Two Omics Methods Expose Anti-Depression Mechanism of Raw and Vinegar-Baked Bupleurum Scorzonerifolium Willd.

Bupleurum scorzonerifolium willd. (BS) and its vinegar-baked product (VBS) has been frequently utilized for depression management in clinical Chinese medicine. This paper aims to elucidate the antidepressant mechanism of BS and VBS from the perspectives of metabonomics and gut microbiota. A rat model of depression was established by CUMS combined with feeding alone to evaluate the antidepressant effects of BS and VBS. UPLC-Q-TOF-MS/MS-based metabolomics and 16S rRNA sequencing of rat feces were applied and the correlation of differential metabolic markers and intestinal floras was analyzed. The result revealed that BS and VBS significantly improved depression-like behaviors and the levels of monoamine neurotransmitters in CUMS rats. There were 27 differential endogenous metabolites between CUMS and normal rats, which were involved in 8 metabolic pathways. Whereas, BS and VBS could regulate 18 and 20 metabolites respectively, wherein fifteen of them were shared metabolites. On the genus level, BS and VBS could regulate twenty-five kinds of intestinal floras in CUMS rats, that is, they increased the abundance of beneficial bacteria and decreased the abundance of harmful bacteria. In conclusion, both BS and VBS exert excellent antidepressant effects by regulating various metabolic pathways and ameliorating intestinal microflora dysfunction.

[Mechanism of Bupleurum scorzonerifolium and Paeonia lactiflora herbal pair against liver cancer: an exploration based on UPLC-Q-TOF-MS combined with network pharmacology].

This study aimed to decipher the pharmacodynamic material basis and mechanism of herbal pair Bupleurum scorzonerifolium-Paeonia lactiflora(BS-PL) against liver cancer based on UPLC-Q-TOF-MS and network pharmacology. MTT assay and human hepatocellular carcinoma HepG2 cells were used to screen the effective part of BS-PL, the active components of which were further analyzed and identified by UPLC-Q-TOF-MS. Next, we applied Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to screen the active ingredients with OB≥30%. Then TCMSP and SwissTargetPrediction were used to collect and predict component targets, followed by the search of liver cancer-related targets with GeneCards and DisGeNET. The intersection targets were obtained using Venny 2.1.0. Protein-protein interaction(PPI) network was constructed using STRING to uncover the core targets, which were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis based on DAVID. Finally, the effects of active ingredients on the expression of main proteins enriched in the key pathways of HepG2 cells were verified by Western blot. The results indicated that compared with 30%, 50%, and 70% ethanol extracts of BS-PL, the n-butanol extraction part(CSYZ) from 95% ethanol extract of BS-PL exhibited the best anti-tumor effect. UPLC-Q-TOF-MS revealed 31 ingredients, 14 of which showed OB≥30%. A total of 220 intersection targets were obtained, from which 35 were selected as the key targets under the condition of two times the median of degree. Among the 215 items with P<0.05 obtained through GO enrichment analysis, 154 were classified into biological processes, 22 into cell components and 39 into molecular functions. KEGG enrichment analysis revealed 95 significantly affected signaling pathways, and the ones(sorted in a descending order by P value) closely related to the anti-liver cancer effect of herbal pair were PI3 K-AKT signaling pathway, TNF signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, and ErbB signaling pathway. Finally, the PI3 K/AKT signaling pathway involving the largest number of targets was extrapolated, and it was found that this pathway contained 15 core targets and 8 active components. Experimental verification showed that the effective components of BS-PL significantly inhibited the expression of p-PI3 K and p-AKT, consistent with the prediction results of network pharmacology. In conclusion, the main pharmacodynamic substances of BS-PL against liver cancer are 14 components like saikosaponin a, saikosaponin d, and paeoniflorin, which exert the anti-liver cancer effect by regulating PI3 K/AKT pathway.

Therapeutic Effects of Different Animal Bile Powders on Lipid Metabolism Disorders and Their Composition Analysis.

