PBAT-modified starch blended film extract induces in vitro toxicity in L-02 cells: induction of oxidative stress, inflammation, and modulation of AMPK pathway.

PBAT-modified starch blended film are thermoplastic biodegradable materials with good properties and a wide range of applications. In this study, L-02 cells were used as an in vitro toxicity evaluation system for risk assessment of PBAT-modified starch films with migration studies obtained in different food simulants. Determination of total migration and organic matter revealed that the results were in accordance with the standard except for the total organic matter under 95% (v/v) ethanol food simulant which exceeded the standard. The CCK-8 assay showed that these compounds affect the cell viability of L-02 cells. It was observed that the compounds made the cells express increased AST, ALT, TNF-α, IL-6, IL-1ß, and ROS, and decreased SOD, GSH, and ATP. In addition, we explored the effect of migration in PBAT-modified starch composites on protein and gene expression levels in L-02 cells using a transcriptomic approach and found that the AMPK signaling pathway was affected. The expression of AMPK signaling pathway-related proteins was detected by Western Blot, and the expression levels of p-AMPK/AMPK were found to be upregulated, and those of p-mTOR/mTOR, SIRT1, PGC-1α, NRF1 and TFAM were downregulated. The above data suggest that the compounds migrating into the PBAT-modified starch film when exposed to food may induce oxidative stress and inflammation in hepatocytes, and may cause damage to hepatocytes through the AMPK pathway.

Lycium barbarum polysaccharides attenuate nonylphenol and octylphenol-induced oxidative stress and neurotransmitter disorders in PC-12 cells.

Nonylphenol (NP) and octylphenol (OP) are environmental contaminants with potential endocrine disrupting effects. However, there is limited research on the mechanisms and intervention of combined NP and OP exposure-induced neurotoxicity. This study aims to explore the cytotoxicity of combined NP and OP exposure and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. In present study, LBP (62.5, 125 and 250 µg/mL) were applied to intervene rat adrenal pheochromocytoma (PC-12) cells treated with combined NP and OP (NP: OP = 4:1, w/w; 1, 2, 4 and 8 µg/mL). The results showed that NP and OP induced oxidative stress, disrupted the 5-hydroxytryptamine (5-HT) and cholinergic systems in PC-12 cells. Additionally, they activated the p38 protein kinase (p38) and suppressed the expression of silent information regulation type 1 (SIRT1), monoamine oxidase A (MAOA), phosphorylated cyclic-AMP response binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase receptor type B (p-TrkB). However, N-acetyl-L-cysteine (NAC) treatment counteracted the changes of signalling molecule p38, SIRT1/MAOA and CREB/BDNF/TrkB pathways-related proteins induced by NP and OP. LBP pretreatment ameliorated combined NP and OP exposure-induced oxidative stress and neurotransmitter imbalances. Furthermore, the application of LBP and administration of a p38 inhibitor both reversed the alterations in the signaling molecule p38, as well as the proteins associated to the SIRT1/MAOA and CREB/BDNF/TrkB pathways. These results implied that LBP may have neuroprotective effects via p38-mediated SIRT1/MAOA and CREB/BDNF/TrkB pathways.

Lycium barbarum polysaccharides attenuate oxidative stress and mitochondrial toxicity induced by mixed plasticizers in HepG2 cells through activation of Nrf2.

AIMS: In daily life, it is common for humans to be exposed to multiple phthalate esters (PAEs). However, there is limited research on the mechanisms and intervention of combined PAEs toxicity. This study aims to explore the cytotoxicity of combined PAEs and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. MAIN METHODS: LBP (62.5, 125 and 250 µg/mL) were applied to intervene HepG2 cells treated with DEHP and DBP mixtures (50, 100, 200, 400 and 800 µg/mL). Western Blot and different kits were mainly performed in our study. KEY FINDINGS: DEHP and DBP mixtures suppressed the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and activated MAPK pathway by increasing ROS. Combined DEHP and DBP exposure reduced ATP content and inhibited the mitochondrial biogenesis pathway in HepG2 cells through oxidative stress, which in turn caused cytotoxicity. LBP reduced oxidative stress and cell death induced by mixed plasticizers, upregulated Nrf2 levels and mitochondrial biogenesis pathway levels and inhibited MAPK pathway activation. Notably, after treating HepG2 cells with Nrf2-specific inhibitor (ML385, 0.5 µM), we found that the activation of Nrf2 played a crucial role on LBP intervention of DEHP and DBP induced HepG2 cytotoxicity. SIGNIFICANCE: This study not only enhances our understanding of the toxicological effects caused by combined PAEs exposure, but also has significant implications in devising strategies to mitigate the toxicological consequences of combined exposure to exogenous chemicals through the investigation of the role of LBP.

