Antihypertensive Activity Profile of Bangkirai Leaves (Shorea laevis Ridl.) Ethanol Extract on Angiotensin II (4ZUD) and β-Adrenergic (6PS5) Receptors
DOI:
https://doi.org/10.32382/mf.v20i2.994Kata Kunci:
Bangkirai leaves, Antihypertensive Activity, Angiotensin II Receptors, β-Adrenergic ReceptorsAbstrak
Profil Aktivitas Antihipertensi Ekstrak Etanol Daun Bangkirai (Shorea laevis Ridl.) Pada Reseptor Angiotensin II (4ZUD) dan β-Adrenergic (6PS5)
Hipertensi merupakan gangguan sistem kardiovaskular yang ditandai dengan tekanan sistolik ≥ 140mmHg dan diastolik ≥ 90mmHg. Kenaikan tekanan darah tersebut dikarenakan adanya mekanisme dari reseptor angiotensin II dan β-adrenergik, sehingga dalam pengembangan obat untuk hipertensi diperlukan senyawa dalam penghambatan aktivasi angiotensin I menjadi angiotensin II, serta pada β-adrenergik. Kalimantan, Indonesia memiliki keanekaragaman hayati yang berpotensi sebagai obat seperti Bangkirai (Shorea laevis Ridl.). Berdasarkan penelitian sebelumnya mengenai metabolit sekunder telah teridentifikasi berbagai senyawa yang berpotensi sebagai calon obat baru, misalnya sebagai antihipertensi. Penelitian ini bertujuan untuk mengetahui profil farmakologi dan mekanisme inhibisi angiotensin I pada reseptor 4ZUD serta inhibisi β-adrenergik pada reseptor 6PS5, dari ekstrak etanol daun bangkirai dengan cara melakukan molecular docking yang diawali dengan beberapa tahapan antara lain preparasi dan optimasi struktur senyawa uji serta preparasi struktur 3D reseptor 4ZUD dan 6PS5. Untuk mengetahui kebenaran metode maka dilakukan validasi terhadap senyawa ligand olmesartan untuk 4ZUD dan ligand propranolol untuk 6PS5. Berdasarkan penelitian yang telah dilakukan pada kedua reseptor diperoleh hasil untuk senyawa uji berupa MolDockScore, profil farmakologi absorbsi, distribusi, metabolisme, ekskresi serta toksisitas. Hasil MolDockScore menunjukkan bahwa senyawa Colchicine,N-desacetyl-N-[4-hydroxy-3,5-dimethoxycinnamoyl] memiliki nilai paling rendah yakni -146.503 pada reseptor 4ZUD dan -129.718 pada reseptor 6PS5 yang mendekati nilai ligan alami dibandingkan senyawa metabolit lainnya. Selain itu juga memberikan hasil yang baik berdasarkan profil farmakologi pada reseptor 4ZUD & 6PS5 antara lain HIA (95,73%), Caco2 (35.14nm/detik) dan PPB (87.67%). Hasil uji negatif juga ditunjukkan pada profil toksisitas mutagenik (Ames Test Method), non-mutagenik dan uji karsinogenik yang meliputi genotoksik dan nongenotoksik.
Hypertensive is a cardiovascular system disorder characterized by systolic pressure ≥ 140mmHg and diastolic ≥ 90mmHg. The increase in blod pressure is due to the mechanism of angiotensin II and β-adrenergic receptors, so in developing medicine for hypertension, compounds are needed to inhibit the activation of angiotensin II to angiotensin II, as well as β-adrenergic. Kalimantan, Indonesia has a biodiversity that has the potential as medicine such as Bangkirai (Shorea laevis Ridl.). Based on previous research on secondary metabolites, various compounds have been identified that have potential as new drug candidates, for example as antihypertensive. This study aims to determine the pharmacological profile and mechanism of angiotensin I inhibition at the 4ZUD and β-adrenergic receptors inhibition at the 6PS5 receptor, from ethanol extract of bangkirai leaves by carrying out molecular docking which begins with several stages including preparation and optimization of the structure of the test compound and structure preparation of 3D receptors 4ZUD and 6PS5. To find out the correctness of the method, validation was carried out on the Olmesartan ligand compound for 4ZUD and the propranolol ligand for 6PS5. Based on research carried out on both receptors, results were obtained for the test compounds in the form of MolDockScore, the pharmacological profile of absorption, distribution, metabolism, excretion, and toxicity. MolDockScore results show that the compound Colchicine, N-desacetyl-N-[4-hydroxy-3,5-dimethoxycinnamoyl] has the lowest values, namely -146.503 at the 4ZUD receptor dan -129.718 at the 6PS5 receptor, which is close to the natural ligand value compared to other metabolite compounds. Apart from that, it also provides good results based on the pharmacological profile of the 4ZUD and 6PS5 receptors including HIA (95.73%), Caco2 (35.14nm/second), and PPB (87.67%). Negative test results are also shown in the mutagenic toxicity profile (Ames Test Method), non-mutagenic, and carcinogenic tests which include genotoxic and nongenotoxic.
