A UPLC-Q-TOF/MS and network pharmacology method to explore the mechanism of Anhua fuzhuan tea intervention in nonalcoholic fatty liver disease.

The possible mechanism by which the active components of Anhua fuzhuan tea act on FAM in NAFLD lesions was investigated. 83 components of Anhua fuzhuan tea were analysed by UPLC-Q-TOF/MS. Luteolin-7-rutinoside and other compounds were first discovered in fuzhuan tea. According to the TCMSP database and the Molinspiration website tool to predict and review the literature reports, 78 compounds were identified in fuzhuan tea with possible biological activities. The PharmMapper, Swiss target prediction, and SuperPred databases were used to predict the action targets of biologically active compounds. The GeneCards, CTD, and OMIM databases were mined for NAFLD and FAM genes. Then, a fuzhuan Tea-NAFLD-FAM Venn diagram was constructed. Using the STRING database and CytoHubba program of Cytoscape software, protein interaction analysis was performed, and 16 key genes, including PPARG, were screened. GO function and KEGG enrichment analyses of the screened key genes showed that Anhua fuzhuan tea may regulate FAM in the process of NAFLD through the AMPK signalling pathway, nonalcoholic fatty liver disease pathway, etc. After constructing an active ingredient-key target-pathway map with Cytoscape software, combined with literature reports and BioGPS database analysis, we believe that among the 16 key genes, SREBF1, FASN, ACADM, HMGCR, and FABP1 have potential in the treatment of NAFLD. Animal experiments confirmed the effect of Anhua fuzhuan tea in improving NAFLD and confirmed that this tea can interfere with the gene expression of the above five targets by the AMPK/PPAR pathway, providing support for Anhua fuzhuan tea interfering with FAM in NAFLD lesions.

Efficacy and safety of Zaoren Anshen capsules in the treatment of insomnia: A meta-analysis of randomized controlled trials.

BACKGROUND: Zaoren Anshen capsules (ZRAS) have been widely used to treat patients with insomnia. However, the efficacy and safety of ZRAS for insomnia treatment is not entirely clear. Therefore, it is necessary to clarify the effect of ZRAS for the treatment of insomnia by a systematic meta-analysis. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases and performed a manual search to retrieve relevant articles (available through January 2019) describing randomized controlled trials (RCTs) of ZRAS for the treatment of insomnia. The quality of the selected articles was assessed with the Cochrane risk-of-bias tool. A meta-analysis of the selected articles was performed with RevMan 5.3 software. RESULTS: A total of 13 articles including 1175 patients were included in the study. Overall, our results showed that ZRAS was slightly higher than that of the conventional Western medicine for insomnia in terms of clinical efficacy rate; but there was no statistical difference between the 2 groups (relative risk [RR] = 1.03, 95% confidence interval [CI] = [0.97, 1.09], P = .34). However, it should be noted that ZRAS treatment causes far fewer adverse reaction than treatment with conventional Western medicine (RR = 0.20, 95% CI = [0.14, 0.28], P < .00001). CONCLUSION: Our results suggested that ZRAS is an effective and safe treatment for insomnia, especially in adverse reaction. However, multi-regional and well-designed RCTs studies are needed in the future to validate the results.

The C677T Polymorphism of the Methylenetetrahydrofolate Reductase Gene and Susceptibility to Late-onset Alzheimer's Disease.

Folate metabolism makes a crucial contribution towards late-onset Alzheimer's disease (LOAD). Moreover, methylenetetrahydrofolate reductase (MTHFR) constitutes the primary enzyme of the folate pathway. We hypothesize that there is an association of C677T polymorphism in the MTHFR gene with the susceptibility to LOAD. Previous published research has investigated the link between the MTHFR C677T polymorphisms and LOAD susceptibility; nevertheless, the findings have continued to be not only controversial, but also indecisive. Accordingly, we carried out the present meta-analysis for the assessment of the potential link that exists between the MTHFR C677T polymorphism and the susceptibility to LOAD. Furthermore, we carried out a literature search of the PubMed, EMBASE, Cochrane Library, and WanFang database up to August 10, 2018. The odds ratios (ORs) with the respective 95% confidence interval (95%CI) were put to use for the evaluation of the robustness of the link of the MTHFR C677T polymorphism with the vulnerability to LOAD. All statistical analyses were carried out using STATA 15.0. An aggregate of 14 case-control research works was retrieved, involving 2,467 LOAD patients as well as 2,877 controls. We found that a substantial link exists between C677T polymorphism and LOAD risk in a codominant framework (TC vs. CC: OR=1.22, 95%CI=1.00-1.49, P=0.049). In addition to the stratified analysis based on ethnicity, which suggested that C677T polymorphism was likely linked only to an augmented threat of LOAD in Asians, it did not exist among Caucasians. Furthermore, in the subgroup analysis carried out using APOE ɛ4 status, a substantial increase in the susceptibility to LOAD was detected in APOE ɛ4 carriers as well as non-APOE ɛ4 carriers. In sum, the current meta-analysis revealed that MTHFR C677T polymorphism was associated with susceptibility to LOAD. Further extensive case-control studies are required.