Nicotinamide mononucleotide (NMN) ameliorated Nonylphenol-induced learning and memory impairment in rats via the central 5-HT system and the NAD+/SIRT1/MAO-A pathway.

Nonylphenol (NP) exposure can trigger neurotoxicity and cause learning and memory impairment. Nicotinamide mononucleotide (NMN) has a therapeutic effect on neurodegenerative diseases, but the role of NMN on NP-induced learning and memory impairment is not known. Here, we examined the mitigative effect of NMN on the impaired learning and memory ability of rats exposed to NP. The NP impaired learning and memory in rats, while the low-dose intervention with NMN significantly prolonged the step-through latency of the PAT and improved the NAMPT and NMNAT1 content in brain tissue. At the same time, the NMN intervention also increased the content of 5-HTR1A, 5-HTR4, and 5-HTR6 related to learning and memory in the hippocampus. In line with this, we found that the NMN intervention activated the SIRT1/MAO-A pathway in brain tissue. NMN intervention, especially at 125 mg/kg doses, may improve rats' NP-induced learning and memory impairment via the central 5-HT system and the NAD+/SIRT1/MAO-A pathway in the brain.

Update on new trends and progress of natural active ingredients in the intervention of Alzheimer's disease, based on understanding of traditional Chinese and Western relevant theories: A review.

Alzheimer's disease (AD) is one of the major neurological disorders causing death in the elderly worldwide. As a neurodegenerative disease that is difficult to prevent and cure, the pathogenesis of AD is complex and there is no effective cure. A variety of natural products derived from plants have been reported to have promising anti-AD activities, including flavonoids, terpenes, phenolic acids and alkaloids, which can effectively relieve the symptoms of AD in a variety of ways. This paper mainly reviews the pharmacological activity and mechanisms of natural products against AD. Although the clinical efficacy of these plants still needs to be determined by further high-quality studies, it may also provide a basis for future researchers to study anti-AD in depth.

Structural characterization of pectic polysaccharides from Amaranth caudatus leaves and the promotion effect on hippocampal glucagon-like peptide-1 level.

In this study, decolorized pectic polysaccharides (D-ACLP) with molecular weight (Mw) distribution of 3483- 2,023,656 Da were prepared from Amaranth caudatus leaves. Purified polysaccharides (P-ACLP) with the Mw of 152,955 Da were further isolated from D-ACLP through gel filtration. The structure of P-ACLP was analyzed by 1D and 2D NMR spectra. P-ACLP were identified as rhamnogalacturonan-I (RG-I) containing dimeric arabinose side chains. The main chain of P-ACLP was composed of →4)-α-GalpA-(1→, →2)-ß-Rhap-(1→, →3)-ß-Galp-(1→ and →6)-ß-Galp-(1→. There was a branched chain of α-Araf-(1→2)-α-Araf-(1→ connected to the O-6 position of →3)-ß-Galp-(1→. The GalpA residues were partially methyl esterified at O-6 and acetylated at O-3. The 28-day consecutive gavage of D-ALCP (400 mg/kg) significantly elevated the hippocampal glucagon-like peptide-1 (GLP-1) levels in rats. The concentrations of butyric acid and total short chain fatty acids in the cecum contents also increased significantly. Moreover, D-ACLP could significantly increase the gut microbiota diversity and dramatically up-regulated the abundance of Actinobacteriota (phylum) and unclassified Oscillospiraceae (genus) in intestinal bacteria. Taking together, D-ACLP might promote the hippocampal GLP-1 level through the beneficial regulation of butyric acid-producing bacteria in gut microbiota. This study contributed to making full use of Amaranth caudatus leaves for cognitive dysfunction intervention in food industry.

The mechanisms of learning and memory impairment caused by nonylphenol: a narrative review based on in vivo and in vitro studies.

Learning and memory play a fundamental role on brain cognitive functions which are crucial for human life. Nonylphenol (NP), a serious environmental pollutant over the world, is proven to be harmful for learning and memory mainly via diet exposure. Currently, besides the administrative restrictions for the use of NP, there are rarely other effective approaches against learning and memory impairment caused by NP. This review summarized the mechanisms underlying NP-induced learning and memory impairment according to in vivo and in vitro experiments. Based on the studies involved in behavior tests, these mechanisms were classified as oxidative stress, neurotransmitter disorder, synaptic plasticity impairment, and neuron injury. In addition, according to the studies which did not conduct behavior tests, the possible mechanisms underlying NP-induced learning and memory impairment were proposed as chronic inflammation and gut permeability increment. Furthermore, this review also revealed the demanding questions for the mechanism investigations and therapeutic methods. Notably, the summarized mechanisms might accelerate the prevention and remediation of NP-induced learning and memory impairment.

Learning and memory impairment induced by 1,4-butanediol is regulated by ERK1/2-CREB-BDNF signaling pathways in PC12 cells.

