LC-MS/MS-based chemical profiling of water extracts of Moringa oleifera leaves and pharmacokinetics of their major constituents in rat plasma.

Moringa oleifera leaves (MOL) are native to India and have high biological activities. To better understand the basic pharmacodynamic materials, the chemical components in MOL and their pharmacokinetic properties were studied and quantitated using UPLC-Q-Exactive Orbitrap-MS. Forty-two compounds were identified, including phenolic acids and their derivatives, flavonoids, isothiocyanates, nucleosides, alkaloids, and other compounds. Two phenolic acids and six flavonoids were studied for their pharmacokinetic properties using UHPLC-MS/MS. Precision, accuracy, stability, matrix effects, and extraction recovery were verified. All substances that were measured reached their maximum within 0.5 h. Vicenin-2 had a high peak concentration and bioavailability. Kaempferol-3-O-rutinoside had a longer biological half-life than other components. The results from this study provide the data basis for subsequent comprehensive qualitative evaluation and potential MOL use in clinical applications.

Screening the components in multi-biological samples and the comparative pharmacokinetic study in healthy and depression model rats of Suan-Zao-Ren decoction combined with a network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Suanzaoren Decoction (SZRD) is a classic traditional Chinese prescription, which has been commonly used for treating insomnia, depression and other nerve system diseases for a long time. AIM OF THIS STUDY: The present study aimed to explore the metabolic profiles in multi-biological samples and pharmacokinetic mechanism between healthy and depression model rats combined with a network pharmacology approach after administration of SZRD. MATERIALS AND METHODS: In our study, an ultra-high performance liquid chromatography (UPLC)-Q-Exactive Orbitrap Mass Spectrometry method was firstly used to study the prototype components and metabolites of SZRD in plasma, brain, urine, and feces between healthy and depressed rats. The possible metabolic pathways were also speculated. Then a network pharmacological study was conducted on the components in the plasma of model rats. According to the above components screened by network pharmacology and the other reported representative active components, the comparative pharmacokinetic study was established for the simultaneous determination of mangiferin, spinosin, ferulic acid, liquiritin, formononetin. magnoflorine and isoliquiritin between healthy and depression model rats. Finally, molecular docking was used to validate the binding affinity between key potential targets and active components in pharmacokinetics. RESULTS: A total of 115 components were identified in healthy rats, and 101 components were identified in model rats. The prototype components and metabolites in plasma, brain, urine, and feces were also distinguished. The main metabolic pathways included phase I and phase II metabolic reactions, such as dehydrogenation, oxidation, hydroxylation, gluconaldehyde conjugation, glutathione conjugation and so on. These results provided a basis for the further study of antidepressive pharmacokinetic and pharmacological action in SZRD. Then, according to the degree value of network pharmacological study, it was predicted that 10 components and 10 core targets, which involved in the critical pathways such as neuroactive ligand-receptor interaction, cyclic adenosine monophosphate (cAMP) signaling pathway, serotonergic synapse, phosphatidylinositol-3 kinase (PI3K)-Akt signaling pathway, etc. Finally, the established pharmacokinetic method was successfully applied to compare the pharmacokinetic behavior of these 7 active components in plasma of healthy and depressed rats after oral administration of SZRD. It showed that except magnoflorine, the pharmacokinetic parameters of each component were different between healthy and depressed rats. Molecular docking analysis also indicated that the active compounds in pharmacokinetics could bind tightly to the key targets of network pharmacological study. CONCLUSION: This study may provide important information for studying the action mechanism of SZRD in treating depression.

Effects of Alpinae Oxyphyllae Fructus on microglial polarization in a LPS-induced BV2 cells model of neuroinflammation via TREM2.