OBJECTIVE: To compare the therapeutic effect of different animal bile powders on lipid metabolism disorders induced by high-fat diet in rats, and analyze the bioactive components of each animal bile powder. METHODS: Sixty Sprague-Dawley rats were randomly divided into 6 groups (n=10): normal diet control group, high-fat diet model group, high-fat diet groups orally treated with bear, pig, cow and chicken bile powders, respectively. Serum biochemical markers from the abdominal aorta in each group were analyzed. Changes in the body weight and liver weight were recorded. Pathohistological changes in the livers were examined. High performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was used to determine the composition of bioactive components in each animal bile powder. RESULTS: Treatment with different types of animal bile powders had different inhibitory effects on high-fat diet-induced increase of body weight and/or liver weight in rats, most notably in bear and pig bile powders (P<0.05). High-fat diet induced lipid metabolism disorder in rats, which could be reversed by treatment with all kinds of bile powders. Bear bile and chicken bile showed the most potent therapeutic effect against lipid metabolism disorder. Cow and bear bile effectively alleviated high-fat diet induced liver enlargement and discoloration, hepatocyte swelling, infiltration of inflammatory cells and formation of lipid vacuoles. Bioactive component analysis revealed that there were significant differences in the relative content of taurocholic acid, taurodeoxycholic acid and ursodeoxycholic acid among different types of animal bile. Interestingly, a unique component with molecular weight of 496.2738 Da, whose function has not yet been reported, was identified only in bear bile powder. CONCLUSIONS: Different animal bile powders had varying therapeutic effect against lipid metabolism disorders induced by high-fat diet, and bear bile powder demonstrated the most effective benefits. Bioactive compositions were different in different types of animal bile with a novel compound identified only in bear bile powder.

Metabolomic characteristics of hepatotoxicity in rats induced by silica nanoparticles.

Silica nanoparticles (SiNPs) have become one of the most widely studied nanoparticles in nanotechnology for environmental health and safety. Although many studies have devoted to evaluating the hepatotoxicity of SiNPs, it is currently impossible to predict the extent of liver lipid metabolism disorder by identifying changes in metabolites. In the present study, 40 male Sprague-Dawley (SD) rats were randomly divided into control group and 3 groups with different doses (1.8 mg/kg body weight (bw), 5.4 mg/kg bw, 16.2 mg/kg bw), receiving intratracheal instillation of SiNPs. Liver tissue was taken for lipid level analysis, and serum was used for blood biochemical analysis. Then, the metabolites changes of liver tissue in rats were systematically analyzed using 1H nuclear magnetic resonance (1H NMR) techniques in combination with multivariate statistical analysis. SiNPs induced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride (TG) elevation in treated groups; TG and low-density lipoprotein cholesterol (LDL-C) were significantly higher in SiNPs-treated groups of high-dose, however high-density lipoprotein cholesterol (HDL-C) showed a declining trend in liver tissue. The orthogonal partial least squares discriminant analysis (OPLS-DA) scores plots revealed different metabolic profiles between control and high-dose group (Q2 =0.495, R2Y=0.802, p = 0.037), and a total of 11 differential metabolites. Pathway analysis indicated that SiNPs treatment mainly affected 10 metabolic pathways including purine metabolism, glucose-alanine cycle and metabolism of various amino acids such as glutamate, cysteine and aspartate (impact value>0.1, false discovery rate (FDR)< 0.05). The result indicated that exposure to SiNPs caused liver lipid metabolism disorder in rats, the biochemical criterions related to lipid metabolism changed significantly. The obviously changed metabolomics in SiNPs-treated rats mostly occurred in amino acids, organic acids and nucleosides.

A comparison of the thyroid disruption induced by decabrominated diphenyl ethers (BDE-209) and decabromodiphenyl ethane (DBDPE) in rats.

