Phytocomponents Derived From Naturally Growing Chamaedorea seifrizii as Novel α-Amylase Inhibitors for Diabetes...

Blocking the enzyme alpha-amylase is a promising approach for treating Type 2 diabetes. Although they have been employed as blood-sugar reducers, medicinal phytocompounds have limited ability to inhibit α-amylase. The bamboo plant Chamaedorea seifrizii is mostly used for its esthetic qualities and air-purifying capabilities. Further study is necessary because there are not many studies on this plant's phytochemical composition and anti-α-amylase capability. Therefore, this study's goal was chemical profiling, followed by an in vitro experiment to assess the anti-α-amylase capability of C. seifrizii's flowers and fruits, and an in silico docking of important bioactive chemicals against α-amylase. The bioactive ingredients in C. seifrizii auxiliary inflorescence acetone extract (CIAE) and C. seifrizii fruit acetone extract (CFAE) were identified using GC-FID. The web program Cb-dock2 was utilized for docking. Additionally, two-dimensional interactions between ligands and the target enzyme were examined. After molecular docking, molecular dynamics (MD) simulations, and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) computations were performed. The PASS prediction of every ligand and the in silico ADMET pharmacoinformatic perspective were evaluated. The α-amylase inhibition assay was used for wet lab validation. A total of 17 (in CIAE) and 21 (in CFAE) phytocomponents were identified by GC-FID. Major phytocompounds were phenethyl cinnamate (45%) in CIAE and nezukol in (10%) CFAE along with other minor components, such as resveratrol, hinokione, butylated hydroxyanisole, sandaracopimarinol (CFAE), larixol, taxodione, methyl pentanoate, and cedrene epoxide (CIAE). Docking analysis showed that every ligand from CIAE and CFAE effectively bound to the enzyme but with varied affinity. Sandaracopimarinol from CIAE and taxodione from CFAE were detected as best docked compounds with vina score ranging from 8.9 to 8.3, respectively. The stability of docked complexes was further confirmed by the post-MD analysis of the best docked structure, as seen by the root mean square deviation (RMSD) and radius of gyration (R_g) values. MM-PBSA analysis revealed best docked structure with binding energy -72.2 kJ mol^-1. According to the results of the in silico ADMET analysis, all the ligand molecules showed good absorption and did not cause any harmful effects. In a kinetic study, CIAE and CFAE were found to inhibit α-amylase in a noncompetitive way. To best of our knowledge, this is first time study reporting bioactive chemicals from C. seifrizii extracts exhibiting anti-α-amylase potential. To validate these results, more studies utilizing clinical trials and animal models are required. This study claimed that due to richness of phytocompounds, C. seifrizii extracts may help to block the enzyme α-amylase, which leads to the creation of new drugs for diabetes.