An anthocyanin-rich extract from Zea mays L. var. ceratina alleviates neuronal cell death caused by hydrogen peroxide-induced cytotoxicity in SH-SY5Y cells.

The incidence of dementia is rising, with neuronal cell death from oxidative stress and apoptosis recognized as a significant contributor to its development. However, effective strategies to combat this condition are lacking, necessitating further investigation. This study aimed to assess the potential of an anthocyanin-rich extract from Zea mays L. var. ceratina (AZC) in alleviating neuronal cell death.Neurotoxicity was induced in SH-SY5Y cells using hydrogen peroxide (H2O2) at a concentration of 200 µM. Cells were pretreated with varying doses (31.25 and 62.5 µg/mL) of AZC. Cell viability was assessed using the MTT assay, and molecular mechanisms including reactive oxygen species (ROS) levels, antioxidant enzyme activities (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)), malondialdehyde (MDA) levels for oxidative stress, and the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), cAMP response element-binding protein (CREB), and apoptotic factors (B-cell lymphoma 2 (Bcl-2), caspase 3) were explored.Results showed that AZC significantly improved cell viability, reduced ROS production and MDA levels, and downregulated caspase 3 expression. It enhanced CAT, SOD, and GSH-Px activities, activated ERK1/2 and CREB, and upregulated Bcl-2 expression. These findings support the neuroprotective effects of AZC, suggesting it activates ERK1/2, leading to CREB activation and subsequent upregulation of Bcl-2 expression while suppressing caspase 3. AZC may mitigate neuronal cell death by reducing ROS levels through enhanced scavenging enzyme activities.In conclusion, this study underscores the potential of AZC as a neuroprotective agent against neuronal cell death. However, further investigations including toxicity assessments, in vivo studies, and clinical trials are necessary to validate its benefits in neuroprotection.

The neuroprotective effects of the combined extract of mulberry fruit and mulberry leaf against hydrogen peroxide-induced cytotoxicity in SH-SY5Y Cells.

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.

Integrated molecular network and HPLC-UV-FLD analysis to explore antioxidant ingredients in camellia nitidissima Chi.

At present, screening of active ingredients from natural products for pharmacological and clinical research is mostly time-consuming and costly. In this study, a molecular network (MN) guided high performance liquid chromatography-ultraviolet-fluorescence detector (HPLC-UV-FLD) method was carried out to profile the global antioxidant activity compounds, including the trace amount ingredients in Camellia nitidissima Chi (CNC). Firstly, HPLC-UV-FLD postcolumn derivatization system was utilized to screen the antioxidants. Then the MN of CNC was established via mass spectrometry (MS) data for getting the connection between ingredient structures. As a result, HPLC-UV-FLD indicated three antioxidant ingredients: gallic acid (126.3 mg/g), catechin (564.8 mg/g), and salicylic acid (24.3 mg/g). Combined with the MN, the actives' precise location and connection relationship were clarified based on the structural similarities. A new antioxidant ingredient, okicamelliaside, was suggested and evaluated at free radical scavenging and enzymatic protection. The novel method of activity and structural correlation analysis based on MN could provide a useful guide for screening trace active ingredients in natural products. PRACTICAL APPLICATION: Three main ingredients were screened out from Camellia nitidissima Chi by HPLC-UV-FLD postcolumn derivatization system. Integrated molecular network and HPLC-UV-FLD analysis, a new type of antioxidant okicamelliaside was selected. The novel method of activity and structural correlation analysis based on molecular network could provide a useful guide for screening trace active ingredients in natural products.

Phytosome Loading the Combined Extract of Mulberry Fruit and Ginger Protects against Cerebral Ischemia in Metabolic Syndrome Rats.

