Higher ratio of serum uric acid to serum creatinine (SUA/SCr) increases the risk of metabolic unhealthy phenotype.

BACKGROUND AND AIM: It is very important to understand which factors play roles in switching from a healthy to an unhealthy metabolism. It is unclear if SUA/SCr is an independent risk factor for metabolic unhealthy phenotype. We examined whether SUA/SCr is associated with an increased risk for metabolic unhealthy phenotype in the Chinese population. METHODS AND RESULTS: As many as 3158 subjects aged 25-75 years who had a metabolic healthy phenotype at baseline were included in the retrospective cohort study. They were assigned to four groups based on the quartile of SUA/SCr. We compared the demographic and clinical characteristics among the four groups. The correlation between SUA/SCr and the risk of metabolic unhealthy phenotype in the overall population and stratified by subgroups was examined by logistic regression analyses. Greater SUA/SCr values were correlated with greater BMI, systolic and diastolic BP, TC, TG, RBC, WBC, HB, ALT, SUA and eGFR. During the two-year follow-up, 632 of the study subjects (20.01%) developed new-onset metabolic unhealthy phenotype from the total of 3158 study subjects. A statistically significant increase in the rates of metabolic unhealthy phenotype was observed with increasing SUA/SCr levels within each group. After multivariate adjustment, the adjusted ORs and 95% CIs were 1.44 (1.03-2.00) and 2.11 (1.52-2.94) in the Q3 group and Q4 group, respectively. CONCLUSION: SUA/SCr was positively related to the risk of metabolic unhealthy phenotype in the Chinese subjects, suggesting the potential of SUA/SCr to serve as an independent risk predictor in the development of metabolic unhealthy phenotype.

Chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketoDCA.

Chaihu-Shugan-San (CSS) is a traditional botanical drug formula often prescribed to treat depression in oriental countries, but its pharmacotherapeutic mechanism remains unknown. It was recently reported that CSS alters the composition of intestinal microflora and related metabolites such as bile acids (BAs). Since the intestinal microflora affects physiological functions of the brain through the gut-microbiota-brain axis, herein we investigated whether CSS altered BA levels, gut microflora, and depression-like symptoms in chronic unpredictable mild stress (CUMS) mice, a well-established mouse model of depression. Furthermore, we determined whether BA manipulation and fecal microbiota transplantation altered CSS antidepressant actions. We found that the BA chelator cholestyramine impaired the antidepressant effects of CSS, which was partially rescued by dietary cholic acid. CSS increased the relative abundance of Parabacteroides distasonis in the colon of CUMS mice, and increased serum levels of various BAs including hyocholic acid (HCA) and 7-ketodeoxycholic acid (7-ketoDCA). Furthermore, gut bacteria transplantation from CSS-treated mice into untreated or cholestyramine-treated CUMS mice restored serum levels of HCA and 7-ketoDCA, alleviating depression-like symptoms. In the hippocampus, CSS-treated mice had decreased expression of genes associated with BA transport (Bsep and Fxr) and increased expression of brain-derived neurotrophic factor and its receptor, TrkB. Overall, CSS increases intestinal P. distasonis abundance, leading to elevated levels of secondary BAs in the circulation and altered expression of hippocampal genes implicated in BA transport and neurotrophic signaling. Our data strongly suggest that the gut microbiota-brain axis contributes to the potent antidepressant action of CSS by modulating BA metabolism.

Baicalin Attenuates Continuous Activation of ß-Catenin Induced by Lipopolysaccharide (LPS) and Depression Complicated by Infertility in Male Rats.

