Antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism and its common pharmacodynamic substances / 中国中药杂志

This article is to explore the antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism,and to find out their common pharmacodynamic substances. UPLC-Q-TOF-MS technology was used to establish fingerprints of Shugan Lipi recipe,and 124 components were identified. The depressed mouse model was replicated by triple-one multiple stress method. Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder were administered in groups to observe the changes in body weight and behavior of the mice. The results showed that compared with the model group,the body weight,sucrose preference percentage and autonomous activity behavior of each administration group were improved. Among them,the effect of Chaihu Shugan Powder was better than that of Sini Powder and Xiaoyao Powder. LC-MS/MS method was used to determine the contents of 5-hydroxytryptamine( 5-HT),kynurenine( KYN) and tryptophan( TPP) in blood,liver,brain,colon and other tissues,as well as TDO enzyme activity in liver. Western blot and RT-PCR were used to detect the protein and gene expression of TDO enzyme,respectively. It was found that the three prescriptions increased the ratio of 5-HT/KYN in different degrees,decreased the ratio of KYN/TRP in liver,colon and brain,and decreased the expression level and activity of TDO enzyme in liver. The order of their ability to regulate tryptophan metabolism was Chaihu Shugan Powder>Sini Powder>Xiaoyao Powder. In addition,the correlation between the chromatographic peaks in the fingerprints of Shugan Lipi recipes and the pharmacodynamic indexes of tryptophan metabolism was analyzed by the grey relation analysis. The grey relation analysis found that the chemical components with the highest correlation with tryptophan metabolism were mainly from Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus. UPLC-Q-TOF-MS was used to analyze the migration components in the plasma of mice after administration of Shugan Lipi recipe,and to verify the common pharmacodynamic substances of Shugan Lipi recipe. The migration of these detected components in plasma was studied,and a total of 18 prototype components and 36 metabolites were identified. Therefore,it was believed that Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder could play an antidepressant role by reducing the expression of TDO enzyme in the liver and regulating the metabolism of tryptophan.The components contained in Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus were the common pharmacodynamic substances of Shugan Lipi recipe,which played an important role in regulating tryptophan metabolism.

Screening for bioactive components of Desmodium styracifolium and its mechanisms study based on calcium oxalate monohydrate -induced HK-2 damage model / 药学学报

To screen active components of Desmodium styracifolium in protecting calcium oxalate monohydrate (COM) -induced human proximaltubular epithelial cell (HK-2) damage model, and furtherly explore its mechanism of action, total flavonoids of Desmodium styracifolium (TFDS) and eight flavonoids (schaftoside, isoschaftoside, vicenin-2, isovitexin, isoorientin, apigenin, luteolin and genistein) were tested by COM-induced HK-2 damage model. MTT assay was used to detect the effects of different components on the cell viability of COM-induced HK-2 damage model. The lactate dehydrogenase (LDH) release in the cell supernatant and the activity level of superoxide dismutase (SOD) and reactive oxygen species (ROS) of cell were detected by the kit. Western blot was used to detect the expression levels of NLRP3, caspase-1, HMGB1 in HK-2 of different groups. Compared with the model group, the cell activity was significantly increased after 24 h co-culture with TFDS and four flavonoids (isoorientin, apigenin, genistein and luteolin). These active components can reduce the LDH leakage and ROS in cell supernatant and increase the activity of SOD, with regulating the expression of NLRP3, caspase-1, HMGB1. TFDS, apigenin, isoorientin, luteolin and genistein can protect COM-induced HK-2 cell damage, including enhancing cell viability, protecting cell membrane integrity and enhancing oxidative stress, and regulate the expression of proteins related to NLRP3 inflammasome.