Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec 15;12(12):1267.
doi: 10.3390/metabo12121267.

In Vitro, In Silico and Network Pharmacology Mechanistic Approach to Investigate the α-Glucosidase Inhibitors Identified by Q-ToF-LCMS from Phaleria macrocarpa Fruit Subcritical CO2 Extract

Md Abdur Rashid Mia  1 , Qamar Uddin Ahmed  2 , Sahena Ferdosh  3   4 , Abul Bashar Mohammed Helaluddin  2 , Md Shihabul Awal  5 , Murni Nazira Sarian  6 , Md Zaidul Islam Sarker  1   7 , Zainul Amiruddin Zakaria  8
Affiliations

In Vitro, In Silico and Network Pharmacology Mechanistic Approach to Investigate the α-Glucosidase Inhibitors Identified by Q-ToF-LCMS from Phaleria macrocarpa Fruit Subcritical CO2 Extract

Md Abdur Rashid Mia et al. Metabolites. .

Abstract

The fruit of Phaleria macrocarpa have been traditionally used as an antidiabetic remedy in Malaysia and neighbouring countries. Despite its potential for diabetes treatment, no scientific study has ever been conducted to predict the inhibitor interaction of the protein α-glucosidase identified in an extract prepared with a non-conventional extraction technique. Hence, the major aim of this research was to evaluate the in vitro antioxidant, the α-glucosidase inhibitors, and the molecular dynamic simulations of the α-glucosidase inhibitors identified by Quadrupole Time-of-Flight Liquid Chromatography Mass Spectrometry (Q-ToF-LCMS) analysis. Initially, dry fruit were processed using non-conventional and conventional extraction methods to obtain subcritical carbon dioxide extracts (SCE-1 and SCE-2) and heating under reflux extract (HRE), respectively. Subsequently, all extracts were evaluated for their in vitro antioxidative and α-glucosidase inhibitory potentials. Subsequently, the most bioactive extract (SCE-2) was subjected to Q-ToF-LCMS analysis to confirm the presence of α-glucosidase inhibitors, which were then analysed through molecular dynamic simulations and network pharmacology approaches to confirm their possible mechanism of action. The highest inhibitory effects of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and α-glucosidase on SCE-2 was found as 75.36 ± 0.82% and 81.79 ± 0.82%, respectively, compared to the SCE-1 and HRE samples. The Q-ToF-LCMS analysis tentatively identified 14 potent α-glucosidase inhibitors. Finally, five identified compounds, viz., lupenone, swertianolin, m-coumaric acid, pantothenic acid, and 8-C-glucopyranosyleriodictylol displayed significant stability, compactness, stronger protein-ligand interaction up to 100 ns further confirming their potential as α-glucosidase inhibitors. Consequently, it was concluded that the SCE-2 possesses a strong α-glucosidase inhibitory effect due to the presence of these compounds. The findings of this study might prove useful to develop these compounds as alternative safe α-glucosidase inhibitors to manage diabetes more effectively.

