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.

Schisandra chinensis protects against dopaminergic neuronal oxidative stress, neuroinflammation and apoptosis via the BDNF/Nrf2/NF-κB pathway in 6-OHDA-induced Parkinson's disease mice.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a disorder of both the motor and nonmotor systems due to a loss of dopaminergic (DA) neurons. Herein, we aimed to investigate the potential neuroprotective role of Schisandra chinensis (Sch) and to determine the mechanism by which Sch functions to ameliorate PD in a 6-hydroxydopamin (6-OHDA)-induced PD model. The open field test, sucrose preference test, and Y-maze test were utilized to evaluate the motor and nonmotor symptoms. We found that administration of Sch improved both disorders and DA neurodegeneration in 6-OHDA-induced mice. Additional data confirmed that Sch treatment significantly increased BDNF expression and decreased the activity of GSK-3ß in the striatum and hippocampus. Moreover, Sch was able to alleviate the abnormal levels of ROS and increase SOD by boosting Nrf2 expression. The nuclear translocation of NF-κB was inhibited by Sch, which subsequently led to a downregulation of proinflammatory cytokines. Sch effectively suppressed apoptosis by decreasing expressions of caspase 3, caspase 9, and p53 in the PD mouse model. Our findings demonstrate that Sch protects against DA neurodegeneration in 6-OHDA-induced PD mice by suppressing oxidative stress, neuroinflammation and apoptosis through the involvement of the BDNF/Nrf2/NF-κB signaling pathway.

Schizandrin ameliorates behavioral disorders in hepatic injury mice via regulation of oxidative stress and neuroinflammation.

Aim: The present study was aimed to evaluate the anxiolytic and antidepressant-like effects of schizandrin (from Schisandra chinensis (Turcz.) Baill. which is a functional food) against chronic liver injury in mice.Methods: Chronic liver injury was induced by the treatment of d-galactose (d-GaIN, 200 mg/kg, s.c.) for 8 weeks.Results: Administration of schizandrin (30 mg/kg, i.g.) significantly ameliorated d-GaIN-induced anxiety and depression-like behavior as evident from the results of open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), novelty-suppressed feeding test (NSFT), and elevated plus maze (EPM) test. In addition, schizandrin remarkably reduced the oxidative stress due to its potential to enhance the levels of decreased CAT, GSH/GSSG, SOD, and increased MDA in peripheral and brain, the antioxidant activities might be related with the Nrf2/HO-1 pathway. Furthermore, schizandrin could dramatically inhibit the neuroinflammation in mice by reducing pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) through regulating NF-κB/NLRP3/Iba-1 signaling. Besides, the elevated levels of ammonia, AST, and ALT were significantly reduced by schizandrin.Conclusion: The present data revealed that hyperammonemia produced due to liver injury-induced oxidative stress and neuroinflammation in the hippocampus and prefrontal cortex resulting in anxiety and depression were improved by schizandrin.

Schisandra chinensis ameliorates depressive-like behaviors by regulating microbiota-gut-brain axis via its anti-inflammation activity.

The present study aimed to examine the antidepressant actions of the composition fractions of Schisandra chinensis using LPS-induced mice. Animals were treated with total extracts (SCE), lignans (SCL), polysaccharides (SCPS), and essential oil (SCVO), and then subjected to behavioral tests. The forced swimming test (FST) and tail suspension test (TST) were used as predictive animal models of antidepressant activity. Total extracts and lignans significantly decreased the duration of immobility in FST and TST. We found that treatment with SCE and SCL could significantly decrease the levels of pro-inflammatory cytokines both in the periphery and central nervous system (CNS). This was confirmed by the histopathological examination of the colon. The RT-PCR results demonstrated that SCE and SCL could greatly inhibit the TLR4/NF-κB/IKKα signaling pathway. In addition, the concentrations of Butyric acid and Propionic acid were upregulated by the administration, and the decreased diversity of intestinal microbiota and alterations of the relative proportions of Bacteroidetes and Firmicutes phylum members, Barnesiella and Lactobacillus genus members in LPS-induced mice were restored as well. All results suggested that lignans is the effective fraction of S.chinensis to ameliorating depressive disorders, which its anti-inflammation activity possibly involved in the bidirectional connection between gut microbiota and brain.

