Nuciferine improves high-fat diet-induced obesity via reducing intestinal permeability by increasing autophagy and remodeling the gut microbiota.

Nuciferine (NF) has received extensive attention due to its medicinal value in the treatment of metabolic diseases, such as obesity; however, to date, the effects of NF on obesity-related intestinal permeability, autophagy and the gut microbiota have not been investigated. Herein, C57BL/6J mice were fed either a chow or a high-fat diet (HFD) with or without NF for 8 weeks. The results showed that NF supplement reduced weight gain, fat accumulation and intestinal permeability in the HFD mice accompanied by improved autophagy. Subsequently, an in vitro experiment was performed using Caco-2 and HT-29 cells, which showed that NF supplement not only promoted the formation of autophagosomes and autophagolysosomes, but also alleviated LPS-increased intestinal permeability. Importantly, NF supplement protected from LPS-induced paracellular permeability impairment after the administration of autophagy-related gene (Atg) 5 small-interfering RNA (siRNA). These results demonstrate that NF exerts beneficial effects on the intestinal permeability by improving autophagy. Furthermore, we also found that NF supplement lowered the abundance of Butyricimonas and increased the abundance of Akkermansia, an anti-obesity bacterium. Thus, overall, we demonstrated that NF supplement confers reduced intestinal permeability by improving autophagy and alters the composition of the gut microbiota in HFD-fed mice, thereby producing an anti-obesity effect.

Recent progress in Keap1-Nrf2 protein-protein interaction inhibitors.

Therapeutic targeting the protein-protein interaction (PPI) of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its main regulator, Kelch-like ECH-Associating protein 1 (Keap1) has been emerged as a feasible way to combat oxidative stress related diseases, due to the key role of Nrf2 in oxidative stress regulation. In recent years, many efforts have been made to develop potent Keap1-Nrf2 inhibitors with new chemical structures. Various molecules with diverse chemical structures have been reported and some compounds exhibit high potency. This review summarizes peptide and small molecule Keap1-Nrf2 inhibitors reported recently. We also highlight the pharmacological effects and discuss the possible therapeutic application of Keap1-Nrf2 inhibitors.

A thermo-stable lysine aminopeptidase from Pseudomonas aeruginosa: Isolation, purification, characterization, and sequence analysis.

Pseudomonas aeruginosa NJ-814, isolated from garden soil, produced an extracellular aminopeptidase that was purified using ammonium sulfate precipitation and ion exchange chromatography. The purity was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and the Mr value of the enzyme was estimated to be 55 kDa. The purified enzyme shows maximum activity at pH 9.0 and 80 °C. It exhibits high thermo-stability. Half of the activity can remain after incubation at 80 °C for 119 min. It is stable within pH range of 7.5-10.5. It is strongly activated by Co(2+) and inhibited by Fe(2+) , Cu(2+) , Ni(2+) , Zn(2+) , and ethylene diamine tetraacetic acid (EDTA). The specificity of the enzyme was investigated. Within several aminoacyl-p-nitroanilines (AA-pNA), Lys-pNA is proven to be the optimal substrate. The Michaelis-Menten constant (Km ) of the enzyme for Lys-pNA and Leu-pNA were 2.32 and 9.41 mM, respectively. Peptide map fingerprinting shows that the sequence of the enzyme is highly similar to aminopeptidase Y from P. aeruginosa 18A. It can be speculated that this enzyme is a Zn(2+) -dependent enzyme and contains two zinc ions in its active site.