ETHNOPHARMACOLOGICAL RELEVANCE: As one of the important traditional Chinese medicines, Alpinia oxyphylla could warm and tonify the kidney and spleen. It has been used as anti-salivation, anti-diarrhea in various diseases. In recent years, many studies have reported the significant effect of Alpinia oxyphylla on improving cognitive ability, anti oxidative stress and protecting neurons. AIMS OF THE STUDY: In this paper, we studied whether AE and its main active components could improve M1 and M2 polarization, inhibit neuroinflammation through triggering receptor expressed on myeloid cells 2 (TREM2), and exert anti-inflammatory effects. MATERIALS AND METHODS: In this paper, the concentrations of inflammatory cytokines such as NO, TNF-α, IL-10 were assessed using detection kits respectively. Arg-1 and Iba-1, as polarized markers of M1 and M2, were detected by Immunofluorescence staining. CD86 and CD206 were tested by flow cytometry as surface markers of M1 and M2. Furthermore, RT-PCR was performed to determinate TNF-α, IL-10, Arg-1, and Iba-1. Western blot was used to test the activation of PI3K/AKT/GSK3ß and BDNF/TrkB/TLR4 signaling pathways. TREM2 siRNA treatment further verified the action target of Chrysin, the main active ingredient of Alpinia oxyphylla. Molecular docking study was performed to investigate the binding mode between Chrysin and the human TREM2. RESULTS: We found that AE could promote the phenotypic transformation of microglia from M1 to M2, and similar effects of Chrysin were observed. Furthermore, downregulation of TREM2 blocked the anti-neuroinflammation of Chrysin, and inhibited the shift of M1 phenotype to M2 phenotype. Additionally, TREM2-siRNA suppressed the effects of Chrysin on PI3K/AKT/GSK3ß and BDNF/TrkB/TLR4 signaling pathways. CONCLUSIONS: Our findings indicated that AE could improve the polarization response of microglia. TREM2 plays a vital role in the microglial repolarization effects of Chrysin through PI3K/AKT/GSK3ß and BDNF/TrkB/TLR4 signaling pathways regulated by neuroinflammation.

Combination of Alpinia Oxyphylla Fructus and Schisandra Chinensis Fructus ameliorates aluminum-induced Alzheimer's disease via reducing BACE1 expression.

Being the most common form of dementia, Alzheimer's disease (AD) has a series of modifiable risk factors, including metal ions represented by aluminium. Aluminium (Al) exhibits its neurotoxic effects, especially mainly by affecting amyloid-ß protein (Aß) aggregation and Tau hyperphosphorylation. As reported in our previous study, the combination of Alpinia Oxyphylla Fructus and Schisandra Chinensis Fructus (AS) had a neuroprotective effect. This study aimed to evaluate the anti-AD effect of AS and the mechanism by which AS reduces the neurotoxic effect of Al. Firstly, we used aluminium-maltol (Al(mal)3) to construct a mouse model of AD and performed oral administration of AS, followed by behavioral experiments, and we collected the mouse brain for immunohistochemistry analysis. In vivo results showed that AS significantly improved Al-induced cognitive decline in mice, and reduced the levels of Aß1-42 and P-Tau in the brain, which further proved the anti-AD effect of AS. Then, in order to explore the mechanism by which AS reduced Aß1-42, Al-induced PC12 cells were used for the in vitro experiments. Compared with other ratios, the ratio of Alpinia Oxyphylla Fructus: Schisandra Chinensis Fructus (AO:SC) = 1:2 could better improve the cell viability and reduce the Aß1-42 level. According to western blot and quantitative real-time polymerase chain reaction (qPCR) results, AS ameliorated the pathological process by downregulating the expression of ß-secretase (BACE1), rather than by reducing the expression of amyloid precursor protein (APP) or Tau. These results suggest that AS ameliorated Al-induced AD by affecting the expression of BACE1 and reducing the level of Aß1-42, thereby exerting a neuroprotective effect. Combined with previous studies, this study shows that AS has potential for further research and development in AD treatment.

Salidroside Inhibits Ischemia/Reperfusion-Induced Myocardial Apoptosis by Targeting Mir-378a-3p Via the Igf1r/Pi3k/Akt Signaling Pathway.

BACKGROUND: The present study aimed to investigate the protective effects and mechanism of salidroside (SAL) on hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis and myocardial ischemia/reperfusion (I/R) injury. METHODS: We set up an H/R H9c2 cell model in vitro and an I/R rat model in vivo. Cell viability, apoptosis and histopathologic evaluation were conducted. RESULTS: The cell viability of H/R-induced cardiomyocytes was increased by pretreatment of SAL, whereas the release of lactate dehydrogenase, reactive oxygen species production, and apoptosis were decreased accompanied with reduced Cleaved-caspase-3 and Bax, and increased Bcl-2 expressions. The SAL restored mitochondrial membrane potential both in vitro and in vivo, and improved electrocardiographic abnormality, and attenuated myocardial apoptosis and injury in I/R-induced rats. The transfection of miR-378a-3p inhibitor counteracted the effects of SAL-induced increase of cell viability and decrease of cell apoptosis and mitochondrial membrane potential. SAL reduced the expression of insulin-like growth factor 1 receptor (IGF1R), and increased the expressions of PI3K and Akt, however, these alterations were blocked by miR-378a-3p inhibitor. CONCLUSIONS: miR-378a-3p might participate in the protective effect of SAL in I/R-induced myocardial apoptosis via the IGF1R/PI3K/AKT signaling pathway.

