Semen microbiota in normal and leukocytospermic males.

Large numbers of microbes can be present in seminal fluid, and there are differences in the semen microbiota between normal and abnormal semen samples. To evaluate the semen microbiota in patients with leukocytospermia, 87 seminal fluid samples, including 33 samples with a normal seminal leukocyte count and 54 samples with leukocytospermia, were obtained for a cross-sectional analysis. Twenty samples with a normal seminal leukocyte count had normal sperm parameters (Control group), and 13 samples with a normal seminal leukocyte count were from asthenozoospermia patients (Ast group). However, 32 samples with leukocytospermia were from asthenozoospermia patients (LA group), and only 22 samples with leukocytospermia had normal sperm parameters (Leu group). The 16S ribosomal RNA (rRNA) gene sequencing method was used to sequence the microbiota in the seminal fluid, and multiple bioinformatics methods were utilized to analyze the data. Finally, the results showed that the worse sperm parameters were observed in the leukocytospermia-related groups. Semen microbiota analysis found that there was increased alpha diversity in the leukocytospermia-related groups. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were the primary phyla in the seminal fluid. Two microbiota profiles, namely, Lactobacillus-enriched and Streptococcus-enriched groups, were identified in this study. The majority of the samples in the groups with a normal seminal leukocyte count could be categorized as Lactobacillus-enriched, whereas the majority of the leukocytospermia samples could be categorized as Streptococcus-enriched. Our study indicated that males with leukocytospermia have worse sperm parameters and a different semen microbiota composition compared to males with a normal seminal leukocyte count.

NMR Metabolomics and Random Forests Models to Identify Potential Plasma Biomarkers of Blood Stasis Syndrome With Coronary Heart Disease Patients.

BACKGROUND: Coronary heart disease (CHD) remains highly prevalent and is one of the largest causes of death worldwide. Blood stasis syndrome (BSS) is the main syndrome associated with CHD. However, the underlying biological basis of BSS with CHD is not yet been fully understood. MATERIALS AND METHODS: We proposed a metabolomics method based on 1H-NMR and random forest (RF) models to elucidate the underlying biological basis of BSS with CHD. Firstly, 58 cases of CHD patients, including 27 BSS and 31 phlegm syndrome (PS), and 26 volunteers were recruited from Xiangya Hospital affiliated to Central South University. A 1 mL venous blood sample was collected for NMR analysis. Secondly, principal component analysis (PCA), partial least squares discrimination analysis (PLS-DA) and RF was applied to observe the classification of each group, respectively. Finally, RF and multidimensional scaling (MDS) were utilized to discover the plasma potential biomarkers in CHD patients and CHD-BSS patients. RESULTS: The models constructed by RF could visually discriminate BSS from PS in CHD patients. Simultaneously, we obtained 12 characteristic metabolites, including lysine, glutamine, taurine, tyrosine, phenylalanine, histidine, lipid, citrate, choline, lactate, α-glucose, ß-glucose related to the CHD patients, and Choline, ß-glucose, α-glucose and tyrosine were considered as potential biomarkers of CHD-BSS. CONCLUSION: The combining of 1H-NMR profiling with RF models was a useful approach to analyze complex metabolomics data (should be deleted). Choline, ß-glucose, α-glucose and tyrosine were considered as potential biomarkers of CHD-BSS.

The efficacy of Xue Fu Zhu Yu prescription for hyperlipidemia: A meta-analysis of randomized controlled trials.

Hyperlipidemia is rampant as a crucial risk factor for cardiovascular diseases. Xue Fu Zhu Yu (XFZY), a prescription formula in traditional Chinese medicine, is well-known for treating hyperlipidemia. Herein we conducted meta-analysis and assessed the efficacy of XFZY prescription as mono or adjunctive therapy in patients with hyperlipidemia. Databases including Medline, Cochrane Library, Embase, CNKI, Wanfang Data and VIP Information were comprehensively investigated via searching keywords "Xuefuzhuyu", "Xuefu Zhuyu", "Xue Fu Zhu Yu", "Xuefu-Zhuyu" or "XFZY" in combination with "hyperlipidemia" and "dyslipidemia". Efficacy, methodological quality, and publication bias of recruited trials on XFZY prescription were also assessed. Review Manager version 5.3 software was used for statistical analysis. Twelve trials involving 1305 participants all reported in Chinese were enrolled and, based on our analysis, significant increase of efficacy in XFZY prescription groups compared to control groups was observed, and there was either significance or non-significance of differences in regulating the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). This meta-analysis preliminarily demonstrated that XFZY prescription is effective for treating hyperlipidemia, but due to the poor methodological quality of most analyzed trials, conclusion should be cautiously summarized. Thoroughly designed, large-scale and multicenter trials are needed to estimate efficacy and safety of XFZY prescription for hyperlipidemia in the future.

