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Depression is one of the most complex multifactorial diseases affected by genetic and environmental factors. The molecular mechanism underlying depression remains largely unclear. To address this issue, a novel nervous-endocrine-immune (NEI) network module was used to find the metabolites and evaluate the diagnostic ability of patients with depression. During this process, metabolites were acquired from a professional depression metabolism database. Over-representation analysis was performed using IMPaLA. Then, the metabolite-metabolite interaction (MMI) network of the NEI system was used to select key metabolites. Finally, the receiver operating characteristic curve analysis was evaluated for the diagnostic ability of arachidonic acid. The results show that the numbers of the nervous system, endocrine system, and immune system pathways are 10, 19, and 12 and the numbers of metabolites are 38, 52, and 13, respectively. The selected shared metabolite-enriched pathways can be 97.56% of the NEI-related pathways. Arachidonic acid was extracted from the NEI system network by using an optimization formula and validated by in vivo experiments. It was indicated that the proposed model was good at screening arachidonic acid for the diagnosis of depression. This method provides reliable evidences and references for the diagnosis and mechanism research of other related diseases.

Ethnopharmacological relevance The compatibility of Bupleurum chinense DC (Chaihu)-Paeonia lactiflora Pall (Baishao) is one of the most accepted herb pairs in traditional Chinese medicine (TCM) prescriptions for treating depression. However, the combination mechanisms of this herb pair for anti-depression remain unclear. Materials and methods In this study, the combined effect of Chaihu-Baishao was evaluated by the chronic unpredictable mild stress (CUMS) rat model. Secondly, network pharmacology was constructed to dissect the united mechanisms. Based on the results of network pharmacology analysis, plasma metabolomics based on ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was performed to discover the collaborative effect on metabolite regulation. Furthermore, the targets from network pharmacology and the metabolites from metabolomics were jointly analyzed to select crucial metabolism pathways by MetaScape. Finally, the key metabolic enzymes and metabolites were experimentally validated by ELISA. Results The antidepressant effect of Chaihu-Baishao herb pair was significantly better than Chaihu or Baishao in sucrose preference test (SPT), open-field test (OFT), and forced swim test (FST). In network pharmacology, herb pair played synergetic effect through regulating shared pathways, such as MAPK signaling pathway and arachidonic acid metabolism, etc. Besides, by metabolomics, the herb pair improved more metabolites (14) than a single herb (10 & 9) and has a stronger regulation effect on metabolites. Correspondingly, herb pair adjusted more metabolism pathways (5) than individual herb (4 & 4). Furthermore, the arachidonic acid metabolism was selected as crucial metabolism pathways by a joint analysis of 199 targets and 14 metabolites. The results showed that herb pair regulated arachidonic acid metabolism by synergetic reducing the level of arachidonic acid, and inhibiting the enzyme activity of prostaglandin-endoperoxide synthase 1 (PTGS1) and prostaglandin-endoperoxide synthase 2 (PTGS2). Conclusions This work provided an integrated strategy for revealing the combination mechanisms of Chaihu-Baishao herb pair for treating depression, and also a rational way for clarifying the composition rules of TCM.

This article mainly describes the chemical and crystal structure of attapulgite as its unique crystal structure possess special physicochemical properties such as large specific surface area, adsorption performance, and cation exchangeability. By modification of attapulgite, such as purification, high temperature roasting and other physical modification or acid–base salt modification, organic modification, surfactant modification and other chemical modification can further improve its physicochemical properties. In this article, the modification methods of two aspects of physical modification and chemical modification are summarized, at the same time, the research progress and achievements of many scholars in attapulgite modification are reviewed. Through modified attapulgite the number of pores increased, channel become loose, pore diameter increases, pore volume increases, interlayer spacing increases, specific surface area increases, chargeability and adsorption activity change, and the adsorption performance of attapulgite is greatly improved. Many scholars have applied modified attapulgite to the treatment of radionuclides, and achieved remarkable results. It has been found that modified attapulgite has U(VI), Eu(III), Cs(III), Th(IV), both Eu(III) and Sr(II) have good adsorption properties, and the adsorption rate and adsorption capacity are greatly improved compared with the original soil. Based on the Summary of the attapulgite modification method and its application in the treatment of radionuclide, some suggestions on the research and application of attapulgite modification and the possible key research directions in the future are further proposed.

Baicalein, a flavonoid derived from the roots of Scutellariae baicalensis Georgi, has shown health benefits for an array of human diseases including dementia. The senescence-accelerated mouse prone 8 (SAMP8) strain is extensively used as a senile dementia model. To further investigate the effects of baicalein in SAMP8 mice, behavioral testing, biochemical detection, and gut microbiota analysis were performed. The results demonstrated that treatment with baicalein ameliorated the senescence status of the SAMP8 mice, as manifested by reducing the grading score of senescence. Additionally, baicalein improved the cognitive functions of the SAMP8 mice, including spatial learning and memory abilities, object recognition memory, and olfactory memory. Furthermore, baicalein significantly inhibited the release of proinflammatory cytokines such as interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) in the brain cortex of SAMP8 mice. Gut microbiota analysis revealed that treatment with baicalein markedly altered the abundance of six genera in SAMP8 mice. Correlation analysis indicated that the abundances of Mucispirillum, Bacteroides, and Sutterella were negatively correlated with cognitive abilities and that Christensenellaceae was positively correlated with cognition. Furthermore, the abundance of Christensenellaceae was negatively correlated with the levels of IL-6 and TNF-α, while [ Prevotella] was positively correlated with the levels of IL-1β and IL-6. In addition, Mucispirillum and Bacteroides were positively correlated with the level of IL-6 in the brain cortex. These data indicated that baicalein ameliorates senescence status and improves cognitive function in SAMP8 mice and that this effect might be attributable to suppression of cortical proinflammatory cytokines and modulation of the intestinal microbiome.

Compound Kushen Injection (CKI) is a Traditional Chinese Medicine (TCM) preparation that has been clinically used in China to treat various types of solid tumours. Although several studies have revealed that CKI can inhibit the proliferation of hepatocellular carcinoma (HCC) cell lines, the active compounds, potential targets and pathways involved in these effects have not been systematically investigated. Here, we proposed a novel idea of “main active compound-based network pharmacology” to explore the anti-cancer mechanism of CKI. Our results showed that CKI significantly suppressed the proliferation and migration of SMMC-7721 cells. Four main active compounds of CKI (matrine, oxymatrine, sophoridine and N-methylcytisine) were confirmed by the integration of ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) with cell proliferation assays. The potential targets and pathways involved in the anti-HCC effects of CKI were predicted by a network pharmacology approach, and some of the crucial proteins and pathways were further validated by western blotting and metabolomics approaches. Our results indicated that CKI exerted anti-HCC effects via the key targets MMP2, MYC, CASP3, and REG1A and the key pathways of glycometabolism and amino acid metabolism. These results provide insights into the mechanism of CKI by combining quantitative analysis of components, network pharmacology and experimental validation.