In recent years, decabromodiphenyl ethane (DBDPE), a new alternative flame retardant to the decabrominated diphenyl ethers (BDE-209), is widely used in a variety of products. Previous studies have indicated that DBDPE, like BDE-209, could disrupt thyroid function. However, compared with BDE-209, the degrees of thyrotoxicosis induced by DBDPE were not clear. In addition, the mechanism of thyrotoxicosis induced by DBDPE or BDE-209 was still under further investigation. In this study, male rats as a model were orally exposed to DBDPE or BDE-209 by 5, 50, 500 mg/kg bw/day for 28 days. Then, we assessed the thyrotoxicosis of DBDPE versus BDE-209 and explored the mechanisms of DBDPE and BDE-209-induced thyrotoxicosis. Results showed that decreased free triiodothyronine (FT3) and increased thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) in serum were observed in both 500 mg/kg bw/day BDE-209 and DBDPE group. Decreased total thyroxine (TT4), total T3 (TT3), and free T4 (FT4) were only observed in BDE-209 group but not in DBDPE group. Histological examination and transmission electron microscope examination showed that high level exposure to BDE-209 and DBDPE both caused significant changes in histological structure and ultrastructure of the thyroid gland. Additionally, oxidative damages of thyroid gland (decreased SOD and GSH activities, and increased MDA content) were also observed in both BDE-209 and DBDPE groups. TG contents in the thyroid gland was reduced in BDE-209 group but not in DBDPE group. Both BDE-209 and DBDPE affected the expression of hypothalamic-pituitary-thyroid (HPT) axis related genes. These findings suggested that both BDE-209 and DBDPE exposure could disrupt thyroid function in the direction of hypothyroidism and the underlying mechanism was likely to be oxidative stress and perturbations of HPT axis. However, DBDPE was found to be less toxic than BDE-209.

A novel high-performance liquid chromatography-fluorescence analysis coupled with in situ degradation-derivatization technique for quantitation of organophosphorus thioester pesticide residues in tea.

A novel high-performance liquid chromatography-fluorescence analysis in combination with in situ degradation-derivatization (ISD-D) technique was developed for simultaneous determination of seven organophosphorus thioester pesticides (OPTPs) in tea. The ISD-D technique was based on degradation of OPTPs by a nucleophilic substitution reaction between phenylbutane-1,2,3-trione-2-oxime and OPTPs, which can give thiol degradation products (DPs). The thiol DPs obtained were derivatized with the novel derivatization reagent N-(4-(carbazole-9-yl)-phenyl)-N-maleimide (NCPM) in a syringe. Attractively, NCPM itself did not fluoresce, whereas the derivatives of the thiol DPs fluoresced intensely, with excitation and emission maxima at 290 nm and 368 nm, respectively, which extraordinary reduced the background interference and increased the detection sensitivity for thiol DPs. Excellent linearity (R2 > 0.995) for all OPTPs was achieved, with limits of detection and limits of quantitation ranging from 0.23 to 0.45 µg/kg and from 0.75 to 1.43 µg/kg, respectively. Satisfactory recoveries ranging from 90.5% to 96.0% were obtained for all OPTPs. The ISD-D technique provided a novel and sensitive strategy for quantitation of trace amounts of OPTPs in real samples. Graphical abstract ᅟ.

Silica nanoparticle exposure inducing granulosa cell apoptosis and follicular atresia in female Balb/c mice.