Background: Baicalin (BA) is a potential candidate drug to inhibit depressive behavior. However, the mechanism of BA's role on depression complicated with male infertility (DCMI) is still unclear. This study aimed to investigate the role of BA in alleviating inflammatory factor-induced DCMI by regulating ß-catenin. Methods: Firstly, we performed sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), and forced swim test (FST) in the chronic unpredictable mild stress (CUMS) + lipopolysaccharide (LPS) model rats to study the effect of BA on depressive behavior. The levels of neuropeptide Y (NPY), testosterone (T), and IL-1ß, IL-6, TNF-α, IL-10, and IL-4 in the peripheral blood plasma of normal people, patients with depression, and patients with DCMI were measured. Then, the levels of IL-1ß, IL-6, TNF-α, IL-10, IL-4, ß-catenin in rat testis and peripheral blood and ANXA2, APP, SEMG1, and SEMG2 in seminal plasma proteins were examined. Moreover, the level of ß-catenin in the testicular tissue was detected. LPS was used to treat Sertoli cells, and the level of ß-catenin was detected. Finally, we evaluated the reproductive phenotype and sperm motility of rats. Results: BA (especially 100 mg/kg) could notably ameliorate depression-like behavior induced by CUMS + LPS. The levels of IL-4, IL-10, T, and NPY in depression patients, DCMI patients, and CUMS + LPS model rats elevated, while the levels of IL-1ß, IL-6, and TNF-α were reduced. However, BA alleviated the changes in these factors. Moreover, BA alleviated male rat depression induced by CUMS + LPS. LPS upregulated ß-catenin (NP) but could not adjust ß-catenin (TP) level in rat Sertoli cells. BA relieved the symptoms of DCMI by regulating ß-catenin. Furthermore, BA ameliorated the reproductive ability of depressed rats. Conclusion: BA modulated ß-catenin in the relief of inflammatory factor-induced DCMI.

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.

1H NMR-based metabolomics study of the dynamic effect of Xue-Fu-Zhu-Yu capsules on coronary heart disease rats induced by high-fat diet, coronary artery ligation.

An 1H NMR-based metabolomics approach was conducted to holisticly explore the effect of Xue Fu Zhu Yu (XFZY) capsule (a well-known Chinese herbal medicine) on high-fat diets combined with coronary artery ligation induced coronary heart disease (CHD) model rats. 1H NMR-based metabolomics approach combined with multivariate analysis was performed to explore potential biomarkers, a total of 20 metabolites were confirmed as contributors to the discrimination of model group and sham group. We investigated the dynamic metabolic characteristics of XFZY capsule on CHD rats, lactate, glutamine, pyruvate, citrate, choline and taurine were potential biomarkers of early effect. More potential biomarkers changed after 28 days of medication, XFZY capsules primarily influenced the taurine and hypotaurine metabolism, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, purine metabolism, glycolysis/gluconeogenesis, amino sugar and nucleotide sugar metabolism, primary bile acid biosynthesis.

DHZCP Modulates Microglial M1/M2 Polarization via the p38 and TLR4/NF-κB Signaling Pathways in LPS-Stimulated Microglial Cells.

Intracerebral hemorrhage (ICH) is a disease with a significantly high rate of morbidity, mortality and disability. Inhibition of inflammation is considered a potential strategy for improving the clinical symptoms induced by ICH. The hallmark of neuroinflammation is microglial activation. Microglia can polarize into either the classically activated M1 (proinflammatory) phenotype, exacerbating neuronal damage, or the alternatively activated M2 (antiinflammatory) phenotype, exerting neuroprotection and promoting neuronal recovery. Promoting microglial polarization to the M2 phenotype may be a viable strategy for treating neuroinflammation. Several studies have indicated that promoting blood circulation and removing blood stasis exhibits therapeutic effects on intracerebral hemorrhage. Dahuang Zhechong Pill (DHZCP), a classical recipe that promotes blood circulation and removes blood stasis, has been reported to improve the clinical outcome of ICH. DHZCP has been shown to exert antiinflammatory effects. However, the detailed antiinflammatory mechanism of DHZCP in ICH has rarely been investigated. In this study, DHZCP inhibited lipopolysaccharide (LPS)-induced M1 microglial activation. DHZCP exerted antiinflammatory effects, by inhibiting LPS-induced M1 proinflammatory cytokine (TNF-α and IL-6), and iNOS production and increasing M2 antiinflammatory cytokine (IL-10) production. DHZCP also switched microglial polarization from M1 to M2, as indicated by significantly increased expression of M2 polarization markers (CD209, and CD206) and markedly decreased expression of an M1 polarization marker (CD54). In addition, DHZCP inhibited p38 and TLR4/NF-κB signaling activation, as demonstrated by inhibition of LPS-induced increases in p-p38, TLR4 and nuclear factor kappa B p-65 (NF-κB p-65) protein expression. Taken together, DHZCP modulates microglial M1/M2 polarization via the p38 and TLR4/NF-κB signaling pathways to confer antiinflammatory effects.

Antidepressant-Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF-ERK-CREB Signaling Pathway in the Hippocampus and Frontal Cortex.