Buyang Huanwu Decoction () reduces infarct volume and enhances estradiol and estradiol receptor concentration in ovariectomized rats after middle cerebral artery occlusion.

OBJECTIVE: To investigate the effect of Buyang Huanwu Decoction (, BYHWD) on estradiol (E2) and estradiol receptor (ER) in serum and brain in ovariectomized rats after middle cerebral artery occlusion (MCAO). METHODS: Adult female rats were ovariectomized and focal cerebral ischemic was induced by MCAO. Rats were randomly divided into normal, ovariectomy (OVX), MCAO, OVX+MCAO, OVX+MCAO+E2, and OVX+MCAO+BYHWD group. Rats were administered BYHWD 5 g/kg daily, estradiol valerate 500 µg/kg per day or distilled water for 7 consecutive days. Neuronal function and infarct volume were measured on day 7 after artery occlusion, and E2 and ER concentration in serum and brain were checked by enzyme-linked immunosorbent assay. RESULTS: BYHWD significantly improved the neurological behavior, reduced the infarction volume, increased E2 concentration in serum and brain, and increased ER concentration in the brain in ovariectomized rats after MCAO. CONCLUSION: The neuroprotective effects of BYHWD are associated with estrogen and its receptor.

Simotang enhances gastrointestinal motility, motilin and cholecystokinin expression in chronically stressed mice.

AIM: To investigate the effect of Simotang (Decoction of Four Powered Drugs) on gastrointestinal motility, motilin and cholecystokinin expression in chronically stressed mice. METHODS: Forty mice were randomly divided into control group, stress group (model group), mosapride group and Simotang group, 10 in each group. A variety of unpredictable stimulations were used to induce chronic stress in mice. Then, the mice were treated with distilled water, mosapride or Simotang for 7 d. Gastric emptying and intestinal propulsion function were detected. Serum level of motilin was measured by enzyme-linked immunosorbent assay. Expression of cholecystokinin (CCK) in intestine, spinal cord and brain of mice was detected by immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction, respectively. RESULTS: Simotang improved the gastric emptying and intestinal propulsion in chronically stressed mice. Furthermore, the serum motilin level was significantly higher and the expression levels of CCK-positive cells and genes were significantly lower in intestine, spinal cord and brain of Simotang group than in those of model group (P < 0.05). No significant difference was found in serum motilin level and expression levels of CCK-positive cells and genes between the mosapride and Simotang groups. CONCLUSION: Simotang enhances the gastrointestinal motility in chronically stressed mice by regulating the serum motilin level and the expression of cholecystokinin.

[Effect of ultra-micronized Buyang Huanwu decoction on neurological function, quality of life, and serum vascular endothelial growth factor in patients convalescent from cerebral infarction].

OBJECTIVE: To study effect of Buyang Huanwu decoction (BYHWD) on neurological function, quality of life, and serum vascular endothelial growth factor (VEGF) in patients convalescent from cerebral infarction, and to evaluate the effect of ultra-micronized BYHWD. METHODS: Two hundred and fifty-one patients met the inclusion criteria were randomly assigned to traditional BYHWD (TB) group (n=83), ultra-micronized BYHWD (UB) group (n=85) and the control group (n=83) according to time of entrance into the study with 1:1:1. All patients received rehabilitation training, but for patients in the TB and UB groups, traditional BYHWD (15 g, twice a day) or ultra-micronized BYHWD (5 g, twice a day) was given respectively, for a course of 12 weeks. Clinical curative effect and curative effect of syndrome according to traditional Chinese medicine (TCM) were evaluated. Nerve function and quality of life in patients were evaluated, serum VEGF was determined before and after treatment. The level of VEGF in 23 healthy volunteers was also determined to serve as normal control. RESULTS: The total effective rate was 83.5%, 85.5% and 77.1% in UB group, TB group and the control group, respectively, and the total symptomatic effective rate in TCM was 87.0%, 89.2% and 77.1%, respectively. Compared with the control group, there was significant difference in UB or TB group (all P<0.05), but there was no significant difference between UB and TB groups (both P >0.05). Serum VEGF levels (ng/L) were significantly lower before treatment in control group, TB group and UB group than those in normal control group (79.87±2.81, 80.19±3.23, 80.23±3.18 vs. 68.13±3.39, all P<0.05). Neurologic deficit score (NDS), quality of life and serum VEGF were improved after treatment in three groups, but they were better in UB or TB group than the control group [NDS: 11.95±5.03, 12.68±4.67 vs. 15.23±5.12, quality of life score: 64.71±6.73, 63.56±6.53 vs. 59.09±6.81, serum VEGF (ng/L): 76.38±3.02, 76.84±3.18 vs. 70.26±3.15 , all P<0.05], but there was no significant difference between UB and TB groups (all P >0.05). CONCLUSION: BYHWD can improve neurological function and quality of life, and increase serum VEGF in patients convalescent from cerebral infarction, and ultra-micronized BYHWD, the dosage can be decreased.

