Likopen Tomat sebagai Agen Epigenetik dalam Regulasi Gen Proinflamasi melalui Jalur NF-ΚB

Rayhana Azzahra Kusmana

doi:10.55606/jurrike.v4i2.6361

Authors

Rayhana Azzahra Kusmana Universitas Gadjah Mada

DOI:

https://doi.org/10.55606/jurrike.v4i2.6361

Keywords:

Antioxidants, Epigenetics, Inflammation, Lycopene, NF-ΚB

Abstract

Chronic inflammation is a complex condition that involves the activation of the transcription factor NF-κB, which plays an important role in inducing the expression of proinflammatory genes such as TNF-α, IL-1β, and IL-6. Activation of this pathway is often associated with degenerative diseases, including cancer, cardiovascular disease, as well as metabolic disorders. Lycopene, the main carotenoid pigment in tomatoes, is known as a potent antioxidant with anti-inflammatory properties, but its epigenetic mechanism in the regulation of inflammatory gene expression is still a growing area of research. This article aims to review the recent literature on the role of lycopene as an epigenetic agent capable of modulating the expression of proinflammatory genes through epigenetic pathways associated with NF-KB. This research method uses a systematic literature review through PubMed, Google Scholar, and Scopus databases with a publication range of 2015–2025. The results of the study show that lycopene works through several important mechanisms. First, lycopene can affect DNA methylation in the promoter region of inflammatory genes by inhibiting the enzyme DNA methyltransferases (DNMT), which has an impact on decreased transcription of proinflammatory genes. Second, lycopene plays a role in histone modification, especially by inhibiting histone deacetylases (HDAC) thereby increasing histone acetylation of H3K9 in anti-inflammatory genes. Third, lycopene is able to regulate microRNA expression such as lowering miR-155 and miR-21 which strengthen the NF-κB pathway, while increasing miR-146a which plays a role in suppressing inflammation. Fourth, lycopene directly inhibits NF-κB activation by targeting IκB kinase (IKK), preventing IκB degradation, and lowering the translocation of the p65 subunit to the nucleus. With such a dual mechanism, tomato lycopene has the potential to be an effective nutraceutical agent for chronic inflammatory therapy.

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References

Assar, E. A., Vidalle, M. C., Chopra, M., & Hafizi, S. (2016). Lycopene acts through inhibition of IκB kinase to suppress NF-κB signaling in human prostate and breast cancer cells. Tumor Biology, 37(7), 9375–9385. https://doi.org/10.1007/s13277-016-4843-9

Das, D., Karthik, N., & Taneja, R. (2021). Crosstalk between inflammatory signaling and methylation in cancer. Frontiers in Cell and Developmental Biology, 9, 756458. https://doi.org/10.3389/fcell.2021.756458

Dong, J., Li, W., Cheng, L. M., & Wang, G. G. (2019). Lycopene attenuates LPS-induced liver injury by inactivation of NF-κB/COX-2 signaling. International Journal of Clinical and Experimental Pathology, 12(3), 817–826.

Jeong, Y., Lim, J. W., & Kim, H. (2019). Lycopene inhibits reactive oxygen species-mediated NF-κB signaling and induces apoptosis in pancreatic cancer cells. Nutrients, 11(4), 762. https://doi.org/10.3390/nu11040762

Kamel, S., Zeidan, D. W., Khaled, H. E., Ali, Z. A. E., Elrefaei, N. G., & El-Naggar, M. S. (2022). In vivo assessment of lycopene effect on obesity-induced inflammation. Biomedical and Pharmacology Journal, 15(3), 1285–1293. https://doi.org/10.13005/bpj/2515

Karaköy, Z., Cadirci, E., & Dincer, B. (2022). A new target in inflammatory diseases: Lycopene. The Eurasian Journal of Medicine, 54(Suppl 1), S23–S28. https://doi.org/10.5152/eurasianjmed.2022.22117

Lee, H. T., Oh, S., Yoo, H., & Kwon, Y. W. (2020). The key role of DNA methylation and histone acetylation in epigenetics of atherosclerosis. Journal of Lipid and Atherosclerosis, 9(3), 419–434. https://doi.org/10.12997/jla.2020.9.3.419

Martoyo, T. (2024). Pengertian. Jurnal Pendidikan Indonesia (PJPI).

Moody, L., Crowder, S. L., Fruge, A. D., Locher, J. L., Demark-Wahnefried, W., Rogers, L. Q., ... & Arthur, A. E. (2020). Epigenetic stratification of head and neck cancer survivors reveals differences in lycopene levels, alcohol consumption, and methylation of immune regulatory genes. Clinical Epigenetics, 12, 1–14. https://doi.org/10.1186/s13148-020-00866-4

Saleh, H. A., Yousef, M. H., & Abdelnaser, A. (2021). The anti-inflammatory properties of phytochemicals and their effects on epigenetic mechanisms involved in TLR4/NF-κB-mediated inflammation. Frontiers in Immunology, 12, 606069. https://doi.org/10.3389/fimmu.2021.606069

Shafe, M. O., Gumede, N. M., Nyakudya, T. T., & Chivandi, E. (2024). Lycopene: A potent antioxidant with multiple health benefits. Journal of Nutrition and Metabolism, 2024(1), 6252426. https://doi.org/10.1155/2024/6252426

Sima, F. M., Majawati, E., & Kurniawan, H. (2019). Uji kadar likopen dan aktivitas antioksidan pada buah tomat. Jurnal Kedokteran Meditek, 25(3), 94–99. https://doi.org/10.36452/jkdoktmeditek.v25i3.1730

Sujana, D., Wardani, D., & Nurul, N. (2020). Review artikel: Potensi likopen dari buah tomat (Solanum lycopersicum L.) sebagai antiaging topikal. Jurnal Insan Farmasi Indonesia, 3(1), 56–65. https://doi.org/10.36387/jifi.v3i1.513

van Steenwijk, H. P., Bast, A., & de Boer, A. (2020). The role of circulating lycopene in low-grade chronic inflammation: A systematic review of the literature. Molecules, 25(19), 4378. https://doi.org/10.3390/molecules25194378

Yang, P. M., Chen, H. Z., Huang, Y. T., Hsieh, C. W., & Wung, B. S. (2017). Lycopene inhibits NF-κB activation and adhesion molecule expression through Nrf2-mediated heme oxygenase-1 in endothelial cells. International Journal of Molecular Medicine, 39(6), 1533–1540. https://doi.org/10.3892/ijmm.2017.2964