Licorice, an edible and officinal plant material, has attracted considerable attention for its wide range of pharmacological activities. Our previous study showed that licorice can ameliorate cognitive damage and improve oxidative stress and apoptosis in aging rats induced by d-galactose (d-gal). In this study, in order to further explore the changes of the metabolic profile during the aging process and the antiaging mechanism of licorice, the 1H NMR-based metabolomics approach was used to analyze serum and urine samples and identify a potential biomarker in d-gal induced aging rats. The results revealed that the taurine metabolic pathway was significantly correlated with the ageing process in d-gal induced rats. Furthermore, the taurine contents were significantly decreased in both the serum and urine samples of aging rats compared with the controls. At the same time, the levels of cysteine dioxygenase type I (CDO1), cysteine sulfinic acid decarboxylase (CSAD) and glutamate decarboxylase type I (GAD1), which are the key enzymes affecting the synthesis reactions, were decreased in aging rats compared with the controls. After licorice administration, the levels of taurine, CDO1 and CSAD were all significantly increased. These findings firstly demonstrated that the regulation of the taurine metabolic pathway is involved in the anti-aging effect of licorice in d-gal induced aging rats.

Drosophila melanogaster is increasingly used for study aging mechanism and evaluating anti-aging drugs, but the changes of metabolites and differences of metabolites change between male and female during the aging process are not well known. Metabolomics technology, a massive information provider, has promoted the understanding of metabolic profile and overall changes of metabolites in organism. In this study, 1H NMR based metabonomics was employed to investigate the dynamic changes of metabolites in whole bodies of male and female Drosophila melanogaster at 3, 15, 30, 45days and to research the gender gap of metabolites changes in aging process. The results showed that the metabolic profile at different ages in both male and female Drosophila melanogaster were separated obviously by multivariate analysis. Besides, the variety track of metabolites between male and female Drosophila melanogaster were different, the change speed in female was significantly slow than that in male. In addition, the results showed 14 metabolites (including leucine, valine, alanine, methionine, cysteine, phenylalanine, glycine, glutamine, tyrosine, tryptophan and histidine, succinate, xanthine and DMA) were associated with aging and 7 metabolites (including leucine, valine, methionine, cysteine phenylalanine, succinate and DMA) were associated with gender gap in the aging process of Drosophila melanogaster. Corresponding metabolic mechanisms referenced to the KEGG database and literatures were discussed. This study demonstrate that metabolomics is promising as a valuable method not only to reveal metabolites that related to senescence, but also to help us understand differences between male and female flies in aging process.

This study aimed to explore the protective effects and possible mechanisms of baicalein on AβThioflavin-T (Th-T) dye was used to determine the effects of baicalein on AβThe results showed that baicalein could inhibit the aggregation of AβOur study revealed that baicalein has a protective effect on Aβ

Ethnopharmacological relevance Xiaoyaosan (XYS), composed of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae, is a valuable traditional Chinese medicine (TCM) which is used for the treatment of depression in China. In our previous experiments, we found that coniferyl ferulate (CF) was the main active constituent of Xiaoyaosan based on UPLC-PDA guided isolation technique. However, the antidepressant effect and mechanisms of CF is still unknown. Aim of the study In the current study, we aim to explore the possible mechanisms involved in the neuroprotective effect of CF in glutamate-injured PC12 cells, and further to confirm the anti-depressant effect of CF on the model of behavioral despair in vivo. Material and methods The model of glutamate-injured PC12 cells was employed to investigate the possible mechanisms involved in the neuroprotective effect of CF. The model of behavioral despair was carried out to examine the in vivo anti-depressant effect of CF. Results The results showed that CF significantly attenuated the decrease of cell viability, the release of lactate dehydrogenase (LDH), and the increase of apoptosis rates induced by glutamate. CF could also suppress the influx of Ca2+ and the elevation of p-NR2B, p-CaMK II, p-JNK, and p-p38 level induced by glutamate. Besides, CF could also inhibit the generation of reactive oxygen species (ROS), the decrease of SOD activity, the elevation of malondialdehyde (MDA) level, and suppress the loss of mitochondrial membrane potential (MMPs) and the activation Bcl-2/Bax mediated apoptotic pathways induced by glutamate. Furthermore, CF obviously decreased the immobility time in tail suspension test (TST) and forced swimming test (FST). Conclusion In conclusion, CF exert the indeed anti-depressant effect. The inhibition of NMDAR-CaMKII-MAPKs signaling pathway, oxidative stress, and mitochondrial apoptotic pathways were involved in the anti-depressant effect of CF.

Our previous work suggested that baicalein could delay senescence and improve cognitive dysfunction in senescence-accelerated mouse prone 8 (SAMP8). Although baicalein has shown therapeutical benefits in improving learning and memory impairment, the exact molecular mechanisms have not been fully understood. In the present work, transcriptomics was integrated with gene network analysis for revealing the potential mechanisms of baicalein in improving learning and memory in SAMP8 mice. The results showed that baicalein regulated fifty hub differently expressed genes (DEGs) that were enriched in eight signaling pathways. Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway was especially significant among them, therefore, the DEGs (Gh1, Il5, Il7, Il20rb, Prlr and Socs1) in JAK-STAT signaling pathway were verified by quantitative real-time PCR, and the key proteins (JAK2, p-JAK2, STAT1 and p-STAT1) and related proteins including β-amyloid peptide (Aβ1-42) and receptor for advanced glycation end products (RAGE) were assayed by Western blot and enzyme-linked immunosorbent assay. Our results suggest that baicalein prevented the activation of JAK2/STAT1 signaling pathway and decreased the levels of Aβ1-42 and RAGE in the cortex of SAMP8 mice. Taken together, our study unmasks the mechanism of baicalein on improving learning and memory impairment in SAMP8 mice, which is dependent upon the inhibition of Aβ1-42 and RAGE/JAK2/STAT1 cascade.

Angelicae Sinensis Radix (AS), a well-known herb in traditional Chinese medicine (TCM), has been wildly used for replenishing the blood and promoting circulation, in Asia for thousands of years. It has been confirmed that AS also possesses the pharmacological activity of anti-depression. At the same time, recent studies suggested that depression is associated with anemia, and depression could be ameliorated via modulating the blood system. However, it is still unknown whether the anti-depression effect of AS is related to its pharmacological activity of modulating the blood system. In the current study, hematological examination and metabonomic techniques were performed to explore potential anti-depression mechanisms of AS, related to the function of modulating the blood system in a chronic unpredictable mild stress (CUMS) model. The results demonstrated that AS could significantly improve CUMS-induced depressive symptom, hematological anomalies, and hypoxia symptoms. The analysis of metabonomics demonstrated that 26 potential biomarkers in depression could be regulated by the administration of AS. Among them, eight biomarkers participate in the metabolic pathways of amino acid and sphingolipid, and energy metabolism could also be regulated in an anemia model through the administration of AS, as reported in previous literatures. Further results proved that AS modulated energy metabolism in depression through the inhibition of the expression of pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK-1) and lactate dehydrogenase A (LDHA). These results suggested that the modulation of the blood system was involved in the anti-depression effect of AS. The mechanism may be associated with the promotion of the body's energy metabolism, the stabilization of cell membranes, the promotion of serum protein synthesis, and the enhancement of immunity.