Schisandra chinensis (Turcz.) Baill. essential oil exhibits antidepressant-like effects and against brain oxidative stress through Nrf2/HO-1 pathway activation.

The present study aimed to evaluate the antidepressant-like effect of essential oils from Schisandra chinensis (Turcz.) Baill. (SEO) and its possible mechanisms of SEO. The behavioral despair mouse model in vivo and H2O2-induced PC12 cells model in vitro were employed. And the potential effective components were identified by the spectrum-effect relationships analysis. SEO significantly decreased the immobility time in the forced swimming test and tail suspension test, which indicated a promising antidepressant-like effect of SEO in depressed mice. The decreased levels of SOD, GSH, and CAT, and increased levels of MDA were significantly reversed by SEO treatment, which showed good antioxidant activities both in vitro and in vivo. Besides, SEO significantly promoted the nuclear translocation of Nrf2 and the expression of HO-1 in depressed mice and H2O2-induced PC12 cells. The histopathological examination results showed a potential neuronal protective effect of SEO in the hippocampus and cortex. Furthermore, the upregulation of PI3K/AKT/GSK3ß signaling was observed after SEO treatment in the H2O2-induced PC12 cells. Additionally, based on the spectrum-effect relationship analysis, 9 peaks were identified as positively correlated with the antioxidant activity of SEO. These results suggested that SEO promoted Nrf2/HO-1 pathway to improve the oxidative stress status and exerted the antidepressant-like effects.

Alpinae Oxyphyllae Fructus alleviated LPS-induced cognitive impairments via PI3K/AKT/NF-κB signaling pathway.

Herein, we aim to investigate the effect of Alpinae Oxyphyllae Fructus (AOF) on cognitive impairments and neuroinflammation in a lipopolysaccharide (LPS)-induced models of AD. Mice were injected intracerebroventricularly with LPS, and then administrated AOF using a gavage for 6 weeks. Spatial working memory was assessed using the Y-maze and Morris water maze test, whereas the levels of PI3K, AKT, p-AKT, p-GSK3ß, GSK3ß, NF-κB, IL-1ß, IL-6, and TNF-α were evaluated using western blot and ELISA assay. Our data showed that AOF was able to significantly alleviate the memory decline in LPS-induced AD mice. Moreover, AOF was able to protect neurons through the PI3K/AKT signaling pathway and significantly decrease NF-κB, IL-6, IL-1ß, and TNF-α levels in the hippocampal and cortex tissues, which were reversed through the use of LY294002. Additionally, we discovered that AOF could significantly decrease the high expression of cytokines as well as the expression and translocation of NF-κB induced by LPS in PC12 cells. These results demonstrate the anti-neuroinflammatory effect of AOF in both cell and animal models of AD, thereby slowing down the process and development of the disease.

The flavonoids of okra insulates against oxidative stress, neuroinflammation and restores BDNF levels in Aß1-42 induced mouse model of Alzheimer's disease.

