Coal gangue-based magnetic porous material for simultaneous remediation of arsenic and cadmium in contaminated soils: Performance and mechanisms.

Remediation of arsenic (As) and cadmium (Cd) co-contaminated soil is a challenge in environmental remediation. In this study, coal gangue-based magnetic porous material (MPCG) was designed for simultaneous immobilization of As and Cd in contaminated soil. After the incubation experiment, the effects of CG and MPCG on the availability and fractions of As and Cd and the related microbial functional genes were analyzed to explore the potential remediation mechanisms of MPCG for As and Cd in contaminated soil. The results showed that the stabilization effect of MPCG on As and Cd was significantly higher than that of coal gangue. It reduced the available As and Cd by 17.94-29.81% and 14.22-30.41%, respectively, and transformed unstable As/Cd to stable. The remediation mechanisms of MPCG on As included adsorption, oxidation, complexation and precipitation/co-precipitation. Meanwhile, the remediation mechanisms of MPCG for Cd included adsorption, ion exchange, complexation and precipitation. In addition, MPCG increases the abundance of sulfate-reducing bacteria (dsrA) by 43.39-381.28%, which can promote sulfate reduction. The sulfide can precipitate with As and Cd to reduce the availability of As and Cd in soil. Thus, MPCG is a promising amendment for achieving the remediation of As and Cd co-contaminated soil.

Baicalein Attenuates Neuroinflammation in LPS-Treated BV-2 Cells by Inhibiting Glycolysis via STAT3/c-Myc Pathway.

More and more evidence shows that metabolic reprogramming is closely related to the occurrence of AD. The metabolic conversion of oxidative phosphorylation into glycolysis will aggravate microglia-mediated inflammation. It has been demonstrated that baicalein could inhibit neuroinflammation in LPS-treated BV-2 microglial cells, but whether the anti-neuroinflammatory mechanisms of baicalein were related to glycolysis is unclear. Our results depicted that baicalein significantly inhibited the levels of nitric oxide (NO), interleukin-6 (IL-6), prostaglandin 2 (PGE2) and tumor necrosis factor (TNF-α) in LPS-treated BV-2 cells. 1H-NMR metabolomics analysis showed that baicalein decreased the levels of lactic acid and pyruvate, and significantly regulated glycolytic pathway. Further study revealed that baicalein significantly inhibited the activities of glycolysis-related enzymes including hexokinase (HK), 6-phosphate kinase (6-PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and inhibited STAT3 phosphorylation and c-Myc expression. By using of STAT3 activator RO8191, we found that baicalein suppressed the increase of STAT3 phosphorylation and c-Myc expression triggered by RO8191, and inhibited the increased levels of 6-PFK, PK and LDH caused by RO8191. In conclusion, these results suggested that baicalein attenuated the neuroinflammation in LPS-treated BV-2 cells by inhibiting glycolysis through STAT3/c-Myc pathway.

Study on the targeted regulation of Scutellaria baicalensis leaf on glutamine-glutamate metabolism and glutathione synthesis in the liver of d-gal ageing rats.

OBJECTIVES: Scutellaria baicalensis leaf (SLE), the above-ground part of the traditional Chinese medicine Scutellaria baicalensis Georgi, is rich in resources and contains a large number of flavonoids with anti-inflammatory, antioxidant and neuroprotective functions. The present study evaluated the ameliorative effects and related mechanisms of SLE on d-gal-induced ageing rats, providing a theoretical basis for the exploitation of SLE. METHODS: This experiment investigated the mechanism of SLE for anti-ageing by non-targeted metabonomics technology combined with targeted quantitative analysis and molecular biology technology. KEY FINDINGS: Non-targeted metabonomics analysis showed that 39 different metabolites were screened out. Among them, 38 metabolites were regulated by SLE (0.4 g/kg), and 33 metabolites were regulated by SLE (0.8 g/kg). Through enrichment analysis, glutamine-glutamate metabolic pathway was identified as the key metabolic pathway. Subsequently, the results of targeted quantitative and biochemical analysis displayed that the contents of key metabolites and the activities of enzymes in glutamine-glutamate metabolic pathway and glutathione synthesis could be regulated by SLE. Furthermore, the results of Western blotting indicated that SLE significantly modulated the expression of Nrf2, GCLC, GCLM, HO-1, and NQO1 proteins. CONCLUSION: To sum up, the anti-ageing mechanism of SLE was related to glutamine-glutamate metabolism pathway and Nrf2 signalling pathway.

Integrating UHPLC-MS/MS quantitative analysis and exogenous purine supplementation to elucidate the antidepressant mechanism of Chaigui granules by regulating purine metabolism.