Licorice, an edible and officinal plant, has attracted considerable attention for its wide range of pharmacological activities. The present study focused on the protective effect of licorice on aging rats and on exploring its potential mechanisms. Aging in rats was induced by D-gal (300 mg kg−1) for 5 weeks continuously with intraperitoneal injection, while control rats received physiological saline, and other groups received different concentrations of licorice extract (1, 5 and 10 g of herb per kg) by oral gavage after being D-gal induced. Their spatial and learning memory abilities were evaluated by the Morris water maze test and an object-place recognition test. Some related biochemical indices were also determined by assay kits. Neuronal cell injury in the hippocampal region was observed by hematoxylin and eosin (HE) staining. The expression levels of Bax, Bcl-2, caspase-3 and Cyt-C in the hippocampus were detected by western blot. The results showed that licorice extract could significantly ameliorate the learning and memory abilities impaired by D-gal. The licorice extract significantly increased the SOD, GSH-Px and CAT activity and synchronously decreased the content of MDA in the hippocampus. It also ameliorated the dysfunction of the cholinergic system induced by D-gal. Furthermore, the licorice extract also protected the hippocampal neurons against damage and could significantly reduce the expression of the Bax/Bcl-2 protein ratio, caspase-3 and Cyt-C protein in the hippocampus. These findings indicate that the licorice extract effectively attenuated cognitive damage, improved oxidative stress and apoptosis in aging rats induced by D-gal, and played a significant role in antioxidation and anti-neuronal apoptosis.

Xiaoyaosan, one of the best-known traditional Chinese medicine prescriptions, has been widely used in China for the treatment of mental disorders such as depression. Although both clinical application and animal experiments indicate that Xiaoyaosan has an obvious antidepressant effect, the mechanism still remains unclarified, and there are few studies quantitatively measured the biomarkers of Xiaoyaosan treatment by metabolomics to determination. In this study, 25 depressed patients and 33 healthy volunteers were recruited. A GC-MS based metabolomics approach and the multivariate statistical methods were used for analyzing the urine metabolites of depressed patients before and after treatment compared with healthy controls. Then the biomakers through metabolomics determination were carried out the quantitative analysis. In total, 5 metabolites were identified as the potential diseased and therapeutic biomarkers of depression and Xiaoyaosan. Alanine, citrate and hippurate levels were significantly increased in the urine samples from depressed patients compared with healthy controls, while phenylalanie and tyrosine levels were significantly decreased. However, after Xiaoyaosan treatment for 6 weeks, phenylalanie and tyrosine levels were significantly increased (p

Liquiritin, a flavone derived from the medicine food homology plant liquorice, possesses neuroprotective. However, the neuroprotective mechanism is not clear. In this study, metabolomics based LC-MS was performed to discover the metabolite changes in PC12 cells treated with corticosterone-induced neurotoxicity after liquiritin treatment. A total of 30 metabolites were identified as differential metabolites. Among them, 11 metabolites were regulated by liquiritin, and involved in the D-glutamine and D-glutamate metabolism, and glutathione metabolism, etc. Based on the results of metabolomics, three cell signaling pathways related to these metabolic pathways were verified. The results showed that the ERK1/2-NF-κB pathway related to the D-glutamine and D-glutamate metabolism was attenuated by liquiritin via down-regulation phospho-ERK1/2, phospho-IκBα, phospho–NF–κB protein expression levels. Furthermore, the Nrf2-Keap1 pathway related to glutathione metabolism was activated by liquiritin via up-regulation Nrf2, Keap1, HO-1, NQO1 protein expression levels, and increased SOD, CAT, GSH-PX enzyme activity, thus exerting antioxidant activity. Additionally, liquiritin inhibited the mitochondrial apoptosis by decreasing the Ca2+ concentration, improving MMP, up-regulating Bcl-2, and down-regulating Bax, cytochrome C, cleaved-Caspase-3 expression levels. These results suggest that the neuroprotective mechanisms of liquiritin are connected to the regulation of metabolic disorders, activation Nrf2/Keap1 pathway, attenuation ERK1/2/NF-κB pathway, and inhibition mitochondrial apoptosis pathway.

In this study, powdery aerobic activated sludge (PAAS) was first prepared, and the removal rate, sorption capacity and mechanism of sorption uranium on PAAS was investigated. Before and after sorption, the surface morphology and structure of PAAS were characterized systematically using the Fourier transform infrared spectrometer (FTIR), the X-ray photoelectron spectrometer (XPS), and the scanning electron microscope (SEM-EDX). In this work, the sorption mechanism and efficiency of uranium on the PAAS was study with static batch and ion exchange experiments, meanwhile, some influencing factors such as solution pH, contact temperature, adsorbent dose of PAAS and different initial uranium concentrations were studied. The batch sorption experiments illustrated that pH had a little effect in the process of sorption uranium on PAAS and it has a good removal capacity in a wide pH range (pH = 3–8). When the pH of solution was 7, the removal efficiency of about 93% for uranium when the initial concentration of uranium was 10 mg/L and the concentration of PAAS was 1 g/L. The XPS demonstrated that there are some active functional groups for instance carboxyl (-COOH), Hydroxyl (-OH), Amino (-NH2) and so on in the PAAS, and that all can combine with uranium. After sorption, there is an obviously U signal (marked in green) in the PAAS by charactering with the FE-SEM. In addition, kinetic parameters were fitted by the first-order kinetic (R2 = 0.9738) model and the second-order kinetic model (R2 = 0.9998), the pseudo-secondary kinetic model was better to illustrate the sorption process, so the chemical action was dominant, and existed physical sorption. The sorption isotherms date of PAAS was well-fitted to the Langmuir model (R2 = 0.9688). In the experiment of ion exchange, the concentration of Na+ in the solution hardly changed, the release of the other three ions was K+

Aims This study aimed to explore the protective effects and possible mechanisms of baicalein on Aβ25–35-induced toxicity. Main methods Thioflavin-T (Th-T) dye was used to determine the effects of baicalein on Aβ25–35 aggregation in vitro. PC12 cells were stimulated with Aβ25–35, then the effects of baicalein on apoptosis, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), mitochondrial respiratory complex I, reactive oxygen species (ROS) and nitric oxide (NO) levels were determined. Moreover, LC-MS metabolomics approach was used to detect metabolic changes induced by baicalein in Aβ25–35-injured PC12 cells. Key findings The results showed that baicalein could inhibit the aggregation of Aβ25–35 in vitro. Furthermore, pretreatment with baicalein significantly prevented Aβ25–35-induced cell apoptosis, as manifested by increasing the levels of MMP, ATP and mitochondrial respiratory complex I, decreasing the contents of ROS and NO. LC-MS metabolomics revealed that baicalein can regulate 5 metabolites, mainly involving two metabolic pathways, arginine and proline metabolism, nicotinate and nicotinamide metabolism. Significance Our study revealed that baicalein has a protective effect on Aβ25–35-induced neurotoxicity in PC12 cells, which may be related to inhibition of apoptosis and metabolic disorders.