Given that the effects of ultrafine fractions (< 0.1 µm) on reproductive diseases are gaining attention, this study aimed to explore the influence of silica nanoparticle (SiNP)-induced female reproductive dysfunction. In this study, 80 female mice were randomly divided into four groups including a control group and three concentrations of SiNP groups (7, 21, 35 mg/kg). Mice were exposed to the vehicle control and silica nanoparticles by tracheal perfusion every 3 days a total of five times in 15 days. Then, half of the mice in each group were sacrificed on 15 and 30 days after the first dose, respectively. Our findings indicated that SiNPs can result in ovarian damage, cause an imbalance of sex hormones, increase the number of atretic and primary follicles, and induce oxidative stress and DNA strand breaks in ovary by day 15. The protein expressions of ATM, CHK-2, P53, E2F1, P73, BAX, Caspase-9, and Caspase-3 were significantly increased, while expressions of RAD51 were down-regulated after SiNP exposure by days 15. Estradiol increased, while progesterone increased in low dose and decreased in high dose after SiNP exposure by 15 days. However, these changes were recovered by 30 days. The results suggest that SiNPs can cause reversible damage to follicles in mice. SiNPs could primarily cause DNA damage and DNA damage response through oxidative stress, while DNA damage repair failure because of severe DNA damage activated the mitochondrial apoptosis pathway and therefore resulted in apoptosis of granulosa cell. In addition, the disorder of reproductive endocrine function caused by SiNPs could be another reason for SiNP-induced reproductive dysfunction in mice. These events in turn induce the follicles to undergo atresia.

Silica nanoparticles induce autophagy dysfunction via lysosomal impairment and inhibition of autophagosome degradation in hepatocytes.

Autophagy dysfunction is considered as a potential toxic mechanism of nanomaterials. Silica nanoparticles (SiNPs) can induce autophagy, but the specific mechanism involved remains unclear. Therefore, the aim of this study was to confirm the effects of SiNPs on autophagy dysfunction and explore the possible underlying mechanism. In this article, we reported that cell-internalized SiNPs exhibited dose- and time-dependent cytotoxicity in both L-02 and HepG2 cells. Multiple methods verified that SiNPs induced autophagy even at the noncytotoxic level and blocked the autophagic flux at the high-dose level. Notably, SiNPs impaired the lysosomal function through damaging lysosomal ultrastructures, increasing membrane permeability, and downregulating the expression of lysosomal proteases, cathepsin B, as evidenced by transmission electron microscopy, acridine orange staining, quantitative reverse transcription-polymerase chain reaction, and Western blot assays. Collectively, these data concluded that SiNPs inhibited autophagosome degradation via lysosomal impairment in hepatocytes, resulting in autophagy dysfunction. The current study not only discloses a potential mechanism of autophagy dysfunction induced by SiNPs but also provides novel evidence for the study of toxic effect and safety evaluation of SiNPs.

Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling.

Environmental exposure to silica nanoparticles (SiNPs) is inevitable due to their widespread application in industrial, commercial, and biomedical fields. In recent years, most investigators focus on the evaluation of cardiovascular effects of SiNPs in vivo and in vitro. Endothelial injury and dysfunction is now hypothesized to be a dominant mechanism in the development of cardiovascular diseases. This study aimed to explore interaction of SiNPs with endothelial cells, and extensively investigate the exact effects of reactive oxygen species (ROS) on the signaling molecules and cytotoxicity involved in SiNPs-induced endothelial injury. Significant induction of cytotoxicity as well as oxidative stress, apoptosis, and autophagy was observed in human umbilical vein endothelial cells following the SiNPs exposure (P<0.05). The oxidative stress was induced by ROS generation, leading to redox imbalance and lipid peroxidation. SiNPs induced mitochondrial dysfunction, characterized by membrane potential collapse, and elevated Bax and declined bcl-2 expression, ultimately leading to apoptosis, and also increased number of autophagosomes and autophagy marker proteins, such as LC3 and p62. Phosphorylated ERK, PI3K, Akt, and mTOR were significantly decreased, but phosphorylated JNK and p38 MAPK were increased in SiNPs-exposed endothelial cells. In contrast, all of these stimulation phenomena were effectively inhibited by N-acetylcysteine. The N-acetylcysteine supplement attenuated SiNPs-induced endothelial toxicity through inhibition of apoptosis and autophagy via MAPK/Bcl-2 and PI3K/Akt/mTOR signaling, as well as suppression of intracellular ROS property via activating antioxidant enzyme and Nrf2 signaling. In summary, the results demonstrated that SiNPs triggered autophagy and apoptosis via ROS-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling in endothelial cells, and subsequently disturbed the endothelial homeostasis and impaired endothelium. Our findings may provide experimental evidence and explanation for cardiovascular diseases triggered by SiNPs. Furthermore, results hint that the application of antioxidant may provide a novel way for safer use of nanomaterials.