Keywords: Phaleria macrocarpa fruit; bioactive compounds; molecular dynamic simulations; network pharmacology; subcritical CO2 extract; α-glucosidase.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chromatogram of Q-ToF-LCMS identified compounds.
Figure 2
Figure 2
2D structures of the tentative compounds identified by Q-ToF-LCMS analysis.
Figure 2
Figure 2
2D structures of the tentative compounds identified by Q-ToF-LCMS analysis.
Figure 3
Figure 3
3D superimposed diagram of the bioactive compounds (m-coumaric acid, pantothenic acid, xestoaminol C, 2,3,4′-trihydroxy-4-methoxybenzophenone, C16 sphinganine, swertianin, emmotin A, phytosphingosine, 1-monopalmitin, lupenone, 3-lsomangostin hydrate, swertianolin, 8-C-glucopyranosyleriodictylol, longispinogenin), quercetin and their binding site on the domain A of α-glucosidase enzyme (3A4A).
Figure 4
Figure 4
The 2D diagram of the α-glucosidase (3A4A) and 14 compounds, quercetin and ADG binding interactions.
Figure 5
Figure 5
The RMSD values of the selected six compounds, viz., lupenone (CID: 92158), swertianolin (CID: 5281662), m-coumaric acid (CID: 637541), pantothenic acid (CID: 6613), phytosphingosine (CID: 122121), and 8-C-glucopyranosyleriodictylol (CID: 42607963), in association with the targeted protein α-glucosidase (PDB ID: 3A4A) are depicted by specific colour.
Figure 6
Figure 6
The RMSF values of the six selected compounds, viz., lupenone (CID: 92158), swertianolin (CID: 5281662), m-coumaric acid (CID: 637541), pantothenic acid (CID: 6613), phytosphingosine (CID: 122121), and 8-C-glucopyranosyleriodictylol (CID: 42607963), in association with the targeted protein α-glucosidase (PDB ID: 3A4A) are shown by specific colour.
Figure 7
Figure 7
The molecular surface area (MolSA) of the of the selected six compounds, viz., lupenone (CID: 92158), swertianolin (CID: 5281662), m-coumaric acid (CID: 637541), pantothenic acid (CID: 6613), phytosphingosine (CID: 122121), and 8-C-glucopyranosyleriodictylol (CID: 42607963), in association with the targeted protein α-glucosidase (PDB ID: 3A4A) are shown by specific colour.
Figure 8
Figure 8
The radius of gyration (Rg) of the selected six compounds, viz., lupenone (CID: 92158), swertianolin (CID: 5281662), m-coumaric acid (CID: 637541), pantothenic acid (CID: 6613), phytosphingosine (CID: 122121), and 8-C-glucopyranosyleriodictylol (CID: 42607963), in association with the targeted protein α-glucosidase (PDB ID: 3A4A) are shown by specific colour.
Figure 9
Figure 9
The solvent accessible surface area (SASA) of the selected six compounds, viz., lupenone (CID: 92158), swertianolin (CID: 5281662), m-coumaric acid (CID: 637541), pantothenic acid (CID: 6613), phytosphingosine (CID: 122121), and 8-C-glucopyranosyleriodictylol (CID: 42607963), in association with the targeted protein α-glucosidase (PDB ID: 3A4A) are shown by specific colour.
Figure 10
Figure 10
The polar surface area (PSA) of the selected six compounds, viz., lupenone (CID: 92158), swertianolin (CID: 5281662), m-coumaric acid (CID: 637541), pantothenic acid (CID: 6613), phytosphingosine (CID: 122121), and 8-C-glucopyranosyleriodictylol (CID: 42607963), in association with the targeted protein α-glucosidase (PDB ID: 3A4A) are shown by specific colour.
Figure 11
Figure 11
Network of protein interaction.
Figure 12
Figure 12
Compound-Target-Pathway Network.
Figure 13
Figure 13
GO Molecular function (A), GO cellular component (B), GO Biological Process (C), KEGG pathway 2021 (D).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Hossain U., Das A.K., Ghosh S., Sil P.C. An overview on the role of bioactive α-glucosidase inhibitors in ameliorating diabetic complications. Food Chem. Toxicol. 2020;145:111738. doi: 10.1016/j.fct.2020.111738. - DOI - PMC - PubMed
    1. Kumar Thakur A., Kumar Y., Goyal R.K. Pharmacotherapeutics of miglitol: An α-glucosidase inhibitor. J. Anal. Pharm. Res. 2018;7:617–619. doi: 10.15406/japlr.2018.07.00292. - DOI
    1. Chaudhury A., Duvoor C., Reddy Dendi V.S., Kraleti S., Chada A., Ravilla R., Mirza W. Clinical review of antidiabetic drugs: Implications for type 2 diabetes mellitus management. Front. Endocrinol. 2017;8:6. doi: 10.3389/fendo.2017.00006. - DOI - PMC - PubMed
    1. Brownlee I.A., Gill S., Wilcox M.D., Pearson J.P., Chater P.I. Starch digestion in the upper gastrointestinal tract of humans. Starch-Starke. 2018;70:1700111. doi: 10.1002/star.201700111. - DOI
    1. He J.H., Chen L.X., Li H. Progress in the discovery of naturally occurring antidiabetic drugs and in the identification of their molecular targets. Fitoterapia. 2019;134:270–289. doi: 10.1016/j.fitote.2019.02.033. - DOI - PubMed

LinkOut - more resources