A dual-site multifunctional fluorescent probe for selective detection of endogenous H2O2 and SO2 derivatives based on ICT process and its bioimaging application.

In this paper, we reported a coumarin-based fluorescent probe for selective detection of H2O2/SO2 derivatives via ICT process. To the best of our knowledge, it was few reported with the same probe to enable visual detection of H2O2/SO2 derivatives in vivo and in vitro. H2O2 and SO32- were selectively sensed over other analytes, and the probe displayed 20-fold and 220-fold relative fluorescence intensity respectively, as well as the good linear relationship and the excellent detection limits of 2.7 * 103 nM and 19.3 nM. Furthermore, the probe was successfully used for fluorescence imaging of the HeLa cells and the mice to monitor exogenous and endogenous H2O2 and SO32-, suggesting its potential biomedical application for investigation and detection the intermediate indicator of oxidative stress in vitro and in vivo.

The Two-Steps Reaction Fluorescent Probe for the Selective Detection of Cysteine and Its Applications.

We reported the specific fluorescent probe (MC-BOD-XDS) with two-steps reaction based on monosulfanyl-coumarin-BODIPY for selective detection of cysteine, high activity sulfanyl-coumarin as the multiple reaction group instead of a group internal standard fluorophore. The reaction mechanism of MC-BOD-XDS for detecting cysteine was different from the reported probes about the nucleophilic aromatic substitution reaction (SNAr) of chlorinated BODIPY. The fluorescent color of MC-BOD-XDS changed from yellow to red, and then to orange. The linear calibration diagram showed that it can potentially be used for quantitatively detection of Cys. Its potential applications were demonstrated by employing it for detection of Cys in artificial urine and in fluorescent imaging in HeLa cells.

Network pharmacology study on the active components of Pterocypsela elata and the mechanism of their effect against cerebral ischemia.

OBJECTIVE: The aim of this study was to identify the active anti-ischemic components of Pterocypsela elata (P. elata) using a network pharmacology approach to construct an effective component anti-cerebral ischemic target network and systematically analyze this medicinal material. METHODS: Pharmacological studies have shown that P. elata has an obvious effect against cerebral ischemia. To identify the potential targets, 14 components of P. elata were docked to each structural element of the targets in the DRAR-CPI database by reverse docking technology. We then compared the identified potential targets with FDA-approved targets for stroke/cerebral infarction treatment in the DrugBank database and identified the active components of P. elata and their potential targets for stroke/cerebral infarction treatment. The active component-target networks were constructed using Cytoscape 3.5.1 software. The target protein-protein interactions were analyzed using the STRING database. KEGG pathway analysis and gene ontology (GO) enrichment analysis were performed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: There were 14 active components identified from P. elata and 21 potential targets identified for cerebral ischemia treatment, including carbonic anhydrase 2, ribosyldihydronicotinamide dehydrogenase, cholinesterase, and glutathione S-transferase P. The main involved pathways include metabolic pathways, complement and coagulation cascades and steroid hormone biosynthesis. CONCLUSION: Through a network pharmacology approach, we predicted the active components of P. elata and their potential targets for cerebral ischemia treatment. Our results provide new perspectives and clues for further studies on the anti-cerebral ischemia mechanism of P. elata.

Alterations in splenic function and gene expression in mice with depressive-like behavior induced by exposure to corticosterone.

Depressed patients present with increased cortisol levels and attenuated immune responses. However, little is known about the association between depression and the spleen, as this is the largest peripheral immune organ. In this study, we examined alterations in splenic function and gene expression in mice with depressive-like behavior, well as the expression of certain proteins in related pathways. A mouse model of depression was established with the use of corticosterone. Splenic function and histopathology were assessed using Wright and H&E staining. The Agilent Whole Mouse Genome Oligo Microarray containing >41,174 transcript probes was used to measure the levels of gene-expression in the spleens from control and model mice, and the levels of certain proteins associated with depression were measured by western blot analysis in the brain and spleen separately. We found that splenic function and immunity in the mice with depressive-like behavior were markedly impaired. A total of 53 genes exhibited a differential response in the mice with depressive-like behavior, 11 of which were more notable, including collagen, type VI, α5 (Col6a5), immunoglobulin superfamily, member 11 (Igsf11), D site albumin promoter binding protein (Dbp), tachykinin 2 (Tac2) and γ-aminobutyric acid B receptor 2 (Gabbr2). Pathway analysis revealed that the amino acid biosynthesis and the clock gene pathways were more meaningful among these genes. The levels of GABBR2, DBP and substance P (SP; encoded by the Tac2 gene) related proteins in the brain were markedly downregulated, and similar results were observed in the spleen. The anti-depressant, fluoxetine, reversed the changes in the levels of these proteins. The findings of our study regarding changes occurring in the spleen during depression may indirectly elucidate and shed light into the pathogenesis of depression and depressive-like behavior.