A novel recombinant 6Aß15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer's disease-like pathology, cognitive decline and synaptic loss in aged 3 × Tg-AD mice.

Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-ß (Aß) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Aß15-THc-C immunogen was formulated with alum adjuvant as a novel Aß B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3 × Tg-AD mice. Using a toxin-derived carrier protein, the rCV02 vaccine elicited robust Aß-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3 × Tg-AD mice. Along with the behavioral improvement in aged 3 × Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble Aß or oligomeric forms of Aß, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing Aß levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong Aß-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine.

Accurate Analysis and Evaluation of Acidic Plant Growth Regulators in Transgenic and Nontransgenic Edible Oils with Facile Microwave-Assisted Extraction-Derivatization.

Determination of plant growth regulators (PGRs) in a signal transduction system (STS) is significant for transgenic food safety, but may be challenged by poor accuracy and analyte instability. In this work, a microwave-assisted extraction-derivatization (MAED) method is developed for six acidic PGRs in oil samples, allowing an efficient (<1.5 h) and facile (one step) pretreatment. Accuracies are greatly improved, particularly for gibberellin A3 (-2.72 to -0.65%) as compared with those reported (-22 to -2%). Excellent selectivity and quite low detection limits (0.37-1.36 ng mL(-1)) are enabled by fluorescence detection-mass spectrum monitoring. Results show the significant differences in acidic PGRs between transgenic and nontransgenic oils, particularly 1-naphthaleneacetic acid (1-NAA), implying the PGRs induced variations of components and genes. This study provides, for the first time, an accurate and efficient determination for labile PGRs involved in STS and a promising concept for objectively evaluating the safety of transgenic foods.

Saponins from Panax japonicus attenuate D-galactose-induced cognitive impairment through its anti-oxidative and anti-apoptotic effects in rats.

OBJECTIVE: To investigate the neuroprotective effects of saponins from Panax japonicus (SPJ) on D-galactose (D-gal)-induced brain ageing, and further explore the underlying mechanisms. METHODS: SPJ were analysed using high-pressure liquid chromatography. Male Wistar rats weighing 200 ± 20 g were randomly divided into four groups: control group (saline), D-gal-treated group (400 mg/kg, subcutaneously), D-gal + SPJ groups (50, 100 and 200 mg/kg, orally) and vitamin E group (100 mg/kg). Rats were injected corresponding drugs once daily for 8 weeks. Neuroprotective effects of SPJ were evaluated by Morris water maze, histopathological observations, biochemical assays, western blot analysis and quantitative real-time polymerase chain reaction (PCR) analysis in vivo as well as reactive oxygen species (ROS) measurement and apoptosis assay in vitro. KEY FINDINGS: Our present study showed that D-gal had a neurotoxic effect in rats and in SH-SY5Y cells due to oxidative stress induction, including decreased total anti-oxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase activity, ultimately leading to spatial learning and memory impairment in rats and ROS accumulation in SH-SY5Y cells. SPJ improved spatial learning and memory deficits, attenuated hippocampus histopathological injury and restored impaired anti-oxidative as well as anti-apoptotic capacities in D-gal-induced ageing rats. In addition, SPJ remarkably decreased lipofuscin levels, increased hippocampus nuclear factor erythroid 2-related factor 2 (Nrf2) and silent mating type information regulation 2 homologue (SIRT1) protein levels and anti-oxidant genes expression such as manganese superoxide dismutase (Mn-SOD), heme oxygenase (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1) and cysteine ligase catalytic (GCLC) in D-gal-induced brain ageing. CONCLUSIONS: Our data suggested that D-gal induced multiple molecular and functional changes in brain similar to natural ageing process. SPJ protected brain from D-gal-induced neuronal injury through decreasing oxidative stress and apoptosis, and ultimately improving cognitive performance in D-gal-induced brain ageing. It is possibly related to Nrf2 and SIRT1-mediated anti-oxidant signalling pathways.