BACKGROUND: Fluoxetine (FLU) is the first-line and widely used medication for depression; however, FLU treatment is almost ineffective in 30%-40% of patients with depression. In addition, there are some problems in FLU treatment, such as delayed efficacy, large side effects, and poor tolerance. Chaihu Shugan San (CSS) is a classic and effective antidepressant Chinese herbal medicine that has been used in China for thousands of years. CSS or coadministration of CSS and FLU has become one of the most recommended methods in the treatment of depression in China. However, the specific pathways of CSS and coadministration of CSS and FLU for antidepressant are still unclear. OBJECTIVE: This study was designed to evaluate the antidepressant effects of CSS and coadministration of CSS and FLU. METHODS: The chronic unpredictable mild stress (CUMS) rat model was used to simulate depression. 120 healthy adult male Sprague-Dawley (SD) rats were randomly divided into seven groups: the control group, CUMS group, low-dose CSS group, high-dose CSS group, FLU group, coadministration of low-dose CSS and FLU group, and coadministration of high-dose CSS and FLU group. The rats in different groups were given different interventions. Then, the depression-like behavior and cognitive function were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and Y-maze test. What is more, the antidepressant mechanism of CSS and coadministration of CSS and FLU were studied through BDNF mRNA, ERK mRNA, CREB mRNA, BDNF, p-ERK/ERK, and p-CREB/CREB levels in the hippocampus and frontal cortex by Western blot and RT-PCR. RESULTS: Compared with the CUMS group, CSS and coadministration of CSS and FLU could alleviate the depressive symptoms and improve cognitive function in CUMS rats (p < 0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (p < 0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (p < 0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (Discussion and Conclusion. Finally, we found that both CSS and coadministration of CSS and FLU play an antidepressant role, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway in the hippocampus and frontal cortex. Among them, the coadministration of CSS and FLU can enhance the antidepressant effect of CSS or FLU alone, and the underlying mechanism needs further investigation.

The Herb-Drug Pharmacokinetic Interaction of Fluoxetine and Its Metabolite Norfluoxetine with a Traditional Chinese Medicine in Rats by LC-MS/MS.

BACKGROUND: Fluoxetine (FLU) is the first-line and widely used medication for depression. The combination of Chaihu Shugan san (CSGS) and FLU is commonly used to enhance antidepressant effects and reduce side effects. OBJECTIVE: The primary objective of this study was to investigate the potential pharmacokinetic effect of CSGS on FLU. MATERIALS AND METHODS: Thirty-two healthy adult male Sprague-Dawley (SD) rats were randomly divided into four groups, the fluoxetine group and multiple dose groups A, B, and C. The rats in the different groups were orally administered with a combination of FLU and different doses of CSGS for 14 d. On the fifteenth day, serial blood samples were taken from the caudal vein before the administration and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 h after the administration. A liquid-liquid extraction method was applied to extract the analytes from serum. Then, the concentrations of FLU and its metabolite, norfluoxetine (NOF), were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by DAS 3.2.8 program and compared by statistic analysis. RESULTS: Compared with the FLU group, the FLU and NOF area under the plasma concentration-time curve (AUC) (0-∞) in multiple dose group C was significantly increased, while the NOF AUCs (0-∞) in multiple dose group A and multiple dose group B were decreased. Compared with the FLU group, the NOF clearance (CL) in multiple dose group C was decreased, while the CL in multiple dose groups A and B was increased. DISCUSSION AND CONCLUSION: There were some differences in pharmacokinetic parameters between the FLU group and multiple dose groups, and CSGS can affect the pharmacokinetics of fluoxetine.