Efficacy and Safety of a Formulated Herbal Granula, Jiu Wei Zhen Xin, for Generalized Anxiety Disorder: A Meta-Analysis.

BACKGROUND: The traditional Chinese medicine formula Jiu Wei Zhen Xin Granula (JWZXG) is prescribed to treat generalized anxiety disorder (GAD) in China. This study was to assess the efficacy and safety of JWZXG in patients with GAD. METHOD: Data were pooled from 14 randomized controlled trials involving the assessment of mean changes of Hamilton Anxiety Rating Scale (HAMA) total scores, response rates, adverse event rates, quality, publication bias, and risk of bias. RESULTS: Pooled analysis showed no significant difference in response rate (risk ratio 1.01, 95% CI [0.93-1.08]; Z test = 0.17, P = 0.86) and no significant difference between JWZXG group and azapirones group (RR 0.69, 95% CI [0.45, 1.06]; Z test = 1.69, P = 0.09) in rate of adverse events. Though no difference exists between JWZXG group and azapirones group in HAMA total score from baseline, JWZXG group was inferior to selective serotonin reuptake inhibitors (SSRIs) group (WMD -0.93, 95% CI [-1.64, -0.23]; Z test = 2.6, P = 0.009) which had more adverse events than JWZXG group (RR 0.64, 95% CI [0.46, 0.89]; Z test = 2.63, P = 0.009). CONCLUSIONS: This meta-analysis preliminarily suggests that JWZXG is as effective as azapirones, though having the same possibility of suffering AEs. JWZXG was inferior to SSRIs but causes fewer AEs in the treatment of GAD.

Comparison of ferulic acid content in Radix Angelicae Sinensis, Danggui-Buxue-Tang and Danggui-Sini-Tang.

The aim of the present study was to determine the ferulic acid (FA) content of Radix Angelicae Sinensis (AS), Danggui-Buxue-Tang (DBT) and Danggui-Sini-Tang (DST) using the same ultra performance liquid chromatography system and method. FA was eluted using an Acquity BEH C18 column (100×2.1 mm inner diameter; 1.7 µm). A mobile phase of methanol and 0.5% acetic acid was used and a flow rate of 0.3 ml/min was selected. The calibration curve exhibited a good linear regression (R2=0.9997). The inter- and intra-day precision measurements of FA ranged between 0.27 and 3.03% and the recovery ranged between 98.44 and 101.64% with relative standard deviation (RSD) values ≤4.73%. The method was reliable and simple. The results of the chromatographic analyses indicate that the FA contents of the DBT and DST decoctions were increased compared with that of AS due to the presence of other herbs.

Meranzin hydrate exhibits anti-depressive and prokinetic-like effects through regulation of the shared α2-adrenoceptor in the brain-gut axis of rats in the forced swimming test.

BACKGROUND: In recent years, the brain-gut axis theory has received increasing attention in studies of depression. However, most studies separately address potential antidepressant and prokinetic treatments. Investigations of drugs that could potentially treat comorbid depression and gastrointestinal (GI) dysfunction via a common mechanism of action have not yet been performed in detail. AIM: To find a common mechanism of action of our patented drug, meranzin hydrate (MH), in the antidepressant and prokinetic treatment. METHODS: The forced swimming test (FST) model of depression, plasma ghrelin measurement, and in vivo and in vitro measurements of GI motility were used. RESULTS: 1. Administration of MH (9 mg/kg) decreased the immobility time during the FST after acute treatment; this effect was inhibited by the alpha 2-adrenoceptor antagonist, yohimbine, but not by the alpha 1-adrenoceptor antagonist, prazosin. 2. After chronic treatment, the immobility time of rats during the FST was decreased significantly by MH (2.25 mg/kg). 3. MH (9 mg/kg) increased plasma ghrelin levels in rats subjected to the FST; this increase was enhanced by the ghrelin receptor agonist, GHRP-6. 4. MH (9 mg/kg) also promoted gastric emptying and intestinal transit in rats with or without FST. 5. In vitro, MH (10 µM) increased jejunal contractions in rats subjected to the FST; this effect was inhibited by yohimbine. Furthermore, the inhibitory effect of yohimbine was partly reversed by the ghrelin receptor agonist, GHRP-6. CONCLUSION: Our study revealed that MH from natural resources exhibits antidepressive and prokinetic-like effects through the regulation of the common mediator, the alpha 2-adrenoceptor.

The involvement of AMPA-ERK1/2-BDNF pathway in the mechanism of new antidepressant action of prokinetic meranzin hydrate.

