The prevalence of dementia is increasing, and most of the causes are related to neuronal cell death. Unfortunately, no effective strategy is available for protecting against this condition. Based on the use of the synergistic concept together with the positive modulation effect of both mulberry fruit and mulberry leaf on dementia, we hypothesized that the combined extract of mulberry fruit and mulberry leaf (MFML) should mitigate neuronal cell death. Neuronal cell damage was induced in SH-SY5Y cells by exposure to hydrogen peroxide at a dose of 200 μM. SH-SY5Y cells were given MFML at doses of 62.5 and 125 μg/mL before induced cytotoxicity. Then, the cell viability was determined via MTT assay, and the possible underlying mechanisms were investigated via the alterations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nuclear factor-κB (NF-κB), and tumor necrosis factor-alpha (TNF-α), together with apoptotic factors including (B-cell lymphoma 2) BCL2, Casapase-3 and Caspase-9. The results showed that MFML significantly enhanced cell viability. It also significantly decreased MDA level, NF-κB, TNF-α, Casapase-3, Caspase-9, but increased SOD, GSH-Px and BCL2. These data demonstrated the neuroprotective effect of MFML. The possible underlying mechanisms might occur partly via the improvement of the inappropriate apoptotic mechanisms via BCL2, Casapase-3 and Caspase-9 together with the decrease in neurodegeneration induced by the reduction of inflammation and oxidative stress. In conclusion, MFML is a potential neuroprotectant candidate against neuronal cell injury. However, toxicity, animal studies, and clinical trials are essential to confirm these benefits.

The rising prevalence of neurodegenerative disorders underscores the urgent need for effective interventions to prevent neuronal cell death. This study evaluates the neuroprotective potential of phytosome-encapsulated 6-gingerol- and 6-shogaol-enriched extracts from Zingiber officinale Roscoe (6GS), bioactive compounds renowned for their antioxidant and anti-inflammatory properties. The novel phytosome encapsulation technology employed enhances the bioavailability and stability of these compounds, offering superior therapeutic potential compared to conventional formulations. Additionally, the study investigates the role of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)-signaling pathway, a key mediator of the neuroprotective effects of 6GS. Neurotoxicity was induced in SH-SY5Y cells (a human neuroblastoma cell line) using 200 μM of hydrogen peroxide (H₂O₂), following pretreatment with 6GS at concentrations of 15.625 and 31.25 μg/mL. Cell viability was assessed via the MTT assay alongside evaluations of reactive oxygen species (ROS), antioxidant enzyme activities (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px]), oxidative stress markers (malondialdehyde [MDA]), and molecular mechanisms involving the PI3K/Akt pathway, apoptotic factors (B-cell lymphoma-2 [Bcl-2] and caspase-3), and inflammatory markers (tumor necrosis factor-alpha [TNF-α]). The results demonstrated that 6GS significantly improved cell viability, reduced ROS, MDA, TNF-α, and caspase-3 levels, and enhanced antioxidant enzyme activities. Furthermore, 6GS treatment upregulated PI3K, Akt, and Bcl-2 expression while suppressing caspase-3 activation. Activation of the PI3K/Akt pathway by 6GS led to phosphorylated Akt-mediated upregulation of Bcl-2, promoting neuronal survival and attenuating oxidative stress and inflammation. Moreover, Bcl-2 inhibited ROS generation, further mitigating neurotoxicity. These findings suggest that phytosome encapsulation enhances the bioavailability of 6GS, which through activation of the PI3K/Akt pathway, exhibits significant neuroprotective properties. Incorporating these compounds into functional foods or dietary supplements could offer a promising strategy for addressing oxidative stress and neuroinflammation associated with neurodegenerative diseases.

Epigenetic modulation plays a crucial role in neuroprotection by regulating cellular responses to stress, inflammation, and oxidative damage, particularly in neurodegenerative diseases. Recognizing the therapeutic potential of epigenetic regulators, this study investigated the synergistic neuroprotective effects of curcumin-enriched turmeric extract combined with L-ascorbic acid, focusing on its modulation of epigenetic pathways in oxidative stress-induced neuronal damage. SH-SY5Y neuronal cells were treated with the combination at 20 and 40 µg/mL, and subsequently exposed to 200 µM hydrogen peroxide (H₂O₂) to induce oxidative stress. Cell viability was assessed using the MTT assay, while neuroprotective mechanisms were evaluated by analyzing the markers of epigenetic modulation, oxidative stress, inflammation, and apoptosis. The combination significantly enhanced cell viability, upregulated sirtuin-1 (SIRT1), and reduced DNA methyltransferase 1 (DNMT1) expression, indicating effective epigenetic modulation. Enhanced antioxidant defenses were observed, as evidenced by increased activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), along with decreased malondialdehyde (MDA) and reactive oxygen species (ROS) levels, alleviating oxidative stress. Additionally, it suppressed nuclear factor kappa B (NF-κB) activity and its downstream mediator interleukin-6 (IL-6), thereby mitigating inflammation. The treatment also increased anti-apoptotic Bcl-2 expression while reducing pro-apoptotic markers, including caspase-3 and caspase-9, suggesting inhibition of the intrinsic apoptotic pathway. These findings highlight the novel neuroprotective effects of this combination, demonstrating its ability to modulate epigenetic pathways while reducing oxidative stress, suppressing inflammation, and preventing undesired apoptosis. Its multifaceted neuroprotective properties make it a promising functional ingredient in functional foods for neurodegenerative disease intervention. However, further investigations, including animal studies and clinical trials, are essential to evaluate its safety and therapeutic potential.