[Prevention of abdominal adhesions in rats by rhynchophylline through inhibition of Smad singnaling pathway].

Postoperative intra-abdominal adhesion is one of the most common complications in the postoperative period. Current remedies are very ineffective to prevent the pathological outcomes except steroid hormones. Rhynchophylline is deemed as a pharmacologically active component from traditional Oriental medicine Uncaria rhynchophylla (Miq.) Jacks. (Rubiaceae). This study was designed to investigate the preventative effect of rhynchophylline on the abdominal adhesions in rats. Rhynchophylline relieved the experimental abdominal adhesion and decreased the levels of interleukin-1 ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the blood serum in a dose-dependent manner. The levels of transforming growth factor- ß1 (TGF-ß1) and connective tissue growth factor (CTGF) were reduced significantly in the peritoneal fluid. The potential mechanism of the activity is related to inhibition of the TGF- ß1/Smad signaling pathway.

Anti-hepatoma activity of a novel compound glaucocalyxin H in vivo and in vitro.

Glaucocalyxin H (GLH) is a new compound isolated from a traditional Chinese medical herb Isodon japonica var. glaucocalyx which has been used for folk medicine. This study was carried out for the first time to investigate the potential role of GLH in anti-hepatoma activity and underlying mechanisms in it. GLH could inhibit the growth of tumor in mice and induce HepG2 cells to death as assessed by the tumor reduction assay, toxic assay, morphological change, and survival rate assay. Many antitumor drugs originated from plants could inhibit the growth of tumor by inducing cells to apoptosis. The morphological changes of HepG2 cells treated with different concentrations of GLH under fluorescence and electron microscope and apoptotic rates were detected to verify its effect on apoptosis. As shown in the study, GLH could induce HepG2 cells to apoptosis in a dose-dependent manner. Bcl2 and Bax proteins played important roles in apoptosis and the disequilibrium between Bcl2 and Bax might result in apoptosis. The expression of Bax protein was upregulated and Bcl2 protein was downregulated in HepG2 cells treated with GLH assessed by Western blotting, and they were in a dose-dependent manner. Taken together, GLH can inhibit the growth of hepatoma cells in vivo and in vitro by inducing cell apoptosis due to the decreased Bcl2 and increased Bax proteins suggesting that GLH could be a potential candidate as an anti-hepatoma agent for the therapeutic treatment of hepatoma.

Effect of intranasal arginine vasopressin on human headache.

Arginine vasopressin (AVP), a nonapeptide hormone of posterior pituitary, reaches the central nervous system from systemic blood circulation with a difficulty because of the blood-brain barrier (BBB). The interest has been expressed in the use of the nasal route for delivery of AVP to the brain directly, exploiting the olfactory pathway. Our previous study has demonstrated that AVP in the brain rather than the spinal cord and blood circulation plays an important role in rat pain modulation. For understanding the role of AVP on pain modulation in human, the communication tried to investigate the effect of intranasal AVP on human headache. The results showed that (1) AVP concentration in both plasma and cerebrospinal fluid (CSF) increased significantly in headache patients, who related with the headache level; (2) there was a positive relationship between plasma and CSF AVP concentration in headache patients; and (3) intranasal AVP could relieve the human headache in a dose-dependent manner. The data suggested that intranasal AVP, which was delivered to the brain through olfactory region, could treat human headache and AVP might be a potential drug of pain relief by intranasal administration.

Effect of arginine vasopressin on the behavioral activity in the behavior despair depression rat model.

