Percutaneous mastoid electrical stimulator improves Poststroke depression and cognitive function in patients with Ischaemic stroke: a prospective, randomized, double-blind, and sham-controlled study.

BACKGROUND: Poststroke depression can lead to functional dependence, cognitive impairment and reduced quality of life. The aim of this study was to evaluate the effects of a percutaneous mastoid electrical stimulator (PMES) plus antidepressants on poststroke depression and cognitive function. METHODS: This study was a prospective, randomized, double-blind, and sham-controlled study. A total of 258 clinically depressed ischaemic stroke patients within 14 days of index stroke were randomly assigned to the PMES plus antidepressant (PMES group, N = 125) and sham plus antidepressant (sham group, N = 133) groups. All patients underwent the Montreal Cognitive Assessment (MoCA) and Hamilton Rating Scale for Depression (HRSD) test at 2 weeks (baseline), and 6 months(M6) after ischaemic stroke. Primary outcomes were the percentage of patients showing a treatment response (≥50% reduction in HRSD score) and depression remission (HRSD score ≤ 9) at 6 months. The secondary outcome was the percentage of patients with a MoCA score < 26. RESULTS: The percentages of patients showing a treatment response and depression remission were significantly higher in the PMES group than in the sham group (57.60% vs 41.35%, P = 0.009; 44.00% vs 29.32%, P = 0.014 respectively). The mean value of the HRSD score change [M (month)6-baseline] was significantly higher in the PMES group than in the sham group at 6 months (- 11.93 ± 5.32 vs - 10.48 ± 6.10, P = 0.036, respectively). The percentage of patients with MoCA scores < 26 was lower in the PEMS group than in the sham group (12.0% vs 24.06%, P = 0.012,respectively), and the mean value of the MoCA score change (M6-baseline) was higher in the PMES group than in the sham group (3.50 ± 2.55 vs 2.72 ± 2.52, P = 0.005, respectively). CONCLUSION: These findings demonstrate that PMES adjunctive to antidepressant therapy is effective in reducing depression, achieving remission in the short term, and improving cognition. TRIAL REGISTRATION: This trial was retrospectively registered (registration number: ChiCTR1800016463) on 03 June 2018.

Metabolite profiling of ginsenosides in rat plasma, urine and feces by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Panax ginseng extract.

Panax ginseng is widely consumed as a functional food in the form of tea, powder, capsules, among others, and possesses a range of pharmacological activities including adaptogenic, immune-modulatory, anti-tumor, anti-aging and anti-inflammatory effects. The aim of this study was to identify and quantify the major ginsenosides and their metabolites in rat plasma, urine and feces after administration of P. ginseng extract using LC-MS/MS. We collected rat plasma samples at 0.5, 1, 2, 4, 8, 12, 24 and 48 h, and the amounts of urine and fecal samples accumulated in 24 h. Fourteen major ginsenosides and their metabolites were observed in fecal samples at high levels; however, low levels of 11 ginsenosides were detected in urine samples. The pharmacokinetics of the major ginsenosides and their metabolites was investigated in plasma. The results indicated that the maximum plasma concentration, time to maximum concentration and area under the curve of compound K were significantly greater than those of other ginsenosides. This study thus provides valuable information for drug development and clinical application of P. ginseng.

Comparative Analysis of the Rats' Gut Microbiota Composition in Animals with Different Ginsenosides Metabolizing Activity.

Following oral intake of Panax ginseng, major ginsenosides are metabolized to deglycosylated ginsenosides by gut microbiota before absorption into the blood. As the composition of gut microbiota varies between individuals, metabolic activities are significantly different. We selected 6 rats with low efficiency metabolism (LEM) and 6 rats with high efficiency metabolism (HEM) from 60 rats following oral administration of Panax ginseng extract, and analyzed their gut microbiota composition using Illumina HiSeq sequencing of the 16S rRNA gene. The components of gut microbiota between the LEM and HEM groups were significantly different. Between the 2 groups, S24-7, Alcaligenaceae, and Erysipelotrichaceae occupied most OTUs of the HEM group, which was notably higher than the LEM group. Furthermore, we isolated Bifidobacterium animalis GM1 that could convert the ginsenoside Rb1 to Rd. The result implies that these specific intestinal bacteria may dominate the metabolism of Panax ginseng.

