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Alpha glucosidase inhibition activity of phenolic fraction from Simarouba glauca: An in-vitro, in-silico and kinetic study.

ABSTRACT: A phenolic rich fraction purified from Simarouba glauca leaves was effective in alpha glucosidase inhibition. The purified fraction named 'fraction-14' had shown significant inhibition of yeast alpha glucosidase enzyme activity (IC50 = 2.4 ± 0.4 ?g/mL) when compared to anti-diabetic drug acarbose (IC50 = 2450 ± 24 ?g/mL). The purified fraction also had reasonable DPPH (IC50 = 14.4 ± 0.1 ?g/mL) and ABTS (IC50 = 7.6 ± 0.5 ?g/mL) free radical scavenging activity when compared to the standard ascorbic acid. The LC-MS analysis of bioactive 'fraction-14' revealed four compounds, eclalbasaponin-v (1), cyanidin-3-O-(2'galloyl)-galactoside (2), kaempferol-3-O-glucoside (3) and kaempferol-3-O-pentoside (4) for the first time in S. glauca in this study. The kinetic study of the 'fraction-14' indicates a mixed type of inhibition on the alpha glucosidase enzyme with K i , 6.2 ?g/mL. Docking studies showed promising binding energy for the compounds 2 (-7.769 kJ/mol), 3 (-7.04 kJ/mol) and 4 (-7.127 kJ/mol) against yeast alpha glucosidase which was better than acarbose (-6.867 kJ/mol). In conclusion, the phenolic rich fraction from S. glauca possessing good in-vitro antioxidant property and alpha glucosidase enzyme inhibition potential along with mixed inhibition kinetics. Also, better binding energy of compounds (1, 2 & 3) appears to contain potential lead-molecule for antidiabetic therapy.

SUBMITTER: Mugaranja KP

PROVIDER: S-EPMC7350133 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Alpha glucosidase inhibition activity of phenolic fraction from Simarouba glauca: An in-vitro, in-silico and kinetic study.

Mugaranja Kirana P KP Kulal Ananda A

Heliyon 20200708 7

A phenolic rich fraction purified from Simarouba glauca leaves was effective in alpha glucosidase inhibition. The purified fraction named 'fraction-14' had shown significant inhibition of yeast alpha glucosidase enzyme activity (IC50 = 2.4 ± 0.4 μg/mL) when compared to anti-diabetic drug acarbose (IC50 = 2450 ± 24 μg/mL). The purified fraction also had reasonable DPPH (IC50 = 14.4 ± 0.1 μg/mL) and ABTS (IC50 = 7.6 ± 0.5 μg/mL) free radical scave ...[more]

PMID: 32671273

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Project description:Simarouba glauca has been widely reported to be effective against a number of diseases and possesses medicinal benefits. Thus, the study was conducted to evaluate the toxic effect of aqueous leaf extract of Simarouba glauca (AESG) on relevant organs of male Wistar rats. The oral acute toxicity of AESG was evaluated according to the method described by Lorke. Sub-chronic toxicity of AESG was carried out in line with the guidelines of the Organization for Economic Co-operation and Development (OECD), using a total of twenty-four (24) male Wistar rats divided into four groups of six rats each. Test rats were orally administered AESG at doses of 500, 1000 and 2000 mg /kg body weight, respectively, daily for thirty (30) days. At the end of the study, rats were fasted overnight and sacrificed; the relevant biochemical and histopathology evaluation was carried out. Statistical analysis was conducted using the GraphPad Prism®, version 7. The data obtained indicated that the LD50 exceeded 5000 mg/kg. There were significant increases (P < 0.05) in percentage (%) body weight of test rats. There were no significant differences (P < 0.05) in mean liver, kidney, and heart weight/body weight (IOW/BWT) ratios. The AST activity was significantly lowered (P < 0.05) in rats administered AESG 2000 mg/kg. The ALP activities were significantly elevated (P < 0.05), while the GGT activities were significantly lowered (P < 0.05) in all groups of rats administered AESG. Plasma conjugated and unconjugated bilirubin were significantly lowered and elevated (P < 0.05), respectively in rats administered AESG 1000 and 2000 mg/kg. Plasma urea was significantly elevated (P < 0.05) in rats given AESG 1000 mg/kg. Test rats given AESG 2000 mg/kg recorded significant reduction (P < 0.05) in plasma sodium ions concentration. Rats given AESG 500 mg/kg recorded significant reduction (P < 0.05) in plasma bicarbonate ion levels. The findings suggest that AESG was not significantly toxic to the liver, kidney, and heart.

Project description:IntroductionThe current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays.MethodsIn this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis-Menten kinetics.ResultsIn AChE inhibitory assay, compounds 1 and 2 exhibited IC50 of 343.45 and 422.98 µM, respectively, against AChE enzyme. Similarly, both the compounds showed IC50 of 276.86 and 357.91 µM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC50 of 157.71 and 471.79 µM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC50 values of 297.98, 332.94, and 825.92 µM against DPPH, ABTS, and H2O2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2.ConclusionBoth succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.

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Alpha glucosidase inhibition activity of phenolic fraction from Simarouba glauca: An in-vitro, in-silico and kinetic study.

Publications

Alpha glucosidase inhibition activity of phenolic fraction from <i>Simarouba glauca</i>: An <i>in-vitro</i>, <i>in-silico</i> and kinetic study.

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