Marsectohexol and other pregnane phytochemicals derived from Gongronema latifolium as α-amylase and α-glucosidase inhibitors: in vitro and molecular docking studies

Abstract

This study employed in vitro and in silico techniques to screen isolated pregnane phytochemicals (P1-P4), as well as their source pregnane-rich chromatographic fractions, which were derived from Gongronema latifolium Benth (GLB), for their inhibitory potentials against α-amylase, α-glucosidase, and sucrase enzyme activities. The results show that, most pregnane-rich chromatographic fractions and isolated compounds exhibited good inhibitory activities against α-amylase, and α-glucosidase enzymes. Among the isolated compounds, marsectohexol (P2) is the most favourable structure that showed inhibition against α-amylase (IC 50 = 3.712 µg/mL) when compared with the reference inhibitor, acarbose ((IC 50 = 15.418 µg/mL). Based on negative and low value of ∆G (Gibb's free energy), docking scores revealed that, marsectohexol has the highest binding affinity (− 8.8 kcal/mol) to human pancreatic α-amylase (HPA) as compared to the standard acarbose (− 8.1 kcal/mol). Marsectohexol and the other phytocompounds were also found to dock into the active site of HPA; interacting with key catalytic amino acid residues (ASP197, GLU233 and ASP300), which are known to involve in the nucleophilic, and the acid/base catalysis of the enzyme. Although, the pregnane phytocompounds have considerable high affinity binding to the human lysosomal α-glucosidase, they interacted with pockets other than the active site. In conclusion, at least, marsectohexol and three other constituent pregnane phytochemicals of GLB are potential inhibitors of the carbohydrate-hydrolyzing enzymes. These compounds may account for the anti-hyperglyceamic and antidiabetic potentials of this food herb.

Inhibition mechanism of alpha-amylase, a diabetes target, by a steroidal pregnane and pregnane glycosides derived from Gongronema latifolium Benth

“…was reported. The observed inhibitory activity of the pregnane-rich plant extracts against the porcine pancreatic amylase in vitro ( Figure 2 ) and that of the isolated SPPs ( Figure 3 ) was expected as the fraction F1 (previously combined Fr.5 and Fr.6) is the source chromatographic fraction of compounds P1 and P2, while the F3 (derived from further fractionation of Fr.8) afforded P3 and P4 as reported earlier ( Gyebi et al, 2018 ; Ogunyemi et al, 2020 ). Depending on the experimental conditions, several studies have reported the range of alpha-amylase and alpha-glucosidase inhibitory activity of acarbose as 55%–82% ( Mohamed et al, 2012 ; Perez-Gutierrez and Damian-Guzman, 2012 ; Olubomehin et al, 2013 ).…”

“…Three bioactive pregnane-rich chromatographic fractions and the isolated steroidal pregnanes were selected for the current study. The isolated pregnane compounds comprise a pregnane marsectohexol (P1) and three pregnane glycosides, viz: iloneoside (P2), 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl]-17β-marsdenin (P3), and 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-canaropyranosyl]-17β-marsdenin (P4) ( Gyebi et al, 2018 ; Ogunyemi et al, 2020 ) as depicted in Figure 1 .…”

“…The enzyme alpha-amylase (1,4-α-D-glucan glucanohydrolase, EC 3.2.1.1) is a key therapeutic target that has been exploited for developing several synthetic drugs such as acarbose, voglibose, and miglitol ( Alqahtani et al, 2019 ). Several amylase inhibitors have also been identified from natural sources ( Ogunyemi et al, 2020 ; Lankatillake et al, 2021 ; Ogunyemi et al, 2022 ). The alpha-amylase mainly occurring in the saliva and pancreas ( Stiefel and Keller, 1973 ) helps to start the chemical process of carbohydrate breakdown by hydrolyzing the glycosidic bonds in starch and related substrate polysaccharides, transforming them into oligosaccharides and simple absorbable sugars.…”

“…is an antidiabetic plant that has been used in African traditional medicine against diabetic conditions ( Al-Hindi et al, 2016 ; Ogunyemi et al, 2020 ). Several experimental pieces of evidence also support the ethnopharmacological use of this plant as the antidiabetic potentials of its bioactive extracts, and fractions have been documented in vitro and in vivo for over a decade ( Akah et al, 2011 ; Chime et al, 2014 ; Al-Hindi et al, 2016 ; Ogunyemi et al, 2020 ). Such plants possessing antidiabetic activity mostly contain glycosides, pregnanes, alkaloids, terpenes, flavonoids, and carotenoids ( Malviya et al, 2010 ; Ardalani and Hejazi Amiri, 2021 ).…”

Structure-based virtual screening suggests inhibitors of 3-Chymotrypsin-Like Protease of SARS-CoV-2 from Vernonia amygdalina and Occinum gratissimum

“…Ethnopharmacological uses of herbs, spices, and medicinal plants are due to their wide range of biological activities in human health and diseases [61][62][63]. Among these, Vernonia amygdalina and Occinum gratissimum and their extracts have been extensively reported for their antiviral activities in vitro [19,20,22]; and thereby may be suggested as vegetal resources for bioactive compounds for the development of preventive nutraceuticals and drug candidates in COVID-19 infection [23].…”