Safety evaluation of aqueous extracts of Sanghuangporus vaninii fruiting body in Sprague-Dawley rats.

Sanghuangporus vaninii, called "Sanghuang," is orally used for health care, tumor, and inflammation treatment in Asia. However, the safety of S. vaninii has not been evaluated. The major compounds analysis showed that aqueous extracts of S. vaninii fruiting body were rich in polysaccharides, nucleotides, and polyphenols. Then, the aqueous was given orally to Sprague-Dawley rats for toxical test. In acute toxicity study, the maximum tolerated dose was 21 g/kg. In 17-week repeated dose toxicity experiment, all rats had no abnormal reaction among control group, low dose group (0.15 g/kg) and middle dose group (1.00 g/kg). At high dose group (6.00 g/kg), the feces began to darken on 16th day (D16), and turned to drug stained stool on D21, all rats recovered on the 3rd day (D92) of recovery period. During the whole experiment, there were no animal death and no treatment-related changes in any of the parameters under the all doses. These results indicated the No-Observed Adverse Effect Level of aqueous extract of S. vaninii fruiting body was 1.0 g/kg.

Quzhou Fructus Aurantii Extract suppresses inflammation via regulation of MAPK, NF-κB, and AMPK signaling pathway.

The anti-inflammatory activity of Quzhou Fructus Aurantii Extract (QFAE) has been reported recently. Thus, present study aims to explore the mechanism of anti-inflammation of QFAE in vitro and in vivo to develop a lung phylactic agent. The anti-inflammatory mechanism of QFAE in RAW 264.7 cells and acute lung injury (ALI) mice model was determined by cytokines analysis, histopathological examination, Western blot assay, immunofluorescence, and immunohistochemistry analysis. The results showed that QFAE restrained mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways in LPS-induced RAW 264.7 cells, whereas AMP-activated protein kinase (AMPK) signaling pathways were activated, as revealed by prominent attenuation of phosphorylation of ERK, JNK, p38, p65, IκBα, RSK and MSK, and overt enhancement of phosphorylation of ACC and AMPKα. The levels of pro-inflammatory cytokines TNF, IL-6, and IL-1ß were suppressed, whereas the level of anti-inflammatory cytokine IL-10 increased after pretreatment with QFAE in vivo and in vitro. Moreover, QFAE prevented mice from LPS-provoked ALI, bases on alleviating neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF) and mitigatingpulmonary histological alters, as well as hematological change. The MAPK and NF-κB signaling pathways in LPS-stimulated ALI mice were dampened by QFAE pretreatment, whereas AMPK signaling pathways were accelerated, as testify by significant restraint of phosphorylation of ERK, JNK, p38, p65, and IκBα, and distinct elevation of phosphorylation of ACC and AMPKα. The remarkable anti-inflammatory effect of QFAE is associated with the suppression of MAPK and NF-κB signaling pathways and the initiation of AMPK signaling pathway.

Comparative pharmacokinetics of tedizolid in rat plasma and cerebrospinal fluid.

To investigate the possibility of tedizolid phosphate's application in the treatment of intracranial infection, a preclinical comparative pharmacokinetic study was designed. Based on the assumption that the classic efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may participate in the transportation of TDZ, two groups of rats were intravenously administered 6 mg/kg tedizolid phosphate alone or 6 mg/kg tedizolid phosphate combined with 1 mg/kg elacridar which was an inhibitor of P-gp and BCRP. Plasma and cerebrospinal fluid samples were collected according to a pharmacokinetic schedule. All the plasma and cerebrospinal fluid samples were assessed with a validated LC-MS/MS method. The penetration ratio of tedizolid from the blood to cerebrospinal fluid was calculated, and a comparison of the penetration ratios between the two groups was made. The mean Cmax of tedizolid in the CSF in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 154 ng/mL and 300 ng/mL, respectively, and the mean penetration ratio of tedizolid in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 2.16% and 3.53%, respectively. The relatively high Cmax in the CSF proved the possibility of tedizolid phosphate's application in the treatment of intracranial infection, and the higher penetration ratios, Cmax, csf and AUCcsf of the rats in co-administered elacridar group than those in the single-administration group indicated that the transporters P-gp and BCRP might be involved in the transportation of tedizolid.