There is still no approved treatment for Alzheimer’s disease (AD), a progressive neurodegenerative disorder characterized by amyloid plaques, neurofibrillary tangles, and synaptic dysfunction. In an in vitro AD model, this study aimed to comparatively assess the neuroprotective effects of the citrus flavonoid Hesperidin and the casein kinase 2 (CK2) inhibitor 5,6-dichloro-1-β-D-ribofuranosyl benzimidazole (DRB) as potential therapeutic targets for AD. First, SH-SY5Y neuroblastoma cells were differentiated into cholinergic neuron-like cells using all-trans retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). Then, to generate an in vitro AD model, 20 μM Aβ_1–42 was applied to induce neurotoxicity in differentiated SH-SY5Y cells. The neuroprotective effects of the CK2 inhibitor DRB and Hesperidin on the in vitro AD model were evaluated using MTT, RT-qPCR, and ELISA methods. Both Hesperidin and DRB, at high concentrations, reduced cell viability in differentiated SH-SY5Y cells for 24 and 48 h (p < 0.05 to p < 0.01). Pre-treatment with Hesperidin at 25 and 50 µM and DRB at 0.25 and 0.5 µM for 24 h increased ADAM10 gene expression and decreased BACE1 gene expression, both of which are associated with AD markers, compared to the 20 µM Aβ_1-42 treatment group (p < 0.05). Pre-treatment with the DRB at 0.25 and 0.5 µM concentrations for 24 h decreased CK2α gene expression in the in vitro AD model compared to the 20 µM Aβ_1-42 treatment group (p < 0.05), whereas Hesperidin had no effect (p > 0.05). Both pre-treatment with Hesperidin and DRB significantly decreased Aβ_1-42 levels (p < 0.01), p-Tau (T181) levels (p < 0.05), and the Bax/Bcl-2 ratio (p < 0.05). As a result, our study showed that both Hesperidin and DRB inhibited Aβ production by suppressing the amyloidogenic pathway and activating the non-amyloidogenic pathway while also exerting an inhibitory effect on neuronal apoptosis. CK2 may be a potential therapeutic target and could contribute to the pathophysiology of AD. However, these findings should be validated by further studies.

Breast cancer is one of the most common causes of deaths worldwide. Major obstacles to treatment have contributed to the increasing popularity of complementary or alternative therapies. Although recent results support the mechanism that honey induces cell death, the full mechanisms are still unknown. This study investigates the potential use of Pervari honey (PH) as an in vitro therapeutic agent in breast cancer. Firstly, the antioxidant capacity and total phenolic content of PH were tested. In addition, MCF-7 and MDA-MB-231 breast cancer cells treated with PH were examined for cell viability, reactive oxygen species production, oxidative deoxyribonucleic acid (DNA) damage, and apoptosis. Our results show that PH treatment decreased cell viability dose-dependently and increased reactive oxygen species (ROS) levels, oxidative DNA damage, and apoptosis rate. The present study suggests that honey is a promising source to produce pharmaceuticals and nutraceuticals for breast cancer therapy.

Microalgae are rich sources of essential biomolecules, including proteins, pigments, and a diverse array of secondary metabolites such as carotenoids, polyphenols, sterols, polyunsaturated fatty acids, and polysaccharides, which they secrete at various growth stages. Owing to this property, microalgae are gaining significant research interest as natural product producers with cell-protective potential and minimal or no side effects compared to synthetic drugs. This study explores the potential of the methanol extract of Dunaliella sp. (mD) as an in vitro therapeutic agent for breast cancer. The antioxidant activity and total phenolic content of mD were assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Folin-Ciocalteu methods. Additionally, its cytotoxic and oxidative effects were evaluated in vitro. mD exhibited a radical scavenging activity (RSA) of 40.27, 1.8% below the expected value, and a total phenolic content of 25.4 mg GAE/g dry extract. The MTT cell viability assay further indicated that this microalgal extract has cytotoxic potential against breast cancer cells. The IC50 values were 768 and 728 µg/mL for MCF-7 and MDA-MB-231 cells, respectively. While the use of H2O2 alone led to an increase in ROS production in the cells, treatment with mD reduced ROS production. According to the current study, mD could be an interesting candidate for the synthesis of drugs and nutraceuticals for the treatment of breast cancer.