Work

Mechanistic Insights into the Neuroprotective Potential of Aegle marmelos (L.) Correa Fruits against Aβ-Induced Cell Toxicity in Human Neuroblastoma SH-SY5Y Cells

Year: 2025

Type: article

Abstract: Background/Objectives: Amyloid-β (Aβ) plaque accumulation, oxidative stress, and cholinergic dysfunction are hallmarks of Alzheimer’s disease (AD), a neurodegenerative disability that progresses over time, ultimately resulting in the loss of neurons. The side effects and limitations of current synthetic drugs have shifted attention toward natural alternatives. This study investigates the ethanolic extract of Aegle marmelos (L.) Corrêa fruits for their antioxidant, AChE-inhibitory, and anti-amyloidogenic properties, as well as their neuroprotective effects against amyloid beta-peptide (Aβ1–42). Methods: Phytochemical constituents were identified through HR-LCMS analysis and their antioxidant (DPPH, FRAP) and neuroprotective activities (AChE inhibition, ThT binding, MTT assay, ROS reduction, MMP restoration, and AD-related gene expression via qRT-PCR) were assessed using SHSY-5Y neuroblastoma cells. Results: The extract revealed the existence of flavonoids, phenols, and other bioactive substances. In vitro assays demonstrated strong antioxidant and AChE-inhibitory activities, while the ThT binding assay showed protection against amyloid-β aggregation. The extract exhibited no cytotoxicity in SHSY-5Y cells, even at a concentration of 500 μg/mL, whereas Aβ1–42 at 20 μM induced significant cytotoxicity. Co-treatment with Aβ1–42 (10 μM and 20 μM) and the extract improved cell viability (˃50%) and reduced ROS levels. Additionally, the extract restored mitochondrial membrane potential in Aβ1–42 treated cells, highlighting its role in preserving mitochondrial function. Conclusions: These findings suggest that A. marmelos fruits serve as a powerful source of natural antioxidants, AChE inhibitors, and anti-amyloidogenic agents, positioning them as a compelling option for AD treatment.

Source: Pharmaceuticals

DOI: 10.3390/ph18040489

Authors: Mohd Adnan, Arif Jamal Siddiqui, Fevzi Bardakci, Malvi Surti, Riadh Badraoui, Mitesh Patel

Institutions: University of Ha'il, King Salman Center for Disability Research, Parul University

Language: English

Topic: Medicinal Plants and Neuroprotection

Subfield: Complementary and alternative medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499