Alzheimer’s disease (AD) is characterized by the presence of amyloid-beta (Aβ) plaques, which trigger oxidative stress and neuronal cell death. The present study investigated the neuroprotective effects of Oroxylum indicum (L.) leaf (OIL) extract against Aβ-induced oxidative stress and cellular damage in SH-SY5Y cells. The cells were treated with OIL extract with and without Aβ25−35, and their viability was investigated. Moreover, the mechanism of action of OIL was assessed by determining caspase-3 levels, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, enzymatic activity of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and cAMP-responsive element-binding protein (CREB), and expression of B-cell lymphoma-2 (Bcl-2) proteins. The results indicated that OIL reduced Aβ-induced neurotoxicity in a concentration-dependent manner, improving cell viability, reducing ROS levels and MDA production, increasing antioxidant enzyme activity of CAT, SOD, and GSH-Px, and decreasing caspase-3 expression. In addition, OIL enhanced phosphorylation of Akt, ERK1/2, and CREB and upregulated Bcl-2 protein expression. High-performance liquid chromatography (HPLC) analysis identified oroxylin A, baicalein, and chrysin as the major phenolic constituents of the OIL extract. The findings suggest that the extract holds promise as a therapeutic intervention against Aβ-induced neurotoxicity, offering potential implications for the treatment of AD. Further studies are needed to investigate the activity of OIL in primary neurons or in vivo.

Oxidative stress, which contributes to neuronal cell dysfunction, is a critical factor in the pathogenesis of neurodegenerative diseases. Anthocyanins and α-tocopherol have shown potential in mitigating oxidative damage, and their combination may provide synergistic effects. This study investigated the combined effects of a cyanidin-3-glucoside (C3G)-enriched extract derived from Oryza sativa L. cv. RD83 and α-tocopherol (C3GE) on hydrogen peroxide (H₂O₂)-induced oxidative stress in SH-SY5Y cells. Cells were treated with C3GE during exposure to 200 µM H₂O₂. Cell viability, intracellular reactive oxygen species (ROS), and oxidative stress biomarkers, including the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as malondialdehyde (MDA) levels, were evaluated. Protein expression levels of histone deacetylase 1 (HDAC1), nuclear factor erythroid 2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and SOD1 were also assessed. The combined treatment markedly improved cell viability, suppressed ROS accumulation, enhanced antioxidant enzyme activities, and significantly reduced MDA levels, suggesting effective protection against oxidative damage. Mechanistically, C3GE downregulated HDAC1 expression while upregulating Nrf2, HO-1, and SOD1, indicating that its antioxidant and neuroprotective effects are mediated, at least in part, through epigenetic modulation of redox-related signaling pathways. These results demonstrate a synergistic interaction between C3G and α-tocopherol that enhances cellular antioxidant defenses and supports redox homeostasis. In conclusion, the C3GE combination offers a promising therapeutic approach for preventing or attenuating oxidative stress-induced neuronal injury, with potential relevance for the treatment of neurodegenerative disorders.

Oxidative stress-induced mitochondrial dysfunction and apoptosis are critical factors in the pathogenesis of neurodegenerative diseases. This study investigated the synergistic neuroprotective effects of anthocyanin-enriched Morus alba L. extract combined with vitamin C (MAC) against hydrogen peroxide (H₂O₂)-induced oxidative stress in SH-SY5Y neuronal cells. Exposure to H₂O₂ triggered excessive reactive oxygen species (ROS) production and apoptosis, whereas treatment with MAC markedly alleviated these effects. Biochemical analyses revealed that MAC significantly reduced malondialdehyde (MDA) and enhanced the activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), thereby contributing to improved redox balance. Furthermore, MAC modulated apoptosis-related signaling by upregulating extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2), while downregulating the pro-apoptotic protein Bcl-2-associated X (BAX) and cleaved caspase-3. Collectively, these findings demonstrate that MAC acts synergistically as a promising nutraceutical ingredient, supporting the development of functional foods for the prevention or mitigation of oxidative stress-related neurodegenerative disorders.