Efficacy of Weikang Pian in Patients with Functional Dyspepsia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: FD (functional dyspepsia) is a common functional gastrointestinal disorder, which lacks effective and safe treatment. Chinese herbal medicine (CHM) has been applied in FD treatment for thousands of years with satisfactory clinical outcomes. Zhishi is a classical traditional Chinese medicine used to treat FD. Weikang pian (WKP) is made of flavonoids extracted from zhishi which could effectively alleviate the symptoms of FD. This research aimed to assess the efficacy and safety of WKP in FD treatment. METHODS: This was a randomized, double-blinded and placebo-controlled clinical trial. The patients were diagnosed as FD according to RomeIII criteria. Then, FD patients were selected and assigned randomly to either WKP or placebo group. The subjects randomly received WKP or placebo for 4 weeks with 4 tablets each time, 3 times daily. The single dyspepsia symptom (SDS) scale and the gastric emptying function were measured before and after the treatment. Moreover, the safety of the trial and patient compliance were evaluated. RESULTS: A total of 60 FD patients were eventually enrolled in the trial, among them 45 patients in the WKP group and 15 patients in the placebo group. The primary outcome was the SDS scale, including assessments of postprandial distension, early satiety, epigastric burning, and pain. The secondary outcome was the gastric emptying function. Compared with the placebo group, the symptoms of FD in the WKP group were relieved after 4 weeks of treatment (P < 0.05). Some minor changes appeared in the four groups, but there were no significant differences in gastric emptying parameters of GER (2-hour gastric emptying rate) and GET/2 (gastric semiempty time) (P > 0.05). Severe adverse events were absent. The compliance to treatment was 94%-96%, and there was no significant difference between the groups. CONCLUSION: WKP can relieve FD symptoms to some extent. This trial is registered with Chinese Clinical Trial Registry (ChiCTR): CTR 20132482.

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.

Metabolomic Study on Nude Mice Models of Gastric Cancer Treated with Modified Si Jun Zi Tang via HILIC UHPLC-Q-TOF/MS Analysis.

Recently, metabolomic methods have been used to explore the complex pathogenesis of cancer and the mechanism of action of traditional Chinese medicine (TCM) formulae. In this study, first, modified Si Jun Zi Tang (MSJZT) was prepared with strict quality control using the instrument method of ultra performance liquid chromatography and photodiode array detector (UPLC-PDA). Subsequently, in vivo experiments with tumour-bearing nude mice demonstrated that MSJZT exerted good antitumour effects. MSJZT not only significantly increased mouse body weight but also shrank the tumour volume. Then, the HILIC UHPLC-Q-TOF/MS-based metabolomics approach was used for exploring the pathogenesis of gastric cancer and the molecular mechanism of MSJZT. A total of 59 potential biomarkers in plasma were identified, and 6 pathways were found to be disturbed in gastric cancer. In contrast, after 3 weeks of MSJZT intervention, 32 potential biomarkers were identified, and 4 altered pathways were detected. The changes in glycolytic, amino acid, and lipid metabolisms could be partially regulated by MSJZT through decreasing the content of lactic dehydrogenase (LDH), glutamine synthetase (GS), phosphocholine cytidylyltransferase (PCYT2) mRNA, and protein level. In conclusion, we established a HILIC UHPLC-Q-TOF/MS metabolomic analysis method to demonstrate a complex metabolic profile of gastric cancer. The disordered metabolism could be partially regulated by MSJZT. These findings not only establish a solid foundation for TCM to treat gastric cancer but also provide a basis for further exploration of the precise mechanism of MSJZT activity.

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.

Potential Metabolic Drug-Drug Interaction of Citrus aurantium L. (Rutaceae) Evaluating by Its Effect on 3 CYP450.

Aim:Fructus aurantii (FA) is widely used in clinic as an expectorant and digestant herb in traditional Chinese medicine and proven to have a variety of pharmacological functions. FA is close to grapefruit either by botanical taxonomy or by their same components (flavonoids, etc.) and grapefruit has been proven to cause drug-drug interaction when co-administrated with CYP3A4 substrates. Besides, FA contains many compounds, such as flavonoids, which have been reported to impact the expressions of CYP450. However, the effect of FA on CYP450, whose change may affect drug safety and clinical efficacy attributed to drug-drug interaction, still remains unknown. Methods: The protein, mRNA expression and enzyme activity of CYP1A2, CYP3A4, and CYP2E1 in rat were determined by Western Blotting, RT-PCR method, the cocktail method, respectively, after orally administration of FA in succession for 7 days. CYP1A2, CYP3A4, and CYP2E1 mRNA expression were investigated in HepG2 cells following FA-medicated serum incubation for 24 h. Results: In rat, compared to the control group, CYP1A2, CYP3A4 protein, and mRNA expression were significantly induced consistent with the corresponding CYP activities; the protein expression of CYP2E1 was significantly upregulated, while the corresponding mRNA expression and enzyme activity showed no significant change. In HepG2 cells, compared to the control group, the mRNA expression of CYP1A2 and CYP3A4 was up-regulated statistically while CYP2E1 mRNA expression was not significantly induced or inhibited. Conclusion: FA may be a potential slight inducer of CYP1A2 and CYP3A4 and is unlikely to impact CYP2E1 until clinical researches are conducted.