[Determination of L-dopa and dopamine in rat brain microdialysate by ultra high performance liquid chromatography-tandem mass spectrometry using stable isotope-coded derivatization coupled with dispersive liquid-liquid microextraction].

The sensitive detection method of levodopa (L-DOPA) and dopamine (DA) in rat brain microdialysate of Parkinson's disease (PD) is an essential tool for the clinical study and attenuated synergistic drug screening for L-DOPA from traditional Chinese medicines. Using d0/d3-10-methyl-acridone-2-sulfonyl chloride (d0/d3-MASC) as stable isotope derivatization reagent, a novel ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for L-DOPA and DA by stable isotope- coded derivatization coupled with ultrasonic-assisted dispersive liquid-liquid microextraction (UA-DLLME). d3-MASC (light) and d3-MASC (heavy) were used as derivatization reagents for microdialysate samples and standards, respectively. Mixtures of the two solutions were prepared by UA-DLLME for UHPLC-MS/MS analysis with multiple reaction monitoring (MRM) mode. With d3-MASC heavy derivatives as internal standards for corresponding light derivatives from samples, the stable isotope internal standard quantification for L-DOPA and DA was carried out. The stable derivatives were obtained in aqueous acetonitrile (pH 10.8 sodium carbonate-sodium bicarbonate buffer) at 37 °C for 3.0 min, and then were separated within 2.0 min using gradient elution. Linear range was 0.20-1500.0 nmol/L (R > 0.994). LODs were 0.005 and 0.009 nmol/L for DA and L-DOPA (S/N = 3), respectively. This method was validated, and it showed obvious advantages in comparing with the reported methods in terms of sensitivity, analysis speed and anti-matrix interference. This method has been successfully applied to the study of effect of Shouwu Fang on L-DOPA and DA concentration fluctuations in PD rat brain microdialysate.

Protective effect of saponins extract from Panax japonicus on myocardial infarction: involvement of NF-κB, Sirt1 and mitogen-activated protein kinase signalling pathways and inhibition of inflammation.

OBJECTIVE: Inflammation is widely acknowledged to increase morbidity and mortality in myocardial infarction (MI), and the ideal therapeutic methods should be aimed at the inflammation reaction triggers. The aim was to evaluate the protective effect of saponins extracted from Panax japonicus (SPJ) on MI, and based on these results investigate the possible involvement mechanism of the nuclear factor-kappa B (NF-κB), sirtuin1 (SIRT1) and mitogen-activated protein kinases (MAPKs) signalling pathways. METHODS: Sprague-Dawley rats were randomly divided into sham, MI, MI + SPJ 50 and SPJ 100 mg/kg groups. After administration for 3 days, MI rats were created by ligaturing coronary artery, and then underwent the same administration for 7 days as before. Cardiac function and the expressions of pro-apoptosis protein Bax, anti-apoptosis protein Bcl-2, NF-κB, SIRT1, MAPKs signal pathway-related proteins and inflammatory factor, such as tumour necrosis factor alpha (TNF-α) and monocyte chemoattractant protein 1 (MCP-1), were assessed. KEY FINDINGS: SPJ might significantly improve cardiac function, decrease the serum MCP-1 and TNF-α levels, ameliorate the increased Bax protein expression and decrease Bcl-2 protein expression, and suppress the protein expressions of NF-κBp65 subunit, extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 MAPK, but have no effect on c-Jun NH2-terminal kinase, and increase the expression of SIRT1. Histopathological observations provided supportive evidence for aforementioned results, and with the dose of SPJ increasing, the aforesaid improvement became more and more strong. CONCLUSION: The studies demonstrated that SPJ exerted beneficially cardioprotective effects on MI rats, mainly inhibiting NF-κB, ERK1/2 and p38 MAPK activation, but increased the expression of SIRT1, alleviating MI injury and cardiac cell death.