Untargeted metabolomic study on the insomnia effect of Suan-Zao-Ren decoction in the rat serum and brain using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with data processing analysis.

Insomnia is a common clinical disease that can seriously damage the normal lives of sufferers. Suan-Zao-Ren decoction has been used to treat insomnia for a long time. However, the underlying molecular mechanism of Suan-Zao-Ren decoction is still not clear. In this study, the nontargeted metabolomics based on high-resolution mass spectrometry and multiple statistical approaches were initially used to investigate the changes of potential serum and brain biomarkers and metabolic pathways in the insomnia model rat. Principal component analysis-discriminate analysis indicated that the Suan-Zao-Ren decoction treatment improved the metabolic phenotype insomnia. Moreover, the heatmap analysis identified the most important biomarkers involved in insomnia. According to the pathway analysis, phenylalanine metabolism, tryptophan metabolism, and so on were recognized as the most affected metabolic pathways associated with insomnia disease. These findings provided a comprehensive understanding of the regulative effects of Suan-Zao-Ren decoction on the host metabolic phenotype of the insomnia rats. Our work demonstrated that the metabolomics approach is a promising tool that could help us to conduct the exploration of the therapeutic effects and mechanism of traditional Chinese medicines.

Schisandrae Chinensis Fructus inhibits behavioral deficits induced by sleep deprivation and chronic unpredictable mild stress via increased signaling of brain-derived neurotrophic factor.

The present study was undertaken to explore the interactions between sleep deprivation (SD) and Schisandrae Chinensis Fructus (SCF) treatment in the antidepressant-like effects. We observed that SD aggravated the anxiety-like behavior induced by chronic unpredictable mild stress (CUMS) in the elevated plus maze test. However, the forced swimming test and sucrose preference test showed that SD (12 hr) alleviated the depressive symptoms and SD (72 hr) has the opposite effects. Administration of SCF showed a promising therapeutic effect on depression and anxiety induced by CUMS and SD. Moreover, SCF could potential strengthen the antidepressant-like effects of SD (12 hr) according to the behavioral tests. In addition, the BDNF level in hippocampus was elevated by SD (12 hr) and SCF treatment and together with the upregulation of TrkB/CREB/ERK and PI3K/AKT/GSK3ß/mTOR signaling pathways. Besides, the protein levels of p70S6K and PSD95, which are downstream targets of mTOR, also increased by the treatment. These results indicated that the antidepressant-like effect of SCF in the CUMS depends on the activation of BDNF and the modulation of TrkB/CREB/ERK and PI3K/AKT/GSK3ß/mTOR signaling cascades, and SD (12 hr) shared a common etiology consisting of complex bidirectional interactions with SCF.

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.

The investigation of immunoprotective and sedative hypnotic effect of total polysaccharide from Suanzaoren decoction by serum metabonomics approach.

Suanzaoren decoction, as one of the traditional Chinese medicine prescriptions, has been most commonly used in Asian countries and reported to inhibit the process of immunodeficiency insomnia. Polysaccharide is important component which also contributes to the role of immunoprotective and sedative hypnotic effects. This study was aimed to explore the immunoprotective and sedative hypnotic mechanisms of polysaccharide from Suanzaoren decoction by serum metabonomics approach. With this purpose, complex physical and chemical immunodeficiency insomnia models were firstly established according to its multi-target property. Serum samples were analyzed using UHPLC/Q-TOF-MS spectrometry approach to determine endogenous metabolites. Then, principal component analysis was used to distinguish the groups, and partial least squares discriminate analysis was carried out to confirm the important variables. The serum metabolic profiling was identified and pathway analysis was performed after the total polysaccharide administration. The twenty-one potential biomarkers were screened, and the levels were all reversed to different degrees in the total polysaccharide treated groups. These potential biomarkers were mainly related to vitamin, sphingolipid, bile acid, phospholipid and acylcarnitine metabolisms. The result has indicated that total polysaccharide could inhibit insomnia triggered by immunodeficiency stimulation through regulating those metabolic pathways. This study provides a useful approach for exploring the mechanism and evaluating the efficacy of total polysaccharide from Suanzaoren decoction.