Okra (Abelmoschus esculentus [L.] Moench.) has been used as a natural drug in East or West Africa for many centuries, as well as consumed in most areas of the world as a tropical vegetable. The study aimed to evaluate whether the flavonoids of okra fruit (FOF) administration influence Aß1-42-induced learning and memory impairment, and explore the underlying mechanisms. The Y-maze task and the Morris water maze test were used for evaluating cognition processes. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) were detected by ELISA kits. The expressions of nuclear factor kappa-light chain-enhancer of activated B (NF-κB), brain-derived neurotrophic factor (BDNF), cAMP-response element-binding protein (CREB), extracellular signal-regulated kinase (ERK), phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), glycogen synthase kinase-3ß (GSK-3ß) were studied by western blot. Histopathological changes were observed by H.E. straining. The results showed that intracerebroventricular injection of Aß1-42 was effective in producing memory deficits in mice. Besides, Aß1-42 exposure could significantly increase the levels of NF-κB, TNF-α, IL-1ß, and decreased T-AOC, the activities of SOD and GSH-Px in the hippocampus and cortex. Furthermore, the level of BDNF was also reduced, accompanied by down-regulated CREB/ERK and PI3K/AKT/GSK-3ß signaling pathways in the hippocampus and cortex. Nevertheless, chronic administration of FOF (100 or 300 mg/kg, i.g.) significantly prevented Aß1-42-induced behavioral and biochemical alterations. It also suggested that FOF could improve the cognitive deficits in AD-like model mice, which might be mediated by regulation of BDNF levels in cortex and hippocampus and up-regulating of CREB/ERK and PI3K/AKT/GSK3ß pathways, as well as alleviation of oxidative stress and neuroinflammation.

Nootkatone improves anxiety- and depression-like behavior by targeting hyperammonemia-induced oxidative stress in D-galactosamine model of liver injury.

Acute or chronic liver injury is closely related to hyperammonemia, which will result in oxidative stress and damage to nerve cells, and these factors are vital to the development of anxiety and depression. In this study, the effect of Nootkatone (NKT) on the anxiety- and depression-like behavioral changes in mice induced by liver injury was investigated. Liver injury was induced by D-galactosamine (D-GalN; 350 mg/kg) three times a week for 4 weeks. NKT (5 mg/kg or 10 mg/kg) was given as co-treatment daily for 4 weeks. NKT (5 mg/kg) co-treatment remarkably ameliorates D-GalN-induced anxiety- and depression-like behaviors as evident from the results of sucrose preference test, forced swimming test, tail suspension test, and novelty suppressed feeding test. Results showed that NKT could induce an elevation in serum alanine transaminase and aspartate transaminase level, alleviate the oxidative stress induced by hyperammonemia through activating Keap1/Nrf2/HO-1 antioxidant pathways, decrease the expression of inducible nitric oxide synthase and NOX2 in hippocampus and prefrontal cortex, enhance the vitality of superoxide dismutase, catalase, and glutathione levels in serum, liver, and brain, and significantly reduce the generation of malondialdehyde. At the same time, NKT also reduces the level of ammonia in serum and brain and upgrades the activity of glutamine synthetase in the hippocampus and prefrontal cortex. Taken together, the present results suggested that NKT has a significant antidepressant effect through modulation of oxidative stress induced by D-GalN administration.

Spinosin protects N2a cells from H2 O2 -induced neurotoxicity through inactivation of p38MAPK.

OBJECTIVES: Previous studies have suggested that spinosin (SPI) exerted neuroprotective effects through inhibition of oxidative damage, but the underlying mechanisms are still unclear. Herein, the mechanisms underlying the protective effects of SPI against oxidative stress induced by hydrogen peroxide (H2 O2 ) were examined in neuro-2a (N2a) mouse neuroblastoma cells. METHODS: N2a cells were pretreated with H2 O2 for 2 h, followed by a 24-h incubation with SPI. Intracellular reactive oxygen species (ROS) production was analysed by flow cytometry. Levels of Aß1-42 production were determined by ELISA assay. Levels of expression of c-Jun N-terminal kinase (JNK), p-JNK, extracellular signal-regulated kinase (ERK), p-ERK, p38 mitogen-activated protein kinase (p38MAPK), p-p38MAPK, p-Tau (Ser199), p-Tau (Ser202), p-Tau (Ser396), synaptophysin (SYP) and postsynaptic scaffold postsynaptic density-95 (PSD-95) were detected by Western blot analysis. KEY FINDINGS: Our results showed that H2 O2 treatment enhanced intracellular ROS production in N2a cells. SPI prevented H2 O2 -induced oxidative damage via inhibiting Aß1-42 production, decreasing Tau phosphorylation and improving synaptic structural plasticity. Notably, H2 O2 -increased p38MAPK activation was attenuated by SPI administration, and p38MAPK inhibitor BIRB796 markedly reduced H2 O2 -induced oxidative damage in N2a cells. CONCLUSIONS: Our findings suggest that SPI protects N2a cells from H2 O2 -induced oxidative damage through inactivation of p38MAPK.

