<p>In silico and in vitro studies of lupeol and iso-orientin as potential antidiabetic agents in a rat model</p>

Abstract

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.

Apoptotic, Anti-Inflammatory Activities and Interference with the Glucocorticoid Receptor Signaling of Fractions from Pistacia lentiscus L. var. chia Leaves

“…We propose that the increased southern medium-polar anti-gluconeogenic activity is associated with the triterpenoids’ composition of the fraction, especially lupeol ( 2 ) and α-amyrenone ( 1 ), as revealed by 1 H-NMR analysis and the chemical characterization of the fraction. Our results are in line with previous observations demonstrating the anti-diabetic action of lupeol [ 35 , 36 ] and a-amyrenone [ 37 ]. Our results are also in agreement with the results of a recent study, revealing that Algerian P. lentiscus L. leaves extract exhibited hypoglycemic actions by reducing blood glucose levels in diabetic rats in vivo and pancreatic a-amylase activity in vitro [ 38 ].…”

Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes

“…This could also highlight the limited investigations that have assessed the bioactivity properties of isoorientin against metabolic complications using in vivo models. Nevertheless, plant extracts containing this flavone have been shown to have an enhanced effect in lowering blood glucose levels, in protecting against β-cell damage, and improving the antioxidant status of diabetic rats [38,39]. Consistently, others show that plants, such as buckwheat containing this flavone, can ameliorate the insulin resistance and improve energy and glucose metabolism in fructose-diet exposed or estrogen-deficient rats [40,41].…”

Antioxidant Activity, α-Glucosidase Inhibition and UHPLC–ESI–MS/MS Profile of Shmar (Arbutus pavarii Pamp)

“…However, these synthetic drugs have brought about unfavorable side effects to the diabetic patients, such as abdominal distention, flatulence, meteorism, and diarrhea [ 7 ]. Recent studies have shown the remarkable effectiveness of some phytochemicals in controlling diabetes mellitus [ 10 ]. Therefore, there is an increased interest of seeking natural-based drugs from plants that contain a substantial amount of α-glucosidase inhibitory compounds [ 11 , 12 ].…”