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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.

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.

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+

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.

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.

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.

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.

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.

Two new compounds, 6′-O-caffeoyl-p-hydroxyacetophenone-4-O-β-D-glucopyranoside(1) and 6-amino-9-[1-(3,4-dihydroxyphenyl)ethyl]-9H-purine (2) wereisolated from the aerial parts of Artemisia capillaris Thunb. The structures wereestablished on the basis of spectral data.

Two new acetylenic glucosides, 4',6'-acetonide-8Z-decaene-4,6-diyne-1-O-beta-D-glucopyranoside named carthamoside A(1) (1) and 4,6-decadiyne-1-O-beta-D-glucopyranoside named carthamoside A(2) (2), along with one known acetylenic glucoside, 8Z-decaene-4,6-diyne-1-O-beta-D-glucopyranoside (3), have been isolated from the air-dried flower of Carthamus tinctorius, these structures have been identified on the basis of spectroscopic methods.