Black mulberry (Morus nigra L.) polysaccharide ameliorates palmitate-induced lipotoxicity in hepatocytes by activating Nrf2 signaling pathway.

Black mulberry (Morus nigra L.) has shown health benefits against metabolic disorders. Lipotoxicity is considered as a potentially cause of metabolic syndrome, and there is no effective treatment. However, the protective effect and its mechanism of black mulberry against lipotoxicity are unclear. In this study, three polysaccharide fractions (BP1, BP2, BP3) were isolated from black mulberry by stepwise precipitation with 30%, 60%, and 90% of ethanol and analyzed by GPC, HPLC and FT-IR methods. BP1 exhibited a better protective effect than BP2 and BP3 on palmitic acid (PA)-induced lipotoxicity in HepG2 cells. BP1 effectively reduced PA-induced lipotoxicity by eliminating accumulation of ROS, improving mitochondrial function, reversing glutathione depletion and enhancing antioxidant enzyme activities. Mechanistically, BP1 activated the Nrf2 signaling pathway, a master regulator of the antioxidant defense system, through increasing Nrf2 nuclear translocation and phosphorylation. Collectively, these results demonstrate that BP1 has the great potential for applications in lipid disorders.

Lysosomal Reacidification Ameliorates Vinyl Carbamate-Induced Toxicity and Disruption on Lysosomal pH.

Ethyl carbamate (EC) is a carcinogen toxicant, commonly found in fermented foods and beverages. The carcinogenic and toxic possibility of EC is thought to be related to its metabolite vinyl carbamate (VC). However, we found interesting mechanisms underlying VC-induced toxicity in this study, which were greatly different from EC. We first conducted a simple synthesis procedure for VC and found that VC possessed higher toxicity but failed to regulate levels of reactive oxygen species, glutathione, and autophagy. Notably, VC treatment resulted in upregulation of lysosomal pH, which was responsible for its cytotoxicity. Cyclic adenosine monophosphate (cAMP) pretreatment could enhance restoration of lysosomal acidity and ameliorate VC-induced damage. Inhibition of protein kinase A and cystic fibrosis transmembrane conductance regulator can block cAMP-induced cytoprotection. Together, our results provided the evidence for novel mechanisms of toxicity and possible protection method under VC exposure, which might give new perspectives on the study of EC-induced toxicity.

Pyrolyzed fabrication of N/P co-doped biochars from (NH4)3PO4-pretreated coffee shells and appraisement for remedying aqueous Cr(VI) contaminants.

In this study, an agricultural residue-derived biochar was fabricated by pyrolyzing coffee shells using (NH4)3PO4 pretreatment. The influence of pyrolysis temperature on the structure and properties of biochars was investigated. The elemental analysis, spectroscopic and textural studies showed that the biochars were endued sufficient N and P co-doping and large specific surface area by (NH4)3PO4-pretreatment. The appraisement for remedying aqueous Cr(VI) contaminants demonstrated that the N/P co-doped biochars offered high efficiencies above 95% for aqueous Cr(VI) removal. The mechanism investigation displayed that the adsorption and reduction of Cr(VI) were boosted by the synergistic effect between the hierarchical pore structure and the groups related to oxygen, nitrogen and phosphorus. Moreover, the biochar can be readily regenerated by HCl solution soaking for reuses several times. This work should permit for providing a convenient utilization of coffee shell agricultural residues, and the coffee shell-derived biochars supplied potential for remedying Cr(VI) in effluents.

Polysaccharide from Mulberry Fruit (Morus alba L.) Protects against Palmitic-Acid-Induced Hepatocyte Lipotoxicity by Activating the Nrf2/ARE Signaling Pathway.

This study was aimed to investigate the protective effects of three different mulberry fruit polysaccharide fractions (MFP-I, MFP-II, and MFP-III) against palmitic acid (PA)-induced hepatocyte lipotoxicity and characterize the functional polysaccharide fraction using gel permeation chromatography, high-performance liquid chromatography, Fourier transform infrared spectroscopy, and nuclear magnetic resonance analyses. MFP-I, MFP-II, and MFP-III were isolated from mulberry fruit by stepwise precipitation with 30, 60, and 90% ethanol, respectively. MFP-II at 0.1 and 0.2 mg/mL dramatically attenuated PA-induced hepatic lipotoxicity, while MFP-I and MFP-III showed weak protection. It was demonstrated that MFP-II not only increased nuclear factor erythroid-2-related factor 2 (Nrf2) phosphorylation and its nuclear translocation, thereby activating the Nrf2/ARE signaling pathway, but also enhanced heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1, and γ-glutamate cysteine ligase gene expressions and promoted catalase and glutathione peroxidase activities, which protected hepatocytes against PA-induced oxidative stress and lipotoxicity. Further investigation indicated that the molecular weight of MFP-II was 115.0 kDa, and MFP-II mainly consisted of galactose (30.5%), arabinose (26.2%), and rhamnose (23.1%). Overall, our research might provide in-depth insight into mulberry fruit polysaccharide in ameliorating lipid metabolic disorders.

Systematic study of the quality and safety of chilled pork from wet markets, supermarkets, and online markets in China.

