In silico and in vitro studies of lupeol and iso-orientin as potential antidiabetic agents in a rat model
Received 26 October 2018
Accepted for publication 14 March 2019
Published 6 May 2019 Volume 2019:13 Pages 1501—1513
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Professor Manfred Ogris
Arif Malik,1 Uzma Jamil,2 Tariq Tahir Butt,3 Sulayman Waquar,1 Siew Hua Gan,4 Hassan Shafique,1 Tassadaq Hussain Jafar1
1Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan; 2Department of Physiology, Shalamar Medical and Dental College Lahore, Lahore, Pakistan; 3Department of Biochemistry, Khawaja Muhammad Safdar Medical College, Sialkot, Pakistan; 4School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia
Background: In silico characterization can help to explain the interaction between molecules and predict three-dimensional structures. Various studies have confirmed the glucose-lowering effects of plant extracts, ie, lupeol and iso-orientin, which enable them to be used as antidiabetic agents.
Purpose: Aims of the present study were to evaluate the hypoglycemic activities of lupeol and iso-orientin in a rat model. The study proposed the effects of alloxan on blood glucose level, body weight, and oxidative stress.
Materials and Methods: Thirty (n=30) Wistar albino rats were divided into six groups and were subjected to different combinations of the compounds. Levels of different stress markers, ie, malondialdehyde, superoxide dismutase, catalase, nitric oxide, glutathione, glutathione peroxide, glutathione reductase, and blood glucose levels were estimated with their respective methods. Whereas, for their in silico analysis, identified target proteins, GPR40, glucose-6-phosphatase, UCP2, glycogen phosphorylase, aldose reductase, and glucose transporter-4 were docked with lupeol and iso-orientin. Three-dimensional structures were predicted by ERRAT, Rampage, Verify3D, threading and homology approaches.
Results: Blood glucose levels were significantly increased in rats receiving intraperitoneal injection of alloxan (208±6.94 mg/dL) as compared to controls (90±7.38 mg/dL). Infected rats were administered plant extracts; combined treatment of both extracts (lupeol+iso-orientin) significantly reduced the levels of blood glucose (129.06±6.29 mg/dL) and improved the antioxidant status. Fifteen structures of each selected protein were evaluated using various techniques. Consequently, satisfactory quality factors [GPR40 (96.41%), glucose-6-phosphatase (96.56%), UCP2 (72.56%), glycogen phosphorylase (87.24%), aldose reductase (82.46%), and glucose transporter-4 (94.29%)] were selected. Molecular docking revealed interacting residues, effective drug properties and their binding affinities (ie, −8.9 to −12.6 Kcal/mol).
Conclusion: Results of the study affirmed the antidiabetic activities of lupeol and iso-orientin. Administration of these extracts (either individually or in combination) significantly reduced blood glucose levels and oxidative stress. Hence, it may be considered beneficial in the treatment of diabetes.
Keywords: AutoDock vina, molecular docking, Iso-orientin, lupeol, diabetes, GLUT-4
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