Analisis In-Silico Senyawa Diterpenoid Lakton Herba Sambiloto (Andrographis Paniculata Nees) Pada Reseptor Alpha-Glucosidase Sebagai Antidiabetes Tipe II
Abstract
ABSTRAK Diabetes mellitus (DM) tipe II merupakan penyakit kronis dengan jumlah penderita jutaan orang di dunia. Diabetes mellitus tipe II disebabkan oleh hormon insulin yang tidak mencukupi atau tidak efektif, sehingga tidak dapat bekerja secara normal. Enzim α-glukosidase bekerja pada dinding usus halus, dimana α-glukosidase akan memecah oligosakarida atau polisakarida menjadi glukosa yang dapat diserap oleh usus halus sehingga terjadi peningkatan kadar gula dalam darah. Herba sambiloto memiliki banyak senyawa diterpenoid lakton yang mampu menurunkan kadar glukosa dalam darah. Senyawa diterpenoid lakton dapat menghambat penyerapan glukosa melalui penghambatan enzim α-glukosidase dan α-amilase. Penelitian ini bertujuan untuk mendapatkan kandidat obat yang berasal dari senyawa diterpenoid lakton herba sambiloto yang diharapkan mampu menurunkan kadar glukosa dalam darah dengan metode molecular docking. Sepuluh senyawa aktif diterpenoid lakton sambiloto akan dibandingkan dengan acarbose. Hasil dari penelitian ini, dua senyawa diterpenoid lakton yang memiliki energi bebas terendah dan residu asam amino yang sesuai adalah 14-deoksiandrografolida dengan nilai energi -8,0 kkal/mol dan 19-O-asetilanhidroandrografolida dengan nilai energi -8,7 kkal/mol, sedangkan acarbose memiliki nilai energi -7,6 kkal/mol. Bioavaibilitas oral menurut aturan Lipinski, ligan 14-deoksiandrografolida dan 19-O-asetilanhidroandrografolida juga memiliki bioavaibilitas oral yang tinggi dibandingkan acarbose. Dapat disimpulkan bahwa 14-deoksiandrografolida dan 19-O-asetilanhidroandrografolida dapat menurunkan kadar glukosa dalam darah. Kata kunci: α-glukosidase, diterpenoid lakton, sambiloto. ABSTRACT Diabetes mellitus type II is a chronic disease with the high prevalence worldwide. Diabetes mellitus is caused by insulin insufficiency or infectivity, so it cannot work normally. Sambiloto herb is one of medicinal herbs used to prevent diabetes mellitus. Sambiloto herb contained many diterpenoid lactone compounds that is active in lowering blood glucose levels. A diterpenoid lactone compound inhibits the absorption of glucose through inhibition of α-glucosidase and α-amilase enzymes. This research aims to obtain drug candidate derived from diterpenoid lactone compounds of sambiloto with molecular docking method. Ten active diterpenoid lactone compounds of sambiloto will be compared to acarbose. The result, two diterpenoid lactone compounds have the lowest free energy and suitable residue of amino acid, they are 14-deoxyandrographolide and 19-O-acetilanhydroandrographolide with the value of energy are -8,0 kcal/mol and -8,7 kcal/mol, respectively. Acarbose has the value of energy -7,6 kcal/mol. Oral bioavailability according to Lipinski rules, 14- deoxyandrographolide and 19-O-acetilanhydroandrographolide are also have high oral bioavailability compared to acarbose. The conclusion is, 14-deoxyandrographolide and 19-O-acetylanhydroandrographolide can lower glucose blood levels. Key words: α-glucosidase, diterpenoid lactone, docking, sambiloto.References
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