Search

Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities. In this study, apigenin, luteolin, and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant (IR) HepG2 cells. All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4 (GLUT4) and phosphor-glycogen synthase kinase (GSK-3β). These flavonoids significantly inhibited the production of reactive oxygen species (ROS) and advanced glycation end-products (AGEs), which were closely related to the suppression of the phosphorylation form of NF-κB and P65. The expression levels of insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in IR-HepG2 cells were all partially activated by the flavonoids, with variable effects. Furthermore, the intracellular metabolic conditions of the flavonoids were also evaluated.

Fisetin (Fis), quercetin (Que), and myricetin (Myr) are flavonols with similar structure but different number of hydroxyl groups. The present research focused on the anti-inflammatory effect of these three flavonols in lipopolysaccharide-stimulated RAW264.7 cells. The number and site of hydroxyl group in flavonols obviously affected their anti-inflammation activity. These flavonols suppressed the overproduction of nitric oxide. Fis showed the best activity with an inhibition rate of 52% at 20 μM. Moreover, the flavonols reduced the levels of ROS, TNF-α, and IL-6. The mechanistic study showed that they inhibited the activation of NF-κB and MAPK pathways by suppressing the phosphorylation of IκBα, p65, JNK, ERK, p38, MEK, and reducing the nuclear translocation of NF-κB p65. In addition, the metabolism of the flavonols was examined. The results indicated that Fis was both methylated and glucuronidated. Que and Myr were mainly transformed into methylated products. This study highlights the anti-inflammatory activity of flavonols, particularly Fis, which has the potential for the prevention or treatment of inflammation as an adjuvant medicine or food additive.

This research aimed to investigate the antidiabetic activity, underlying mechanisms, and gut microbiota regulation of aloin. The insulin-resistant HepG2 (IR-HepG2) cell model and the type 2 diabetic (T2D) mouse model were successfully established using dexamethasone and a high-fat high-sucrose diet with low-dose streptozotocin, respectively. Aloin intervention increased glucose consumption and stimulated the activity of hexokinase and pyruvate dehydrogenase in IR-HepG2 cells. Additionally, it diminished the weight loss, reduced fasting blood glucose levels and hemoglobin A1c activity, and promoted glucose tolerance and fasting serum insulin activity in T2D mice. Histopathological analysis of the liver indicated hepatic protection by aloin. Additionally, aloin treatment inhibited the protein expression of c-Jun N-terminal kinases and activated that of IRS1/PI3K/Akt in the liver. Moreover, aloin modulated the bacterial community in the gut by raising the abundance of Bacteroidota and reducing the richness of Firmicutes, Proteobacteria, and Actinobacteriota. Thus, aloin ameliorated IR via activating IRS1/PI3K/Akt signaling pathway and regulating the gut microbiota, and it may be promising candidate as functional food for diabetic therapy.

Fucosylated oligosaccharides have important biological functions as well as an excellent antiviral activity. A novel α 1–2-fucosyltransferase (α 2FT) from Treponema primitia (Tp2FT) was cloned and expressed in Escherichia coli BL21(DE3) and purified as an N-His6-tagged fusion protein (His6-Tp2FT). Mass spectrometry was carried out to identify the products of enzymatic reaction. The Tp2FT exhibited strict acceptor substrate specificity for type 1 structure (Galβ1-3GlcNAc)-containing glycans. It might be a promising emzyme for the chemo-enzymatic synthesis of lacto-N-fucopentaose I (LNFP I), which is one of the important fucosylated oligosaccharides. In this study, different in vitro experiments were used to study the biological activities of LNFP I. It could reduce the concentrations of inflammatory cytokines and effectively inhibit the synthesis of enterovirus 71 proliferation. LNFP I was an inhibitor of enterovirus 71 in the early stages of infection, it can used in infant nutrition and might provide a new drug for hand foot mouth disease.