Chaigui granules (CG) are a compound composed of six herbal medicines with significant antidepressant effects. However, the antidepressant mechanism of CG remains unclear. In the present study, we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling. First, the regulatory effect of CG on purine metabolites in the prefrontal cortex (PFC) of chronic unpredictable mild stress (CUMS) rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) targeted quantitative analysis. Meanwhile, purinergic receptors (P2X7 receptor (P2X7R), A1 receptor (A1R) and A2A receptor (A2AR)) and signaling pathways (nod-like receptor protein 3 (NLRP3) inflammasome pathway and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway) associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay (ELISA). Besides, antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro. An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG. Additionally, purinergic receptors (P2X7R, A1R and A2AR) and related signaling pathways (NLRP3 inflammasome pathway and cAMP-PKA pathway) were also significantly regulated by CG. The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway, and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway, which was significantly ameliorated by CG. Overall, CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.

Synergistic neuroprotective effect of saikosaponin A and albiflorin on corticosterone-induced apoptosis in PC12 cells via regulation of metabolic disorders and neuroinflammation.

BACKGROUND: Saikosaponin A (SSA) and albiflorin (AF) are major bioactive compounds of Radix Bupleuri and Radix Paeoniae alba respectively, which possess antidepressant effects in pharmacological experiments. However, whether SSA and AF have synergistic neuroprotective effects and the synergistic mechanisms are still unknown. METHODS AND RESULTS: The corticosterone-induced PC12 cells apoptosis model was employed to assess the neuroprotective effects of SSA and AF, and the synergistic effect was analyzed using three mathematical models. Meanwhile, cell metabolomics was used to detect the effects on metabolite regulation of SSA and AF. Furthermore, the key metabolites, metabolic enzymes, and cellular markers were verified by ELISA and Western blotting. The results showed that the combination of SSA and AF has a synergistic neuroprotective effect. Besides, the combination could regulate more metabolites than a single agent and possessed a stronger adjustment effect on metabolites. The TCA cycle was regulated by SSA and AF via improving mitochondrial function. The purine metabolism was regulated by SSA via inhibition xanthine oxidase activity and the glutamate metabolism was regulated by AF via inhibition glutaminase activity. Moreover, the oxidative stress induced by the purine metabolism was attenuated by SSA via a reduction in the ROS level. Additionally, the inflammation induced by the oxidative stress was attenuated by the SSA and AF via inhibition of the NLRP3 protein expression. CONCLUSIONS: This study for the first time demonstrated the synergistic neuroprotective effects of SSA and AF, and the synergistic mechanisms were involved in metabolic disorders regulation and neuroinflammation inhibition.

Integration of Non-Targeted Metabolomics and Targeted Quantitative Analysis to Elucidate the Synergistic Antidepressant Effect of Bupleurum Chinense DC-Paeonia Lactiflora Pall Herb Pair by Regulating Purine Metabolism.

Bupleurum chinense DC (Chaihu)-Paeonia lactiflora Pall (Baishao) is among the most accepted herb pairs in many classic antidepressant prescriptions. Our previous study has shown that the Chaihu-Baishao herb pair (CBHP) had a better antidepressant effect than Chaihu or Baishao. Nevertheless, the synergistic antidepressant mechanism of this herb pair was not clearly understood. This study aimed to investigate the compatibility mechanism of Chaihu and Baishao for treating depression through a strategy of non-targeted metabolomics combined with targeted quantitative analysis and molecular biology techniques. First, the compatibility effects of CBHP were assessed by the chronic unpredictable mild stress (CUMS) rat model. Next, cortex metabolomics based on ultra-high-performance liquid chromatography combined with quadrupole orbitrap mass spectrometry (UPLC-Q-Orbitrap/MS) was used to discover the metabolic pathway that was synergistically regulated by CBHP. Based on the results of metabolomics analysis, metabolites were quantitatively validated by UPLC-MS/MS combined with the MRM mode in the crucial metabolic pathway. In addition, the signaling pathway associated with this metabolic pathway was detected by molecular biology techniques to further identify the biological meaning of the crucial metabolite on the synergistic antidepressant effect of CBHP. The antidepressant effect of CBHP was significantly better than that of Chaihu or Baishao single administrated in the behavioral test. According to cortex metabolomics, a total of 21 differential metabolites were screened out, and purine metabolism was selected as the crucial metabolic pathway by the enrichment analysis of differential metabolites. Subsequently, purine metabolism was confirmed as disorder in the CUMS group by targeted quantitative analysis, CBHP regulated more purine metabolites (six) than individual administration (two and two). The results showed that purine metabolism was modulated by CBHP through synergistically decreasing xanthine levels and inhibiting the conversion of xanthine dehydrogenase (XDH) to xanthine oxidase (XOD). Finally, the synergistic regulation effect of CBHP on xanthine synthesis was found to be related to inhibition of malondialdehyde (MDA) production, Nod-like receptor protein 3 (NLRP3) inflammasome expression, and interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α secretion. The present study demonstrated that the regulation of purine metabolism, the suppression of oxidative stress, and inflammatory responses in the cortex were involved in the synergistic antidepressant effect of CBHP.

Facile preparation of UiO-66@PPy nanostructures for rapid and efficient adsorption of fluoride: Adsorption characteristics and mechanisms.

