Evaluation of betanin-loaded liposomal nanocarriers in AlCl 3 -induced Alzheimer's disease in rats: Impact on cognitive function, neurodegeneration, and TREM2/ADAM10 pathways.

Autor: Salama RM; Pharmacology and Toxicology Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt., Yehia R; Clinical Pharmacy Practice Department, Faculty of Pharmacy, British University in Egypt (BUE), Cairo, Egypt., Elmongy NF; Physiology Department, Damietta Faculty of Medicine, Al-Azhar University, Damietta, Egypt., Sallam AA; Biochemistry Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Cairo, Egypt.; Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt., Abd-Elgalil MM; Histology and Cell Biology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt., Schaalan MF; Clinical Pharmacy Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt., Abdel-Mottaleb MMA; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt., Bazan LS; Pharmaceutical Technology Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2024 Dec 02, pp. e2400641. Date of Electronic Publication: 2024 Dec 02.
DOI: 10.1002/ardp.202400641
Abstrakt: Betanin (BET) has been studied for its therapeutic benefits in various diseases, but its low bioavailability and uncertain brain penetration limit its efficacy. Accordingly, this study aimed to explore BET-loaded liposomal nanocarriers (LPN) as a novel treatment for Alzheimer's disease (AD), focusing on the triggering receptor expressed on myeloid cells 2 (TREM2)/DNAX-activating protein of 12 kDa (DAP12) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways implicated in AD. In an AlCl 3 -induced AD rat model, 48 male Wistar rats were divided into four groups: control, AlCl 3 (50 mg/kg, intraperitoneal), AlCl 3 +BET (100 mg/kg, per os), and AlCl 3 +BET LPN (25 mg/kg, intranasally), with treatments administered for 28 days. Morris water maze test and histopathological examination showed that BET LPN-treated rats had improved spatial and learning memory and less hippocampal and cortical degeneration compared with the AlCl 3 and oral BET groups. Mechanistically, BET LPN treatment corrected AD biomarkers, increased miR-132 and ADAM10 expression, and reduced oxidative stress, inflammation, and apoptosis. Additionally, BET LPN treatment suppressed the expression of TREM2, DAP12, ERK1/2, and mitogen-activated protein kinase 1/2 (MEK1/2), showing greater improvement than oral BET. These findings suggest that BET LPN enhances cognitive function and neuroprotection in AD by modulating miR-132 and ADAM10 and inhibiting ERK1/2 and TREM2/DAP12 pathways, providing a more effective treatment compared with traditional oral BET administration.
(© 2024 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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