The pursuit of longevity has been the goal of humanity since ancient times. Genetic alterations have been demonstrated to affect lifespan. As increasing numbers of pro-longevity genes and anti-longevity genes have been discovered in Drosophila, screening for functionally important genes among the large number of genes has become difficult. The aim of the present study was to explore critical genes and pathways affecting longevity in Drosophila melanogaster. In this study, 168 genes associated with longevity in D. melanogaster were collected from the Human Ageing Genomic Resources (HAGR) database. Network clustering analysis, network topological analysis, and pathway analysis were integrated to identify key genes and pathways. Quantitative real-time PCR (qRT-PCR) was applied to verify the expression of genes in representative pathways and of predicted genes derived from the gene-gene sub-network. Our results revealed that six key pathways might be associated with longevity, including the longevity-regulating pathway, the peroxisome pathway, the mTOR-signalling pathway, the FOXO-signalling pathway, the AGE-RAGE-signalling pathway in diabetic complications, and the TGF-beta-signalling pathway. Moreover, the results revealed that six key genes in representative pathways, including Cat, Ry, S6k, Sod, Tor, and Tsc1, and the predicted genes Jra, Kay, and Rheb exhibited significant expression changes in ageing D. melanogaster strain w1118 compared to young ones. Overall, our results revealed that six pathways and six key genes might play pivotal roles in regulating longevity, and three interacting genes might be implicated in longevity. The results will not only provide new insight into the mechanisms of longevity, but also provide novel ideas for network-based approaches for longevity-related research.

Xiaoyao powder (XYP) is a valuable traditional Chinese Medicine (TCM) prescription developed for depression. Previous findings have suggested that the low polar extract of XYP (XYP-A) was more effect than other parts and its main ingredients included ligustilide, (2Z,8Z,10E)-pentadecatriene-4,6-diyn-1-ol (RB-1), (2Z,8E,10E)-pentadecatriene-4,6-diyn-1-ol (RB-2), (2Z,8Z,10E)-heptadecatriene-4,6-diyn-1-ol (RB-3), and bupleurynol (RB-4). However, the correlation between concentration of main ingredients and effects is still indeterminate. This study developed an ultra performance lipid chromatography combined with photo-diode array detector (UPLC-PDA) method to determine the contents of main ingredients in serum and tissues for pharmacokinetics and tissue distribution analysis. And, norepinephrine (NE) and 5-hydroxytryptamine (5-HT) were selected as the pharmacodynamic index and determined using the method of high performance lipid chromatography combined with fluorescence detector (HPLC-FD) in the serum for pharmacodynamics analysis. The DAS3.0 software was used to fit the pharmacokinetics-pharmacodynamics (PK-PD) model. The pharmacokinetic assay revealed that the absorption of polyacetylene compound was more favorable under pathological status. And, the result of tissue distribution showed that RB-2 and RB-4 were rapidly and widely distributed in tissues, and easy to cross the blood-brain barrier. The comparison of the value of NE and 5-HT in chronic unpredictable mild stress (CUMS) and control group rats suggested that 5-HT might be the main targets for the four polyacetylene compounds. The present study demonstrated that XYP-A showed the certain therapeutic effect of for depression safely and that polyacetylene compounds might be active ingredient for depression.

Ethnopharmacological relevance In traditional Chinese medicine (TCM) theory, depression is considered to be “liver qi stagnation”, and relieving “liver qi stagnation” is regarded as an effective method for treating depression. Xiaoyao San (XYS) is a well-known TCM formula for the treatment of depression by relieving “liver qi stagnation”. This formula consists of Radix Paeoniae Alba (Paeonia lactiflora Pall.), Radix Bupleuri (Bupleurum chinense DC.), Poria (Poria cocos (Schw.) Wolf), Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Rhizoma Zingiberis Recens (Zingiber officinale Roscoe) and Herba Menthae Haplocalycis (Mentha haplocalyx Briq.). Aim of the study Several studies have suggested that depression is associated with liver injury. XYS was a well-known TCM formula for the treatment of depression and liver stagnancy. However, it was still unknown whether the antidepressant effect of XYS is related to the pharmacological activity of hepatoprotection. The aim of this study was to elucidate the potential link between the antidepressant and hepatoprotective effect of XYS. Materials and methods A depression rat model was established by the CUMS (chronic unpredictable mild stress) procedure. The antidepressant effect of XYS was assessed by the behavioral indicators, and the hepatoprotective effect of XYS was evaluated through biochemical assays. 1H-NMR and LC/MS-based liver metabolomics were performed to discover key metabolic pathways involved in the antidepressant and hepatoprotective effects of XYS. Further, the key pathway was validated using commercial kits. Results The results demonstrated that XYS pretreatment could significantly improve the depressive symptom induced by CUMS. More importantly, the results demonstrated that liver injury was observed in the CUMS model rats, and XYS had a hepatoprotective effect by reducing the activities of AST and ALT in serum, increasing the levels of SOD and GSH-Px and reducing the contents of MDA, IL-6, and IL-1β in the liver. In addition, the NMR and LC/MS-based metabolomics results indicated that XYS improved 23 of the 35 perturbed potential liver biomarkers that were induced by CUMS. Among them, 9 biomarkers were significantly correlated with both depression and liver pathology, according to Pearson correlation analysis. Metabolic pathway analyses of these 9 biomarkers showed that glutamine and glutamate metabolism were the most important metabolic pathways. Furthermore, to verify glutamine and glutamate metabolism, the levels of glutamine and glutamate, and the activity of glutamine synthetase (GS) and glutaminase (GLS) were quantitatively determined in the liver by commercial kits, and these results were consistent with the metabolomics results. Conclusions XYS could significantly improve the depressive and liver injury symptoms induced by CUMS. The metabolomics results indicate that the regulation of glutamine and glutamate metabolism to maintain the balance of ammonia and promote energy metabolism is a potential junction between the antidepressant and hepatoprotective effects of XYS.

