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Exploring the antidiabetic potential of Rhamnus alaternus: A combined in vitro, in vivo and in silico approach

Lookup NU author(s): Dr Jie ZhangORCiD

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Abstract

© 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies. Diabetes mellitus is a complex metabolic disorder associated with oxidative stress, inflammation, and progressive organ damage. This study investigated the phytochemical composition, antioxidant potential, antidiabetic activity, and possible molecular mechanisms of a methanolic extract of Rhamnus alaternus leaves (RME) using in vitro, in vivo, histopathological, and in silico approaches. Phytochemical analysis revealed high levels of total phenolics (223.25 mg GAE/g extract) and flavonoids (92.37 mg QE/g), along with strong antioxidant activity measured by DPPH radical scavenging (IC50 = 184.80 μg/mL) and lipid peroxidation inhibition (IC50 = 29.03 μg/mL). HPLC/UV profiling identified sixteen phenolic compounds, mainly flavonoids, including quercetin (2.56 mg/g), rutin (2.13 mg/g), and kaempferol (1.95 mg/g). In vivo experiments showed that alloxan-induced diabetic rats developed severe hyperglycemia (4.22 g/L), dyslipidemia, hepatic and renal dysfunction, oxidative stress, and inflammatory responses. Oral administration of RME (200 mg/kg for 90 days) significantly reduced blood glucose levels by approximately 58%, improved lipid parameters, restored protein and albumin levels, and normalized hepatic (AST, ALT, ALP, γ-GT) and renal (urea, creatinine, uric acid) biomarkers. RME also reduced malondialdehyde levels and restored antioxidant enzymes (SOD, CAT, GPx) in liver and kidney tissues, while significantly decreasing tumor necrosis factor-α and prostaglandin E2 levels. Histopathological analysis confirmed protective effects on liver, pancreas, and kidney tissues. Molecular docking suggested strong multi-target interactions of flavonoids, particularly rutin and chrysin, with α-glucosidase, dipeptidyl peptidase-4, Glucokinase, and PPAR-γ. Overall, RME exhibited significant antidiabetic, antioxidant, anti-inflammatory, and organ-protective effects, highlighting its potential as a natural therapeutic candidate for diabetes management.

Publication metadata

Author(s): Reffas AI, Boufadi MY, Moulai-Hacene F, Keddari S, Mekraf S, Tou A, Demmouche A, Moussa H, Nasrallah N, Elfalleh W, Bendif H, Ali MAM, Rahman S, Zhang J, Amrane A, Tahraoui H

Publication type: Article

Publication status: Published

Journal: Food Bioscience

Year: 2026

Volume: 80

Print publication date: 01/06/2026

Online publication date: 30/04/2026

Acceptance date: 29/04/2026

ISSN (print): 2212-4292

ISSN (electronic): 2212-4306

Publisher: Elsevier Ltd

URL: https://doi.org/10.1016/j.fbio.2026.109010

DOI: 10.1016/j.fbio.2026.109010

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