Biotransformation of gypenoside XVII to compound K by a recombinant ß-glucosidase.

OBJECTIVE: To study the ß-glucosidase gene (bgy1) from Lactobacillus brevis that was cloned and expressed in Escherichia coli BL21 (DE3) and then using it for the biotransformation of gypenoside XVII. RESULTS: The bgy1 gene consists of 2283 bp encoding 761 amino acids, with homology to the glycosyl hydrolase family-3 protein domain. The enzyme (Bgy1) hydrolyzed the glucose moieties at the C-3 position and the outer glucose moieties at the C-20 position of gypenoside XVII. Using 0.1 mg enzyme ml(-1) in 20 mM sodium phosphate buffer at 30 °C and pH 6.0, 1 mg gypenoside XVII ml(-1) was transformed into 0.58 mg compound K ml(-1) within 6 h, with a corresponding molar conversion yield of 89 %. CONCLUSION: The recombinant Bgy1 is considered potentially useful for the practical preparation of compound K.

[The effect of fastigial nucleus electrical stimulation on the therapeutic window of opportunity for intervention of focal cerebral ischemia].

OBJECTIVE: To investigate the effect of cerebellar fastigial nucleus (FN) electrical stimulation on the therapeutic window of opportunity for intervention of focal cerebral ischemia. METHODS: Thirty-five healthy male Wistar rats were divided into focal cerebral ischemia/reperfusion group (I/R group, undergoing ischemia by embolism of middle cerebral artery for 3, 6 or 8 hours and then undergoing reperfusion for 24 hours, thus subdivided into I/R 3 hours, 6 hours, and 8 hours subgroups of 5 rats), focal cerebral ischemia/reperfusion plus FN electrical stimulation group (I/R-FN group, n = 15, undergoing FN electrical stimulation followed by focal cerebral ischemia/reperfusion as in the I/R group), and sham operation group (n = 5). Twenty-four hours after the reperfusion or sham operation, the rats were killed. The brain slices underwent Nissl's staining. Two slices of each rat were examined to observe the neuronal number and morphology, and the status or Nissl's staining, and make a scoring of the affected somatosensory cortex. RESULTS: The survival rates of neurons of the I/R 3, 6 and 8 hours subgroups 3.2% +/- 11.3%, 2.6% +/- 4.5% and 3.8% +/- 3.2% respectively without a significant difference between any 2 subgroups (all P > 0.05). The scores of these 3 subgroups all reached the highest grade (4.0 +/- 0.0). The neuron survival rate of the I/R FN 3 hours subgroup was 64.2% +/- 11.3%, significantly higher than those or other I/R subgroup at the same time point (all P < 0.01), however, the neurons being obviously shrunken. The score of the I/R FN 3 hours subgroup 2.1 +/- 0.2, significantly lower than that of the I/R 3 hours subgroup (P < 0.01). The neuron survival rate of the I/R FN 6 hours subgroup was 32.8% +/- 6.5%, significantly higher than that of the I/R 6 hours subgroup (P < 0.05), however, the neurons being shrunken and irregular in shape. The score of the I/R FM subgroup was 3.0 +/- 0.0, significantly lower than that of the I/R 6 hours subgroup (P < 0.05). The I/R FN 8 hours subgroup showed a neuron survival rate of 4.1% +/- 3.5%, not significantly different from that of the I/R 9 hours subgroup (P > 0.05), and the same score as that of the I/R 8 hours subgroup. The sham operation group showed a survival rate of neurons of 96.9% +/- 17.3% and a score of 0.00 +/- 0.00. CONCLUSION: FN electrical stimulation prolongs the therapeutic window of opportunity for intervention of focal cerebral ischemia. The complete recovery of survived neurons may need further interventions.