Atractylenolide III (ATL-III), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuroprotective effect. This study aimed to evaluate the cytoprotective efficiency and potential mechanisms of ATL-III on corticosterone injured rat phaeochromocytoma (PC12) cells. Our results demonstrate that ATL-III increases cell viability and reduces the release of lactate dehydrogenase (LDH). The results suggest that ATL-III protects PC12 cells from corticosterone-induced injury by inhibiting the intracellular Ca2+ overloading, inhibiting the mitochondrial apoptotic pathway and modulating the MAPK/NF-ΚB inflammatory pathways. These findings provide a novel insight into the molecular mechanism by which ATL-III protected the PC12 cells against corticosterone-induced injury for the first time. Our results provide the evidence that ATL-III may serve as a therapeutic agent in the treatment of depression.

Extracellular polymeric substances (EPS) of uranium adsorbent was first extracted from the aerobic activated sludge of municipal wastewater treatment plant as raw material. The structure and surface morphology of EPS was characterized by FTIR, SEM-EDX, 3D-EEM, and XPS. The 3D-EEM spectra of EPS revealed that there are Tryptophan-like protein and Humus which can adsorb uranium in the EPS. The results of XPS indicated that the EPS surface contained active functional groups (COOH,CONH2,-H2PO4,OH,NH2 and so on) which all react with uranium, and the C, N, O elements play an important role in the reaction. The static batch test was used to study the adsorption behavior of uranium on the EPS, and the effects of pH, dosage of EPS and initial concentration of the solution on the removal of uranium by EPS were investigated. The adsorption isotherm, thermodynamics and kinetic models were used to match the mechanism of the interaction between EPS and uranium. Batch adsorption experiments revealed that the pH value had a great influence on the adsorption effect of EPS, and the optimal solution pH for uranium adsorption was around 6.0 with the removal efficiency of uranium was about 93% in the condition of neutral. Freundlich (R2 ≈ 0.997) and Langmuir (R2 ≈ 0.9931) models can get a good fitting effect, indicating that the adsorption of uranium by EPS had both monolayer adsorption and multilayer adsorption. EPS and uranium were combined disorderly and ion exchange mechanism could be involved. In this study, the active groups on the surface of EPS were also involved in the chemisorption process of uranium adsorption. The maximum adsorption capacity of EPS by Langmuir fitting was 333.3 mg/g. We conclude EPS is a potential adsorbent for radionuclide treatment.

D-galactose (D-gal)-induced aging model is widely used in the study of the pharmacodynamics of antiaging drugs. The model has a shorter life-span, disorders in learning and memory, reduced immune function and other aging characteristics. Regular and quantitative injection of D-gal solution to rats can produce symptoms of natural aging models that are used in screening of antiaging drugs, and their pharmacological activities. This paper provides a summary of the mechanism of rat model induced with D-gal solution. The methods of building and evaluation of the aging models are provided. The theoretical basis is included to facilitate the subsequent research and experiment in the mechanism study of aging and antiaging medicines.

In order to explore the anti-aging effect of baicalein, female Drosophila melanogaster as a model organism was used to study the effects of baicalein on natural aging model and aging models induced by hydrogen peroxide（H2O2） and paraquat. The bioinformatics approach was used to predict the possible target for the anti-aging activity of baicalein, and the target pathways were identified. The oxidative stress pathway was a focus in experiment. Baicalein at concentrations of 0.04 mg·m L-1 and 0.2 mg·m L-1 extended the mean and maximum lifespans in the natural aging model, and effectively reduced the damages of oxidative stress by H2O2 and paraquat. 31 senescence-related targets together with the oxidative stress pathway were modulated by baicalein. The experiments revealed that baicalein might delay aging process through attenuation of the oxidative stress response by decreasing the reactive oxygen species（ROS）, malondialdehyde（MDA） and oxidized glutathione（GSSG） in Drosophila melanogaster.

Background: Aging is a complex process accompanied with the decline of the different physiological functions. Numerous differentially expressed genes (DEGs) have been found in the aging brain of senescence-accelerated mouse P8 (SAMP8), however, it was challenging to screen out the crucial ones. Objective: This study aimed to explore the crucial genes and pathways in aging brain of SAMP8 mice, which would be beneficial for understanding the pathogenesis of brain aging. Methods: Firstly, 430 genes that are differentially expressed in SAMP8 mice versus SAMR1 mice were obtained from 9 gene expression studies, and gene-gene network was constructed. Clustering analysis and topological analysis were used to single out the hub genes from this network. Secondly, pathway enrichment analysis was utilized to identify the key pathways from the 430 DEGs, and the DEGs in key pathways were considered as functional genes. Thirdly, the inner-network between hub genes and functional genes was constructed, and the key genes were predicted. Parts of the key genes were experimentally verified by quantitative real-time PCR (qRT-PCR), and the associated transcription factors (TFs) were predicted. Results: Our results revealed that 12 crucial genes might affect brain aging, including Trp53, Bcl2, Tnf, Casp9, Fos, Il6, Ptgs2, Il1b, Bdnf, Cdkn1a, Pik3c3, Rps6ka1, among which Casp9, Fos, Ptgs2, Cdkn1a, Pik3c3, and Rps6ka1 had been verified by qRT-PCR in 10-moth-old SAMP8 mice. Five functional groups including mitogen-activated protein kinase (MAPK) signaling pathway, neurotrophin signaling pathway, Hepatitis B, Alzheimer's disease and Oxytocin signaling pathway were significantly changed during aging process in SAMP8 mice. Two key transcription factors of c-Fos and C/EBPbeta were predicted by constructing a TF-target gene network. Conclusion: These putative genes and pathways are closely related to brain senescence and our results would gain new insight into the pathogenesis of brain aging.

There are three types of differentiated (un-, poorly- and well-differentiated) PC12 cells, which have been widely used as a model system for depression studies after the administration of corticosterone (CORT). In order to investigate the underlying metabolic profiles of CORT-induced PC12 cells and evaluate the suitable differentiated types of PC12 cells for use in depressive studies, proton nuclear magnetic resonance (1H NMR) metabolomics coupled with network analysis approaches were employed. The results showed that CORT induced metabolic alterations in PC12 cells. There were 8 and 13 common differential metabolites in intracellular and extracellular extracts, respectively, of the three types of differentiated PC12 cells in response to CORT treatment, and the perturbed metabolic pathways were involved in amino acid metabolism, glutathione metabolism, pyruvate metabolism and inositol phosphate metabolism. Eighteen protein targets of depression were identified from the five different metabolic pathways from metabolomics and network analysis among the three types of CORT-induced differentiated PC12 cells, and these proteins were all found in the pathways that were perturbed by CORT treatment of poorly-differentiated PC12 cells. These results may indicate that the metabolism of CORT-induced PC12 cells is similar to the pathogenesis of depression, and poorly-differentiated PC12 cells are the most suitable cells for depressive research among the distinct types of differentiated PC12 cells. Thus, an effective predicative strategy to evaluate the in vitro disease models could be referenced.