Development of an Ultra-High Performance Liquid Chromatography Method for Simultaneous Determination of Six Active Compounds in Fructus aurantii and Rat Plasma and Its Application to a Comparative Pharmacokinetic Study in Rats Administered with Different Doses.

A rapid, accurate, and sensitive ultra-high performance liquid chromatography (UHPLC) method was established for simultaneously detecting naringin, hesperidin, neohesperidin, meranzin hydrate, naringenin, and hesperetin in Fructus aurantii (FA) decoction. Analysis was performed on Waters BEH (R) C18 (50 mm × 2.1 mm, 1.7 µm) at a flow rate of 0.2 mL/min by using (A) acetonitrile and (B) 0.5% acetic acid-water as the mobile phase. The method was well validated on linearity, precision, recoveries, and stability. Then, we used the same UHPLC conditions for quantitative analysis of meranzin hydrate, naringenin, and hesperetin in rat plasma. The method proved to be linear within the concentration ranges of 3.3-3300 ng/mL for meranzin hydrate, 6.95-3555 ng/mL for naringenin, and 1.8-236 ng/mL for hesperetin. The RSD of precision ranged from 1.22% to 9.08%, and the average extraction recovery ranged from 96.49 ± 1.42% to 102.01 ± 3.16%. Besides, we performed a comparative pharmacokinetic study after oral administration of FA decoction at a low dose of 15 g/kg and high dose of 30 g/kg body weight for seven days to rats. The AUC(0-t) and Cmax of meranzin hydrate, naringenin, and hesperetin were multiplied significantly with the increase of FA dosage, and the t1/2 of meranzin hydrate was faster than naringenin and hesperetin in the two groups.

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.

Metabolomics-based evidence of the hypoglycemic effect of Ge-Gen-Jiao-Tai-Wan in type 2 diabetic rats via UHPLC-QTOF/MS analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ge-Gen-Jiao-Tai-Wan (GGJTW) formula, derived from traditional Chinese herbal medicine, is composed of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (Ge-Gen in Chinese), Coptis chinensis Franch (Huang-Lian), and Cinnamomum cassia (L.) J. Presl (Rou-Gui). GGJTW is used for treatment of diabetes in China, reflecting the potent hypoglycemic effect of its ingredients. However, little is known of the hypoglycemic effect of GGJTW and the underlying metabolic mechanism. AIM OF THE STUDY: This study aimed to investigate the hypoglycemic effect of GGJTW in type 2 diabetic rats and the metabolic mechanism of action. MATERIALS AND METHODS: Ultra high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-QTOF/MS)-based metabolomics approach was used for monitoring hyperglycaemia induced by high-sugar high-fat fodder and streptozotocin (STZ), and the protective effect of GGJTW. Dynamic fasting blood glucose (FBG) levels, body weight, and biochemical parameters, including lipid levels, hepatic-renal function, and hepatic histopathology were used to confirm the hyperglycaemic toxicity and attenuation effects. An orthogonal partial least squared-discriminant analysis (OPLS-DA) approach highlighted significant differences in the metabolome of the healthy control, diabetic, and drug-treated rats. The metabolomics pathway analysis (MetPA) and Kyoto encyclopedia of genes and genomes (KEGG) database were used to investigate the underlying metabolic pathways. RESULTS: Metabolic profiling revealed 37 metabolites as the most potential biomarker metabolites distinguishing GGJTW-treated rats from model rats. Most of the metabolites were primarily associated with bile acid metabolism and lipid metabolism. The most critical pathway was primary bile acid biosynthesis pathway involving the up-regulation of the levels of cholic acid (CA), chenodeoxycholic acid (CDCA), taurocholic acid (TCA), glycocholic acid (GCA), taurochenodesoxycholic acid (TCDCA), and taurine. CONCLUSIONS: The significantly-altered metabolite levels indicated the hypoglycemic effect of GGJTW on diabetic rats and the underlying metabolic mechanism. This study will be meaningful for the clinical application of GGJTW and valuable for further exploration of the mechanism.

