ABSTRACT
Objective:Metabolomics was used to analyze the brain tissue samples of model mice with chronic unpredictable mild stress (CUMS) depression, in order to find out the differential metabolites related to depression and to explore the possible antidepressant mechanism of iridoid part of Valerianae Jatamansi Rhizoma et Radix (IEFV). Method:Forty-two Kunming mice were randomly divided into 6 groups, including the normal group, the model group, the fluoxetine group (2.5 mg·kg-1) and the IEFV low, medium, and high dose groups (doses were 5.73, 11.47, 22.94 mg·kg-1, respectively). The behavioral and biochemical indicators of CUMS model mice were used for pharmacodynamic evaluation with IEFV and a positive drug (fluoxetine) as the intervention drugs. Then, the effect of IEFV on endogenous substances of the brain tissue in CUMS model mice were analyzed by nuclear magnetic resonance hydrogen spectrum (1H-NMR) metabolomics, and multivariate statistical analysis was used to identify the differential metabolites and to enrich the metabolic pathways involved in the differential metabolites. Result:After modeling, the immobility time of the model mice increased significantly, their sucrose preference rate and the excitatory neurotransmitters [5-hydroxytryptamine (5-HT) and norepinephrine (NE)] decreased significantly, indicating the success of modeling. The depression was relieved after IEFV administration, mainly manifested by the recovery of the immobility time, sucrose preference rate and the excitatory neurotransmitters (5-HT and NE). Principal component analysis (PCA) of endogenous metabolites in brain tissue showed that the model group could be significantly separated from the normal group, while the IEFV groups and fluoxetine group all showed a trend of deviating from the model group to the normal group, which was consistent with the behavioral results. The results of orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 16 different metabolites between the model group and the normal group, including 12 water-soluble metabolites and 4 liposoluble metabolites. Seven potential metabolism pathways were obtained through MetPA analysis, including metabolism of phenylalanine, metabolism of phenylalanine, tyrosine and tryptophan, metabolism of taurine and hypotaurine acid, metabolism of alanine, aspartic acid and glutamic acid, biosynthesis of valine, leucine and isoleucine, metabolism of D-glutamine and D-glutamate and tricarboxylic acid cycle (TCA). IEFV-high dose group could significantly recall 11 differential metabolites. Conclusion:IEFV may play an antidepressant role mainly by affecting energy metabolism, amino acid metabolism and neurotransmitter levels, which provides a reference for further study on the antidepressant mechanism of IEFV.
ABSTRACT
OBJECTIVE To assess the efficancy of Yangxue Qingnao granules on simvastatin-induced vascular injury model in zebrafish. METHODS Since statins can inhibit vascular development in zebrafish,in this study,we developed a novel animal model using 1 to 3 day post-fertilization larval zebrafish by optimizing the doses and duration of simvastatin exposure.Five pro-angiogenic drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model. Zebrafish was treated with different concentration of Yangxue Qingnao granules( 62.5,125 and 250 μg·mL-1)for 2 d then tested for the area of subintestinal vein vessels. RESULTS Vascular regeneration promoting effect of five pro-angiogenic drugs (calycosin, astragaloside, chlorogenic acid, ferulic acid and Panax Notoginseng Saponins)were 8-48%,24-51%,35-58%,28-75% and 37-69%,respectively.In 62.5,125 and 250 μg·mL-1Yangxue Qingnao granules group,vascular regeneration promoting effect were 21% (P>0.05), 84%(P<0.01) and 53%(P<0.01). CONCLUSION Our results demonstrate that the zebrafish vascular injury model validated in this study could be used for in vivo angiogenesis studies and drug screening and for assessing pro-angiogenic drugs with different mechanisms.Yangxue Qingnao granules could promote the vascular regeneration in zebrafish.