Screening the components in multi-biological samples and the comparative pharmacokinetic study in healthy and depression model rats of Suan-Zao-Ren decoction combined with a network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Suanzaoren Decoction (SZRD) is a classic traditional Chinese prescription, which has been commonly used for treating insomnia, depression and other nerve system diseases for a long time. AIM OF THIS STUDY: The present study aimed to explore the metabolic profiles in multi-biological samples and pharmacokinetic mechanism between healthy and depression model rats combined with a network pharmacology approach after administration of SZRD. MATERIALS AND METHODS: In our study, an ultra-high performance liquid chromatography (UPLC)-Q-Exactive Orbitrap Mass Spectrometry method was firstly used to study the prototype components and metabolites of SZRD in plasma, brain, urine, and feces between healthy and depressed rats. The possible metabolic pathways were also speculated. Then a network pharmacological study was conducted on the components in the plasma of model rats. According to the above components screened by network pharmacology and the other reported representative active components, the comparative pharmacokinetic study was established for the simultaneous determination of mangiferin, spinosin, ferulic acid, liquiritin, formononetin. magnoflorine and isoliquiritin between healthy and depression model rats. Finally, molecular docking was used to validate the binding affinity between key potential targets and active components in pharmacokinetics. RESULTS: A total of 115 components were identified in healthy rats, and 101 components were identified in model rats. The prototype components and metabolites in plasma, brain, urine, and feces were also distinguished. The main metabolic pathways included phase I and phase II metabolic reactions, such as dehydrogenation, oxidation, hydroxylation, gluconaldehyde conjugation, glutathione conjugation and so on. These results provided a basis for the further study of antidepressive pharmacokinetic and pharmacological action in SZRD. Then, according to the degree value of network pharmacological study, it was predicted that 10 components and 10 core targets, which involved in the critical pathways such as neuroactive ligand-receptor interaction, cyclic adenosine monophosphate (cAMP) signaling pathway, serotonergic synapse, phosphatidylinositol-3 kinase (PI3K)-Akt signaling pathway, etc. Finally, the established pharmacokinetic method was successfully applied to compare the pharmacokinetic behavior of these 7 active components in plasma of healthy and depressed rats after oral administration of SZRD. It showed that except magnoflorine, the pharmacokinetic parameters of each component were different between healthy and depressed rats. Molecular docking analysis also indicated that the active compounds in pharmacokinetics could bind tightly to the key targets of network pharmacological study. CONCLUSION: This study may provide important information for studying the action mechanism of SZRD in treating depression.

High phosphorus level leads to aortic calcification via ß-catenin in chronic kidney disease.

AIMS: Vascular calcification is a risk factor for causing cardiovascular events and has a high prevalence among chronic kidney disease (CKD) patients. However, the molecular mechanism underlying this pathogenic process is still obscure. METHODS: Vascular smooth muscle cells (VSMCs) were induced by a concentration of phosphorus (Pi) of 2.5 mM, and were subjected to cell calcification analyses. The effect of high Pi on the Wnt/ß-catenin pathway was measured using a TOP/FOP-Flash reporter assay. The transcriptional regulation of ß-catenin on PIT1 (a type III sodium-dependent phosphate cotransporter) was confirmed by promoter reporter and chromatin immunoprecipitation assays. The 5/6 nephrectomized rat was used as an in vivo model and was fed a high Pi diet to induce aortic calcification. Serum levels of phosphate, calcium, creatine, and blood urea nitrogen were measured, and abdominal aortic calcification was examined. RESULTS: High Pi induced VSMC calcification, downregulated expression levels of VSMC markers, and upregulated levels of osteogenic markers. High Pi activated the Wnt/ß-catenin pathway and ß-catenin activity. ß-Catenin was involved in the process of high Pi-induced VSMC calcification. Further investigation revealed that ß-catenin transcriptionally regulated Pit1, a necessary player in VSMC osteogenic phenotype change and calcification. The in vivo study showed that ß-catenin was involved in rat abdominal aortic calcification induced by high Pi. When knockdown expression of ß-catenin in the rat model was investigated, we found that aortic calcification was reduced. CONCLUSION: These results suggest that ß-catenin is an important player in high phosphorus level-induced aortic calcification in CKD.

Effects of Tai Chi Chuan combined with vibration training on the reflex activity of peripheral neuron / 医用生物力学

Objective To investigate the effects of Tai Chi Chuan combined with vibration training on the excitability of α-motorneuron pool and γ-reflex arc. Methods 55 healthy college students were divided into Tai Chi Chuan + vibration training (TAV) group, Tai Chi Chuan training (TAI) group, vibration training (VB) group, and control group (CON) for 8 weeks with 3 times training per week. Each time at pre-and post-training, H-reflex and M-wave were recorded by electrical stimulus induced on soleus muscle. T-reflex was also collected by knocking on the Achill tendon. Results After 8-week training, the ratios of Hmax/Mmax and T-reflex/Mmax in VB group were significantly decreased (P<0.05), while the ratio of T-reflex/Mmax in TAV group was significantly increased (P<0.05), and the change percentage of T-reflex/Mmax was significantly higher than that in VB group (P<0.05). Conclusions Although the vibration training could decrease the resting excitability of α-motorneuron pool, the Tai Chi Chuan combined with vibration training could give the muscle spindle stronger excitement so as to further induce the high excitability of γ-reflex arc. It indicated that the Tai Chi Chuan combined with vibration training is feasible since the neural adaptation around peripheral neuron system could be induced after such kind of training.