Analisis Potensi Senyawa Aktif Ekstrak Daun Kesambi (Schleichera Oleosa (Lour.) Oken) Dalam Penghambatan Reseptor TGF- β1 Untuk Terapi Fibrosis Hati: Studi In Silico

INDONESIA:

Fibrosis merupakan kondisi yang membahayakan dan dapat menyebabkan kematian. Fibrosis hati pada stadium lanjut dapat menyebabkan sirosis, gagal hati, serta seringkali memerlukan tindakan transplantasi hati. Kesambi (Schleichera oleosa (Lour.) Oken) mengandung metabolit sekunder yang dianggap berpotensi sebagai antifibrosis. Analisis senyawa aktif yang terdapat dalam ekstrak daun kesambi serta potensinya dalam menghambat Reseptor TGF- β1 secara in in silico berdasarkan kriteria Lipinski Rule of Five, non Brain Blood Barrier (BBB) Permeant, Human Intestinal Absorption (HIA), dan sifat P-glycoprotein (P-gp) non substrat. Penelitian ini menggunakan metode LC-HRMS untuk mengetahui senyawa aktif dalam ekstrak daun Kesambi. Molecular docking digunakan untuk memprediksi interaksi senyawa hasil metabolite profiling dengan TGF- βR1 melalui perangkat lunak PyRx dan Discovery Studi Visualizer. Skrining ADME (Absorption, Distribution, Metabolism, and Excretion) senyawa dilakukan dengan software SwissADME. Dari hasil metabolite profiling ditemukan 98 senyawa aktif. Hasil skrining menggunakan SwissADME menghasilkan 22 dari 98 senyawa yang berpotensi sebagai obat oral dengan bioavailabilitas yang baik. Senyawa Nobiletin dan 3-[(3-Fluoro-4-methoxybenzyl)sulfonyl]-N-(2-methyl-2-propanyl)propanamide yang memiliki nilai binding affinity -7.7 dan -7.3, serta jenis ikatan hidrogen, elektrostatik, hidrofobik serta halogen yang cukup stabil dan kuat. Senyawa aktif ekstrak daun Kesambi memiliki potensi sebagai agen antifibrosis melalui penghambatan reseptor TGF- β1 secara in silico.

ENGLISH:

Fibrosis is a life-threatening condition that can lead to death. Liver fibrosis in its advanced stages can cause cirrhosis, liver failure, and often requires liver transplantation. Kesambi (Schleichera oleosa (Lour.) Oken) contains secondary metabolites that are considered to have antifibrotic potential. To analyze the active compounds in Kesambi leaf extract and their potential to inhibit TGF-β1 receptors in silico based on the Lipinski Rule of Five criteria, non-blood-brain barrier (BBB) permeant, human intestinal absorption (HIA), and P-glycoprotein (P-gp) non-substrate. This study used LC-HRMS to identify the active compounds in Kesambi leaf extract. Molecular docking was used to predict the interaction of compounds resulting from metabolite profiling with TGF-βR1 using PyRx and Discovery Studio Visualizer software. ADME (Absorption, Distribution, Metabolism, and Excretion) screening of compounds was performed using SwissADME software. Metabolite profiling identified 98 of active compounds. Screening using SwissADME identified 22 of 98 compounds potentially suitable as oral drugs with good bioavailability. The compounds Nobiletin and 3-[(3-Fluoro-4-methoxybenzyl)sulfonyl]-N-(2-methyl-2-propanyl)propanamide have binding affinities of -7.7 and -7.3, and also the types of hydrogen bonds, electrostatic bonds, hydrophobic bonds, and halogen bonds are quite stable and strong. The active compounds in Kesambi leaf extract have Potency as antifibrotic agents through the inhibition of TGF-β1 receptors through in silico studies.