Inhaled formaldehyde induces bone marrow toxicity via oxidative stress in exposed mice.

Formaldehyde (FA) is an economically important chemical, and has been found to cause various types of toxic damage to the body. Formaldehyde-induced toxic damage involves reactive oxygen species (ROS) that trigger subsequent toxic effects and inflammatory responses, which may increase risk of cancer. Therefore, in the present study, we aimed to investigate the possible toxic mechanism in bone marrow caused by formaldehyde. In accordance with the principle of randomization, the mice were divided into four groups of 6 mice per group. One group was exposed to ambient air and the other three groups were exposed to different concentrations of formaldehyde (20, 40, 80 mg/m3) for 15 days in the respective inhalation chambers, 2h a day. At the end of the 15-day experimental period, all mice were killed. Bone marrow cells were obtained. Some of those were used for the determination of blood cell numbers, bone marrow karyote numbers, CFU-F, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content; others were used for the determination of mitochondrial membrane potential (MMP), cell cycle and Bcl-2, Bax, CytC protein expression. WBC and PLT numbers in median and high dose groups were obvious reduced, but there was no change on RBC numbers. There was also reduced numbers of bone marrow karyotes and CFU-F in the high dose group. SOD activity was decreased, but MDA content was increased. MMP and Bcl-2 expression were decreased with increasing formaldehyde concentration, while expression of Bax and Cyt C was increased. We also observed change in cell cycling, and found that there was S phase arrest in the high dose group. Our study suggested that a certain concentration of formaldehyde could have toxic effects on the hematopoietic system, with oxidative stress as a critical effect.

Selenium-platinum coordination compounds as novel anticancer drugs: selectively killing cancer cells via a reactive oxygen species (ROS)-mediated apoptosis route.

We report the preparation of selenium-containing platinum-based anticancer drug EG-Se/Pt. EG-Se/Pt was obtained from the coordination of selenium-containing molecules (EG-Se) with cisplatin (CDDP). The structure of EG-Se/Pt was characterized by (1) H and (77) Se NMR spectroscopy, XPS, ESI-MS, and MALDI-TOF. In aqueous solution, EG-Se/Pt self-assembles to form spherical aggregates. EG-Se/Pt shows enhanced stability against dilution and high salt concentration compared with EG-Se. EG-Se/Pt induces cell apoptosis via reactive oxygen species (ROS), which leads to high selectivity between cancer cells and normal cells in cytotoxicity assays. More importantly, EG-Se/Pt effectively inhibits tumor growth in vivo in tumor-bearing mice. It is anticipated that tuning the ROS level through the assembly of selenium-containing molecules can be a general method to realize anticancer selectivity.

[Comparative study of wild and cultivated product of Panax japonicus from the west of Hubei province].

OBJECTIVE: To compare the difference of macroscopic and microscopic characteristics and total saponin content between wild and cultivated product of Panax japonicus from the west of Hubei province. METHODS: Cleared the difference of wild and cultivated product of Panax japonicus by macroscopic and microscopic characteristics of powder and transversection and determined the content of total sponin by the vanillin-perchloric acid. RESULTS: Compared with cultivated product, in medicinal properties, the wild one was darker, with shorter diameter and rougher surface. In microscopic features, wild product had pigment, while the cultivated one had none; Moreover, the calcium oxalate crystal were more and the xylem bigger in wild product. As for total saponins, cultivated product had more total ginsenosides than the wild one. CONCLUSION: There are certain differences in macroscopic and microscopic characteristics and total ginsenosides between wild and cultivated product of Panax japonicus.

Visible-light-induced disruption of diselenide-containing layer-by-layer films: toward combination of chemotherapy and photodynamic therapy.

