Phytochemical analysis and antidiabetic potential of  Elaeagnus umbellata  (Thunb.) in streptozotocin-induced diabetic rats: pharmacological and computational approach

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Abstract

Background

The fruit of Elaeagnus umbellata has high medicinal values and is an excellent source of phytochemicals. This study was aimed to evaluate the antioxidant, enzyme inhibitory and antidiabetic potential of Elaeagnus umbellata.

Methods

The antioxidant potential of the crude extract and subfractions of E. umbellata fruit were determined using DPPH (2, 20-diphenyl-1-picrylhydrazyl) and ABTS (2, 2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) assays. The enzyme inhibitory potentials of extracts against α-amylase and α-glucosidase enzymes were also determined. The in vivo anti-hyperglycemic effects of the extract in STZ-induced type 2 diabetes were determined using Sprague Dawley adult rats. HPLC system (Agilent 1260) was used for the identification of bioactive compounds present in extracts. Molecular docking was used to identify and compare the interaction between the compounds (active constituents) and standard inhibitor acarbose with the α-amylase and α-glucosidase active sites.

Results

The chloroform, ethyl acetate, and butanol fractions showed significant antioxidant potential with IC ₅₀ values of 40, 45 and 60 μg/mL against DPPH and 57, 70 and 120 μg/mL against ABTS free radicals respectively. The chloroform and ethyl acetate were highly active against α-amylase and α-glucosidase (IC ₅₀ values 58 and 200 μg/ml against α-amylase 60 and 140 μg/ml against α-glucosidase. The crude extract, chloroform, and ethyl acetate fractions were more potent in controlling the hyperglycemia in STZ-induced type 2 diabetes in rats and considerable reduction of glucose level was observed compared to the non-treated group. Furthermore, the extracts were also found useful in controlling the secondary complications associated with type 2 diabetes mellitus which was evident from the observed substantial reduction in the blood level of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, total cholesterol, low-density lipoproteins, and triglycerides. The molecular docking approach indicated the favorable inhibitory interaction between the docked compounds and the active sites of the α-amylase and α-glucosidase. All docked compounds occupied the same binding site as occupied by acarbose.

Conclusion

It was concluded that E. umbellata can be used in the treatment of type 2 diabetes and oxidative stress. The extracts were also found to be effective in relieving the secondary complications associated with type 2 diabetes.

Graphical abstract

Electronic supplementary material

The online version of this article (10.1186/s12906-018-2381-8) contains supplementary material, which is available to authorized users.

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A method for the screening of antioxidant activity is reported as a decolorization assay applicable to both lipophilic and hydrophilic antioxidants, including flavonoids, hydroxycinnamates, carotenoids, and plasma antioxidants. The pre-formed radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) is generated by oxidation of ABTS with potassium persulfate and is reduced in the presence of such hydrogen-donating antioxidants. The influences of both the concentration of antioxidant and duration of reaction on the inhibition of the radical cation absorption are taken into account when determining the antioxidant activity. This assay clearly improves the original TEAC assay (the ferryl myoglobin/ABTS assay) for the determination of antioxidant activity in a number of ways. First, the chemistry involves the direct generation of the ABTS radical monocation with no involvement of an intermediary radical. Second, it is a decolorization assay; thus the radical cation is pre-formed prior to addition of antioxidant test systems, rather than the generation of the radical taking place continually in the presence of the antioxidant. Hence the results obtained with the improved system may not always be directly comparable with those obtained using the original TEAC assay. Third, it is applicable to both aqueous and lipophilic systems.

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Author and article information

Contributors

Nausheen Nazir: nausheen.nazir@uom.edu.pk

Muhammad Zahoor: mohammadzahoorus@yahoo.com

Mohammad Nisar: mnshaalpk@yahoo.com

Imran Khan: drimran.khan@hotmail.com

Nasiara Karim: nasiara.karim@hotmail.com

Heba Abdel-Halim: habdelhalim@uop.edu.jo

Akhtar Ali: gultkr@yahoo.com

Journal

Journal ID (nlm-ta): BMC Complement Altern Med

Journal ID (iso-abbrev): BMC Complement Altern Med

Title: BMC Complementary and Alternative Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1472-6882

Publication date (Electronic): 13 December 2018

Publication date PMC-release: 13 December 2018

Publication date Collection: 2018

Volume: 18

Electronic Location Identifier: 332

Affiliations

[1 ]GRID grid.440567.4, Department of Chemistry, , University of Malakand, ; Chakdara Dir (L), Khyber Pakhtunkhwa Pakistan

[2 ]GRID grid.440567.4, Department of Botany, , University of Malakand, ; Chakdara Dir (L), Khyber Pakhtunkhwa Pakistan

[3 ]Department of Pharmacy, University of Swabi, Swabi, Khyber Pakhtunkhwa Pakistan

[4 ]GRID grid.440567.4, Department of Pharmacy, , University of Malakand, ; Chakdara Dir (L), Khyber Pakhtunkhwa Pakistan

[5 ]ISNI 0000 0004 0640 2983, GRID grid.412494.e, Faculty of Pharmacy and Medical Sciences, , University of Petra, ; Amman, 11196 Jordan

[6 ]ISNI 0000 0004 0532 8339, GRID grid.258676.8, Global Research Laboratory, Department of BioSciences, and Engineering, , Konkuk University Seoul, ; Seoul, South Korea

Article

Publisher ID: 2381

DOI: 10.1186/s12906-018-2381-8

PMC ID: 6293591

PubMed ID: 30545352

SO-VID: 5193cb1f-e31a-4170-83cc-7e6855545288

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.