Kaempferide prevents cognitive decline via attenuation of oxidative stress and enhancement of brain-derived neurotrophic factor/tropomyosin receptor kinase B/cAMP response element-binding signaling pathway.

Kaempferide (KF) is a compound of flavonoids from Alpinae oxyphylla Miq, and the herb itself is used as a classical tonic agent. This paper aims to investigate the effects of KF on cognitive function impairment and neurodegeneration in the mouse model of Alzheimer's disease induced by intracerebroventricular (ICV) injection of Aß1-42 . The mice were treated with KF at doses of 0.02 and 0.2 mg/kg/day (ICV) for five consecutive days after Aß1-42 exposures. The behavioral test results showed that KF could prevent cognitive decline in mice induced by Aß1-42 as assessed by the locomotor activity test, Y-maze test, and Morris water maze test. Furthermore, the activities of superoxide dismutase and malondialdehyde in the hippocampus and cerebral cortex were elevated by KF administration. Results of hippocampus slices showed that neurons were integrated and regularly arranged in the groups, which were administered along with KF. In addition, we found KF could boost brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element-binding (CREB) protein signal in the hippocampus. All results illustrated that KF could exert neuroprotective effects at least partly through alleviating oxidative stress and enhancing the BDNF/TrkB/CREB pathway in Aß1-42 -induced mice.

Neuroprotective Effects of Spinosin on Recovery of Learning and Memory in a Mouse Model of Alzheimer's Disease.

Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer's disease (AD) induced by Aß1₋42 and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin (100 µg/kg/day), the cognitive impairment of mice induced by Aß1₋42 was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and Aß1₋42 accumulation in hippocampus. Aß1₋42 induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression, suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.

Schisandrin rescues depressive-like behaviors induced by chronic unpredictable mild stress via GDNF/ERK1/2/ROS and PI3K/AKT/NOX signaling pathways in mice.

The current study aimed to prove the antidepressant-like effects and the probable mechanisms of Schisandrin on depression, which induced by chronic unpredictable mild stress (CUMS) in mice. Four weeks of CUMS exposure resulted in depressive-like behavior, as indicated by the significant decrease in sucrose consumption and increase the immobility time in the forced swim test, but without any influence on the locomotor activity. Further, there were significant downregulations of GDNF/ERK1/2/ROS and PI3K/AKT/NOX signaling pathways in the hippocampus and prefrontal cortex in depressed mice. Treatment of mice with Schisandrin (30mg/kg) and Fluoxetine (10mg/kg) significantly ameliorated all the behavioral and biochemical changes induced by CUMS. These results suggest that Schisandrin produces an antidepressant-like effect in CUMS-induced mice, which possibly mediated, at least in part, by rectifying the signaling pathways of GDNF/ERK1/2/ROS and PI3K/AKT/NOX.

Identification and analysis of chemical constituents and rat serum metabolites in Suan-Zao-Ren granule using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with multiple data processing approaches.

Suan-Zao-Ren granule is widely used to treat insomnia in China. However, because of the complexity and diversity of the chemical compositions in traditional Chinese medicine formula, the comprehensive analysis of constituents in vitro and in vivo is rather difficult. In our study, an ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and the PeakView® software, which uses multiple data processing approaches including product ion filter, neutral loss filter, and mass defect filter, method was developed to characterize the ingredients and rat serum metabolites in Suan-Zao-Ren granule. A total of 101 constituents were detected in vitro. Under the same analysis conditions, 68 constituents were characterized in rat serum, including 35 prototype components and 33 metabolites. The metabolic pathways of main components were also illustrated. Among them, the metabolic pathways of timosaponin AI were firstly revealed. The bioactive compounds mainly underwent the phase I metabolic pathways including hydroxylation, oxidation, hydrolysis, and phase II metabolic pathways including sulfate conjugation, glucuronide conjugation, cysteine conjugation, acetycysteine conjugation, and glutathione conjugation. In conclusion, our results showed that this analysis approach was extremely useful for the in-depth pharmacological research of Suan-Zao-Ren granule and provided a chemical basis for its rational.

Polyamine Metabolites Profiling for Characterization of Lung and Liver Cancer Using an LC-Tandem MS Method with Multiple Statistical Data Mining Strategies: Discovering Potential Cancer Biomarkers in Human Plasma and Urine.

