In Silico Testing of Cocoa Pod Husk (Theobroma cacao L.) and Kersen Leaves (Muntingia calabura L.) Extracts as Candidate Drugs for Type 2 Diabetes

Diabetes mellitus is a metabolic disorder caused by elevated blood glucose levels. The incidence of diabetes mellitus continues to rise globally, including in Indonesia. Type 2 diabetes mellitus is the most common type due to the inability of pancreatic beta cells to produce sufficient insulin. Kersen leaves (Muntingia calabura L.) and cocoa pod husk (Theobroma cacao L.) are natural ingredients rich in quercetin and are widely found in Indonesia. A higher quercetin content correlates with its potential as an antidiabetic candidate. The aim of this research is to develop a standardized comprehensive herbal medicine from a combination of cocoa pod husk extract and kersen leaves extract, which is expected to produce more potent antidiabetic activity with a clearly understood mechanism. This research employs an experimental laboratory method, including in silico testing, to determine the target proteins of bioactive compounds and analyze their interactions with alpha-glucosidase and GLUT4, as well as to obtain preliminary toxicity data. The in silico results show that quercetin has the best binding affinity compared to natural AGI ligands and GLUT4 target macromolecules. There is no amino acid residue similarity interaction was found between quercetin and the target macromolecules of AGIs and GLUT4, suggesting that quercetin may potentially bind to eNOS and HIF-1? receptors. The pharmacokinetic predictions indicate that quercetin has a good pharmacokinetic profile, as it meets several of Lipinski's Rule of Five criteria, making it suitable for oral use.