ABSTRACT
This study aims to identify the phytochemical profile of Apis mellifera propolis and explore the potential of its anti-diabetic activity through inhibition of α-amylase (α-AE), α-glucosidase(α-GE), as well as novel antidiabetic compounds of propolis. Apis mellifera propolis extract (AMPE) exhibited elevated polyphenol 33.26±0.17 (mg GAE/g) and flavonoid (15.45±0.13â mg RE/g). It also indicated moderate strong antioxidant activity (IC50 793.09±1.94â µg/ml). This study found that AMPE displayed promising α-AE and α-GE inhibition through inâ vitro study. Based on LC-MS/MS screening, 18 unique AMPE compounds were identified, with majorly belonging to anthraquinone and flavonoid compounds. Furthermore, in silico study determined that 8 compounds of AMPE exhibited strong binding to α-AE that specifically interacted with its catalytic residue of ASP197. Moreover, 2 compounds exhibit potential inhibition of α-GE, by interacting with crucial amino acids of ARG315, ASP352, and ASP69. Finally, we suggested that 2,7-Dihydroxy-1-(p-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene and 3(3-(3,4-Dihydroxybenzyl)-7-hydroxychroman-4-one as novel inhibitors of α-AE and α-GE. Notably, these compounds were initially discovered from Apis mellifera propolis in this study. The molecular dynamic analysis confirmed their stable binding with both enzymes over 100â ns simulations. The inâ vivo acute toxicity assay reveals AMPE as a practically non-toxic product with an LD50 value of 16,050â mg/kg. Therefore, this propolis may serve as a promising natural product for diabetes mellitus treatment.
Subject(s)
Antioxidants , Hypoglycemic Agents , Molecular Docking Simulation , Phytochemicals , Propolis , alpha-Amylases , alpha-Glucosidases , Propolis/chemistry , Propolis/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Antioxidants/pharmacology , Antioxidants/chemistry , Bees , Animals , alpha-Glucosidases/metabolism , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/metabolism , Phytochemicals/chemistry , Phytochemicals/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Molecular Dynamics Simulation , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacologyABSTRACT
MATERIALS AND METHODS: Fifty-six premolars were used in this study and divided by two evaluations: 28 teeth for apical sealing ability and 28 others for bond strength. Each study was assigned randomly into two groups of fourteen teeth: Group-1, final irrigation with 17% EDTA; Group-2, with 0.5% chitosan nanoparticles. Each group was further divided into two groups of 7 each: Group-A, final irrigation was applied for 1 minute; Group-B, for 3 minutes. All teeth were obturated with epoxy resin-based sealer and gutta-percha. In the apical sealing ability study, the obturated teeth were immersed in 2% methylene blue and observed under a stereomicroscope (8x magnification). In the bond strength study, the teeth were tested using the push-out technique and observed under a stereomicroscope (40x magnification) to determine the failure type. Data from each evaluation were analysed with two-way ANOVA followed by the LSD test. RESULTS: Final irrigation using 0.5% chitosan nanoparticles produced the same apical sealing ability and bond strength as 17% EDTA (p > 0.05). A significant difference occurred between application times (p < 0.05). The failure type was observed predominantly as cohesive, and the least was adhesive. CONCLUSION: Regardless of the final irrigation solution used, 3-minute application time produced greater apical sealing ability and push-out bond strength than 1-minute application time.
