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PREDIKSI TOKSISITAS SENYAWA JAMU ANTI-HIPERTENSI DENGAN RESEPTOR ANGIOTENSIN II TIPE 1 (AGTR1) SECARA IN SILICO

Rizky Lestari | Lusi Agus Setiani Bio | Usep Suhendar Bio
DOI: https://doi.org/10.20956/mff.v27i2.27045
Article History

Submited : June 7, 2023
Published : August 31, 2023

Keywords:
Penggunaan jamu antihipertensi dimasyarakat merupakan salah satu pengobatan hipertensi. Kombinasi tanaman sebagai antihipertensi terdiri dari Imperatae rhizoma, Centella herba, Pyllanthi herba, Orhosiphonis folium, Curcumae rhizoma, dan Apii graviolentis. Jamu diketahui bekerja secara sinergis pada banyak reseptor, salah satunya adalah reseptor AGTR1. Sebagai skrining awal keamanan jamu antihipertensi dilakukan prediksi toksisitas berdasarkan interaksinya pada reseptor. Penelitian ini bertujuan memprediksikan interaksi senyawa jamu antihipertensi terhadap reseptor AGTR1 (PDB ID: 4ZUD) dan memprediksi toksisitas senyawa dengan interaksi terbaik secara in silico. Terdapat 196 senyawa dalam jamu antihipertensi yang akan diskrining menggunakan parameter Lipinski’s Rule of Five (ROF). Autodock 4.2 digunakan untuk memprediksi interaksi 126 senyawa yang memenuhi ROF. Dari hasil penambatan diperoleh 14 senyawa dan diambil 5 senyawa dengan interaksi terbaik untuk diprediksikan toksisitas akut dengan nilai LD50 dan toksisitas kronisnya dengan parameter, karsinogen, mutagen, hepatotoksik, dan nefrotoksik menggunakan tools Ochem, Protox II, dan Toxtree. Berdasarkan hasil penelitian menunjukan senyawa dengan interaksi terbaik adalah  alnustone, hinokinin, nirtetralin,  3-O-cis-p-coumaroylkaempferol, dan hypophyllanthin. Hypophyllanthin memiliki interaksi terbaik dengan  nilai konstanta inhibisinya 3,16 µM, energi bebas Gibbs (∆G) -7,5 kkal/mol, dan berikatan dengan 12 asam amino. Dari kelima senyawa tidak ada yang bersifat hepatotoksik; Senyawa alnustone diprediksi karsinogen mutagen; senyawa alnustone dan 3-O-cis-p-coumaroylkaempferol diprediksi nefrotoksik; serta senyawa hypophyllanthin dan nirtetralin diprediksi toksik dengan nilai LD50 500 mg/kg.

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Lestari, R., Lusi Agus Setiani, & Usep Suhendar. (2023). PREDIKSI TOKSISITAS SENYAWA JAMU ANTI-HIPERTENSI DENGAN RESEPTOR ANGIOTENSIN II TIPE 1 (AGTR1) SECARA IN SILICO. Majalah Farmasi Dan Farmakologi, 27(2), 52-57. https://doi.org/10.20956/mff.v27i2.27045

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