¹Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Sriwijaya, Indralaya, Sumatera Selatan 30662, Indonesia
²Phytopharmaceutical Research Center (PRC), Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Sriwijaya, Indralaya, Sumatera Selatan 30662, Indonesia
³Department of Pharmacy, STIKES Aisyiyah Palembang, Sumatera Selatan 30152, Indonesia
⁴Research Center for Food Technology and Processing, National Research and Innovation Agency (BRIN), Playen Gunung Kidul, D.I. Yogyakarta 55861, Indonesia
⁵Research Center for Vaccine and Drug, Research Organization for Health, National Research and Innovation Agency (BRIN), Cibinong, Bogor 16911, Indonesia
⁶Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Sriwijaya, Indralaya, Sumatera Selatan 30662, Indonesia
⁷Faculty of Pharmacy, Universitas Gadjah Mada, Sleman, D.I. Yogyakarta 55281, Indonesia
⁸PT Ronature Teknologi Indonesia, Druwo Sewon Bantul, D.I. Yogyakarta 55188, Indonesia
⁹Faculty of Medical, Universitas Sriwijaya, Palembang Sumatera Selatan 30114, Indonesia DOI : 10.29228/jrp.2022.00 The gambier leaf from Uncaria gambir (W.Hunter) Roxb. is one of the promising natural agents as an antidiabetic candidate. Through an in silico approach, the study delves into the mechanisms of the extract's potential compounds, aiming to comprehend the molecular mechanisms underlying its antidiabetic activity. Additionally, an investigation was conducted to determine the most advantageous outcome of gambier leaf extract and the characteristics of the ideal extract. The extraction method used in the study was ultrasound-assisted extraction (UAE). Data analysis was done using a full factorial design 23 modeling approach. The extraction process involved three key factors: time, temperature, and material-solvent ratio. The observed responses included yield, total flavonoid content (TFC), and antioxidant activity (IC50). Optimal results for the gambier leaf extract were achieved with a 30-minute extraction duration at 50°C using a material-solvent ratio of 1:10, which resulted in an extract yield value of 11.87%; total flavonoid content of 467.51 mgCE/g and antioxidant activity value (IC50) of 66.01 μg/mL with a desirability value of 0.998. The optimal gambier leaf extract characteristics are a moisture content of 0.13% and a drying shrinkage of 0.15. The optimal extract has been demonstrated to contain phenolic compounds, flavonoids, and tannins. The validation results for the optimal extract condition obtained are 95% PI low and 95% PI high. Network pharmacology identified five compounds and three target proteins associated with gambier leaf in treating type 2 diabetes mellitus. Molecular docking analysis indicated that the interactions between SRC receptor and nicotiflorin, AKT1, and nicotiflorin, as well as TNF and procyanidin B2, have biological activity in treatment type 2 diabetes mellitus. Keywords : Uncaria gambir (W.Hunter) Roxb.; diabetes mellitus; ultrasound-assisted extraction; factorial design; network pharmacology; molecular docking