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 (IC 50 = 2.4 ± 0.4 μg/mL) when compared to anti-diabetic drug acarbose (IC 50 = 2450 ± 24 μg/mL). The purified fraction also had reasonable DPPH (IC 50 = 14.4 ± 0.1 μg/mL) and ABTS (IC 50 = 7.6 ± 0.5 μg/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 μg/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.

Investigation of effective natural inhibitors for starch hydrolysing enzymes from Simaroubaceae plants by molecular docking analysis and comparison with in-vitro studies

“…The acarbose, miglitol, and voglibose which are standard inhibitors were used as controls during the study. The present study revealed that some of the ‘lead hit compounds’ including the recently identified compounds by our group have better binding affinity than the available drugs ( Mugaranja and Kulal, 2020 ). Further, the drug likeliness properties of the ‘lead hit compounds’ evaluated by absorption, distribution, metabolism, excretion, and toxicity (ADMET) test provides additional evidence to consider them as effective starch hydrolysing enzyme inhibitors.…”

“…In the present study total of 218 compounds have been docked against starch hydrolysing enzymes along with standard AAI and AGIs. Recently identified four compounds from Simarouba glauca ( Mugaranja and Kulal, 2020 ) are also included in this study along with the compounds identified by others ( Alves et al., 2014 ; Jiao et al., 2011 ; Kubo et al., 1993 ; Tan et al., 2012 ). The 2D structures of the majority of the compounds were retrieved from the PubChem database ( https://pubchem.ncbi.nlm.nih.gov/ ) in sdf format.…”

“…The plants from this family are traditionally known for the treatment of various diseases like malaria ( Muhammad et al., 2004 ), cancer ( Bedikian et al., 1979 ), and diseases caused by viruses and parasites ( Silva et al., 2010 ). Surprisingly, the detailed studies on antidiabetic and starch hydrolysing enzyme inhibition properties of the Simaroubaceae family were lacking except for a few studies on Quassia amara ( Husain et al., 2011 ), Brucea javanica ( NoorShahida et al., 2009 ), and Simarouba glauca ( Mugaranja and Kulal, 2020 ). Thus, in this study natural compounds identified in the Simaroubaceae family were used as ligands to find the ‘lead hit compounds’ as potent AAIs and/or AGIs using the molecular docking approach.…”

GC–MS analysis of phytocompounds and antihyperglycemic property of Hydrocotyle sibthorpioides Lam.

“…The purified fractions of Simarouba glauca and isolated phytocompound, Cyanidin-3-O-(2′galloyl)-galactoside exhibited stronger α-glucosidase enzyme inhibition both in in-vitro and in-silico study. The major interacting amino acids involved were His245, Pro309, Asp408, 349, Glu304, Arg439, Phe157, − 177, − 310, − 231, − 311, − 158, − 300, and Tyr313 for Cyanidin-3-O-(2′galloyl)-galactoside and Pro309, His239, − 279, Asp349, Ser156, Arg439, Thr215, Glu276, Asp214, Phe310, − 300, − 157, − 177, − 311, − 158, Tyr17, and Tyr313 for acarbose, respectively [44]. The biological properties of any plant extracts may be attributed to the phytochemicals present in the plant.…”

Antidiabetic Activity of Extract Combination of Orthosiphon aristatus and Oryza sativa L. var glutinosa

“…A total of 1 mg of an α-glucosidase enzyme from S. The inhibitory activity of α-glucosidase was calculated based on the absorption values at the wavelength of 400 nm using a UV-Vis spectrophotometer 13 . The IC50 value, whereas the extract concentration can inhibit 50% of the α-glucosidase enzyme activity, was calculated based on the linear regression equation 14 .…”