Liver injury in septic mice were suppressed by a camptothecin-bile acid conjugate via inhibiting NF-κB signaling pathway.

BACKGROUND AND OBJECTIVES: Sepsis is a life-threatening organ dysfunction syndrome arising from uncontrolled inflammatory responses. Liver injury is a crucial factor for the prognosis of sepsis. Camptothecins (CPTs) have been reported to suppress the inflammatory response induced by sepsis. G2, a CPT-bile acid conjugate, has been demonstrated the property of liver targeting in our previous research. This study aimed to research the effects of G2 on liver injury induced by cecal ligation and puncture (CLP). METHODS: C57BL/6 mice were subjected to CLP surgery, and effects of G2 on liver damage and survival rates of CLP-induced mice were evaluated. To detect the related markers of hepatic injury or neutrophil infiltration, inflammatory cytokines and protein levels, hematoxylin-eosin staining assay, corresponding Detection Kits assay, ELISA and Western blot analysis were performed. RESULTS: Intraperitoneal administration of G2 reduced liver injury and enhanced the survival rates in mice with sepsis. Treatment with G2 decreased the levels of hepatic injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum of mice induced by CLP. The hepatic level of neutrophil infiltration marker myeloperoxidase (MPO) was reduced in G2 administration group. And the levels of serum inflammatory cytokines, including Tumor Necrosis Factor-α (TNFα), Interleukin-6 (IL-6) and IL-1ß, were decreased by G2. Furthermore, the results of Western blot analysis indicated that G2 suppressed the up-regulation of NF-κB p-P65 and p-IκBα. It suggested that G2 suppressed the activation of NF-κB signaling pathway. CONCLUSION: G2 alleviated sepsis-induced liver injury via inhibiting the NF-κB signaling pathway.

Microwave-Assisted Degradation of Polysaccharide from Polygonatum sibiricum and Antioxidant Activity.

Four polysaccharide fractions (P-1: 71.40%, P-2: 1.95%, P-3: 1.14%, P-4: 1.64%) were isolated from crude Polygonatum sibiricum polysaccharide (PSP), processed by water extraction, ethanol precipitation, and further separated with diethylaminoethyl cellulose-52 anion-exchange chromatography. Their molecular weights and monosaccharide compositions were characterized by high performance gel chromatography with evaporative light scattering detector and ultraviolet-visible detector. The antioxidant activity of four polysaccharides fractions were assessed by the electron transfer menchanism (DPPH, ferric reducing power, and ABST assays) and chelation of transition metals (Fe2+ and Cu2+ chelation ability). The highest content fraction P-1 exhibited the lowest antioxidant activity, and the ranking of antioxidant capacity was P-4 > P-3 > P-2 > PSP > P-1. After processed by microwave-assisted degradation, the molecular weight of P-1 was decreased from 2.99 × 105 to 2.33 × 103 Da, while the antioxidant activity of degraded P-1 was about eightfold higher than natural P-1. These results indicated that the proposed microwave-assisted degradation approach was an efficacious methodology to improve their bioactivity by lower the molecular weight of polysaccharides. PRACTICAL APPLICATION: This study provided an environmentally friendly, convenient and efficient microwave-assisted degradation technology to process the neutral polysaccharides from Polygonatum sibiricum. The results could be used for the development and utilization of various plant polysaccharides as a kind of food supplement in our daily life.