Phenolic Extracts from Extra Virgin Olive Oils Inhibit Dipeptidyl Peptidase IV Activity: In Vitro, Cellular, and In Silico Molecular Modeling Investigations

Abstract

Two extra virgin olive oil (EVOO) phenolic extracts (BUO and OMN) modulate DPP-IV activity. The in vitro DPP-IV activity assay was performed at the concentrations of 1, 10, 100, 500, and 1000 μg/mL, showing a dose-dependent inhibition by 6.8 ± 1.9, 17.4 ± 6.1, 37.9 ± 2.4, 57.8 ± 2.9, and 81 ± 1.4% for BUO and by 5.4 ± 1.7, 8.9 ± 0.4, 28.4 ± 7.2, 52 ± 1.3, and 77.5 ± 3.5% for OMN. Moreover, both BUO and OMN reduced the DPP-IV activity expressed by Caco-2 cells by 2.9 ± 0.7, 44.4 ± 0.7, 61.2 ± 1.8, and 85 ± 4.2% and by 3 ± 1.9, 35 ± 9.4, 60 ± 7.2, and 82 ± 2.8%, respectively, at the same doses. The concentration of the most abundant and representative secoiridoids within both extracts was analyzed by nuclear magnetic resonance (1H-NMR). Oleuropein, oleacein, oleocanthal, hydroxytyrosol, and tyrosol, tested alone, reduced the DPP-IV activity, with IC50 of 472.3 ± 21.7, 187 ± 11.4, 354.5 ± 12.7, 741.6 ± 35.7, and 1112 ± 55.6 µM, respectively. Finally, in silico molecular docking simulations permitted the study of the binding mode of these compounds.

Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes Therapy

“…In this study, chlorogenic acid, ellagic acid and Diprotin A interacted with Ser630 and His740 of the catalytic triad at the active site of DPP-IV ( Figure 2 ) and this observation was in line with the work of Poonam et al [ 14 ] where Ser630 was identified as one of the amino acid residues through which chrysin interacted with DPP-IV. Interaction with the catalytic triad is characteristic of potential DPP-IV inhibitors, preventing endogenous peptides, such as GLP-1 and GIP from interacting with the active site, thus, hindering their subsequent cleavage [ 32 ]. The findings from this study regarding the modulatory role of chlorogenic acid on the active site amino acid residues of DPP-IV could provide insights into the possible mechanisms through which chlorogenic acid increased GLP-1 levels, improved the glycaemic index [ 33 ], and improved glucose homeostasis and insulin resistance in vivo [ 34 ], as previously reported.…”

Dietary Olive Leaf Extract Differentially Modulates Antioxidant Defense of Normal and Aeromonas hydrophila-Infected Common Carp (Cyprinus carpio) via Keap1/Nrf2 Pathway Signaling: A Phytochemical and Biological Link

“…Many other additives, such as probiotics, yeast, antioxidants, algae, and plant extracts, are frequently added to the diets of farmed fish to improve nutrient consumption, growth performance, appetite stimulation, and survival [ 10 , 11 , 13 , 91 , 92 , 93 ]. The OLE was effective in the current study in modulating A. hydrophila infection because it is a rich source of flavonoids and phenolics in addition to dimethyl oleuroside-10-carboxylic acid, which helps to increase the antioxidative response and stimulate the immune system [ 90 , 93 , 94 ].…”

“…In our study, oleanolic acid was detected in the OLE, which can exert the same effect on GLP-1. Thus, oleuropein and all its derivatives can be considered potential anorexic compounds [ 94 , 101 ]. Moreover, oleuroside and the new compounds—oleuroside-10-carboxylic and its dimethyl form, verbasoside, isoverbascoside, and verbascoside—have a structural similarity with oleuropein; therefore, they are anticipated to exert the same effect.…”

Natural products from plants targeting key enzymes for the future development of antidiabetic agents

“…These compounds were generally less active than flavonoids, and no kinetic analysis has been performed. The active compounds are listed in Table 3, 100–109 and so far, boswelic acid derivative ( 151 ) showed the best activity level among terpenoids.…”