. Fadhilah A, Parwati AD, Muflihah CH, Wahyuni AS. Immunomodulatory activity of kasumba turatea (Carthamus tinctorius L.) extract against non-specific and specific immune responses in mice. 2023;20(1). doi: 10.23917/pharmacon.v20i1.22629.

16. Xia Z, Wu L-Y, Xhou X, Wong STC. Semi-supervised drug-protein interaction prediction from heterogeneous biological spaces. BMC Systems Biology. 2010;4(S2). doi: 10.1186/1752-0509-4-s2-s6.

17. Hodos RA, Kidd BA, Shameer K, Readhead BP, Dudley JT. In silico methods for drug repurposing and pharmacology. Wiley Interdisciplinary Reviews Systems Biology and Medicine. 2016;8(3):186–210. doi:10.1002/wsbm.1337.

18. Cheng F, Liu C, Jiang J, Lu W, Li W, Liu G, et al. Prediction of drug-target interactions and drug repositioning via network-based inference. Plos Computational Biology. 2012;8(5):e1002503. doi: 10.1371/journal. pcbi.1002503.

19. Arpornsuwan, T, Petvises S, Thim-uam A, Boondech A. Effects of Carthamus tinctorius L. solvent extracts on anti-proliferation of human colon cancer (SW620 cell line) via apoptosis and the growth promotion of lymphocytes. Songklanakarin Journal of Science and Technology. 2012;34(1):45–51.

20. Suhadi A, Rizarullah R, Feriyani F. Simulasi docking senyawa aktif daun binahong sebagai inhibitor enzyme aldose reductase. Sel Jurnal Penelitian Kesehatan. 2019;6(2):55–65. doi: 10.22435/sel.v6i2.1651.

21. Dona R, Frimayanti N, Ikhtiarudin I, Iskandar B, Maulana F, Silalahi NT. Studi in silico, sintesis, dan uji sitotoksik senyawa p-metoksi kalkon terhadap sel kanker payudara MCF-7. Jurnal Sains Farmasi & Klinis. 2019;6(3):243–49. doi: 10.25077/jsfk.6.3.243-249.2019.

22. Scott, P. Human interferon-beta (PDB ID: 1AU1) from Homo sapiens, collab.its.virginia.edu.

23. Orhan IE, Mesaik MA, Jabeen A, Kan Y. Immunomodulatory properties of various natural compounds and essential oils through modulation of human cellular immune response. Industrial Crops and Products. 2016;(81):117–22. doi: 10.1016/j.indcrop.2015.11.088.

24. Luca E, Redaelli M, Zaffino C, Bruni S. A SERS and HPLC study of traditional dyes from native Chinese plants. Vibrational Spectroscopy. 2018;95:62–7. doi: 10.1016/j.vibspec.2018.01.008.

25. Piehler J, Thomas C, Garcia KC, Schreiber G. Structural and dynamic determinants of type I interferon receptor assembly and their functional interpretation. Immunological Reviews. 2012;250(1):317–34. doi:10.1111/imr.12001.

26. Montalban X, Sastre-Garriga J, Tintoré M, Brieva L, Aymerich FX, Río J, et al. A single-center, randomized, double-blind, placebo-controlled study of interferon beta-1b on primary progressive and transitional multiple sclerosis. Multiple Sclerosis Journal. 2009;15(10):1195-205. doi: 10.1177/1352458509106937.

27. Theofilopoulos AN, Baccala R, Beutler B, Kono, DH. Type I interferons (α/α) in immunity and autoimmunity. Annual review of immunology. 2005; 23: 307-36. doi: 10.1146/annurev.immunol.23.021704.115843.

28. Navarro A, Anand-Apte B, Tanabe Y, Feldman G, Larner AC. A PI-3 kinase-dependent, Stat1-independent signaling pathway regulates interferon-stimulated monocyte adhesion. Journal of Leukocyte Biology. 2003;73(4):540–5. doi: 10.1189/jlb.1002508.

29. Raftery N, Stevenson NJ. Advances in anti-viral immune defence: revealing the importance of the IFN JAK/STAT pathway. Cellular and Molecular Life Sciences. 2017; 74(14): 2525–35. doi: 10.1007/s00018-017-2520-2.

30. Tolomeo M, Cavalli A, Cascio A. STAT1 and its crucial role in the control of viral infections. International Journal of Molecular Sciences. 2022;23(8):4095. doi: 10.3390/ijms23084095.

31. Abdolvahab MH, Mofrad MRK, Schellekens H. Interferon beta: from molecular level to therapeutic effects. International Review of Cell and Molecular Biology. Elsevier Inc. 2016;326:343–72. doi: https://doi.org/10.1016/bs.ircmb.2016.06.001.

32. Sunil Kumar Mohanty, KSL. Textbook of Immunology. Second edition. New Delhi: Jaypee Brothers Medical Publisher. 2014.

33. Daffis S, Suthar MS, Gale M Jr, Diamond MS. Measure and countermeasure: type I IFN (IFN-alpha/beta) antiviral response against West Nile virus. Journal of innate immunity. 2009; 1(5):435–45. doi:10.1159/000226248.

34. Wulan IGAK, Agusni I. Penggunaan imunomodulator untuk berbagai infeksi virus pada kulit (immunomodulators for a variety of viral infections of the skin). Berkala ilmu kesehatan kulit dan kelamin. 2015; 27(1):63–9.

35. Liu YL, Liu YJ, Liu Y, Li XS, Liu SH, Pan YG, et al. Hydroxysafflor yellow A ameliorates lipopolysaccharide induced acute lung injury in mice via modulating toll-like receptor 4 signaling pathways. International

Immunopharmacology. 2014; 23(2):649–57. doi: 10.1016/j.intimp.2014.10.018.

36. Lee JS, Bukhari SN, Fauzi NM. Effects of chalcone derivatives on players of the immune system. Drug design, development and therapy. 2015(9):4761–78. doi: 10.2147/DDDT.S86242.