Ameliorating effect of Alpinia oxyphylla-Schisandra chinensis herb pair on cognitive impairment in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia. In our previous study, we found both Alpinia oxyphylla and Schisandra chinensis can improve the cognitive function of AD. To investigate whether the Alpinia oxyphylla - Schisandra chinensis herb pair (ASHP) has ameliorating effect on cognitive impairment, we used scopolamine to induce learning and memory impairments, as a mouse model of AD. Subsequently, we carried out Y-maze test and Morris water maze test to observe the behavior of mice. Finally, the level of Acetylcholine (Ach) and muscarinic receptor (M1) receptors, the activity of choline acetyltransferase (ChAT) and acetyl cholinesterase (AChE) were measured by commercial assay kits and ELISA kit. And we used hematoxylin-eosin (HE) staining to check the changes in cortex and the CA1 region of hippocampus. ASHP significantly protected against learning and memory impairments induced by scopolamine in Y-maze test and Morris water maze test. Besides, ASHP was able to increase the level of ACh and M1 receptors, and decrease the activity of AChE, but did not significantly affect the activity of ChAT. In addition, from the results of histopathological examination, we speculated ASHP may have neuroprotective effects. This study provided an experimental basis for further study of Alpinia oxyphylla - Schisandra chinensis herb pair in AD therapy.

Antidepressant-like effects and cognitive enhancement of Schisandra chinensis in chronic unpredictable mild stress mice and its related mechanism.

The aim of this study was to evaluate whether Schisandra chinensis extract (SCE) administration influences chronic unpredictable mild stress (CUMS)-induced depression and cognitive impairment, and explores underlying mechanisms. Sucrose preference test (SPT) and forced swimming test (FST) were used for assessing depressive symptoms, and Y-maze, Morris water maze were used for evaluating cognition processes. The results showed that CUMS (4 weeks) was effective in producing both depression and memory deficits in mice. Additionally, CUMS exposure significantly decreased brain derived neurotrophic factor (BDNF) levels in hippocampus as indicated by ELISA, immunohistochemistry and immunofluorescence assays, accompanied by down-regulated tyrosine kinase receptor B (TrkB)/cAMP-response element binding protein (CREB)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT)/ glycogen synthase kinase-3ß (GSK-3ß) signaling pathways. Chronic administration of SCE (600 or 1200 mg/kg, i.g.) significantly prevented all these CUMS-induced behavioral and biochemical alterations. It suggested that SCE could improve the depression-like emotional status and associated cognitive deficits in CUMS mice, which might be mediated by regulation of BDNF levels in hippocampus, as well as up-regulating of TrkB/CREB/ERK and PI3K/AKT/GSK-3ß pathways.

An integrative investigation of the toxicity of Aconiti kusnezoffii radix and the attenuation effect of its processed drug using a UHPLC-Q-TOF based rat serum and urine metabolomics strategy.

Aconiti kusnezoffii radix (AKR), the root of Aconitum kusnezoffii Reichb., is commonly used in the treatment of the rheumatoid arthritis. However, the clinical application is limited due to its potential toxicity. Therefore, to investigate the mechanism of its potential neurotoxicity and nephrotoxicity, a comprehensive metabolomics study combined with serum biochemistry and histopathology measurements was carried out. A UHPLC-Q-TOF mass spectrometry based metabolomics approach was applied to characterize the AKR toxicity, while the toxicity attenuation effects of Aconiti kusnezoffii radix cocta (AKRC) on Wistar rats were also investigated. Two chromatographic techniques involving reversed-phase chromatography and hydrophilic interaction chromatography were combined for the serum and urine detection, which balanced the integrity and selectivity of the two matrices. Principal component analysis was used to determine the groups, and principal component analysis discriminant analysis was carried out to confirm the important variables. Then, the developed integrative toxicity evaluation method was applied to assess the toxicity of AKR and the attenuation effect of AKRC. The highly sensitive and specific toxic biomarkers, which can provide practical bases were identified for the diagnosis of the neurotoxicity and nephrotoxicity induced by AKR. In all, a total of 19 putative biomarkers were characterized, and related metabolic pathways were identified. The study demonstrated that the established metabolomics strategy is a powerful approach for investigating the mechanisms of herbal toxicity and the attenuation effect of a processing method and would provide medical solutions for other toxic herbal medications and further clinical evidence on how AKR improves symptoms of rheumatoid arthritis patients.

