Analisis in silico peran seenyawa aktif ekstrak daun kesambi (Schleichera oleosa (Lour.) Oken) dalam inhibisi platelet derived growth factor receptor (PDGFR) untuk terapi fibrosis hati

INDONESIA:

Latar Belakang: Fibrosis hati merupakan awal dari berbagai penyakit hati mematikan yang berujung pada sirosis hati, kondisi di mana hati sudah tidak dapat menjalankan fungsinya dengan baik dan memerlukan transplantasi hati. Tanaman kesambi (Schleichera oleosa (Lour.) Oken) menjadi kandidat terapi fibrosis hati melaui kemampuan antikanker, antioksidan, dan antimikroba yang dimiliki pada metabolit sekundernya, terutama pada bagian daun. Oleh karena itu, penelitian in silico kandungan senyawa aktif pada daun kesambi penting dilakukan, terutama terhadap inhibisi PDGFR sebagai salah satu mediator fibrosis. Metode: Identifikasi senyawa aktif dilakukan menggunakan LC-HRMS. Senyawa dinyatakan layak uji apabila sebelumnya lolos tahap skrining dengan kriteria memenuhi Aturan Lima Lipinski, non blood-brain barrier permeant, dapat terserap usus manusia dengan baik, dan bersifat p-glycoprotein nonsubstrat. Skrining senyawa layak uji dilakukan menggunakan perangkat lunak SwissADME. Molecular docking dan visualisasi sesnyawa dilakukan menggunakan perangkat lunak PyRx dan Discovery Studio Visualizer. Hasil: Dari 98 senyawa yang ditemukan melalui metabolite profiling, 22 senyawa dinyatakan layak uji setelah skrining. Penelitian ini menemukan bahwa senyawa nobiletin adalah senyawa yang berpeluang menjadi kandidat terapi fibrosis hati, karena binding affinity sebesar -7.4kcal/mol yang mendekati ligan kontrol, disertai dengan sifat ikatan senyawa yang stabil serta tidak memiliki unfavorable bump. Kesimpulan: Senyawa aktif ekstrak daun kesambi memiliki potensi sebagai kandidat terapi bagi fibrosis hati melalui inhibisi PDGFR secara in silico.

ENGLISH:
Background: Liver fibrosis is the beginning of various fatal liver diseases that lead to liver cirrhosis, a condition in which the liver can no longer function properly and requires a liver transplant. The kesambi plant (Schleichera oleosa (Lour.) Oken) is a candidate for liver fibrosis therapy through its anticancer, antioxidant, and antimicrobial properties in its secondary metabolites, especially in the leaves. Therefore, in silico research on the content of active compounds in kesambi leaves is important, especially regarding PDGFR inhibition as a mediator of fibrosis. Method: Identification of active compounds was carried out using LC-HRMS. Compounds were declared eligible for testing if they previously passed the screening stage with the criteria of fulfilling Lipinski's Rule of Five, non-blood-brain barrier permeant, well absorbed by the human intestine, and p-glycoprotein non-substrate. Screening of eligible compounds was carried out using SwissADME software. PyRx and Discovery Studio Visualizer software were used to do the molecular docking process and compounds visualization. Results: Of the 98 compounds found through metabolite profiling, 22 compounds were declared eligible for testing after screening. This study found that the nobiletin compound is a potential candidate for liver fibrosis therapy, because the binding affinity is -7.4kcal/mol which is close to the control ligand, accompanied by stable compound binding properties and no unfavorable bumps. Conclusion: The active compound of kesambi leaf extract has potential as a candidate therapy for liver fibrosis through PDGFR inhibition in silico.