Abstract Fisetin is one of the most popular flavonoids found in vegetables and fruits with several health benefits such as antidiabetic, anticancer, and anti‐inflammatory activities. Biotechnology or chemosynthesis tools were used for the synthesis of fisetin and its analogs to improve their yield and efficacy. Structure activity relationships (SARs) revealed that the aromatic hydroxyl groups especially the 3,4‐dihydroxylation at ring B were crucial for fisetin biological activities, whereas substitution of several hydroxyl groups in fisetin appeared to impact its original effects. The ongoing or upcoming clinical trials containing fisetin are applied in drugs and dietary supplements. Noteworthily, fisetin has been successfully incorporated into nutraceuticals in the market. Furthermore, the delivery system of fisetin‐loaded nanocochleates showed the best bioavailability compared to other formulations. This review presents the latest research progress of fisetin on its synthesis, structure–activity relationships, pharmacokinetics, biological activities, and underlying mechanisms, bioavailability, delivery systems, and clinical trials to provide a comprehensive insight into the research and application of this valuable natural compound.

ABSTRACTInfection with a novel H10N8 influenza virus in humans was first described in China in December 2013, which raised concerns related to public health. This novel virus was subsequently confirmed to have originated from a live poultry market. However, whether this virus can infect other mammals remains unclear. In the present study, antibody specific for H10N8 influenza virus was detected in swine herds in southern China during serological monitoring for swine influenza virus. The pathogenicity and transmissibility of this H10N8 influenza virus to swine was examined. The results showed that swine are susceptible to infection with human-origin H10N8 influenza virus, which causes viral shedding, severe tissue lesions, and seroconversion, while infection with avian-origin H10N8 influenza virus causes only seroconversion and no viral shedding. Importantly, human-origin H10N8 influenza virus can inefficiently be transmitted between swine and cause seroconversion through direct contact. This study provides a new perspective regarding the ecology of H10N8 influenza virus and highlights the importance of epidemiological monitoring of the H10N8 influenza virus in different animal species, which will be helpful for preventing and controlling future infections by this virus.

A novel bacterial α 1–2-fucosyltransferase (α 2FT) from Thermosynechococcus sp. NK55a (Ts2FT) has been discovered and characterized. It shares 28–62% protein sequence homology to α 2FTs reported previously. The Ts2FT was cloned as an N-terminal His6-tagged recombinant protein (His6-Ts2FT) and expressed in E. coli BL21 (DE3). It was expressed at a level of 6.2 mg/L culture after induction with 0.05 mM of isopropylβ-d-1-thiogalactoside (IPTG) at 16 °C for 20 h. It showed the optimal activity at a reaction temperature of 40 °C and pH of 7.0. The presence of a Mg2+ improved its catalytic efficiency. Ts2FT displayed a strict acceptor specificity and could recognize only β1–3-galatoside acceptors. It was used efficiently for one-pot multienzyme synthesis of fucosylated oligosaccharides. One of the products, lacto-N-fucopentaose I was shown to promote the growth of intestinal probiotics including those belonging to Acidobacteria, Actinobacteria, Proteobacteria, Planctomycetes, and Chloroflexi.

The Eurasian avian-like swine (EA) H1N1 virus has affected the Chinese swine industry, and human infection cases have been reported occasionally. However, little is known about the pathogenic mechanism of EA H1N1 virus. In this study, we compared the mouse pathogenicity of A/swine/Guangdong/YJ4/2014 (YJ4) and A/swine/Guangdong/MS285/2017 (MS285) viruses, which had similar genotype to A/Hunan/42443/2015 (HuN-like). None of the mice inoculated with 106 TCID50 of YJ4 survived at 7 days post infection, while the survival rate of the MS285 group was 100%. Therefore, a series of single fragment reassortants in MS285 background and two rescued wild-type viruses were generated by using the reverse genetics method, and the pathogenicity analysis revealed that the PB2 gene contributed to the high virulence of YJ4 virus. Furthermore, there were 11 amino acid differences in PB2 between MS285 and YJ4 identified by sequence alignment, and 11 single amino acid mutant viruses were generated in the MS285 background. We found that the R251K mutation significantly increased the virulence of MS285 in mice, contributed to high polymerase activity and enhanced viral genome transcription and replication. These results indicate that PB2-R251K contributes to the virulence of the EA H1N1 virus and provide new insight into future molecular epidemiological surveillance strategies.