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. 2020 Nov 1;25(21):5073.
doi: 10.3390/molecules25215073.

In-Vivo Antidiabetic Activity and In-Silico Mode of Action of LC/MS-MS Identified Flavonoids in Oleaster Leaves

Hamza Mechchate  1 , Imane Es-Safi  1 , Mohammed Bourhia  2 , Andrii Kyrylchuk  3 , Abdelfattah El Moussaoui  1 , Raffaele Conte  4 , Riaz Ullah  5 , Essam Ezzeldin  6 , Gamal A Mostafa  6 , Andriy Grafov  7 , Hicham Bekkari  1 , Dalila Bousta  1
Affiliations

In-Vivo Antidiabetic Activity and In-Silico Mode of Action of LC/MS-MS Identified Flavonoids in Oleaster Leaves

Hamza Mechchate et al. Molecules. .

Abstract

Background: Olea europea L. subsp. europaea var. sylvestris (Mill) Lehr (Oleaster) is a wild endemic olive tree indigenous to the Mediterranean region. Olea europea leaves represent a natural reservoir of bioactive molecules that can be used for therapeutic purposes.

Aim of the study: This work was conducted to study antidiabetic and antihyperglycemic activities of flavonoids from oleaster leaves using alloxan-induced diabetic mice. The mode of action of flavonoids against eight receptors that have a high impact on diabetes management and complication was also investigated using molecular docking.

Results: During 28 days of mice treatment with doses 25 and 50 mg/kg b.w, the studied flavonoids managed a severe diabetic state (<450 mg/dL), exhibiting a spectacular antidiabetic and antihyperglycemic activity, and improved mice health status compared to diabetic control. The in-silico mode of action of oleaster flavonoids revealed the inhibition of protein tyrosine phosphatase 1B (PTP1B), Dipeptidyl-peptidase 4 (DPP4), α-Amylase (AAM), α-Glucosidase inhibition, Aldose reductase (AldR), Glycogen phosphorylase (GP), and the activation of free fatty acid receptor 1 (FFAR1).

Conclusion: The findings obtained in the present work indicate that the flavonoids from the oleaster may constitute a safe multi-target remedy to treat diabetes.

Keywords: Olea europea L. subsp. europaea var. sylvestris (Mill) Lehr; diabetes; flavonoids; molecular docking; oleaster.

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Conflict of interest statement

The authors declare that there are no conflicts of infest.

Figures

Figure 1
Figure 1
LC/MS-MS qualitative results of oleaster flavonoids.
Figure 2
Figure 2
Effect of flavonoids on fasting blood glucose Alloxan-induced diabetic mice during the experimental period of 28 days. Values are expressed as mean ± SD (n = 5 mice). *** p < 0.001 compared to diabetic control.
Figure 3
Figure 3
Effect of oleaster leaves on hyperglycemic status of Alloxan-induced diabetic mice during the experimental period of 12 h. Values are expressed as mean ± SD (n = 5 mice). NS: non-significant; *** p < 0.001 compared to diabetic control.
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