A photoresponsive polyelectrolyte multilayer film containing a diselenide functional group is fabricated using an unconventional layer-by-layer method. The polycation backbone is constructed through copolymerization of di-(1-hydroxylundecyl) diselenide and 1,4-bis(2-hydroxyethyl)piperazine with 2,4-diisocyanatotoluene. A common polyanion poly(styrene sulfonate) is selected as the polyanion. The obtained film can be gradually disrupted under the irradiation of mild visible light, and this process can be monitored with UV-vis spectroscopy. The residue of the film is estimated to be 17% after 5 h of irradiation. The intensity of the visible light can be as low as 50 mW cm⁻², which is even weaker than the sunlight. The cytotoxicity of the building blocks is evaluated in MTT assays using human hepatic cell line (L-02), and the results are satisfactory. Further tests show that cells can grow in a regular manner on this film, indicating good biocompatibility. In addition, the film can be used to achieve cargo loading and controlled release. Considering that light can not only trigger controlled release but also act as part of the therapy itself (photodynamic therapy), this system shows hope for further development into a platform for the combination of chemotherapy and photodynamic therapy, especially for applications concerning skin.

Anti-diabetic effect of Coptis Chinensis polysaccharide in high-fat diet with STZ-induced diabetic mice.

For the past few years, numerous polysaccharides and polysaccharide-protein complexes have been isolated from plant or animal and used as a promising source of therapeutic agents for diabetes mellitus (DM). In this study, a water-soluble polysaccharide, named as CCPW-1, was extracted and fractioned from the roots of Coptis Chinensis by DEAE Sepharose Fast Flow anion-exchange and Sephadex G-100 column chromatography. The determination of the monosaccharide composition in CCPW-1 with gas chromatography (GC) showed that CCPW-1 was composed of glucose (54.8%), arabinose (22.3%), xylose (11.5%), galactose (7.6%) and galacturonic acid (3.8%). Diabetic mice induced by high-fat diet (HFD) with streptozotocin (STZ) were administered CCPW-1 (100, 50, 25 mg/kg b.w.). Effects of CCPW-1 on bodyweight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), fasting serum insulin (FINS), total glycerin (TG), total cholesterol (TC), super oxygen dehydrogenises (SOD), catalase (CAT) and methane dicarboxylic aldehyde (MDA) were investigated. CCPW-1 could improve the bodyweight, reduce the content of FBG and enhance FINS level. Meanwhile, CCPW-1 significantly suppressed the rise in blood glucose after 30 min in OGTT. TG and TC levels of diabetic mice also decreased after CCPW-1 treatment. Furthermore, CCPW-1 showed an obvious antioxidant effect through increasing SOD, CAT activities and decreasing MDA content in pancreas. These results indicate that CCPW-1 could be developed to a potent drug used for the treatment of DM in the future.

[Effects of total saponin from Panax japonicus on acute myocardial ischemia injury induced by ligating coronary artery left anterior descending branch in rats].

OBJECTIVE: To investigate the cardioprotective effects of total saponin from Panax japonicus pretreating on acute myocardial ischemia injury induced by ligating coronary artery left anterior descending branch (LAD) in rats. METHODS: Rats were divided into sham group, model group and total saponin group. The treatment group was given total saponin of Panax japonicus. After pretreating for 7 days, the rats' acute myocardial ischemia model was induced by LAD. The electrocardiogram, hemodynamics, infarct size and histomorphology were assessed 12 h after LAD, the serum levels of phosphokinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were also measured. RESULTS: Compared with the model group, total saponin from Panax japonicus significantly improved heart function, heart histomorphology, opposed ECG T wave decreased and decreased infarct size; Remarkably decreased the contents of LDH, CK and MDA, increased the activity of SOD, CAT. CONCLUSION: Total saponin from Panax japonicus has cardioprotective effects on acute myocardial ischemic injury and the mechanism may be related to antioxidation.