Polyamines, one of the most important kind of biomarkers in cancer research, were investigated in order to characterize different cancer types. An integrative approach which combined ultra-high performance liquid chromatography-tandem mass spectrometry detection and multiple statistical data processing strategies including outlier elimination, binary logistic regression analysis and cluster analysis had been developed to discover the characteristic biomarkers of lung and liver cancer. The concentrations of 14 polyamine metabolites in biosamples from lung (n = 50) and liver cancer patients (n = 50) were detected by a validated UHPLC-MS/MS method. Then the concentrations were converted into independent variables to characterize patients of lung and liver cancer by binary logic regression analysis. Significant independent variables were regarded as the potential biomarkers. Cluster analysis was engaged for further verifying. As a result, two values was discovered to identify lung and liver cancer, which were the product of the plasma concentration of putrescine and spermidine; and the ratio of the urine concentration of S-adenosyl-l-methionine and N-acetylspermidine. Results indicated that the established advanced method could be successfully applied to characterize lung and liver cancer, and may also enable a new way of discovering cancer biomarkers and characterizing other types of cancer.

Proton pump inhibitors therapy vs H2 receptor antagonists therapy for upper gastrointestinal bleeding after endoscopy: A meta-analysis.

AIM: To compare the therapeutic effects of proton pump inhibitors vs H2 receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy. METHODS: We searched the Cochrane library, MEDLINE, EMBASE and PubMed for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration's tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios (OR) and mean difference with 95% confidence interval (CI). RevMan 5.3.3 software and Stata 12.0 software were used for data analyses. RESULTS: Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors (PPI) group and the remaining 605 subjects were in the H2 receptor antagonists (H2RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H2RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate (OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate (OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality (OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference (WMD), -0.70 unit; 95%CI: -1.64 - 0.25] and the time that patients remained hospitalized [WMD, -0.77 d; 95%CI: -1.87 - 0.34]. The Begg's test (P = 0.283) and Egger's test (P = 0.339) demonstrated that there was no publication bias in our meta-analysis. CONCLUSION: In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H2RA, PPI may be a more effective therapy.

A UFLC-MS/MS method coupled with one-step protein precipitation for determination of docetaxel in rat plasma: comparative pharmacokinetic study of modified nanostructured lipid carrier.

A rapid, simple and sensitive ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method coupled with one-step protein precipitation procedure has been developed and validated for the pharmacokinetic study of docetaxel in rat plasma to investigate the influence of polyethylene glycol (PEG) molecular weights (chain length) using in the modified formulations. Separation was achieved on a Venusil MP C18 column (100 mm × 2.1 mm, 3.0 µm) with a mobile phase consisting of methanol-water, and the total running time was 3.5min. The standard curve was linear over the range of 5-5000 ng/mL, with lower limits of quantification (LLOQ) of 5 ng/mL. The method was shown to be reliable and reproducible with intra-day precision below 10.7%, inter-day precision below 11.2%, accuracy within ±5.2%, and mean extraction recovery of 84.6-90.2%. The validated method was successfully applied to the comparative pharmacokinetic study of docetaxel in rat plasma after intravenous administration of docetaxel-loaded nanostructured lipid carrier modified by copolymers consisting of series of PEG molecular weights (2000, 4000, 10,000 Da), respectively. The results indicated that PEG-4000 possessed a better and longer circulation effect, which made the modified formulation one of the promising suspensions for the delivery of docetaxel in cancer.

Comparative pharmacokinetics of three triterpene acids in rat plasma after oral administration of Poria extract and its formulated herbal preparation: GuiZhi-FuLing capsule.

A sensitive liquid chromatographic-mass spectrometric technique coupled with liquid-liquid extraction method was developed and validated for simultaneous determination of dehydro-tumulosic acid, tumulosic acid and polyporic acid C in rat plasma. The analytes were separated on a Kromasil C(18) column with a total running time of 12.5 min. Author had compared the pharmacokinetics of dehydro-tumulosic acid, tumulosic acid and polyporic acid C after oral administration of the extract of Poria and its formulated herbal preparation (GuiZhi-FuLing capsule). The improved pharmacokinetic profiles of the three compounds were found in the GuiZhi-FuLing capsule, indicating the more effective absorption and the slower elimination, compared with the Poria extract. Furthermore, this study revealed that as far as the Poria extract was concerned, it is very valuable to be used as a clinical instruction of GF capsule.