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.

Simultaneous quantitative determination of 13 active components in the traditional Chinese medicinal preparation Suanzaoren oral liquid by HPLC coupled with diode array detection and evaporative light scattering detection.

To control the quality of different forms of Suanzaoren decoction, an effective and reliable method for the simultaneous determination of 13 major components (neomangiferin, mangiferin, spinosin, liquiritin apioside, liquiritin, 6'''-feruloylspinosin, senkyunolide I, timosaponin BII, isoliquiritoside, timosaponin C, jujuboside A, jujuboside B, and timosaponin AIII) was developed and validated for the first time in this study using high-performance liquid chromatography with diode array detection and evaporative light scattering detection. The chromatographic separation was performed on a Venusil MP C18 column (250 mm × 4.6 mm, 5 µm) at 30°C with a gradient of acetonitrile/redistilled water as the mobile phase. Diode array detection was carried out at a wavelength of 275 nm. The drift tube temperature and the nitrogen gas flow rate of the evaporative light scattering detection were set at 50°C and 1.6 L/min, respectively. The newly developed method was successfully applied to the determination of 13 components in lab-prepared Suanzaoren oral liquid, Suanzaoren mixture, and clinical Suanzaoren granules, and this study showed that this was a useful way to comprehensively evaluate the quality of Suanzaoren decoction in different forms of the preparation.

Simultaneous determination of multiple active components in rat plasma using ultra-fast liquid chromatography with tandem mass spectrometry and application to a comparative pharmacokinetic study after oral administration of Suan-Zao-Ren decoction and Suan-Zao-Ren granule.

Suan-Zao-Ren decoction has been used to treat insomnia for many years. In this work, a rapid and sensitive ultra-fast liquid chromatography with tandem mass spectrometry method was first developed and fully validated for the simultaneous quantification of seven main active components, spinosin, mangiferin, neomangiferin, ferulic acid, liquiritin, isoliquiritin, and liquiritin apioside in rat plasma. The method was also successfully applied to compare the pharmacokinetics of these active ingredients after oral administration of Suan-Zao-Ren decoction and Suan-Zao-Ren granule. The separation was achieved on a Venusil MP C18 column and the detection was conducted by the multiple reaction monitoring mode using negative ion mode. Each calibration curve had good linearity over a wide concentration range. The precision of intra- and interday were all within 15%, and the extraction recoveries at different analyte concentrations were all above 82.0%. The established method was successfully applied to compare the pharmacokinetic profiles of the analytes between Suan-Zao-Ren decoction and Suan-Zao-Ren granule groups. The results indicated that all the analytes had similar mean concentration-time curves trend between two groups. No significant differences were observed in pharmacokinetic parameters of mangiferin, while the others had significant differences.

Simultaneous Determinations of Eleven Bioactive Components in Suanzaoren Decoction Granules by High-Performance Liquid Chromatography and Its Application to the Quality Control in Productive Processes.

