Uji Potensi Inhibisi Ekstrak Daun Sirih Merah terhadap Lipase Pankreas sebagai Antiobesitas secara In Silico

Abstract

Obesitas menjadi pemicu munculnya berbagai penyakit degeneratif, seperti stroke, jantung, diabetes tipe 2, dan resistensi insulin. Inhibitor lipase pankreas merupakan agen obat antiobesitas dengan kerja menginhibisi enzim lipase pankreas. Penelitian ini bertujuan melakukan pencarian dan prediksi aktivitas inhibisi terhadap lipase pankreas dari senyawa aktif daun sirih merah. Penelitian dimulai dengan penapisan virtual 60 ligan uji, prediksi stabilitas dan toksisitas ligan, validasi penambatan molekuler, penambatan molekuler, dan visualisasi 2D serta 3D. Hasil menunjukkan bahwa benzethonium octyloxyacetate, hydroxybenzoic acid β-D-glucosyl ester, dan anthocyanins memiliki potensi terbaik dalam menginhibisi enzim lipase pankreas berdasarkan penapisan virtual, stabilitas ligan, toksisitas ligan, energi afinitas, jumlah ikatan hidrogen dengan sisi aktif, jarak ikatan, dan konstanta inhibisi (Ki). Benzethonium octyloxyacetate memiliki nilai afinitas sebesar -8 kkal/mol, memiliki interaksi ikatan hidrogen pada residu His349 sisi aktif reseptor lipase pankreas (6KSM) dengan jarak ikatan 2,94 Å, dan nilai Ki sebesar 1,347 μM.

Obesity triggers the emergence of various degenerative diseases, such as stroke, heart disease, type 2 diabetes, and insulin resistance. Pancreatic lipase inhibitors are anti-obesity drug agents that work by inhibiting pancreatic lipase enzymes. This study aims to search and predict the inhibitory activity of pancreatic lipase from the active compound of red betel leaf. The research began with virtual screening of 60 test ligands, prediction of ligand stability and toxicity, validation method of molecular docking, molecular docking, 2D and 3D visualization. The results showed that benzethonium octyloxyacetate, hydroxybenzoic acid β-D-glucosyl ester, and anthocyanins had the best potential in inhibiting pancreatic lipase enzymes based on virtual screening, ligand stability, ligand toxicity, energy affinity, number of hydrogen bonds with active site, bond distance, and constants inhibition (Ki). Benzethonium octyloxyacetate has an affinity value of -8 kcal/mol, has a hydrogen bond interaction on the His349 residue on the active site of the pancreatic lipase receptor (6KSM) with a bond distance of 2,94 Å and Ki value of 1,347 μM.