Simultaneous Determination of Ten Bioactive Components from Shenling Baizhu San in Rat Plasma by UHPLC-MS/MS: Application to a Comparative Pharmacokinetic Study in Normal and Two Models of Ulcerative Colitis Rats

Shenling Baizhu San, a traditional formula, has a long history of treating spleen asthenic diarrhea by invigorating the spleen and dispelling dampness in China. A rapid and accurate UHPLC-MS/MS method was developed and fully validated for the simultaneous determination of ten active constituents in rat plasma: panaxadiol, ginsenoside Rg1, atractylenolide I, atractylenolide III, pachymic acid, neferine, nuciferine, diosgenin, platycodin D, and isoliquiritigenin. The plasma samples were pretreated by the protein precipitation method with acetonitrile. The analytes and puerarin (internal standard) were determined with high selectivity and sensitivity (LLOQ, 0.31–0.68 ng·mL−1) within 10 minutes. The validation parameters, including intra-/interday precisions, accuracy, recovery, matrix effect, and stability, were within acceptable ranges. The validated method was successfully applied to the pharmacokinetics study of ten components in normal and two rat models of ulcerative colitis (i.e., spleen deficiency with dampness retention-ulcerative colitis (SDDR-UC) rats and pure-ulcerative colitis (P-UC) rats). The pharmacokinetic parameters were significantly different among the three groups of rats. Overall, the absorption of the components was shown as follows: normal group > SDDR-UC group > P-UC group. The study could provide a scientific basis for further studies on pharmacokinetics and clinical differential application of SDDR-UC and P-UC patients.

Effect of Shenling Baizhu San on Lipid Metabolism and Intestinal Barrier of UC with Spleen Deficiency

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease and spleen-deficiency (SD) is considered as the common Chinese medicine syndrome of UC. However, the mechanism of Shenling Baizhu San (SLS) on UC with spleen-deficiency has not been clarified. The aim of this study was to explore the influence of SD on lipid metabolism and intestinal barrier in UC mice and reveal the underlying mechanism of SLS on UC mice with spleen-deficiency. Methods: The male C57BL/6 mice were randomly divided into control group, Dextran Sulfate Sodium (DSS) group, DSS+SD group and SLS group. The data of disease activity index, body weight and length of colon were recorded to evaluate the colitis, the spleen and thymus weight were recorded to evaluate the spleen-deficiency, the serum metabolites were detected by untargeted metabolomics, the tight junction and intestinal mucus barrier were evaluated by Alcian Blue-Periodic acid Schiff staining and immunochemical, the activity of ATPase were detected by spectrophotometer, the proinflammatory factors and the copy number of mitochondrial DNA were detected by RT-PCR, the relative expression of Sirtuin 1 (SIRT1), Peroxisome proliferator-activated receptor γcoactivators-1α (PGC-1ɑ) and Mitochondrial transcription factor A (TFMA) were detected by RT-PCR and western blot. Results: The mice treated by compound method showed decreased spleen and thymus weight as well as more serious intestinal inflammation than DSS group. Compared with DSS+SD group, SLS improved intestinal inflammation and spleen deficiency, ameliorated lipid metabolism and intestinal barrier as well as promoted expression of SIRT1, PGC-1ɑ and TFMA in UC mice with spleen-deficiency. Conclusion: SLS could be considered as an effective treatment for spleen-deficiency in UC and its underlying mechanism might be related to improve lipid metabolism and intestinal barrier through mediating SIRT1/PGC-1ɑ pathway.

Efficacy and Safety of Xiaoyao Pills for Mild to Moderate Depression With Syndrome of Liver Stagnation and Spleen Deficiency: Study Protocol for a Randomized Controlled Trial

Background: Depression is one of the most frequent and severe psychiatric conditions. Many chemical drugs to treat depression are associated with adverse reactions and have shortcomings. Traditional Chinese medicine is of great significance in the prevention and treatment of depression. Xiaoyao pills has achieved good results in clinical application, which has the advantages of quick effect and no obvious adverse reactions. The aim of our study is to evaluate the efficacy and safety of Xiaoyao pills on mild to moderate depression patients with syndrome of liver stagnation and spleen deficiency.Methods: This study is a multi-center, double-blinded, randomized and placebo-controlled clinical trial. A total of 108 participants will be assigned to three groups: Xiaoyao pill group taking Xiaoyao pills twice daily for 4 weeks, placebo group taking placebos twice daily for 4 weeks and normal group without taking any drug. The primary and secondary outcome measures are the Hamilton Depression Scale (HAMD) and Traditional Chinese Medicine (TCM) Syndrome Scale. The assessment is at baseline(before treatment initiation), 1 week, 2 weeks 4 weeks after the first treatment. Exploratory outcome is also assessed to explore the mechanism of Xiaoyao pills at baseline and 4 weeks.Discussion: The results from this study will provide clinical evidence on the efficacy and safety of Xiaoyao pills in patients with mild to moderate depression with syndrome of liver stagnation and spleen deficiency.Trial registration: International Standard Randomized Controlled Trial Number Register: ISRCTN12746343. Registered on September 25, 2020.

Disrupted Resting-State Functional Connectivity between the Dorsal Attention, Default Mode, and Frontoparietal Networks in Nonorganic Gastrointestinal Disorder Patients with Spleen Deficiency Syndrome

Introduction. Spleen deficiency syndrome (SDS), a common clinical syndrome of traditional Chinese medicine, is manifested with digestive symptoms and cognitive impairments. However, the cognitive neural mechanism in brain networks of SDS still remained unclear. Our aim was to investigate the changes between the default mode, dorsal attention, and frontoparietal networks in SDS. Methods. Twenty nonorganic gastrointestinal disorder (NOGD) patients with SDS and eighteen healthy controls were enrolled to attend functional magnetic resonance imaging scan and participated a continuous performance test (CPT) before scanning. Results. Compared with healthy controls, NOGD patients with SDS showed the significantly increased functional connectivity (FC) between dorsal attention network (DAN) and left frontal-parietal control network (LFPN) and significantly decreased FC between LFPN and default mode network (DMN). The functional network connectivity analysis showed positive correlation coefficients between the DAN and LFPN and DAN and DMN as well as negative correlation between LFPN and DMN in NOGD patients with SDS compared with healthy controls. Correlation analysis revealed that the increased FC between LFPN and DAN was positively correlated with 4-digitnumber reaction time mean (RTM) and 3-digitnumber RTM. Conclusion. Our study may provide novel insights into the relationship among the DMN, DAN, and FPN in NOGD patients with SDS to deepen our understanding of the neuropsychological mechanisms of SDS.