Analisis Potensi Senyawa Aktif Ekstrak Daun Kesambi (Schleichera oleosa (Lour.) Oken) Dalam Mengaktivasi PPAR-γ Untuk Terapi Fibrosis Hati

INDONESIA:

Latar Belakang: Fibrosis hati adalah suatu respon dari kerusakan hati, berupa akumulasi progresif Extracellular Matrix (ECM) yang dapat merusak struktur dan fungsi hati. Daun kesambi (Schleichera oleosa) mengandung senyawa yang berperan sebagai aktivator PPAR-γ melalui penghambatan aktivasi sel stellata hepatik yang dianggap memiliki potensi untuk terapi fibrosis hati. Tujuan: Analisis potensi terapi fibrosis hati ekstrak daun kesambi melalui aktivasi PPAR-γ secara in silico. Metode: Penelitian ini menggunakan molecular docking untuk memprediksi interaksi senyawa yang terkandung dalam ekstrak daun kesambi dengan reseptor PPAR-γ. LC-HRMS digunakan untuk melakukan metabolite profiling ekstrak daun kesambi. Analisis menggunakan SwissADME digunakan untuk skrining senyawa berdasarkan kriteria Hukum Lima Lipinski, human intestinal absorption (HIA), non blood-brain barrier (BBB) permeant, dan P-glycoprotein (P-gp) nonsubstrat. Perangkat lunak PyRx dan Discovery Studio Visualizer digunakan untuk melakukan uji in silico. Hasil: Dari hasil metabolite profiling didapatkan 98 senyawa yang selanjutnya dilakukan skrining menggunakan SwissADME sehingga didapatkan 22 senyawa yang lolos skrining. Analisis molecular docking menunjukkan senyawa Fahydroxy(4:0)]N-(3S-hydroxy-butanoyl)-homoserinelactone memiliki binding affinity sebesar -6,6 kcal/mol sehingga didapatkan hasil afinitas yang kuat terhadap reseptor PPAR-γ mendekati binding affinity obat pioglitazone. Visualisasi hasil docking mengidentifikasi interaksi hidrogen dan hidrofobik antara senyawa tersebut dan PPAR-γ. Kesimpulan: Senyawa Fahydroxy(4:0)]N-(3S-hydroxy-butanoyl)-homoserinelactone memiliki binding affinity dari ekstrak daun kesambi memiliki potensi sebagai terapi fibrosis hati melalui aktivasi PPAR-γ secara in silico.

ENGLISH:

Background: Liver fibrosis is a response to liver damage, characterized by the progressive accumulation of Extracellular Matrix (ECM) that can damage liver structure and function. Kesambi leaves (Schleichera oleosa) contain compounds that act as PPAR-γ activators by inhibiting the activation of hepatic stellate cells, which are considered to have potential for liver fibrosis therapy. Objective: To analyze the therapeutic potential of kesambi leaf extract for liver fibrosis through PPAR-γ activation in silico. Methods: This study used molecular docking to predict the interaction of compounds contained in kesambi leaf extract with the PPAR-γ receptor. LC-HRMS was used to perform metabolite profiling of kesambi leaf extract. Analysis using SwissADME was used to screen compounds based on the criteria of Lipinski's Five Rules, human intestinal absorption (HIA), non-blood-brain barrier (BBB) permeant, and P-glycoprotein (P-gp) nonsubstrate. PyRx and Discovery Studio Visualizer software were used to perform in silico testing. Results: From the metabolite profiling results, 98 compounds were obtained, which were then screened using SwissADME, resulting in 22 compounds passing the screening. Molecular docking analysis showed that the compound Fahydroxy(4:0)]N-(3S-hydroxy-butanoyl)-homoserinelactone had a binding affinity of -6.6 kcal/mol, indicating a strong affinity for the PPAR-γ receptor, close to the binding affinity of the drug pioglitazone. Visualization of the docking results identified hydrogen and hydrophobic interactions between the compound and PPAR-γ. Conclusion: The compound Fahydroxy(4:0)]N-(3S-hydroxy-butanoyl)-homoserinelactone from kesambi leaf extract has the potential as a therapy for liver fibrosis through PPAR-γ activation in silico.