The prevalence of ischemic stroke in metabolic syndrome (MetS) is continually increasing and produces a great impact on both qualities of life and annual healthcare budget. Due to the efficiency limitation of the current therapeutic strategy, the poor availability of polyphenol substances induced by the first pass effect and the beneficial effects of mulberry fruit and ginger on brain and MetS-related diseases together with the synergistic concept, the neuroprotective effect against ischemic stroke in MetS condition of phytosome containing the combined extract of mulberry fruit and ginger (PMG) has been considered. To explore the neuroprotective effect and possible underlying mechanism of PMG on brain damage in cerebral ischemic rat with MetS, male Wistar rats were induced MetS by high-carbohydrate high-fat diet (HCHF) for 16 weeks and subjected to the cerebral ischemia/reperfusion injury (CIRI) at the right middle cerebral artery (Rt. MCAO). PMG at doses of 50, 100, and 200 mg/kg were orally fed with for 21 days, and they were assessed brain damage, neurological deficit score, and the changes of oxidative stress markers, inflammatory markers, PPARγ expression, and epigenetic modification via DNMT-1 were performed. All doses of PMG significantly improved brain infarction, brain edema, and neurological deficit score. In addition, the reduction in DNMT-1, MDA level, NF-κB, TNFα, and C-reactive protein together with the increase in SOD, CAT, and GPH-Px activities, and PPARγ expression in the lesion brain were also observed. The current data clearly revealed the neuroprotective effect against cerebral ischemia with MetS condition. The possible underlying mechanism might occur partly via the suppression of DNMT-1 giving rise to the improvement of signal transduction via PPARγ resulting in the decreasing of inflammation and oxidative stress. In conclusion, PMG is the potential neuroprotectant candidate against ischemic stroke in the MetS condition. However, the clinical trial is still essential.

Memory-Enhancing Effect of a Phytosome Containing the Combined Extract of Mulberry Fruit and Ginger in an Animal Model of Ischemic Stroke with Metabolic Syndrome.

The prevalence of dementia following cerebral ischemia in metabolic syndrome (MetS) condition is increasing, and most of the cases are often severe. Unfortunately, no effective strategy for treating this condition is available. Based on the positive modulation effect of a polyphenol-rich substance on dementia and the improvement in bioavailability and stability of polyphenols induced by the phytosome technique together with the use of the synergistic concept, we hypothesized that a phytosome containing the combined extract of mulberry fruit and ginger (PMG) should mitigate dementia and memory impairment following ischemic stroke in MetS. MetS was induced in male Wistar rats weighing 180-200 g by exposure to a 16-week feeding period of high-carbohydrate high-fat (HCHF) diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg·kg-1 BW 21 days before and 21 days after the occlusion of the right middle cerebral artery (Rt. MCAO). Then, their spatial memory was determined and the possible underlying mechanisms explored via the alterations of acetylcholinesterase (AChE), neuron density, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), and signal transduction via extracellular signal-regulated kinase (ERK) pathway in both the cerebral cortex and the hippocampus. It was found that PMG significantly enhanced memory. It also decreased AChE, IL-6, and MDA but increased SOD, CAT, GSH-Px, neuron density, and phosphorylation of ERK. These data suggested the cognitive enhancing effect of PMG. The possible underlying mechanisms might occur partly via the improvement of cholinergic function via the ERK pathway together with the decrease in neurodegeneration induced by the reduction of oxidative stress and inflammation. However, a subchronic toxicity study is also required to assure the safety of PMG consumption before moving forward to a clinical trial study.

Antimetabolic Syndrome Effect of Phytosome Containing the Combined Extracts of Mulberry and Ginger in an Animal Model of Metabolic Syndrome.

Due to the antimetabolic syndrome effect of mulberry and ginger together with the advantages of the synergistic effect and phytosome encapsulation technique, we hypothesized that phytosome containing the combined extracts of mulberry and ginger (PMG) should be able to manage MetS. PMG was developed and assessed the phenolic content and biological activities associated with the pathophysiology of MetS. The antimetabolic syndrome effect and the possible underlying mechanisms in the animal model of MetS were also assessed. Male Wistar rats induced MetS by subjecting to a 16-week high-carbohydrate high-fat diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg/kg for 21 days. They were determined metabolic parameter changes in serum, histomorphology changes of adipose tissue, the inflammatory cytokines such as IL-6 and TNF-α, oxidative stress status, PPAR-γ, and HDAC3 in adipose tissue. Our in vitro data showed that PMG increased phenolic contents and biological activities. PMG significantly improved MetS parameters including body weight gain, lipid profiles, plasma glucose, HOMA-IR, and ACE. In addition, the density and size of adipocyte, adiposity index, and weights of adipose tissues were also improved. Moreover, the decrease in TNF-α and IL-6, oxidative stress status, and HDAC3 expression together with the increase in PPAR-γ expression in adipose tissue was also observed. These data suggest that PMG exhibit antimetabolic syndrome and the possible underlying mechanism may be associated partly with the modulation effect on HDAC3, PPAR-γ, and adipose tissue. In addition, PMG also improves oxidative stress and inflammation in MetS. Therefore, PMG can be served as the potential supplement to manage MetS. However, a clinical trial study is essential to confirm this health benefit.