Kajian in Silico Aktivitas Antioksidan Senyawa Bioaktif dalam Minyak Serai (Cymbopogon citratus)
Abstract
stress oxidative is a factor promoting metabolic syndrome and other diseases. oxidative stress could be minimalized by exogen and endogen antioxidants. Essential oil from Cymbopogon citratus extract have potential activities as anti-inflammatory and relaxing. This study determined the potential activity as antioxidant through kelch ECH associating protein 1 (KEAP1) inhibition. Four phytosterol compounds from Cymbopogon citratus essential oil, including 3,7-dimethyl-1,3,6-octatriene, decanal, elemol, dan selina- 6-en-4-ol, were downloaded from PubChem database. four compounds were docked with KEAP1 protein and analyzed using Discovery studio ver. 19.0.0. 3,7-dimethyl-1,3,6-octatriene, decanal, elemol, and selina-6-en-4-ol bound to KEAP1 in certain amino acid residues with hydrophobic interaction and hydrogen bond. Interestingly, 3,7-dimethyl-1,3,6-octatriene proved five hydrophobic interaction, higher than decanal and selina-6-en-4-ol. The elemol, and selina-6-en-4-ol interacted with KEAP1 showing lower binding affinity and tight interaction. This study suggested that 3,7-dimethyl-1,3,6-octatriene, decanal, elemol, and selina-6-en-4-ol promoted antioxidant activity.Downloads
References
Abed, D. A., Goldstein, M., Albanyan, H., Jin, H., & Hu, L. (2015). Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents. Acta Pharmaceutica Sinica B, 5(4), 285–299. https://doi.org/10.1016/j.apsb.2015.05.008
Arora, R., Sawney, S., Saini, V., Steffi, C., Tiwari, M., & Saluja, D. (2016). Esculetin induces antiproliferative and apoptotic response in pancreatic cancer cells by directly binding to KEAP1. Molecular Cancer, 15(1), 1–15. https://doi.org/10.1186/s12943-016-0550-2
Avoseh, O., Oyedeji, O., Rungqu, P., Nkeh-Chungag, B., & Oyedeji, A. (2015). Cymbopogon species; ethnopharmacology, phytochemistry and the pharmacological importance. Molecules, 20(5), 7438–7453. https://doi.org/10.3390/molecules20057438
Baird, L., & Yamamoto, M. (2020). The Molecular Mechanism Regulating the KEAP1-NRF2 Pathway. Molecular and Cellular Biology, 40(13), 1–23.
Bare, Yohanes;, Helvina, M., Elizabeth, A., & Sari, D. R. T. (2019). Potensi Asam Kafeat Pada Kopi Sebagai Simultan Gen Peroxixme Proliferator-Activated Receptor Gamma (Ppar-Î3): Studi in Silico. Saintek Lahan Kering, 2(Vol 2 No 2 (2019): JSLK Desember 2019), 52–53. Retrieved from http://savana-cendana.id/index.php/SLK/article/view/866
Bare, Yohanes, Maulidi, A., Sari, D. R. T., & Tiring, S. S. N. D. (2019). Studi in Silico Prediksi Potensi 6-Gingerol sebagai inhibitor c-Jun N-terminal kinases (JNK). Jurnal Jejaring Matematika Dan Sains, 1(2), 59–63. https://doi.org/10.36873/jjms.v1i2.211
Bare, Yohanes, S, M., Putra, S. H. J., L, M. R. W. G., & Sari, D. R. T. (2020). In-silico Approach for The Prediction of Chlorogenic Acid as PPAR-γ Activator. Biota, 13(1). https://doi.org/10.20414/jb.v13i1.197
Bare, Yohanes, S, M., Tiring, S. S. N. D., Sari, D. R. T., & Maulidi, A. (2020). Virtual Screening: Prediksi potensi 8-shogaol terhadap c-Jun N-Terminal Kinase (JNK). Jurnal Penelitian Dan Pengkajian Ilmu Pendidikan: E-Saintika, 4(1), 1. https://doi.org/10.36312/e-saintika.v4i1.157
Bare, Yohanes, Sari, D. R., Rachmad, Y. T., Tiring, S. S. N. D., Rophi, A. H., & Nugraha, F. A. D. (2019). Prediction Potential Chlorogenic Acid As Inhibitor Ace (In Silico Study). Bioscience, 3(2), 197. https://doi.org/10.24036/0201932105856-0-00
Bare, Yohanes, Sari, D. R. T., Rachmad, Y. T., Krisnamurti, G. C., & Elizabeth, A. (2019). In Silico Insight the Prediction of Chlorogenic Acid in Coffee through Cyclooxygenase-2 (COX2) Interaction. Biogenesis: Jurnal Ilmiah Biologi, 7(2), 100–105. https://doi.org/10.24252/bio.v7i2.9847
