Linking the Phytochemicals and the α-Glucosidase and α-Amylase Enzyme Inhibitory Effects of Nigella sativa Seed Extracts

Abstract

Nigella sativa L. (Ranunculaceae), commonly referred to as black seeds or black cumin, is used in popular medicine (herbal) all over the world for the treatment and prevention of several diseases, including diabetes. This study aims to investigate the inhibitory effect of N. sativa extracts and fractions against the activities of intestinal α-glucosidase and pancreatic α-amylase in vitro, and to explain the inhibitory effect of these fractions against these enzymes by identifying their active compounds responsible for this effect and determine their modes of inhibition. To do so, N. sativa hexane and acetone extracts were prepared and analyzed by GC–MS and HPLC–DAD, respectively. The hexane extract was further fractioned into eight different fractions, while the acetone extract generated eleven fractions. The extracts as well as the resulting fractions were characterized and evaluated for their potential in vitro antidiabetic activity using intestinal α-glucosidase and pancreatic α-amylase inhibitory assays in vitro. Hexane extract and fractions were less active than acetone extract and fractions. In the case of intestinal α-glucosidase activity, the acetone fraction SA3 had a high inhibitory effect on intestinal α-glucosidase activity with 72.26 ± 1.42%, comparable to the effect of acarbose (70.90 ± 1.12%). For the pancreatic α-amylase enzymatic inhibitory assay, the acetone fractions showed an inhibitory capacity close to that for acarbose. In particular, the SA2 fraction had an inhibitory effect of 67.70 ± 0.58% and was rich in apigenin and gallic acid. From these fractions, apigenin, (−)-catechin, and gallic acid were further characterized for their inhibitory actions. IC50 and inhibition mode were determined by analyzing enzyme kinetic parameters and by molecular modeling. Interestingly, (−)-catechin showed a possible synergistic effect with acarbose toward α-glucosidase enzyme inhibition, whereas apigenin showed an additive effect with acarbose toward α-amylase enzymatic inhibition. Furthermore, we studied the toxicity of N. sativa hexane and acetone extracts as well as that of acetone fractions. The result of acute toxicity evaluation demonstrated that N. sativa extracts were nontoxic up to a concentration of 10 g/kg, except for fraction SA3. Taken together, these results indicate that N. sativa extracts and/or derived compounds could constitute promising nutraceuticals for the prevention and treatment of type 2 diabetes mellitus.

Phytochemical Profile, α-Glucosidase, and α-Amylase Inhibition Potential and Toxicity Evaluation of Extracts from Citrus aurantium (L) Peel, a Valuable By-Product from Northeastern Morocco

“…In this study, correlation analysis showed a significant positive correlation with naringenin and α-glucosidase inhibition (Pearson coefficient correlation (PCC) = 0.884, p = 0.017), as well as gallic acid and α-amylase inhibition (PCC = 0.833, p = 0.014). In our previous work, we have already demonstrated an interaction between gallic acid and α-amylase [ 16 ]. Here, we confirmed that naringenin has a higher affinity (ΔG = −7.2 kcal/mol) for interacting with α-glucosidase in its active site ( Figure S3 ).…”

“…Discovery Studio 2020 (Dassault Systemes, Vélizy-Villacoublay, France) was used to determine the type of interaction and visualize it in 2D, while UCSF Chimera 1.14 (San Francisco, CA, USA) was used to represent molecules and interaction residues in 3D. The docking protocol employed was described by [ 16 ]. The ligand’s 3D structure was obtained from PubChem (available online: (accessed on 25 August 2021)).…”

“…Currently, the pharmaceutical sector provides various antidiabetic medications to treat diabetic patients, but their side effects are exceedingly hazardous. To address this issue, we have turned to natural resources and herbal therapies that naturally metabolize sugars without causing negative effects [12][13][14][15][16]. mg/mL and 1 mg/mL).…”

“…There are currently several synthetic drugs used to treat diabetic patients; the main goal is to reduce postprandial hyperglycemia by inhibiting digestive enzymes, primarily intestinal α-glucosidase and pancreatic α-amylase, or by reducing glucose absorption by the intestine. Several plant natural products/extracts have emerged as promising α-glucosidase and α-amylase inhibitors in recent decades [ 12 , 13 , 14 , 15 , 16 ]. Furthermore, recent research has emphasized the importance of promoting safer and tolerable inhibitors for the two enzymes that are naturally extracted from medicinal plants, fruits, and vegetables at a lower cost, particularly Citrus fruits.…”

Chemical Composition Related to Antimicrobial Activity of Moroccan Nigella sativa L. Extracts and Isolated Fractions

“…Many studies have explored the biological properties of NS [ 6 – 8 ]. The plant has antibacterial effects against both Gram-positive and Gram-negative bacteria [ 9 ].…”