Depression is one of the prevalent and persistent psychiatric illnesses. It brings heavy socioeconomic burden such as healthcare expenditures and even higher suicide rates. Despite many hypotheses about its mechanism have been put forward, so far it is still unclear, not to mention the precise and effective diagnostic or therapeutic methods. In this paper, the current conditions of pathological and pharmacological mechanism of depression were reviewed systematically. Firstly, the most recent hypotheses and metabolomics based research including hereditary, neurotransmitter systems, brain derived neurotrophic factor (BDNF), hyperactivity of the hypothalamic pituitary adrenal (HPA) axis and inflammatory as well as metabolomics were summarized. Secondly, the present situation and development on antidepressant drugs at home and abroad were reviewed. Finally, a conclusion and prospect on the pathological and pharmacological mechanism of depression were provided primarily.

Scutellaria baicalensis Georgi (SBG), a traditional Chinese herb, has attracted considerable attention for its wide range of pharmacological activities. This study aimed to investigate the intervention effects of SBG ethanol extract on aging rats induced by D-galactose (D-gal) and to explore potential mechanisms by serum and liver metabolic profiles. The aging rats were induced by the D-gal (100 mg/kg) for 10 weeks continuously with subcutaneous injection, while the control rats received physiological saline. Two other groups of rats were administered with 100 mg/kg/day and 200 mg/kg/day of SBG by oral route following D-gal injections. The abilities of spatial and learning memory were evaluated by open-field test and Morris water maze test. Then, some biochemical indexes related to cognitive ability and aging were measured. Histopathological feature in hippocampal region was observed by Hematoxylin and eosin (HE) staining. The changes of metabolic profiles were evaluated using proton nuclear magnetic resonance (1H NMR) spectroscopy coupled with multivariate data analysis. Results showed that SBG could significantly improve the learning and memory functions, reducing oxidative damage and histological abnormalities of hippocampus neurons. In addition, significant differences in the metabolic profiles were observed both in serum and liver between the model group and the control group. After the treatment using SBG, the levels of these metabolites are significantly changed back to their similar levels in the control group. These metabolic changes are related to the disturbance in amino acid metabolism, glycometabolism and choline metabolism. Hence, SBG may have the potential to improve neurodegeneration and provide brain protection.

Baicalein is a flavonoid isolated from the roots of Scutellaria baicalensis Georgi. This study aimed to ascertain the effects and potential underlying mechanisms of baicalein in d-galactose (d-gal)-induced aging rat model by integration of behavior examination, biochemical detection, and 1H nuclear magnetic resonance (NMR)-based metabolomic approach. Our findings suggest that baicalein significantly attenuated memory decline in d-gal-induced aging model, as manifested by increasing recognition index in novel object recognition test, shortening latency time, and increasing platform crossings in Morris water maze test. Baicalein significantly inhibited the releases of inflammatory mediators such as nitric oxide, interleukin-6, interleukin-1 beta, and tumor necrosis factor-α in d-gal-induced aging model. Metabolomic study revealed that 10 endogenous metabolites in cerebral cortex were considered as potential biomarkers of baicalein for its protective effect. Further metabolic pathway analysis showed that the metabolic alterations were associated with alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism, inositol phosphate metabolism, and energy metabolism. These data indicate that baicalein improves learning and memory dysfunction in d-gal-induced aging rats. This might be achieved through attenuation of inflammation and metabolic dysfunction.

Isoliquiritin, a flavonoid glycoside compound from licorice, possesses a broad spectrum of pharmacological activities including antioxidant, anti-inflammatory and anti-depression activities. However, the neuroprotective mechanisms of antidepressant effects remain unclear. In this study, the aim was to investigate the cytoprotective efficiency and potential mechanisms of isoliquiritin in corticosterone-damaged PC12 cells. The results of this study showed that pretreatment of PC12 cells with isoliquiritin significantly prevented corticosterone-induced cell apoptosis. In addition, isoliquiritin increased the activity of dismutase (SOD) and catalase (CAT), decreased the contents of reactive oxygen species (ROS) and malondialdehyde (MDA). These findings suggest that isoliquiritin provides protective action against corticosterone-induced cell damage by reducing oxidative stress. Furthermore, pretreatment with isoliquiritin reduced corticosterone-induced mitochondrial dysfunction by preventing mitochondrial membrane potential dissipation. Our findings indicate that isoliquiritin might exert its therapeutic effects via regulating mitochondrial dysfunction. Moreover, isoliquiritin strongly attenuated intracellular calcium ([Ca2+]i) overload and down-regulation of Bax, caspase-3 and cytochrome C (Cyt-C) protein expression, and up-regulation of Bcl protein expression. In conclusion, isoliquiritin has a cytoprotective effect on corticosterone-induced neurotoxicity in PC12 cells, which may be related to its antioxidant action, inhibition of [Ca2+]i overload and inhibition of the mitochondrial apoptotic pathway.

To establish quantitative methods for determination of polyacetylenes in Bupleuri Radix, an ultra-performance liquid chromatography method coupled with photodiode array detector (UPLC-PDA) was developed. The analysis was performed on a Waters BEH C₁₈ column (2.1 mm×100 mm, 1.7 μm) using a gradient system of methanol and water. The flow rate was 0.3 mL•min⁻¹ and the detection wavelength was 315 nm. Eight polyacetylenes were prepared using traditional extraction and isolation method, of which compounds 7 and 8 were two new polyacetylenes. All calibration curves showed good linearity (r0.999 0) within the concentration range. Both the intra- and inter-day precisions for eight analytes were less than 1.9%, respectively, with the mean recovery at the range of 93.21%-108.4%. Meanwhile, 17 bupleurum samples were examined with this process. The results showed a variety either the chemotaxonomic or content of polyacetylenes. The method indicated good linearity, limit of detection and quantification, precision, accuracy and recovery. The developed method allows quantitative assessment and quality control of polyacetylenes, and might be a good alternative according to detection levels in polyacetylenes from Bupleurum Radix.

The present study aims to predict the action targets of antidepressant active ingredients of Xiaoyaosan to understand the "multi-components, multi-targets and multi-pathways" mechanism. Using network pharmacology, the reported antidepressant active ingredients in Xiaoyaosan (saikosaponin A, saikosaponin C, saikosaponin D, ferulic acid, Z-ligustilide, atractylenolide I, atractylenolide II, atractylenolide III, paeoniflorin, albiflorin, liquiritin, glycyrrhizic acid and pachymic acid), were used to predict the targets of main active ingredients of Xiaoyaosan according to reversed pharmacophore matching method. The prediction was made via screening of the antidepressive drug targets approved by FDA in the DrugBank database and annotating the information of targets with the aid of MAS 3.0 biological molecular function software. The Cytoscape software was used to construct the Xiaoyaosan ingredients-targets-pathways network. The network analysis indicates that the active ingredients in Xiaoyaosan involve 25 targets in the energy metabolism-immune-signal transmutation relevant biological processes. The antidepressant effect of Xiaoyaosan reflects the features of traditional Chinese medicine in multi-components, multi-targets and multi-pathways. This research provides a scientific basis for elucidation of the antidepressant pharmacological mechanism of Xiaoyaosan.