A simple and reliable method using high-performance liquid chromatography coupled with a photodiode array detector (HPLC-PDA) was firstly established for the determinations of eleven bioactive compounds (neomangiferin, mangiferin, spinosin, liquiritin apioside, liquiritin, fumalic acid, 6'''-feruloylspinosin, senkyunolide I, isoliquiritin, glycyrrhizic acid and senkyunolide A) in Suanzaoren decoction (SZRD) extract and its granules. The chromatographic analysis was performed on a C18 column at 30°C. Excellent linear behaviors over the investigated concentration ranges were observed with the values of R(2) being higher than 0.9990 for all analytes. The developed method showed good precision and accuracy with overall intra- and inter-day variations of less than 2.0%, and overall recoveries in the range of 97.2 - 102.1%. The validated method was successfully applied to the determination of eleven components in SZRD samples from different production batches, including SZRD extract, lab-made SZRD granules and clinical medicine. This accurate and reliable HPLC-PDA method will be helpful for improving the quality evaluation of SZRD granules and its quality control in productive processes.

Comprehensive Qualitative Ingredient Profiling of Chinese Herbal Formula Wu-Zhu-Yu Decoction via a Mass Defect and Fragment Filtering Approach Using High Resolution Mass Spectrometry.

The Wu-Zhu-Yu decoction is a traditional Chinese medicine formula for the treatment of headache. To reveal its material basis, a rapid and reliable liquid chromatography-high resolution mass spectrometry method was established for comprehensive profiling of the chemical ingredients in the Wu-Zhu-Yu decoction. The method was used on a quadrupole time-of-flight mass spectrometer along with an advanced data processing procedure consisting of mass accuracy screening, mass defect filtering and fragment filtering. After eliminating interference with a filtering approach, the MS data profiling was made more distinct and accurate. With the optimized conditions of only 35 min LC separation and single sample injection of each positive or negative ion mode, a total of 168 compounds were characterized, including 23 evodiamine and its analogous alkaloids, 12 limonoids, 17 gingerols, 38 ginsenosides, 15 flavonoids, 16 organic acids, 14 alkaloids, 5 saponins, 3 2,2-dimethylchromenes and 25 other compounds. The fragmentation patterns of representative compounds were illustrated as well. Integrative qualitative analysis of the Wu-Zhu-Yu decoction by high resolution mass spectrometry was accomplished and reported for the first time. The study demonstrated that the established method was a powerful and reliable strategy for comprehensive detection and would be widely applicable for identification of complicated components from herbal prescriptions, and may provide a basis for chemical analysis of other complex mixtures.

[Analysis of projects funded by NSFC in field of processing Chinese materia medica in recent five years].

The general situation of the approved and concluded projects of National Natural Science Foundation of China in the field of processing Chinese Materia Medica in recent five years has been reviewed. The progresses and achievements of some projects have been summarized in accordance with research area such as the processing principle, the processing technology, quality evaluation, toxicity and safety evaluation, etc. The researchers and project support units of the funded projects have been analyzed, and the problems of the applications have been also summarized.

Simultaneous quantitation of polygalaxanthone III and four ginsenosides by ultra-fast liquid chromatography with tandem mass spectrometry in rat and beagle dog plasma after oral administration of Kai-Xin-San: application to a comparative pharmacokinetic study.

A fast, selective, and quantitative ultra-fast liquid chromatography with tandem mass spectrometry method has been developed and validated for the simultaneous quantitation of polygalaxanthone III, ginsenoside Rb1, ginsenoside Rd, ginsenoside Re, and ginsenoside Rg1 in the plasma of rat and beagle dog after oral administration of Kai-Xin-San. After addition of the internal standard, salidroside, the plasma samples were extracted by liquid-liquid extraction and separated on a Venusil MP C18 column with methanol/0.01% acetic acid water as mobile phase. The tandem mass spectrometric detection was performed in the multiple reaction monitoring with turbo ion spray source in a switching ionization mode. The method was examined, and found to be precise and accurate with the linearity range of the compounds. The intra- and interday precision and accuracy of the analytes were well within acceptance criteria (±15%). The mean extraction recoveries of analytes and internal standard were all >75.0%. The validated method has been successfully applied to comparing pharmacokinetic profiles of analytes in rat and beagle dog plasma. The results indicated that no significant differences were observed in pharmacokinetic parameters of ginsenoside Rg1, while the others had significant differences, which may due to the different mechanisms of absorption and metabolism.