Syzygium samarangense leaf extract exhibits distinct antidiabetic activities: Evidences from in silico and in vivo studies
Rasha M. H. Rashied, Mohamed A. O. Abdelfattah, Hesham A. El-Beshbishy, Assem M. El‐Shazly, Mona F. Mahmoud, Mansour Sobeh
Abstract
The wax apple, Syzygium samarangense, is widely used in traditional medicine. We have previously described a plethora of biological activities from its leaf extract. These include antioxidant, anti-inflammatory, antiulcer, antitrypanosomal and hepatoprotective effects. Here, we explored the antidiabetic activities from the bioactive leaf extract in silico on two crucial receptors involved in the management of diabetes disease namely peroxisome proliferator activated receptor gamma (PPARɣ) and glucagon like peptide-1 (GLP-1) and in vivo against streptozotocin-induced diabetic rats. Altogether, 457 secondary metabolites belonging to 10 classes (phenolic acids (86 compounds), flavonoids (139 compounds), anthocyanins (61 compounds), alkylphenols (17 compounds), chalcone (15 compounds), stilbenes (9 compounds), lignans (29 compounds), tannins (29 compounds), tyrosols (13 compounds), and terpenes and others (59 compounds), were docked into the active site of PPARɣ and GLP-1 receptors. From the PDB codes used for each receptor, the co-crystallized ligand was extracted and docked together with a known reference ligand. This was done simultaneously with docking the extract’s compounds to serve as references for comparative purposes. Out of the docked candidates, the top 30 compounds affording the best docking scores were compiled for further inspection and they appeared to exhibit better scores than the respective co-crystallized and reference ligands, highlighting the antidiabetic potential of the tested extract. Nine compounds exhibited highly negative scores on both receptors, demonstrating their high probability of being potent antidiabetic agents through forming stable ligand-receptor complexes. These activities were also confirmed in STZ diabetic rats where the extract reduced the elevated levels of serum glucose and lipid peroxides and increased the declined serum insulin hormone level. Taking all together, S. samarangense can be a potential candidate for further investigations for the treatment of numerous health disorders including diabetes.