Skripsi

Skrining Aktivitas Ekstrak Daun Insulin (Smallanthus Sonchifolius) sebagai Insulin Sensitizer pada Diabetes Melitus Tipe 2: Studi In Silico = Screening of Yacon (Smallanthus Sonchifolius) Leaf Extract as Insulin Sensitizer in Type 2 Diabetes Mellitus: In Silico Study.

Diabetes Melitus (DM) tipe 2 menimbulkan beban kesehatan yang krusial di dunia. Diperlukan pengembangan agen terapeutik baru yang memiliki efektivitas setara atau lebih baik dengan efek samping minimal dibandingkan terapi farmakologis yang telah ada. Penelitian ini bertujuan untuk melakukan skrining aktivitas senyawa aktif ekstrak daun insulin (Smallanthus sonchifolius) sebagai insulin sensitizer multitarget potensial menggunakan pendekatan in silico. Penelitian ini menggunakan desain komputasional (in silico) deskriptif. Senyawa bioaktif dari ekstrak daun insulin diidentifikasi melalui tinjauan literatur. Analisis farmakologi jejaring dilakukan untuk memprediksi target terapi. Target protein untuk simulasi penambatan molekuler dipilih dari irisan target terapi senyawa bioaktif dan hub nodes resistensi insulin. Penambatan molekuler dilakukan menggunakan AutoDock Vina pada situs penambatan ligan aktivator dan inhibitor pada ketiga protein target. Sebanyak 61 senyawa bioaktif daun insulin berhasil diidentifikasi. Tiga hub nodes (PIK3CA, AKT1, dan PDPK1) dipilih sebagai target penambatan molekuler. Hasil penambatan molekuler menunjukkan afinitas ikatan yang kuat dan valid dari senyawa bioaktif daun insulin terhadap target, baik pada situs penambatan ligan aktivator maupun inhibitor PI3Kα, Akt1, dan PDK1. Senyawa seperti cynarin, asam kaurenoat, dan quercitrin diprediksi berinteraksi kuat dengan situs penambatan aktivator alosterik protein target (PI3Kα, Akt1, dan PDK1 ) dan merupakan kandidat insulin sensitizer potensial yang memerlukan penyelidikan in vitro dan in vivo lebih lanjut.
Kata Kunci: Daun Insulin, Diabetes Melitus Tipe 2, Farmakologi Jejaring, Insulin Sensitizer, Penambatan Molekuler, Smallanthus sonchifolius


Type 2 Diabetes Mellitus (DM) poses a crucial health burden worldwide. The need exists for the development of new therapeutic agents that possess equivalent or superior effectiveness with minimal side effects compared to existing pharmacological therapies. This study aims to screen the activity of active compounds in Smallanthus sonchifolius leaf extract as potential multi-target insulin sensitizers using an in silico approach. This study utilized a descriptive computational (in silico) design. Bioactive compounds from the insulin leaf extract were identified through a literature review. Network pharmacology analysis was conducted to predict therapeutic targets. Protein targets for molecular docking simulation were selected from the intersection of the predicted therapeutic targets and the hub nodes of insulin resistance. Molecular docking was performed using AutoDock Vina on both the activator and inhibitor ligand binding sites of the target proteins. A total of 61 bioactive compounds from insulin leaves were successfully identified. Three hub nodes (PIK3CA, AKT1, and PDPK1) were selected as molecular docking targets. The molecular docking results demonstrated a strong and valid binding affinity of the insulin leaf bioactive compounds to the targets, at both the activator and inhibitor ligand binding sites of PI3Kα, Akt1, dan PDK1 . Compounds such as cynarin, kaurenoic acid, and quercitrin are predicted to interact strongly with the allosteric activator binding sites of the target proteins (PI3Kα, Akt1, dan PDK1 ). These compounds are identified as potential insulin sensitizer candidates requiring further in vitro and in vivo investigation.
Key words: Insulin Leaf, Insulin Sensitizer, Molecular Docking, Network Pharmacology, Smallanthus sonchifolius, Type 2 Diabetes Mellitus