Proteomic analysis allows for identifying targets of Yinchenwuling Powder in hyperlipidemic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Yinchenwuling Powder (YCL) is a traditional Chinese medicine formula originated from Synopsis of Golden Chamber, which is effective in positively modulating lipid levels in clinics. In this study, we utilized proteomic technology to identify the therapeutic targets of YCL on hyperlipidemic rats. METHODS: We established hyperlipidemic model rats and administrated them with different doses of YCL extracts (0.35g/ml, 0.75g/ml and 1.5g/ml). Serum lipid levels were quantified and proteomic analysis was performed on plasma samples at the end of the study. Total plasma proteins were separated by two-dimensional electrophoresis (2-DE), and protein spots with 1.5-fold difference were excised and then analyzed by MALDI-TOF MS. Proteomic results were verified by Western blotting. RESULTS: The results showed that the serum levels of TC, TG, and LDL-C were significantly decreased, while the HDL-C levels were significantly increased in different doses of YCL treatment groups. After being analyzed by 2-DE and MALDI-TOF MS, 12 proteins were identified. Eight proteins (T-kininogen, C3, C4, C4BPA, Igλ-2 chain C, Mbl2, Hpx and FGL1) were up-regulated in hyperlipidemic model rats, while four proteins (ApoE, ALB, TTR and VDBP) were up-regulated in the control and the YCL-treated rats. Two plasma proteins, ApoE and FGL1, involved in lipid metabolism, were confirmed by western blotting, and the results were consistent with the data from the proteomics results. CONCLUSIONS: In this experiment, we identified 12 differentially-expressed plasma proteins associated with therapeutic effects of YCL. The functions of those proteins are related with lipid metabolism, blood coagulation, anti-inflammation and substance transport. This study provided a clue for the mechanism that underlies the therapeutic effect of YCL on lipid metabolism.

A Metabonomics Profiling Study on Phlegm Syndrome and Blood-Stasis Syndrome in Coronary Heart Disease Patients Using Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry.

A metabonomics approach based on liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) was utilized to obtain potential biomarkers of coronary heart disease (CHD) patients and investigate the ZHENG types differentiation in CHD patients. The plasma samples of 20 CHD patients with phlegm syndrome, 20 CHD patients with blood-stasis syndrome, and 16 healthy volunteers were collected in the study. 26 potential biomarkers were identified in the plasma of CHD patients and 19 differential metabolites contributed to the discrimination of phlegm syndrome and blood-stasis syndrome in CHD patients (VIP > 1.5; P < 0.05) which mainly involved purine metabolism, pyrimidine metabolism, amino acid metabolism, steroid biosynthesis, and arachidonic acid metabolism. This study demonstrated that metabonomics approach based on LC-MS was useful for studying pathologic changes of CHD patients and interpreting the differentiation of ZHENG types (phlegm and blood-stasis syndrome) in traditional Chinese medicine (TCM).

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.

Comparison between the pharmacokinetics of meranzin hydrate in a rat model of chronic depression and in controls following the oral administration of Chaihu-Shugan-San.

Previous studies have shown that meranzin hydrate (MH) may be beneficial in depressive disorders. However, to the best of our knowledge, the pharmacokinetic characteristics of MH in depression have not previously been investigated. Chronic mild stress (CMS) in rats is used as a model of depression. The present study was designed to evaluate and compare the pharmacokinetics of MH in CMS and control rats following the oral administration of Chaihu-Shugan-San (CSS). Rats were randomly divided into CMS and control groups and blood samples were obtained following the oral administration of CSS. The quantification of MH levels in the plasma for pharmacokinetic study was achieved using a simple and rapid ultra-performance liquid chromatography with photodiode array (UPLC-PDA) method. Following the oral administration of CSS to CMS rats and controls, the maximum plasma concentration (Cmax) of MH was 58.66±6.64 and 57.54±12.67 ng/ml at 108.00±26.83 and 54.00±8.22 min, respectively. Compared with the value of the area under the concentration-time curve (AUC)0-1440 in control rats (19,896.76±1,041.95 µg·min/l), the AUC0-1440 value was reduced in CMS rats (18,401.32±4332.65 µg·min/l). There were no significant differences in the majority of the pharmacokinetic parameters of MH, including the values for Cmax, AUC0-1440, clearance rate (CL/F) and mean residence time (MRT0-1440), between the CMS rats and the controls. However, the pharmacokinetic parameters showed that CMS accelerated the absorption of MH in rats following the oral administration of CSS.