1,4-butanediol (1,4-BD) is a known γ-hydroxybutyric acid (GHB) precursor which affects the nervous system after ingestion, leading to uncontrolled behavioral consequences. In the present study, we investigated whether 1,4-BD induces oxidative stress and inflammation in PC12 cells and evaluated the toxic effects of 1,4-BD associates with learning and memory. CCK-8 results revealed a dose-effect relationship between the cell viability of PC12 cells and 1,4-BD when the duration of action was 2 h or 4 h. Assay kits results showed that 1,4-BD decreased the levels of Glutathione (GSH), Glutathione peroxidase (GSH-px), Superoxide dismutase (SOD), Acetylcholine (Ach) and increased the levels of Malondialdehyde (MDA), Nitric oxide (NO) and Acetylcholinesterase (AchE). Elisa kits results indicated that 1,4-BD decreased the levels of synaptophysin I (SYN-1), Postsynaptic density protein-95 (PSD-95), Growth associated protein-43 (GAP-43) and increased the levels of Tumor necrosis factor alpha (TNF-α) and Interleukin- 6 (IL-6). RT-PCR results showed that the mRNA levels of PSD-95, SYN-1 and GAP-43 were significantly decreased. The expression of phosphorylation extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phosphorylation cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) proteins were significantly decreased in PC12 cells by protein blotting. Overall, these results suggest that 1,4-BD may affect synaptic plasticity via the ERK1/2-CREB-BDNF pathway, leading to Ach release reduction and ultimately to learning and memory impairment. Furthermore, oxidative stress and inflammation induced by 1,4-BD may also result in learning and memory deficits. These findings will enrich the toxicity data of 1.4-BD associated with learning and memory impairment.

Potential for non-starch polysaccharides in the prevention and remediation of cognitive impairment: A comprehensive review.

Non-starch polysaccharides (NSPs) are food ingredients proven to be beneficial in a large number of health issues. However, there is no literature systematic review about the effects and corresponding mechanisms of NSPs on the prevention and remediation of cognitive impairment. In this review, studies on prevention and remediation of NSPs for cognitive deficit caused by diseases, menopause, ageing, chronic stress and environmental pollutants were summarized and the corresponding mechanisms were established. The anti-cognitive deficit effects of NSPs were associated with the modulation of amyloid ß (Aß) deposition, p-Tau aggregation, oxidative stress, inflammation, neuron apoptosis, neurogenesis, neurotransmitters, synaptic plasticity, autophagy and gut microbiota. Although the structure-function relationship has not been elucidated, several structural properties of NSPs such as molecular weight, sulfate content, hydroxyl group content, monosaccharide composition and molecular chain linkage might be crucial for the anti-cognitive deficit property. Notably, this review revealed that NSPs had a positive effect on cognitive impairment and proposed the future perspectives for further research on the anti-cognitive dysfunction effects of NSPs.

A Low-Protein High-Fat Diet Leads to Loss of Body Weight and White Adipose Tissue Weight via Enhancing Energy Expenditure in Mice.

Obesity has become a worldwide health problem over the past three decades. During obesity, metabolic dysfunction of white adipose tissue (WAT) is a key factor increasing the risk of type 2 diabetes. A variety of diet approaches have been proposed for the prevention and treatment of obesity. The low-protein high-fat diet (LPHF) is a special kind of high-fat diet, characterized by the intake of a low amount of protein, while compared to typical high-fat diet, may induce weight loss and browning of WAT. Physical activity is another effective intervention to treat obesity by reducing WAT mass, inducing browning of WAT. In order to determine whether an LPHF, along with exercise enhanced body weight loss and body fat loss as well as the synergistic effect of an LPHF and exercise on energy expenditure in a mice model, we combined a 10-week LPHF with an 8-week forced treadmill training. Meanwhile, a traditional high-fat diet (HPHF) containing the same fat and relatively more protein was introduced as a comparison. In the current study, we further analyzed energy metabolism-related gene expression, plasma biomarkers, and related physiological changes. When comparing to HPHF, which induced a dramatic increase in body weight and WAT weight, the LPHF led to considerable loss of body weight and WAT, without muscle mass and strength decline, while it exhibited a risk of liver and pancreas damage. The mechanism underlying the LPHF-induced loss of body weight and WAT may be attributed to the synergistically upregulated expression of Ucp1 in WAT and Fgf21 in the liver, which may enhance energy expenditure. The 8-week training did not further enhance weight loss and increased plasma biomarkers of muscle damage when combined with LPHF. Furthermore, LPHF reduced the expression of fatty acid oxidation-related genes in adipose tissues, muscle tissues, and liver. Our results indicated that an LPHF has potential for obesity treatment, while the physiological condition should be monitored during application.