Neuroprotective Effect of Azadirachta indica Ethanol Extract on Retinal Neurodegeneration in a Diabetic Rat Model

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Date

2025-12

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Lead City University Ibadan

Abstract

Diabetic retinopathy is a leading cause of adult blindness, characterized by neurodegeneration, vascular dysfunction, and progressive loss of retinal integrity. This study investigated the neuroprotective effect of Azadirachta indica ethanol extract (AIEE) on retinal neurodegeneration, through bioactive compound profiling, molecular docking and streptozotocin-induced diabetic rat model. Forty adult male Wistar rats were randomly assigned to five groups (n=8): normal control, diabetic untreated, diabetic treated with 200 mg/kg AIEE, diabetic treated with 400 mg/kg AIEE, and diabetic treated with metformin (7 µg/kg). Treatments were administered orally, twice daily for 21 days. Retina post-mitochondrial fraction was analyzed for gial fribillary acid protein, glutamate, vascular endothelial growth factor, brain derived neurotrophic factor, nerve growth factor, C-reactive protein, and nuclear factor-kappa B using enzyme-linked immunosorbent assay. Biomarkers of oxidative stress including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) were estimated using colorimetric methods. Retina, optic nerve, and visual cortex tissues were analyzed for morphometric characteristics, periodic acid schiff (PAS), and neuronal counts using histological techniques. Data were analyzed using a one-way ANOVA with Tukey’s post hoc test. Findings showed significant levels of oxidative stress, neurotransmitter imbalance, neurotrophin depletion, and inflammation in the untreated experimental animals compared to the control group. Treatment with 200 and 400 mg/kg AIEE ameliorated these effects in a dose-dependent manner by enhancing antioxidant defenses, suppressing pro-inflammatory markers, up-regulating neurotrophic factors, and restoring neurotransmitter balance. 400 mg/kg AIEE notably preserved retinal structure, reduced gliosis, improved neuronal morphology, and decreased PAS-associated glycogen accumulation, closely resembling healthy controls, Metformin produced comparable but slightly lower neuroprotective effects. These findings indicate that AIEE confers substantial neuroprotection against diabetic retinal degeneration, likely through its antioxidant and anti inflammatory phytoconstituents (Ethanone 1-[3-methyl-3-(4-methyl-3-pentenyl) oxiranyl]-, 1,2 Cyclopentanedione,3,3,5,5-tetramethyl-, alpha.-D-Glucopyranoside, methyl). These compounds showed good binding affinities and interactions with key protein targets in neurodegeneration, highlighting A.indica potential as a therapeutic candidate for the management of diabetic retinopathy. Keywords: Azadirachta indica, Diabetic retinopathy, Neuroprotection, Phytochemicals Word count: 298

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Keywords

Azadirachta indica, Diabetic retinopathy, Neuroprotection, Phytochemicals

Citation

Kate Turabian