It was recently discovered that ketamine can relieve depression in a matter of hours through an action on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This is much more rapid than the several weeks required for the available antidepressants to show therapeutic efficacy. However, ketamine has negative side effects. The aim of this study was to determine whether the natural prokinetic drug meranzin hydrate (MH) has a fast-acting antidepressant effect mediated by AMPA receptors. By means of in vivo and in vitro experiments, we found that (1) treatment of rats with MH at 9 mg/kg decreased immobility time in a forced swimming test (FST), as did the popular antidepressant fluoxetine and the AMPA receptor positive modulator aniracetam. Pretreatment of rats with NBQX (10 mg/kg), an antagonist of AMPA receptors, blocked this effect of MH. (2) MH increased number of crossings of forced swimming rats in the open field test. (3) FST enhanced hippocampal ERK1/2, p-ERK1/2 and BDNF expression levels. MH (9 mg/kg) treatment further up-regulated hippocampal p-ERK1/2 and BDNF expression levels, and this effect was prevented by NBQX. (4) MH-increased BDNF expression corresponded with MH-decreased immobility time in the FST. (5) In vitro experiments, we found that incubation of rats hippocampus slices with MH (10, 20 µM respectively) increased concentrations of BDNF and p-ERK1/2. This effect of MH (20 µM) were prevented by NBQX. In conclusion, in animals subjected to acute stress, the natural prokinetic drug MH produced a rapid effect mediated by AMPA receptors and involving BDNF modulation through the ERK1/2 pathway.

Pharmacokinetic study of the prokinetic compounds meranzin hydrate and ferulic acid following oral administration of Chaihu-Shugan-San to patients with functional dyspepsia.

AIM OF THE STUDY: The prokinetic activity of ferulic acid derived from Ligusticum chuanxiong hort in the Chaihu-Shugan-San formula has been shown to be similar to Chaihu-Shugan-San, a popular traditional Chinese medicine for treating functional dyspepsia. The effects of meranzin hydrate, a compound isolated from Fructus aurantii in the Chaihu-Shugan-San formula, are unclear, as the pharmacokinetics have never been studied in patients with functional dyspepsia. This study aimed to describe the pharmacokinetics of ferulic acid and merazin hydrate by evaluating the prokinetics induced by Chaihu-Shugan-San and meranzin hydrate. MATERIALS AND METHODS: Gastric emptying and intestinal transit were measured after oral administration of a single dose of Chaihu-Shugan-San or meranzin hydrate in rats. The tone of rat ileum was selected as direct evidence of the prokinetic activity of meranzin hydrate. Patients with functional dyspepsia were recruited, and meranzin hydrate and ferulic acid were identified by ultra performance liquid chromatography with tandem mass spectrometry in the plasma of patients following a single oral administration of Chaihu-Shugan-San. The resulting pharmacokinetic properties were determined by ultra performance liquid chromatography coupled to photo diode array. RESULTS: In rats, single doses of Chaihu-Shugan-San (20 g/kg) and meranzin hydrate (28 mg/kg) significantly accelerated gastric emptying and intestinal transit (Chaihu-Shugan-San: 68.9 ± 5.6% and 72.3 ± 4.7%, meranzin hydrate: 72.9 ± 3.8% and 75.2 ± 3.1%) compared with the control (55.45 ± 3.7% and 63.51 ± 5.1%, P<0.05), showing similar results as cisapride (69.6 ± 4.8% and 71.6 ± 6.3%). Meranzin hydrate (30, 100 µmol/L) directly increased the amplitude of rat ileum compared with the control (P<0.01). The pharmacokinetics profiles of meranzin hydrate and ferulic acid in patient plasma was fitted with a two-compartment model detected by a simple, rapid and accurate UPLC method. Time to reach peak concentration of meranzin hydrate (0.371 mg/L) and ferulic acid (0.199 mg/L) was 23.57 min and 27.50 min, respectively. The elimination half-life and area under the concentration-time curve from t=0 to the last time of meranzin hydrate and ferulic acid were 139.53 min and 31.445 µg min/mL and 131.27 min and 14.835 µg min/mL, respectively. The absorption constant and volume of distribution of meranzin hydrate and ferulic acid were 0.185 ± 0.065 min(-1) and 3782.89 ± 2686.72 L/kg and 0.524 ± 0.157 min(-1) and 11713 ± 7618.68 L/kg, respectively. The experimental results of the pharmacokinetic parameters of meranzin hydrate and ferulic acid indicate that they were absorbed and distributed rapidly. CONCLUSIONS: The pharmacodynamics and pharmacokinetics of prokinetic Chaihu-Shugan-San and its compounds are useful for monitoring Chaihu-Shugan-San formulas in clinical practice and for understanding therapeutic mechanisms.