Quantitative analysis of urinary endogenous markers for the treatment effect of Radix Scutellariae on type 2 diabetes rats

The effect of Radix Scutellariae treated on type 2 diabetic rats has been investigated by a liquid chromatography coupled with tandem mass spectrometry（LC-MS/MS） based urinary quantitative approach.In this research,multiple reactions monitoring mode of MS/MS in LC-MS/MS analysis was used to quantitatively analyze the concentrations of 7 endogenous compounds in urine of normal control group,type 2 diabetic model group and Radix Scutellariae-treated group,and multivariate statistical analysis was utilized for MS data processing.The above-mentioned three groups can be distinguished via pattern recognition.The obtained results indicated that Radix Scutellariae affect the urinary metabolic profiling of type 2 diabetic rats on the polyol pathway,protein glycation reaction and amino acids metabolism pathway.According to these results,Radix Scutellariae should have the pharmacological effect on preventing or delaying the onset and progression of diabetes and its complications.

Domesticated HERV-W env contributes to the activation of the small conductance Ca^(2+)-activated K^(+)type 2 channels via decreased 5-HT4 receptor in recent-onset schizophrenia

The human endogenous retroviruses type W family envelope(HERV-W env)gene is located on chromosome 7q21-22.Our previous studies show that HERV-W env is elevated in schizophrenia and HERV-W env can increase cal-cium influx.Additionally,the 5-HTergie system and particularly 5-hydroxytryptamine(5-HT)receptors play a prominent role in the pathogenesis and treatment of schizophrenia.5-hydroxytryptamine receptor 4(5-HT4R)agonist can block calcium channels.However,the underlying relationship between HERV-W env and 5-HT4R in the etiology of schizophrenia has not been revealed.Here,we used enzyme-linked immunosorbent assay to detect the concentration of HERV-W env and 5-HT4R in the plasma of patients with schizophrenia and we found that there were decreased levels of 5-HT4R and a negative correlation between 5-HT4R and HERV-W env in schizophrenia.Overexpression of HERV-W env decreased the transcription and protein levels of 5-HT4R but increased small conductance Ca^(2+)-activated K^(+)type 2 channels(SK2)expression levels.Further studies revealed that HERV-w env could interact with 5-HT4R.Additionally,luciferase assay showed that an essential region(-364 to-176 from the transcription start site)in the SK2 promoter was required for HERV-W env-induced SK2 expression.Importantly,5-HT4R participated in the regulation of SK2 expression and promoter activity.Electrophysiological recordings suggested that HERV-Wenv could increase SK2 channel currents and the increase of SK2 currents was inhibited by 5-HT4R.In condusion,HERV-W env could activate SK2 channels via decreased 5-HT4R,which might exhibit a novel mechanism for HERV-Wenv to influence neuronal activity in schizophrenia.