Bayala, B., Coulibaly, A. Y., Djigma, F. W., Nagalo, B. M., Baron, S., Figueredo, G., … Simpore, J. (2020). Chemical composition, antioxidant, anti-inflammatory and antiproliferative activities of the essential oil of Cymbopogon nardus, a plant used in traditional medicine. Biomolecular Concepts, 11(1), 86–96. https://doi.org/10.1515/bmc-2020-0007
Boukhatem, M. N., Ferhat, M. A., Kameli, A., Saidi, F., & Kebir, H. T. (2014). Lemon grass (Cymbopogon citratus) essential oil as a potent anti-inflammatory and antifungal drugs. Libyan Journal of Medicine, 9(25431), 1–10. https://doi.org/10.3402/ijmm.v9.25431
Canning, P., Sorrell, F. J., & Bullock, A. N. (2015). Structural basis of Keap1 interactions with Nrf2. Free Radical Biology and Medicine, 88(Part B), 101–107. https://doi.org/10.1016/j.freeradbiomed.2015.05.034
Chanthai, S., Prachakoll, S., Ruangviriyachai, C., & Luthria, D. L. (2012). Influence of extraction methodologies on the analysis of five major volatile aromatic compounds of citronella grass (cymbopogon nardus) and lemongrass (cymbopogon citratus) grown in thailand. Journal of AOAC International, 95(3), 763–772. https://doi.org/10.5740/jaoacint.11-335
Chartoumpekis, D., & Kensler, T. (2013). New Player on An Old Field; the Keap1/Nrf2 Pathway as a Target for Treatment of Type 2 Diabetes and Metabolic Syndrome. Current Diabetes Reviews, 9(2), 137–145. https://doi.org/10.2174/1573399811309020005
Chen, D., Oezguen, N., Urvil, P., Ferguson, C., Dann, S. M., & Savidge, T. C. (2016). Regulation of protein-ligand binding affinity by hydrogen bond pairing. Science Advances, 2(3). https://doi.org/10.1126/sciadv.1501240
Costa, C. A. R. A., Bidinotto, L. T., Takahira, R. K., Salvadori, D. M. F., Barbisan, L. F., & Costa, M. (2011). Cholesterol reduction and lack of genotoxic or toxic effects in mice after repeated 21-day oral intake of lemongrass (Cymbopogon citratus) essential oil. Food and Chemical Toxicology, 49(9), 2268–2272. https://doi.org/10.1016/j.fct.2011.06.025
Dallakyan, S., & Olson, A. J. (2015). Small molecule library screening by docking with PyRx. Methods Mol Biol, 1263, 243–250.
David, J. A., Rifkin, W. J., Rabbani, P. S., & Ceradini, D. J. (2017). The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus. Journal of Diabetes Research, 2017. https://doi.org/10.1155/2017/4826724
Dayalan Naidu, S., & Dinkova-Kostova, A. T. (2020). KEAP1, a cysteine-based sensor and a drug target for the prevention and treatment of chronic disease: KEAP1, a sensor and a drug target. Open Biology, 10(6). https://doi.org/10.1098/rsob.200105rsob200105
Elsayed Azab, A., A Adwas, Almokhtar, Ibrahim Elsayed, A. S., A Adwas, A., Ibrahim Elsayed, Ata Sedik, & Quwaydir, F. A. (2019). Oxidative stress and antioxidant mechanisms in human body. Journal of Applied Biotechnology & Bioengineering, 6(1), 43–47. https://doi.org/10.15406/jabb.2019.06.00173
Ewansiha, J., Garba, S., Mawak, J., & Oyewole, O. (2013). Antimicrobial Activity of Cymbopogon Citratus (Lemon Grass) and It’s Phytochemical Properties. Frontiers in Science, 2(6), 214–220. https://doi.org/10.5923/j.fs.20120206.14
Gbenou, J. D., Ahounou, J. F., Akakpo, H. B., Laleye, A., Yayi, E., Gbaguidi, F., … Kotchoni, S. O. (2013). Phytochemical composition of Cymbopogon citratus and Eucalyptus citriodora essential oils and their anti-inflammatory and analgesic properties on Wistar rats. Molecular Biology Reports, 40(2), 1127–1134. https://doi.org/10.1007/s11033-012-2155-1
Hypertrophy, I. C. (2020). Cymbopogon Proximus Essential Oil Protects Rats.
