Effect of Shunao Jieyu Decoction on Intestinal Flora in Patients with Post-stroke Depression / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Shunao Jieyu decoction on intestinal flora in patients with post-stroke depression. MethodSixty patients with post-stroke depression of Qi stagnation， blood stasis， and phlegm obstruction were selected and divided into a treatment group （30 cases， Shunao Jieyu decoction） and a control group （n=30， paroxetine hydrochloride tablets） according to the random number table. All patients were treated correspondingly for eight weeks. The scores of traditional Chinese medicine（TCM） syndrome， Hamilton rating scale for depression（HAMD）， National Institutes of Health stroke scale（NIHSS）， and activities of daily living（ADL）before and after treatment were compared between the two groups. High-throughput sequencing was used to analyze the diversity of fecal flora and the distribution of taxonomical levels in two groups before and after treatment. ResultThe post-treatment TCM syndrome score， HAMD score， and NIHSS score were lower than those before treatment in the same group （P<0.05）， while the post-treatment ADL score was higher than that before treatment （P<0.05）. Compared with the control group after treatment， the treatment group showed decreased TCM syndrome score （P<0.05）. No significant difference was observed in the HAMD score， NIHSS score and ADL score between the two groups after treatment. The total effective rate of the treatment group was 90% （27/30）， which was superior to 66.3% （19/30） of the control group （χ2=5.863， P<0.05）. After treatment， the average values of Chao1 index， Observed species index， Shannon index， Simpson index， and Pielou's evenness index of intestinal flora diversity in the treatment group increased without significant difference， while the average value of the Good's Coverage index remained unchanged in the same group. At the phylum level， the abundance of Bacteroidetes increased. At the family level， the abundance of Bacteroidaceae increased. At the genus level， the abundance of Bacteroidetes increased. ConclusionShunao Jieyu decoction can effectively improve the clinical TCM symptoms of patients with post-stroke depression， relieve neurological impairment， improve the ability of daily living， and change the diversity and abundance of the intestinal flora of patients at different taxonomic levels.

Effects of Fish Oil Combined with Selenium and Zinc on Learning and Memory Impairment in Aging Mice and Amyloid Precursor Protein Processing.

Alzheimer's disease is characterized by the aggregation of amyloid-beta (Aß) peptide into plaques and neurofibrillary tangles. Aß peptide is generated by the cleavage of the ß-amyloid precursor protein (APP) by ß- and γ-secretase. The present study was conducted to investigate the effects of fish oil (or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), selenium, and zinc on learning and memory impairment in an aging mouse model and on APP. We performed the Morris water maze and platform recorder tests on male Kunming mice (10/group) grouped as control and D-galactose-induced aging model mice treated with vehicle, fish oil, fish oil + selenium, fish oil + selenium + zinc, and positive control (red ginseng extract). Fish oil + zinc + selenium for 7 weeks significantly improved learning and memory impairments in aging model animals in the Morris water maze and platform recorder tests, as evidenced by shortened incubation periods and number of errors. In vitro analysis of Aß1-40 content in APP695-transfected CHO cells revealed a decrease after treatment with EPA, DHA, and their combinations with selenium or selenium and zinc. Assaying ß- and γ-secretase activities revealed a decrease in PC12 cells and mouse serum as well as a decrease in ß-site APP-cleaving enzyme 1 and presenilin 1 protein levels in the PC12 cells and mouse serum. Taken together, our results show that fish oil combined with selenium and zinc inhibited APP processing and alleviated learning and memory impairment in a mouse model of aging.

Selenium and Zinc against Aß25-35-Induced Cytotoxicity and Tau Phosphorylation in PC12 Cells and Inhibits γ-cleavage of APP.

Amyloid beta (Aß) is the main component of the amyloid plaques that accumulate in the brains of Alzheimer patients. The present study was conducted to investigate whether the combined treatment with selenium (Se) and zinc (Zn) offers more beneficial effects than that provided by either of them alone in reversing Aß25-35-induced neurotoxicity in PC12 cells. Cells were pretreated with 0.1 µmol/L of Se and Zn for 4 h, after treated with 10 mmol/L Aß25-35 for 24 h. Cells were divided into control and five treated groups, and received either 10 mmol/L Aß25-35,10 mmol/L Aß25-35 + 0.1 µmol/L Se, 10 mmol/L Aß25-35 + 0.1 µmol/L Zn, 10 mmol/LAß25-35 + 0.1 µmol/L Se + 0.1 µmol/L Zn, or 0.1 µmol/L Se + 0.1 µmol/L Zn. The result showed that cell viability was decreased in MTT metabolic rate; LDH release and MDA, H2O2, and NO levels were increased and the GSK-3ß and phosphorylated tau protein level were increased in Aß25-35-treated group (P < 0.05 or P < 0.01), which whole changes were attenuated by Se and Zn and Se combined Zn. In order to evaluate whether the Se and Zn have an effect on processing pathway of amyloid precursor protein (APP), we examined the activity of γ-secretase in primary cultured cortical neuron cells. ELISA analysis showed that Se and Zn could inhibit the activity of γ-secretase. Then we also investigated the effect of Se and Zn on the Aß1-40 concentration and APP-N-terminal fragment expression from APP695 stably transfected Chinese hamster ovary (CHO) cells. APP695 stably transfected CHO cells were treated with 0.1 µmol/L Se and Zn; cells were divided into control and four treated groups, which received either 0.5 M DAPT, 0.1 µmol/L Se, 0.1 µmol/L Zn, or 0.1 µmol/L Se + 0.1 µmol/L Zn. Se and Zn could decrease Aß1-40 production and increase the APP-N-terminal fragment protein expression. These experiments indicate that Se and Zn have a protective effect on AD pathology that a possible mechanism is inhibiting the activity of γ-secretase to decreasing Aß1-40 production further influencing the APP processing. Altogether, our findings may provide a novel therapeutic target to treat AD sufferers.