Referensi
Agus, ASR., Siswandono, Butar-Butar, MET., Taufiqurrahman, M., Fernandes, A., Maharani, R. 2024. Molecular Docking of The Keruing's (Dipterocarpus) Genus, Secondary Metabolites of The Dipterocarpaceae Families as Anti-Inflammation Against Cyclooxygenase-2 (Cox-2). International Journal of Applied Pharmaceutics. 16(2), 313-319. doi: 10.22159/ijap.2024v16i2.49836
Ali S, Mouton CD, Jabeen S, Zeng Q, Galloway G, Mendelson J. Suicide, Depression and CYP2D6: how are they linked? Curr Psychiatry. 2013 May;12(5):16-9.
Arwansyah, A., dkk. 2014. Simulasi Docking Senyawa Kurkumin dan Analognya Sebagai Inhibitor Reseptor Androgen pada Kanker Prostat. Current. Biochem. 1 (1).
Cernes, R., et al. 2011. Differential Clinical Profile of Candesartan Compared to Other Angiotensin Receptor Blockers. Vascular Health and Risk Management. Vol 7(1).
Daina A., Michielin O., dan Zoete V. 2017. SwissADME: A Free Web Tool to Evaluate the Pharmacokinetics, Drug-Likeness, and Medicinal Chemistry Friendliness of Small Molecules. Sci. Rep. 7(1). doi: 10.1038/srep42717Farzam, K., & Jan, A. 2023. Beta-blockers. StatPearls Publishing LLC. PMID: 30422501.
Fernandes, A. dan Maharini, R. 2018. KALA IRAI CERIA: Wajah Baru Aplikasi Herbal Karamuntin-Bangkirai-Kersen. Balai Besar Penelitian dan Pengembangan Ekosistem Hutan Dipterokarpa, Samarinda. Bogor: Forda Press.
Fernandes, A., Maharini, R., & Handayani, R. 2020. Bunga Rampai Bioprospeksi Tanaman Obat di Hutan Tropis Indonesia. In Bunga Rampai (Issue December 2019), p.23-45. ISBN:978-602-440-981-4.
Foti RS, Wahlstrom JL. CYP2C19 inhibition: the impact of substrate probe selection on in vitro inhibition profiles. Drug Metab Dispos. 2008;36(3):523-8. doi: 10.1124/dmd.107.019265, PMID 18048485.
Istiqomah, IN., dan Azizah, LN. 2022. Prevalensi Dan Risk Assessment Hipertensi Pada Petani Di Wilayah Kerja Puskesmas. Jurnal Keperawatan. 14(S1): 179-188. doi:10.32583/keperawatan.v14iS1.77
Kemenkes R.I. 2019. Faktor Risiko Penyebab Hipertensi. Diakses dari http://p2ptm.kemkes.go.id/infographic-p2ptm/hipertensi-penyakit-jantung-dan-pembuluh- darah/page/14/faktor-risiko-penyebab-hipertensi
Kemenkes R.I. 2019. Hipertensi Penyakit Paling Banyak Diidap Masyarakat. Diakses dari https://www.kemkes.go.id/article/view/19051700002/hipertensi-penyakit-paling-banyak-diidap-masyarakat.html
Kroemer RT. Structure-based drug design: docking and scoring. Curr Protein Pept Sci. 2007;8(4):312-28. doi: 10.2174/138920307781369382, PMID 17696866.
Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol. 2004 Dec;1(4):337-41. doi: 10.1016/j.ddtec.2004.11.007, PMID 24981612.
Liu YY, Feng XY, Jia WQ, Jing Z, Xu WR, Cheng XC. Identification of novel PI3Kδ inhibitors by docking, ADMET prediction, and molecular dynamics simulations. Comput Biol Chem. 2019;78:190-204. doi:10.1016/j.compbiolchem.2018.12.002, PMID 30557817.
