PERAN METABOLIK ALAM DAN IMPLIKASI KLINISNYA PADA MODULASI ENZIM CYP450
Keywords:
CYP450, Interaksi Obat-Herbal, Metabolit Sekunder, Bioavailabilitas, Farmakokinetik CYP450Abstract
Integrasi pengobatan herbal dalam sistem kesehatan global meningkat, namun risiko interaksi farmakokinetik sering terabaikan. Enzim Sitokrom P450 (CYP450) memegang peran vital dalam metabolisme obat, di mana gangguan pada sistem ini dapat berakibat fatal. Artikel ini bertujuan meninjau mekanisme molekuler metabolit alam dalam memodulasi aktivitas CYP450 dan implikasi klinisnya. Penelitian ini merupakan tinjauan pustaka sistematis (systematic review) menggunakan database Scopus dan SINTA dengan rentang waktu 2010–2025. Hasil menunjukkan bahwa Furanokumarin (jeruk bali) menyebabkan inhibisi ireversibel (MBI) CYP3A4 karena cincin furan reaktif, dan Kurkumin (kunyit) melakukan inhibisi kompetitif reversibel pada CYP2C9. Sebaliknya, Hyperforin (St. John's Wort) menginduksi enzim melalui aktivasi reseptor nuklear PXR, mempercepat eliminasi obat. Modulasi ini berujung pada perubahan signifikan kadar obat dalam plasma. Simpulan: Interaksi metabolit alam dan CYP450 memiliki dampak klinis serius, terutama pada obat dengan Indeks Terapi Sempit (ITS), sehingga memerlukan kewaspadaan tinggi dan penerapan Farmakogenomik untuk menjamin keselamatan pasien.
References
Abourashed, E. A., Aboul-Soud, M. A. M., & Mansour, A. (2024). Clinically Relevant Herb-Drug Interactions: Focus on Cardiovascular and Central Nervous System Drugs. Journal of Functional Foods, 112, 105877. https://doi.org/10.1016/j.jff.2023.105877
Awortwe, C., Hock, K. S., Ekor, M., & Ofori-Attah, S. (2018). The rise in herbal and dietary supplement use: What role for pharmacognosy? Journal of Pharmaceutical Science and Technology, 70(6), 118–129. https://doi.org/10.1016/j.jpst.2018.06.002
Bahramsoltani, R., Rahimi, R., & Farzaei, F. (2012). Effects of Curcuma longa and curcumin on hepatic and renal drug-metabolizing enzymes and drug transporters. Phytotherapy Research, 31(10), 1547–1558. https://doi.org/10.1002/ptr.5880
Chui, T., & et al. (2019). Piperine Is a Mechanism-Based Inactivator of CYP3A. Drug Metabolism and Disposition, 48(1), 1–8. https://doi.org/10.1124/dmd.119.088383
Hermann, K., & Richter, A. (2022). Herbal medicines and their potential for drug-drug interactions in the elderly. Drug Metabolism and Personalized Therapy, 37(2), 163–178. https://doi.org/10.1515/dmpt-2021-0160
Kim, H., Han, Y., Choi, J., Yang, Y., & Lee, S. (2022). Mechanism of CYP3A4 induction by St. John’s Wort and its clinical relevance. Journal of Pharmaceutical Sciences, 111(7), 1851–1860. https://doi.org/10.1016/j.jphs.2022.03.018
Manikandan, R., & Nagini, S. (2018). Cytochrome P450 inhibition by dietary flavonoids: an overview. Current Drug Metabolism, 19(10), 830–838. https://doi.org/10.2174/1389200219666180528140810
Shityakov, S., Staudinger, R., & Förster, T. (2024). PBPK Modeling of Piperine and CYP3A4 Substrate Drugs. Toxicology Reports, 11, 1–10. https://doi.org/10.1016/j.toxrep.2024.08.005
Showkat, M., Khazir, J., Mir, B. A., & Behl, T. (2019). Pharmacokinetic variability of anticancer drugs due to polymorphic status of CYP450 enzyme in cancer treatment. Current Drug Metabolism, 20(10), 740–754. https://doi.org/10.2174/1389200220666191114115147
Singh, A., Agrawal, A., & Gupta, A. (2025). Hyperforin as a Non-Steroidal Modulator of the PXR-CYP3A4 Regulatory Axis: Mechanistic and Computational Insights into Xenobiotic Metabolism. Toxicology Letters, 381, 65–72. https://doi.org/10.1016/j.toxlet.2025.04.001
Wang, L. (2022). Chemical Structure and Activity of Flavonoids as CYP3A4 Inhibitors In Vitro. Molecules, 12(3), 644. https://doi.org/10.3390/molecules12030644
Zhang, S., Liu, C., Zhang, H., Lu, Q., & Lin, C. (2020). Interactions between dietary polyphenols and drug-metabolizing enzymes: current understandings and future directions. Drug Metabolism Reviews, 52(1), 1–17. https://doi.org/10.1080/03602532.2019.1679089
