IN SILICO STUDY OF Hibiscus Sabdariffa Linn. ACTIVE COMPOUNDS IN GLP-1R: POTENTIAL AS ANTIDIABETIC DRUG
Abstract
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to reduced insulin production and/or insulin resistance. GLP-1 can increase insulin secretion, improve insulin sensitivity, and lower the blood glucose levels by binding to the GLP-1 receptor (GLP-1R). Several plants have been used as antidiabetic drugs. This study aims to see the interactions of the active compounds in Hibiscus sabdariffa Linn. and GLP-1R in silico. The research started with internal validation of the receptor GLP-1 (6ORV), and then the native ligand was docked. The 6ORV receptor validation results have an RMSD value of 2.14Å. The results of docking scores of the 3 best active compounds Hibiscus sabdariffa Linn. are myricetin-3-arabinogalactoside (-10.64 kcal/mol), tetra-O-methyljeediflavanone (-9.95 kcal/mol), and ethyl chlorogenate acid (-7.73 kcal/mol). The amino acids that contribute to the affinity at the active site of the ligand bond with the receptor are Trp 297, Trp 203, Met 204, Phe 230, Try 220, Lys 197. These findings indicate that the active compound Hibiscus sabdariffa Linn. can bind directly to GLP-1R.
Keywords: Diabetes mellitus, Hibiscus sabdariffa Linn., GLP-1R
ABSTRAK
Diabetes melitus merupakan gangguan metabolisme yang ditandai dengan kondisi hiperglikemia akibat produksi insulin yang berkurang dan atau kondisi resistensi insulin. GLP-1 dapat meningkatkan sekresi, sensitivitas insulin, dan menurunkan kadar glukosa darah dengan cara mengikat reseptor GLP-1 (GLP-1R). Beberapa tanaman telah digunakan sebagai obat antidiabetes. Penelitian ini bertujuan untuk melihat bagaimana interaksi senyawa aktif dalam Hibiscus sabdariffa Linn. terhadap GLP-1R secara in silico. Penelitian dimulai dengan melakukan validasi internal reseptor GLP-1 (6ORV) kemudian dilakukan proses docking terhadap native ligand. Hasil validasi reseptor 6ORV mempunyai nilai RMSD 2.14Å. Hasil score docking 3 senyawa aktif Hibiscus sabdariffa Linn. terbaik adalah myricetin-3-arabinogalactoside (-10,64 kcal/mol), tetra-O-methyljeediflavanone (-9,95 kcal/mol), dan ethyl chlorogenate acid (-7,73 kcal/mol). Asam amino yang berperan terhadap afinitas pada sisi aktif ikatan ligan dengan reseptor adalah Trp 297, Trp 203, Met 204, Phe 230, Try 220, Lys 197. Temuan ini menunjukkan bahwa senyawa aktif Hibiscus sabdariffa Linn. dapat berikatan langsung dengan GLP-1R.
Kata kunci: Diabetes melitus, Hibiscus sabdariffa Linn., GLP-1R
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