Makatita, FA. 2020. Riset In silico Dalam Pengembangan Sains di Bidang Pendidikan, Studi Kasus: Analisis Potensi Cendana Sebagai Agen Anti-Aging. Jurnal ABDI (Sosial, Budaya dan Sains). 2(1).
Martin YC. A bioavailability score. J Med Chem. 2005 Apr 5;48(9):3164-70. doi: 10.1021/jm0492002, PMID 15857122.
Ma XL, Chen C, Yang J. Predictive model of blood-brain barrier penetration of organic compounds. Acta Pharmacol Sin. 2005;26(4):500-12. doi: 10.1111/j.1745-7254.2005.00068.x. PMID 15780201.
Muchtaridi, M., Dermawan, D. Yusuf, M. 2018. Molecular Docking, 3D Structure-Based Pharmacophore Modeling, and ADME Prediction of Alpha Mangostin and its Derivatives against Estrogen Receptor Alpha. Journal of Young Pharmacists. 10(3): 252-259. doi: 10.5530/jyp.2018.10.58.
Muhammad, N., Ibrahim, N., Ali, N.A.M., Din, L.B., Zakaria, Z., Yacoob, W.A., & Muslim, N. 2011. Chemical Composition, antioxidant and antibacterial properties of the essential oils of Shorea acuminate (Dipterocarpaceae). Journal of Essential Oil-bearing Plants, 14(6), 708-716. doi: 10.1080/0972060X.2011.10643993
Oyesakin YM, George DE, Fadare RY, Idris AY, Fadare OA. 2018. Molecular docking and in silico ADME prediction of substituted (E)-4-styryl-7,8-dihydroquinazolin-5(6H)-ones and 5-(E)-styryl pyrimidine[4,5-dypyrimidine-2,4(1H,3H)-diones as potential SERT inhibitors and antidepressants. Am J Pharmacol Sci., 6(1):25-32. doi: 10.12691/ajps-6-1-5.
Prasetiawati R, Suherman M, Permana B, Rahmawati R. 2021. Molecular docking study of anthocyanidin compounds against epidermal growth factor receptor (EGFR) as anti-lung cancer. Indonesian J Pharm Sci Technol, 8(1):8-20. doi: 10.24198/ijpst.v8i1.29872.
Prieto-Martínez, F. D., Arciniega, M., dan Medina-Franco, J. L. 2018. Acoplamiento Molecular: Avances Recientes y Retos. TIP Revista Especializada En Ciencias Químico-Biológicas. 21: 65–87. ISSN 2395-8723
Shityakov, S., Salvador, E., Forster, C. 2013. In silico, In Vitro And In Vivo Methods to Analyse Drug Permeation Across the Blood–Brain Barrier: A Critical Review. OA Anaesthetics. 1(2):13.
Sudrajat, S.D., & Kartika, R. 2016. Phytochemical analysis and antibacterial activity of leaf of red meranti, Shorea leprosula (Dipterocarpaceae). Jurnal Nusantara Bioscience, 8(1), 111-116. doi:10.13057/nusbiosci/n080119
Tjay, TH. dan Rahardja, K. 2015. Obat-obat Penting: Khasiat, Penggunaan dan Efek-efek Sampingnya. Edisi ke-VII. Departemen Kesehatan Republik Indonesia. Jakarta: PT. Gramedia. p.544.
Van Booven D, Marsh S, McLeod H, Carrillo MW, Sangkuhl K, Klein TE. Cytochrome P450 2C9-CYP2C9. Pharmacogenet Genomics. 2010 Apr;20(4):277-81. doi: 10.1097/FPC.0b013e3283349e84, PMID 20150829.
Wadood, A., Ahmed, N., Shah, L., Ahamd, A., Hassan, H., Shams, SJODD. 2013. In-Silico Drug Design: An Approach Which evolutionarised the Drug Discovery Process. OA Drug Design & Delivery. 1(1), 3.
WHO. 2021. Hypertension. Diakses pada 1 September 2023 dari https://www.who.int/health-topics/hypertension#tab=tab_1
Unduhan
Diterbitkan
Terbitan
Bagian
Lisensi
Hak Cipta (c) 2024 Media Farmasi
Artikel ini berlisensiCreative Commons Attribution-ShareAlike 4.0 International License.