A nanocomposite of a zirconium-based metal-organic framework (UiO-66) @ polypyrrole (PPy) (UiO-66@PPy) was successfully synthesized to eliminate F- from groundwater. The optimum initial pH and adsorbent dose for maximum uptake of F- from aqueous solution were found to be 3.0 and 0.1 g/L, respectively. The fluoride removal performance of UiO-66 was greatly enhanced through the introduction of polypyrrole guests, and the maximum adsorption capacity of UiO-66@PPy, namely, 290.7 mg/g, was reached, which is far superior to those of other previously reported adsorbents. The fluoride adsorption by UiO-66@PPy agreed well with the pseudo-second-order equation model and Langmuir isotherm model. The coexisting PO43- and CO32- substantially influence fluoride removal. The synthesized UiO-66@PPy could be reused five times in adsorption-desorption cycles. The incorporation of conducting polymers opened additional paths for the development of adsorbent materials; thus, UiO-66@PPy could be a viable adsorbent material and contribute to fluoride removal from groundwater.

Liquiritin protects PC12 cells from corticosterone-induced neurotoxicity via regulation of metabolic disorders, attenuation ERK1/2-NF-κB pathway, activation Nrf2-Keap1 pathway, and inhibition mitochondrial apoptosis pathway.

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.

Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway.

A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 µg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.

Highly selective anchoring silver nanoclusters on MOF/SOF heterostructured framework for efficient adsorption of radioactive iodine from aqueous solution.

A series of Ag-modified MOF/SOF heterostructured framework adsorbents (Ag-MSHC) with strong binding of iodine were prepared by anchoring silver nanoclusters on MOF/SOF heterostructured framework (MSHC). Morphological transformation process of six novel Ag-MSHC adsorbents can be realized by tailoring the molar ratio of Fe3+, TMA (1,3,5-Tricarboxybenzen) and MA (melamine), finally resulting in a combination of MOFs (metal-organic frameworks) and SOFs (supramolecular organic framework). Among six adsorbents, Ag-MSHC-6 exhibited an extremely strong affinity towards I-, whereas the maximum adsorption capacity of I- reaches 771.6 mg/g. An increased tendency of I- sorption occurred from Ag-MSHC-1 to Ag-MSCH-6 when the molar ratio of Fe3+ gradually decreased because the content of Fe3+ in topological structure of Ag-MSHC can hinder the incorporation of silver nanoclusters into Ag-MSHC and further influences the irreversible interactions between Ag2O and I-. Besides, FT-IR, XPS, TGA and SEM were used to discuss the microstructures and chemical composition of MSHC and Ag-MSHC, and we also performed batch adsorption experiments to demonstrate the iodine sorption performance and mechanism by Ag-MSHC. Taking advantage of this combination of MOFs and SOFs, high degree of doping of silver nanoclusters as well as its strong binding ability of iodine, Ag-MSHC can be considered as a superior adsorbent for radioactive iodine extraction.

Baicalein protects PC12 cells from Aß25-35-induced cytotoxicity via inhibition of apoptosis and metabolic disorders.

AIMS: This study aimed to explore the protective effects and possible mechanisms of baicalein on Aß25-35-induced toxicity. MAIN METHODS: Thioflavin-T (Th-T) dye was used to determine the effects of baicalein on Aß25-35 aggregation in vitro. PC12 cells were stimulated with Aß25-35, 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 Aß25-35-injured PC12 cells. KEY FINDINGS: The results showed that baicalein could inhibit the aggregation of Aß25-35 in vitro. Furthermore, pretreatment with baicalein significantly prevented Aß25-35-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 Aß25-35-induced neurotoxicity in PC12 cells, which may be related to inhibition of apoptosis and metabolic disorders.

Coniferyl ferulate exerts antidepressant effect via inhibiting the activation of NMDAR-CaMKII-MAPKs and mitochondrial apoptotic pathways.

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.

Involvement of mitochondrial apoptotic pathway and MAPKs/NF-κ B inflammatory pathway in the neuroprotective effect of atractylenolide III in corticosterone-induced PC12 cells.

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.

Metabolomics studies on corticosterone-induced PC12 cells: A strategy for evaluating an in vitro depression model and revealing the metabolic regulation mechanism.

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.

The intervention effect of licorice in d-galactose induced aging rats by regulating the taurine metabolic pathway.

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.

Effects of Baicalein on Cortical Proinflammatory Cytokines and the Intestinal Microbiome in Senescence Accelerated Mouse Prone 8.

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-1ß), 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-1ß 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.

Uncovering the anticancer mechanism of Compound Kushen Injection against HCC by integrating quantitative analysis, network analysis and experimental validation.

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.

Metabonomics approach to assessing the metabolism variation and gender gap of Drosophila melanogaster in aging process.

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.

Baicalein Exerts Beneficial Effects in d-Galactose-Induced Aging Rats Through Attenuation of Inflammation and Metabolic Dysfunction.

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.

Protective effect of isoliquiritin against corticosterone-induced neurotoxicity in PC12 cells.

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.