Seven phthalides, including a new dimeric one named tokinolide C (7), were isolated from Angelicae Sinensis Radix and characterized. The structures of these compounds were elucidated on the basis of comprehensive analysis of spectroscopic data and comparison with literature data. All of the compounds were evaluated for their cytotoxic activities against the A549, HCT-8, and HepG2 cancer cell lines. Riligustilide (4) showed cytotoxicity against three cancer cell lines, with IC50 values of 13.82, 6.79, and 7.92 μM, respectively. Tokinolide A (6) and tokinolide C (6) exerted low cytotoxicity in these cancer cell lines, while the remaining compounds were inactive. Flow cytometry analysis was employed to evaluate the possible mechanism of cytotoxic action of riligustilide (4). We observed that compound 4 was able to arrest the cell cycle in the G1, S phases and induce apoptosis in a time-dependent manner in HCT-8 cell lines. In addition, these compounds were evaluated for neuroprotective effect against SH-SY5Y cells injured by glutamate. The result showed that ligustilide (1), Z-butylidenephthalide (3) and tokinolide A (6) exhibited significant neuroprotective effects.

To elucidate the anti-depressive effect of Fufang Chaigui prescription and its mechanism and investigate its effect on neuroendocrine hormone, rats were included into a chronic unpredictable mild stress (CUMS) model for 28 d, and drugs were administered at the same time. During the period, rats' behaviors were observed and the blood was collected by using ELISA to determine representative hormone concentrations of HPAA, HPTA and HPGA. The changes in endogenous metabolites were analyzed by using H NMR metabolomics to seek the potential biomarkers. Results showed Fufang Chaigui prescription could improve the behaviors of CUMS rats obviously, increase contents of ACTH, CORT, T₃and decrease contents of TSH and TESTO and regulate the levels of lactate, α-glucose, choline, N-acetylglycoprotein, trimethylamine oxide and leucine to get closer to the contents of control group. The results of correlation analysis indicated that HPTA was associated with glycometabolism, amino acid metabolism and choline metabolism. And HPAA was related to glycometabolism and amino acid metabolism. However, HPGA was only correlated with glycometabolism. In conclusion, Fufang Chaigui prescription could show an obvious anti-depressive effect and its underlying mechanism might involve regulations of neuroendocrine function and pathways of glycometabolism, amino acid metabolism and choline metabolism.

A rapid, highly sensitive, and selective method was applied in a non-invasive way to investigate the antidepressant action of Xiaoyaosan (XYS) using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) and chemometrics. Many significantly altered metabolites were used to explain the mechanism. Venlafaxine HCl and fluoxetine HCl were used as chemical positive control drugs with a relatively clear mechanism of action to evaluate the efficiency and to predict the mechanism of action of XYS. Urine obtained from rats subjected to chronic unpredictable mild stress (CUMS) was analyzed by UPLC-MS. Distinct changes in the pattern of metabolites in the rat urine after CUMS production and drug intervention were observed using partial least squares-discriminant analysis. The results of behavioral tests and multivariate analysis showed that CUMS was successfully reproduced, and a moderate-dose XYS produced significant therapeutic effects in the rodent model, equivalent to those of the positive control drugs, venlafaxine HCl and fluoxetine HCl. Metabolites with significant changes induced by CUMS were identified, and 17 biomarker candidates for stress and drug intervention were identified. The therapeutic effect of XYS on depression may involve regulation of the dysfunctions of energy metabolism, amino acid metabolism, and gut microflora changes. Metabonomic methods are valuable tools for measuring efficacy and mechanisms of action in the study of traditional Chinese medicines.

Depression is a prevalent complex psychiatric disorder and its pathophysiological mechanism is not yet well understood. In this study, we investigated the metabolic profiling of urine samples from chronic unpredictable mild stress (CUMS) rats to find potential disease biomarkers and research pathology of depression. Metabolome in urine was analyzed using gas chromatography/mass spectrometry (GC/MS) in conjunction with multivariate statistical techniques. The urine samples of male Sprague–Dawley rats were collected at different time points and then were derivatized by methoximation/silylation. Clear separation between the model and control group was achieved, and 15 metabolites were identified, which suggested that the depressed state may be related to neurotransmitter, energy metabolism and immunity. The time-dependent trajectory of metabolites pattern revealed that the maximum biochemical change happened on the 21st day, which was consistent with the results of behavior tests. The study suggested that the metabonomic approach could be used as a potentially powerful tool to investigate the biochemical change in certain physiopathological conditions, such as depression, as an early diagnostic means.

Objectives To investigate the antidepressant effects of Xiaoyaosan (XYS) in a chronic unpredictable mild stress (CUMS) depression model. Methods The changes in behaviour and plasma metabolic profiles were investigated after four-week CUMS exposure and treatment. Drugs were administered during the four-week period of CUMS, with the healthy group serving as negative controls, and the fluoxetine and venlafaxine groups serving as positive controls. Plasma samples were collected at 28th day, and the plasma metabolic profiling was measured using NMR, followed by multivariate analysis. Key findings Exposure to CUMS for four weeks caused depression-like behaviour in rats, as indicated by significant decreases in weight gain, sucrose consumption and locomotor activity. Eleven potential biomarkers, including seven in the Carr–Purcell–Meiboom–Gill spectra, five in the diffusion-edited spectra, and one in both were identified. It was found that trimethylamine-N-oxide, alanine, β-hydroxybutyrate, valine, leucine/isoleucine, low-density lipoprotein/very low-density lipoprotein and lipids were lower and phosphatidylcholine, high-density lipoprotein, choline and N-acetyl glycoproteins were higher in CUMS-treated rats, as compared with controls. XYS significantly suppressed behavioural changes and attenuated plasma metabolite changes. Conclusions XYS produced an obvious antidepressant effect, and the metabonomic approach benefits estimation of the pharmacodynamic action of traditional Chinese medicine prescriptions.

