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

Rashid Mia, Md. Abdur and Ahmed, Qamar Uddin and Ferdosh, Sahena and Helal Uddin, A.B.M. and Awal, Md. Shihabul and Sarian, Murni Nazira and Sarker, Md. Zaidul Islam and Zakaria, Zainul Amiruddin (2022) 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. Metabolites, 12. p. 1267. ISSN 2218-1989

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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, itwasconcludedthattheSCE-2possessesastrong 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.

Item Type:	Article (Journal)
Uncontrolled Keywords:	Phaleria macrocarpa fruit; subcritical CO2 extract; bioactive compounds; α-glucosidase; molecular dynamic simulations; network pharmacology
Subjects:	Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Pharmacy Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry Kulliyyah of Science Kulliyyah of Science > Department of Plant Science
Depositing User:	Dr Qamar Uddin Ahmed
Date Deposited:	27 Dec 2022 14:52
Last Modified:	27 Dec 2022 14:54
URI:	http://irep.iium.edu.my/id/eprint/102370

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