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Article

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

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Laboratory of Biotechnology, Environment, Agrifood, and Health, Sidi Mohamed Ben Abdellah University, Fez 30050, Morocco
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Laboratory of Chemistry-Biochemistry, Environment, Nutrition, and Health, Faculty of Medicine and Pharmacy, University of Casablanca, B.P 5696, Casablanca 20250, Morocco
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Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska Street 5, 02660 Kyiv, Ukraine
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Research Institute on Terrestrial Ecosystems (IRET)—CNR, Via Pietro Castellino 111, 80131 Naples, Italy
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Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
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Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University, Riyadh 11451, Saudi Arabia
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Department of chemistry, University of Helsinki, P.O. Box 55, FI-00014 Helsinki, Finland
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Author to whom correspondence should be addressed.
Academic Editors: Raffaele Capasso and Lorenzo Di Cesare Mannelli
Molecules 2020, 25(21), 5073; https://doi.org/10.3390/molecules25215073
Received: 6 October 2020 / Revised: 26 October 2020 / Accepted: 28 October 2020 / Published: 1 November 2020
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. View Full-Text
Keywords: Olea europea L. subsp. europaea var. sylvestris (Mill) Lehr; oleaster; diabetes; flavonoids; molecular docking Olea europea L. subsp. europaea var. sylvestris (Mill) Lehr; oleaster; diabetes; flavonoids; molecular docking
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MDPI and ACS Style

Mechchate, H.; Es-Safi, I.; Bourhia, M.; Kyrylchuk, A.; El Moussaoui, A.; Conte, R.; Ullah, R.; Ezzeldin, E.; Mostafa, G.A.; Grafov, A.; Bekkari, H.; Bousta, D. In-Vivo Antidiabetic Activity and In-Silico Mode of Action of LC/MS-MS Identified Flavonoids in Oleaster Leaves. Molecules 2020, 25, 5073. https://doi.org/10.3390/molecules25215073

AMA Style

Mechchate H, Es-Safi I, Bourhia M, Kyrylchuk A, El Moussaoui A, Conte R, Ullah R, Ezzeldin E, Mostafa GA, Grafov A, Bekkari H, Bousta D. In-Vivo Antidiabetic Activity and In-Silico Mode of Action of LC/MS-MS Identified Flavonoids in Oleaster Leaves. Molecules. 2020; 25(21):5073. https://doi.org/10.3390/molecules25215073

Chicago/Turabian Style

Mechchate, Hamza, Imane Es-Safi, Mohammed Bourhia, Andrii Kyrylchuk, Abdelfattah El Moussaoui, Raffaele Conte, Riaz Ullah, Essam Ezzeldin, Gamal A. Mostafa, Andriy Grafov, Hicham Bekkari, and Dalila Bousta. 2020. "In-Vivo Antidiabetic Activity and In-Silico Mode of Action of LC/MS-MS Identified Flavonoids in Oleaster Leaves" Molecules 25, no. 21: 5073. https://doi.org/10.3390/molecules25215073

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