Ethnopharmacological relevance Xiaoyaosan (XYS), composed of Radix Bupleuri , Radix Angelicae Sinensis , Radix Paeoniae Alba , Rhizoma Atractylodis Macrocephalae , Poria , Herba Menthae , Rhizoma Zingiberis Recens and Radix Glycyrrhizae , is a valuable traditional Chinese medicine (TCM) which is used for the treatment of depression in China. In the formula, Radix Bupleuri usually serves as the principal drug, Radix Angelicae Sinensis and Radix Paeoniae Alba serve as the ministerial drugs, Rhizoma Atractylodis Macrocephalae , Poria , Herba Menthae and Rhizoma Zingiberis Recens serve as adjunctive drugs, Radix Glycyrrhizae serves as messenger drug, they coordinate with each other and enhance the effect of the formula. In our previous experiments, the antidepressant effect of XYS was revealed. However, the antidepressant part (or component) of this prescription was still obscure. We divided the XYS into five different polar fractions, and explored the antidepressant activity of five different polar fractions to identify the active fraction. Materials and methods Behavior research and metabonomics method based on 1 H NMR were used for efficacy study of different fractions in chronic unpredictable mild stress (CUMS) model of depression. Rats were divided into 8 groups and drugs were administered during the 21 days model building period. The urine samples of rats were collected overnight (12 h) on 21 day and the metabolic profiling of the urine was measured using NMR. Multivariate analysis was also utilized to evaluate the active fraction of XYS. Results In the behavior research, there were significant difference between the lipophilic fraction group (XY-A) and the model group. In addition, with pattern recognition analysis of urinary metabolites, the results showed a clear separation of the model group and control group, while XY-A group was much closer to the control group in the OSC-PLS score plot. Seven endogenous metabolites contributing to the separation of the model group and control group were detected, while XY-A group regulated the 5 perturbed metabolites showing a tendency of recovering to control group. Conclusions The present work suggested that petroleum ether fraction was the most effective fraction, implying that lipophilic components contribute to the antidepressant effect of XYS.

A metabolomic investigation of chronic unpredictable mild stress (CUMS) rats was carried out. Plasma obtained from Sprague-Dawley (SD) rats treated by CUMS was analyzed using gas chromatography/mass spectrometry. Thirty-seven metabolites were identified among the detected compounds. Subsequent data analysis using the t test and principal component analysis (PCA) revealed significant metabolic changes in the rats' plasma after CUMS treatment. Clear separation between the model and control group was achieved, and the level of twelve metabolites, including amino acids, sugar, organic acids and fatty acids, were significantly different between plasma samples from the controls and CUMS group. These observations suggested that the depressed state may be associated with perturbation of amino acid metabolism, energy metabolism and glycometabolism. The study suggested that the metabolomics approach could be used as a potential powerful tool to investigate the biochemical change in certain physiopathological conditions, such as depression, as an early diagnostic means.

Two new steroidal saponins and two known flavonoid glycosides were isolated from the fruits of Tribulus terrestris. Their structures were assigned by spectroscopic analysis and chemical reaction as 26-O-beta-D-glucopyranosyl-(25R)-5 alpha-furostan-12-one-3beta,22 alpha,26-triol-3-O-beta-D-glucopyranosyl (1 --2)-beta-D-glucopyranosyl(1 --4)-beta-D-galactopyranoside (1), 26-O-beta-D-glucopyranosyl-(25S)-5 alpha-furostan-22-methoxy-2 alpha,3beta,26-triol-3-O-beta-D-glucopyranosyl(1 --2)-beta-D-glucopyranosyl(1 --4)-beta-D-galactopyranoside (2), kaempferol-3-gentiobioside (3), and isorhamnetin-3-gentiobioside (4).

Five new aromatic glycosides, 1–5, named as carthamosides B4–B8, together with three known compounds, 4′-(hydroxyphenacyl)-β-D-glucopyranoside (6), benzyl-O-α-L-rhamnopyranosyl-(16)-β-D-glucopyranoside (7), and 4-(methoxybenzyl)-O-β-D-glucopyranoside (8), have been isolated from the air-dried flower of Carthamus tinctorius. Their structures were identified on the basis of chemical and spectroscopic methods.

Seven new steroidal glycosides (amplexicosides A (4), B (7), C (8), D (9), E (10), F (11), and G (12)), along with six known compounds (cynatratoside A (1), tylophoside A (2), cynatratoside B (3), glaucogenin A (5), glaucoside A (6), and hancoside A (13)) were isolated from the 95% ethanol extract of the roots of Cynanchum amplexicaule (Sieb. et Zucc.). Their structures were determined based on spectral and chemical evidence. Compound 12 has a 14, 15-secopregnane-type skeleton aglycone, which has not been reported in literature.

From the dried petals of Carthamus tinctorius, a new flavonoid, (2R)-4',5-dihydroxyl-6,7-di-O-beta-d-glucopyranosyl flavanone (1) and a new aromatic glucoside, methyl-3-(4-O-beta-d-glucopyranosylphenyl) propionate (4) were isolated along with four known compounds (2S)-4',5-dihydroxyl-6,7-di-O-beta-d-glucopyranosyl flavanone (2), 6-hydroxykaempferol-3,6-di-O-beta-d-glucopyranoside (3), 4-O-beta-d-glucosyl-trans-p-coumaric acid (5), and 4-O-beta-d-glucosyl-cis-p-coumaric acid (6). Their structures were identified on the basis of chemical and spectroscopic methods.

A theoretical study on the decarboxylation reaction of CH3CO2 radical at the MP2 level of theory has been carried out. It is found that the thermal reaction CH3CO2 → CH3 + CO2 may occur on the 2A′(A′) potential energy surface of CH3CO2 via a reaction barrier of 4.2 kcal/mol at the PMP4/6-311+G(3df,3pd)//MP2/6-311+G(2df,2p) level of theory. Another possible reaction path is the CH3CO2(A′) transform into the CH3CO2(A1) and thus undergo a barrier-less dissociation into the products CH3 + CO2. The thermal rate constants of channel CH3CO2(A′) → CH3 + CO2.were evaluated based on the electronic structure and energy information from the PMP4/6-311+G(3df,3pd)//MP2/6-311+G(2df,2p) level of theory with microcanonical variational transition state theory (μVT) in the temperature range of 200–3000 K. The fitted Arrhenius expression from the forward μVT rate constants within the calculated temperature range is K μ VT = 2.196 × 10 11 T 0.294 e ( - 2.304 × 10 3 / T ) s - 1 . It is also found that the geometry of the CH3CO2 radical is sensitive to the basis set used.

A new phenolic glycoside, sinapic acid 4-O-beta-d-(6'-sinapoyl)glucopyranoside (1) and a new sucrose ester, 6,6'-di-O-sinapoylsurcose (3), were isolated from the roots of Cynanchum amplexicaule (Sieb. et Zucc.), along with two known compounds, 6-O-[E]-sinapoyl-d-glucopyranoside (2) and sibricose A1 (4). Their structures were elucidated on the basis of both chemical and spectroscopic methods.

A new bufadienolide named 16beta-acetoxy-bufarenogin (1), together with six known bufadienolides, namely, 11alpha,12beta-dihydroxy-bufalin (2), bufotalin (3), hellebrigenin (4), desacetylbufotalin (5), gamabufotalin (6), and resibufagin (7) were isolated from Chan'Su. Of these, 2 was a new natural product. Their structures were elucidated by spectral methods. The cytotoxic activities in vitro of these compounds have been assayed against HeLa cell line. They all showed strong cytotoxic activities.