[Effect of Buyang Huanwu decoction on interleukin-1ß and tumor necrosis factor-α expression in rats after cerebral infarction].

OBJECTIVE: To explore the effect of Buyang Huanwu decoction (BYHWD) on pro-inflammatory cytokines in rats after focal cerebral infarction. METHODS: Adult Sprague Dawley (SD) rats were randomly divided into following groups: normal control, sham, model, BYHWD. The rats in latter three groups were subdivided into subgroups of 1, 3, and 7 days after medication, with 5 rats in each group. The right side focal cerebral infarction model was reproduced by middle cerebral artery occlusion (MCAO). The rats in BYHWD group were gavaged with BYHWD of 10 ml/kg (14.2 g/kg, once a day) 2 hours after operation. Animals were sacrificed at corresponding time points. The protein and mRNA expression of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: There were low levels expression of IL-1ß and TNF-α protein and mRNA in normal control group and the sham group. After cerebral infarction, the protein and mRNA expression of IL-1ß and TNF-α began to increase in rats 1 day after the insult, and the protein and mRNA expression of IL-1ß reached the peak on 3rd day, and then lowered, and the protein and mRNA expression of TNF-α reached the peak on 7th day. Compared with model group on 1st, 3rd and 7th day, the protein expression of IL-1ß (ng/L: 90.290±8.693 vs. 102.556±13.934 on 1st day, 129.632±11.050 vs. 150.117±8.552 on 3rd day, 66.185±9.020 vs. 91.362±9.901 on 7th day) and TNF-α (ng/L: 210.341±19.247 vs. 236.887±20.137 on 1st day, 267.503±21.006 vs. 322.659±15.068 on 3rd day, 299.637±17.717 vs. 386.678±16.297 on 7th day), and mRNA expression of IL-1ß (1 day: 0.54±0.09 vs. 0.64±0.11, 3 days: 0.80±0.06 vs. 0.89±0.07, 7 days : 0.70±0.09 vs. 0.78±0.08) and TNF-α (1 day: 0.64±0.09 vs. 0.73±0.11, 3 days: 0.74±0.13 vs. 0.85±0.07 , 7 days : 0.82±0.07 vs. 0.93±0.08], were all decreased obviously in BYHWD group ( P<0.05 or P<0.01). CONCLUSION: BYHWD could reduce the protein and mRNA expressions of IL-1ß and TNF-α in levels after cerebral infarction. The result shows that it protects brain by modulating expression of pro-inflammatory mediators.

[Effect of naoyian on phosphorylated Akt in the neural stem cell injured with anoxia].

OBJECTIVE: To determine the effect of naoyian (NYA) on the expression of phosph-Akt in neural stem cells injured with anoxia. METHODS: The hippocampal neural stem cells (NSC) taken from the Sprageu-Dawley rat brain at 5 days after birth were cultured in DMEM/F12 solution containing EGF and bFGF. After being treated with anoxia for 6 hours, the neural stem cells were incubated in solution containing the NYA serum or normal serum. The neural stem cells were then detected for phosph-Akt and TUNEL stain. RESULTS: After the neural stem cells were injured with anoxia, the expression of the phosph-Akt in NYA serum group was higher than that in the normal serum group and the serum-free group. Treated with NYA serum, the amount of apoptotic NSC decreased. CONCLUSION: After the neural stem cell injured by anoxia was treated with NYA serum, the phosphorylation of Akt increased, the apoptosis of NSC was inhibited.

[Effects of nao-yi-an on tumor necrosis factor alpha and insulin resistance of acute intracerebral hemorrhagic patients].

OBJECTIVE: To investigate the effects of nao-yi-an on tumor necrosis factor alpha (TNF-alpha) and insulin resistance of acute intracerebral hemorrhagic patients. METHODS: The patients were randomly divided into two groups: the medicine control group and the nao-yi-an treatment group. TNF-alpha and insulin were checked by radioimmunoassay before and after the treatment. Fifteen healthy people were made as the negative control group. RESULTS: TNF-alpha of both treatment groups was higher while insulin sensitivity index(ISI) was remarkably lower compared with the health group (P < 0.01). After the treatment ISI increased and TNF-alpha was remarkably lower in the treatment group (P < 0.01). Differences of TNF-alpha and ISI between the treatment group and medicine control group were significant (P < 0.05 or P < 0.01). CONCLUSION: nao-yi-an can decrease TNF-alpha and increase ISI, which is a mechanism of reducing cerebral ischemic-reperfusion injury.