Kamble, S. M., Patel, H. M., Goyal, S. N., Noolvi, M. N., Mahajan, U. B., Ojha, S., & Patil, C. R. (2016). In silico Evidence for Binding of Pentacyclic Triterpenoids to Keap1-Nrf2 Protein-Protein Binding Site. Combinatorial Chemistry & High Throughput Screening, 20(3). https://doi.org/10.2174/1386207319666161214111822
Kansanen, E., Kuosmanen, S. M., Leinonen, H., & Levonenn, A. L. (2013). The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biology, 1(1), 45–49. https://doi.org/10.1016/j.redox.2012.10.001
Kumagai, Y., Kanda, H., Shinkai, Y., & Toyama, T. (2013). The role of the Keap1/Nrf2 pathway in the cellular response to methylmercury. Oxidative Medicine and Cellular Longevity, 2013(Table 1). https://doi.org/10.1155/2013/848279
Leite, B. L. S., Bonfim, R. R., Antoniolli, A. R., Thomazzi, S. M., Araújo, A. A. S., Blank, A. F., … Quintans-Júnior, L. J. (2010). Assessment of antinociceptive, anti-inflammatory and antioxidant properties of Cymbopogon winterianus leaf essential oil. Pharmaceutical Biology, 48(10), 1164–1169. https://doi.org/10.3109/13880200903280000
Lo, S. C., Li, X., Henzl, M. T., Beamer, L. J., & Hannink, M. (2006). Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling. EMBO Journal, 25(15), 3605–3617. https://doi.org/10.1038/sj.emboj.7601243
Mitsuishi, Y., Motohashi, H., & Yamamoto, M. (2012). The Keap1–Nrf2 system in cancers: stress response and anabolic metabolism. Frontiers in Oncology, 2(December), 1–13. https://doi.org/10.3389/fonc.2012.00200
Mohamed Hanaa, A. R., Sallam, Y. I., El-Leithy, A. S., & Aly, S. E. (2012). Lemongrass (Cymbopogon citratus) essential oil as affected by drying methods. Annals of Agricultural Sciences, 57(2), 113–116. https://doi.org/10.1016/j.aoas.2012.08.004
Nimse, S. B., & Pal, D. (2015). Free radicals, natural antioxidants, and their reaction mechanisms. RSC Advances, 5(35), 27986–28006. https://doi.org/10.1039/c4ra13315c
Panieri, E., Buha, A., Telkoparan-akillilar, P., Cevik, D., Kouretas, D., Veskoukis, A., … Saso, L. (2020). Potential applications of NRF2 modulators in cancer therapy. Antioxidants, 9(3), 1–48. https://doi.org/10.3390/antiox9030193
Rojas-Armas, J. P., Arroyo-Acevedo, J. L., Palomino-Pacheco, M., Herrera-Calderón, O., Ortiz-Sánchez, J. M., Rojas-Armas, A., … Hilario-Vargas, J. (2020). The essential oil of Cymbopogon citratus stapt and carvacrol: An approach of the antitumor effect on 7,12-dimethylbenz-[α]-anthracene (DMBA)-induced breast cancer in female rats. Molecules, 25(14), 1–15. https://doi.org/10.3390/molecules25143284
Sah, S. Y., Sia, C. M., Chang, S. K., Ang, Y. K., & Yim, H. S. (2012). Antioxidant Capacity and Total Phenolic Content of Lemongrass (Cymbopogon Citratus) Leave. Annals. Food Science and Technology, 13(2), 150–155.
Sari, D. R.T., Safitri, A., Cairns, J. R. K., & Fatchiyah, F. (2020). Virtual screening of black rice anthocyanins as antiobesity through inhibiting TLR4 and JNK pathway. Journal of Physics: Conference Series, 1665(1). https://doi.org/10.1088/1742-6596/1665/1/012024
Sari, Dewi Ratih Tirto;, & Bare, Y. (2020). Physicochemical properties and biological activity of bioactive compound in Pepper nigrum: In silico study. Spizaetus: Jurnal Biologi Dan Pendidikan Biologi, 1(1), 1–6.
Sari, Dewi Ratih Tirto, Cairns, J. R. K., Safitri, A., & Fatchiyah, F. (2019). Virtual prediction of the delphinidin-3-o-glucoside and peonidin-3-o-glucoside as anti-inflammatory of TNF-α signaling. Acta Informatica Medica, 27(3), 152–157. https://doi.org/10.5455/aim.2019.27.152-157
Sari, Dewi Ratih Tirto, Safitri, A., Cairns, J. R. K., & Fatchiyah, F. (2020). Anti-Apoptotic Activity of Anthocyanins has Potential to inhibit Caspase-3 Signaling. Journal of Tropical Life Sciences, 10(1), 15–25. https://doi.org/10.11594/jtls.10.01.03
Silva, M. de F., Pruccoli, L., Morroni, F., Sita, G., Seghetti, F., Viegas, C., & Tarozzi, A. (2018). The Keap1/Nrf2-ARE pathway as a pharmacological target for chalcones. Molecules, 23(7), 1–22. https://doi.org/10.3390/molecules23071803
Viktorová, J., Stupák, M., Řehořová, K., Dobiasová, S., Hoang, L., Hajšlová, J., … Ruml, T. (2020). Lemon grass essential oil does not modulate cancer cells multidrug resistance by citral—its dominant and strongly antimicrobial compound. Foods, 9(5). https://doi.org/10.3390/foods9050585
Wei, R., Enaka, M., & Muragaki, Y. (2019). Activation of KEAP1/NRF2/P62 signaling alleviates high phosphate-induced calcification of vascular smooth muscle cells by suppressing reactive oxygen species production. Scientific Reports, 9(1), 1–13. https://doi.org/10.1038/s41598-019-46824-2
Authors who publish with this journal agree to the following terms:
1) 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.
2) 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.
3)Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).