Prophylactic effect of Tongxieyaofang polysaccharide on depressive behavior in adolescent male mice with chronic unpredictable stress through the microbiome-gut-brain axis.

Major depression disorder is more common among adolescents and is a primary reason for suicide in adolescents. Some antidepressants are ineffective and may possess side effects. Therefore, developing an adolescent antidepressant is the need of the hour. We designed the stress model of adolescent male mice induced by chronic unpredictable stress (CUS). The mice were treated using Tongxieyaofang neutral polysaccharide (TXYF-NP), Tongxieyaofang acidic polysaccharide (TXYF-AP), TXYF-AP + TXYF-NP and fructooligosaccharide + galactooligosaccharides to determine their body weight, behavior, and serum hormone levels. RT-qPCR was used to detect the gene expression of Crhr1, Nr3c1, and Nr3c2 in the hypothalamus and hippocampus and the gene expression of glutamic acid and γ-aminobutyric acid-related receptors in the hippocampus. RT-qPCR, Western blot, and ELISA detected tryptophan metabolism in the colon, serum, and hippocampus. 16s rDNA helped sequence colon microflora, and non-targeted metabolomics enabled the collection of metabolic profiles of colon microflora. In adolescent male mice, CUS induced depression-like behavior, hypothalamic-pituitary-adrenal axis hyperactivity, hippocampal tissue damage, abnormal expression of its related receptors, and dysregulation of tryptophan metabolism. The 16s rDNA and non-targeted metabolomics revealed that CUS led to colon microflora disorder and bile acid metabolism abnormality. Tongxieyaofang polysaccharide could improve the bacterial community and bile acid metabolism disorder by upregulating the relative abundance of Lactobacillus gasseri, Lachnospiraceae bacterium 28-4, Bacteroides and Ruminococcaceae UCG-014 while preventing CUS-induced changes. TXYF-P can inhibit depression-like behavior due to CUS by regulating colonic microflora and restoring bile acid metabolism disorder. Thus, based on the different comparisons, TXYF-NP possessed the best effect.

Antioxidant Activity of Acanthopanax senticosus Flavonoids in H2O2-Induced RAW 264.7 Cells and DSS-Induced Colitis in Mice.

The redox reaction is a normal process of biological metabolism in the body that leads to the production of free radicals. Under conditions such as pathogenic infection, stress, and drug exposure, free radicals can exceed normal levels, causing protein denaturation, DNA damage, and the oxidation of the cell membrane, which, in turn, causes inflammation. Acanthopanax senticosus (A. senticosus) flavonoids are the main bioactive ingredients with antioxidant function. H2O2-treated RAW 264.7 cells and DSS-induced colitis in mice were used to evaluate the antioxidant properties of A. senticosus flavonoids. The results show that A. senticosus flavonoids can significantly downregulate the levels of ROS and MDA in H2O2-treated RAW 264.7 cells and increase the levels of CAT, SOD, and GPx. A. senticosus flavonoids can also increase the body weights of DSS-induced colitis mice, increase the DAI index, and ameliorate the shortening of the colon. ELISA experiments confirmed that A. senticosus flavonoids could reduce the level of MDA in the mouse serum and increase the levels of SOD, CAT, and GPx. Histopathology showed that the tissue pathological changes in the A. senticosus flavonoid group were significantly lower than those in the DSS group. The Western blot experiments showed that the antioxidant capacity of A. senticosus flavonoids was accomplished through the Nrf2 pathway. In conclusion, A. senticosus flavonoids can relieve oxidative stress in vivo and in vitro and protect cells or tissues from oxidative damage.

Adsorption and Desorption Characteristics of Total Flavonoids from Acanthopanax senticosus on Macroporous Adsorption Resins.

We examined the application of six different resins with the aim of selecting a macroporous resin suitable for purifying Acanthopanax senticosus total flavonoids (ASTFs) from Acanthopanax senticosus crude extract (EAS) by comparing their adsorption/desorption capacities, which led to the selection of HPD-600. Research on the adsorption mechanism showed that the adsorption process had pseudo-second-order kinetics and fit the Freundlich adsorption model. Moreover, the analysis of thermodynamic parameters indicated that the adsorption process is spontaneous and endothermic. The optimal conditions for purification of ASTFs were determined as sample pH of 3, 60% ethanol concentration, and 3 BV·h-1 flow rate, for both adsorption and desorption, using volumes of 2.5 and 4 BV, respectively. The application of macroporous resin HPD-600 to enrich ASTFs resulted in an increase in the purity of total flavonoids, from 28.79% to 50.57%. Additionally, the antioxidant capacity of ASTFs was higher than that of EAS, but both were lower than that of L-ascorbic acid. The changes in ASTFs compositions were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), with the results illustrating that the levels of seven major flavonoids of ASTFs were increased compared to that in the crude extract.