BACKGROUND: With increasing media coverage of food safety incidents, such as that of clenbuterol residues in pork, food safety has become a major public health concern in China. Rapidly developing online markets attract increasing numbers of Chinese consumers to purchase food on the Internet. However, the quality and safety of food sold online are uncertain and are less reported on. OBJECTIVE: This research aimed to systematically study the quality and safety of chilled pork from wet markets, supermarkets, and online markets in China. RESULTS: The chilled pork samples from online markets were fresher than those from wet markets and supermarkets based on the surface redness (a* value). Chilled pork contained high levels of nutritional elements, especially the magnesium and phosphorus levels in samples from online markets. The levels of heavy metal element residues and veterinary drug residues in all chilled pork samples were within the standards limits. In addition, huge differences existed in the quality and freshness of the chilled pork samples from online markets according to principal component analysis (PCA). CONCLUSIONS: Most chilled pork sold in Chinese markets was qualified and safe. It is necessary to establish an effective online market supervision system for chilled pork.

Procyanidin B2 ameliorates free fatty acids-induced hepatic steatosis through regulating TFEB-mediated lysosomal pathway and redox state.

Procyanidin B2, a naturally occurring phenolic compound, has been reported to exert multiple beneficial functions. However, the effect of procyanidin B2 on free fatty acids (FFAs)-induced hepatic steatosis remains obscure. The present study is therefore aimed to elucidate the protective effect of procyanidin B2 against hepatic steatosis and its underlying mechanism. Herein, we reported that procyanidin B2 attenuated FFAs-induced lipid accumulation and its associated oxidative stress by scavenging excessive ROS and superoxide anion radicals, blocking loss of mitochondrial membrane potential, restoring glutathione content, and increasing activity of antioxidant enzymes (GPx, SOD and CAT) in hepatocytes. Procyanidin B2 mechanistically promoted lipid degradation via modulation of transcription factor EB (TFEB), a master regulator of lysosomal pathway. Molecular docking analysis indicated a possible ligand-binding position of procyanidin B2 with TFEB. In addition, administration of procyanidin B2 resulted in a significant reduction of hepatic fat accumulation in high-fat diet (HFD)-induced obese mice, and also ameliorated HFD-induced metabolic abnormalities, including hyperlipidemia and hyperglycemia. It was confirmed that procyanidin B2 prevented HFD-induced hepatic fat accumulation through down-regulating lipogenesis-related gene expressions (PPARγ, C/EBPα and SREBP-1c), inhibiting pro-inflammatory cytokines production (IL-6 and TNF-α) and increasing antioxidant enzymes activity (GPx, SOD and CAT). Moreover, hepatic fatty acids analysis indicated that procyanidin B2 caused a significant increase in the levels of palmitic acid, oleic acid and linoleic acid. Intriguingly, procyanidin B2 restored the decreased nuclear TFEB expression in HFD-induced liver steatosis and up-regulated its target genes involved in lysosomal pathway (Lamp1, Mcoln, Uvrag), which suggested a previously unrecognized mechanism of procyanidin B2 on ameliorating HFD-induced hepatic steatosis. Taken together, our results demonstrated that procyanidin B2 attenuated FFAs-induced hepatic steatosis through regulating TFEB-mediated lysosomal pathway and redox state, which had important implications that modulation of TFEB might be a potential therapeutic strategy for hepatic steatosis and procyanidin B2 could represent a promising novel agent in the prevention and treatment of non-alcoholic fatty liver disease (NAFLD).

Systematic evaluation of phenolic compounds and protective capacity of a new mulberry cultivar J33 against palmitic acid-induced lipotoxicity using a simulated digestion method.

This research aimed to investigate the protective effects of a new mulberry cultivar J33 with simulated gastrointestinal digestion against palmitic acid (PA)-induced lipotoxicity. LC-MS analysis revealed that the contents of four flavonoid glycosides (quercetin rhamnosylhexoside hexoside, quercetin rhamnosylhexoside, quercetin hexoside, kaempferol rhamnosylhexoside) increased after digestion. Besides, mulberry digest (MBD) at 0.5-2 mg/mL significantly reduced PA-induced lipotoxicity in human hepatocytes, while mulberry extract without digestion (MBE) showed no protection. Further investigations demonstrated that the protection of MBD was attributed to two aspects. On the one hand, MBD could attenuate PA-induced oxidative stress by suppressing ROS accumulation, regulating intracellular glutathione and ameliorating mitochondrial dysfunction. On the other hand, MBD could promote PA incorporation into inert triglycerides (TG) to deal with the acute lipid overload, reducing the lipotoxicity caused by PA. Overall, our research might provide a new perspective of mulberry cultivar J33 in ameliorating non-alcoholic fatty liver disease (NAFLD).

An effective method for preparation of high-purity pelargonidin-3-O-glucoside from strawberry and its protective effect on cellular oxidative stress.

Accumulating evidence indicates that consumption of berries may exert beneficial effects against oxidative stress mediated diseases. Pelargonidin-3-O-glucoside (Pg3G), a bioactive ingredient in strawberry, has been reported to possess a potent antioxidant capacity. This study was therefore designed to develop an effective method to prepare pure Pg3G from strawberry and investigate its protective effect against H2O2-induced oxidative stress. According to our results, Pg3G occupied 85.55% of total anthocyanin content in strawberry. 240mg of Pg3G with the purity of 97.26% was finally isolated from 320g of strawberry lyophilized powder (SLP) by combination of AB-8 macroporous resin and high-speed counter-current chromatography (HSCCC) technologies. Further study unveiled that Pg3G significantly inhibited H2O2-induced ROS generation, GSH depletion and mitochondrial dysfunction, thereby ameliorating H2O2-induced oxidative stress. Overall, this study suggests that pelargonidin-3-O-glucoside can be used as a natural bioactive agent to prevent cellular oxidative stress.