LC-MS metabolomics and molecular docking approaches to identify antihyperglycemic and antioxidant compounds from Melastoma malabathricum L. Leaf

The dried leaves of Melastoma malabathricum L., locally named Karamunting or Senduduk, is traditionally consumed in many regions in Indonesia as herbal tea to cure different illnesses, including diabetes. To date, information on the compounds responsible for their antidiabetic activity is still very rare. The study aimed to identify bioactive compounds of M. malabathricum L. leaves using LC-MS based metabolomics and molecular docking approaches. The leaves brewed with different methods were subjected to LC−MS measurements and several bioactivity tests (in vivo and in vitro antihyperglycemic, and in vitro antioxidant). LC−MS data were linked to the activity data using multivariate data analysis. Molecular docking using alpha-glucosidase, alpha-amylase, and insulin receptor as protein targets was used to verify the results and study the interaction between the identified compound and protein targets. As results, isoquercetin and myricitrin were identified as compounds strongly associated with alpha-amylase inhibitors, while rutin and epicatechin were identified as alpha-glucosidase inhibitors. Quercitrin, citric acid, quercetin, epicatechin, isoquercitrin, and 7-hydroxycoumarine were strongly correlated with both antihyperglycemic and antioxidant activities. The results of metabolomics were confirmed with molecular docking studies, which showed that some of these compounds acted as competitive inhibitors, while others acted as non-competitive ones. Possible synergism between epicatechin and citric acid in their interaction with IR was detected. Metabolomics combined with molecular docking efficiently identified and confirmed several antihyperglycemic and antioxidant compounds from M. malabathricum L., leaf. This study provides scientific evidence for the traditional use of M. malabathricum L. as an antidiabetic herbal.