Arginine vasopressin (AVP), a nonapeptide posterior hormone of the pituitary, is mainly synthesized and secreted in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). Large numbers of studies have reported that AVP plays a role in depression. The present study was to investigate by which level, brain or periphery, AVP affects the behavioral activity in the behavior despair depression rat model. The results showed that (1) either forced swimming or tail suspension significantly increased AVP concentration not only in the brain (PVN, SON, frontal of cortex, hippocampus, amygdala, lumber spinal cord) but also in the periphery (posterior pituitary and serum); (2) intraventricular injection (icv) of AVP decreased the animal immobility time, whereas V1 receptor antagonist d(CH2)5Tyr(Me)AVP (icv) increased the animal immobility time in a dose-dependent manner not only in FST but also in TST, but the V2 receptor antagonist d(CH2)5[D-Ile, Ile, Ala-NH9]AVP did not change the animal immobility time in FST or TST; (3) V1, not V2 receptor antagonist could inhibit the animal immobility time decrease induced by AVP (icv); (4) neither AVP nor its receptor antagonist (including V1 and V2 receptor antagonist) influenced the animal immobility time in both FST and TST. The data suggested that AVP in the brain rather than the periphery played a role in the behavior despair depression by V1, not V2 receptors, which behavior despair might have a positive feedback effect on central AVP and blood AVP might have a negative feedback on central AVP in the depressive process.

Isolation, structural elucidation, and cytotoxicity of three new ent-kaurane diterpenoids from Isodon japonica var. glaucocalyx.

Three new ENT-kaurane diterpenoids, glaucocalyxin H ( 1), glaucocalyxin I ( 2), and glaucocalyxin J ( 3), together with four known diterpenoids ( 4- 7), were isolated from the leaves of Isodon japonica Hara var. glaucocalyx. Their structures were elucidated by spectroscopic analysis, and the structures of compounds 2 and 3 were further confirmed by X-ray crystallographic analysis. Compounds 1, 4, and 5 were evaluated for their cytotoxicity IN VITRO against CE-1, U87, A-549, MCF-7, Hela, K-562, and HepG-2 human tumor cell lines. Compound 1 showed potent inhibitory activities against six tumor cell lines with IC (50) values ranging from 1.86-10.95 µM, and compounds 4 and 5 exhibited significant selective cytotoxicity on seven tumor cell lines.

Two new diterpenoids and other constituents from Isodon rubescens.

Two new ent-kaurene diterpenoids, 15α-acetoxyl-6,11α-epoxy-6α-hydroxy-20-oxo-6,7-seco-ent-kaur-16-en-1,7-olide (1), 15α-hydroxy-20-oxo-6,7-seco-ent-kaur-16-en-1,7α(6,11α)-diolide (2), together with ten known compounds (5-14) were isolated from the leaves of Isodon rubescens. Their structures were elucidated mainly by various spectroscopic techniques and finally confirmed by single-crystal X-ray diffraction. Compounds 1, 2, 8 and 12 were evaluated for their cytotoxicities against EC-1, U87, A549, MCF-7 and Hela cell lines.

Protective effect of non-mitogenic human acidic fibroblast growth factor on hepatocyte injury.

AIM: To study whether non-mitogenic human acidic fibroblast growth factor (nm-haFGF) has protective effects on H(2)O(2)-induced hepatocyte injury in vitro and CCl(4)-induced hepatocyte injury in vivo. METHODS: (i) HL-7702 hepatocytes were incubated with different concentrations of nm-haFGF for 12 h, and then the activity of lactate dehydrogenase (LDH) in culture medium was detected, and genomic DNA electrophoresis analysis was observed after being exposed to H(2)O(2) (8 mmol/L) for 4 h. Proximately, apoptotic rates and protein expressions of Bcl-2 and Bax of HL-7702 cell were detected after being exposed to H(2)O(2) (0.2 mmol/L) for 20 h. (ii) Being injected intraperitoneally with nm-haFGF, mice were treated with CCl(4) intraperitoneally to induce hepatic injury. Twenty-four hours later, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured and histopathologic changes were evaluated. RESULTS: (i) In vitro tests: LDH activities and apoptotic rates decreased, the protein expression of Bcl-2 increased and Baxdecreased in nm-haFGF-treated groups at the concentrations of 100 150 and 200 ng/mL, compared with that in the model control group, which was treated with H(2)O(2) alone. The genomic DNA remained nearly intact at the concentrations of 150 and 200 ng/mL. (ii) In vivo tests: serum ALT and AST in nm-haFGF-treated groups (10 mug/kg and 20 mug/kg) were much lower as compared to the model control group, which was treated with CCl(4) alone. Histological examination showed that nm-haFGF markedly ameliorated hepatocytes vacuolation, cloudy swelling and inflammatory cells infiltration induced by CCl(4). CONCLUSION: nm-haFGF had protective effects against H(2)O(2)-induced hepatocyte injury in vitro and CCl(4)-induced acute liver injury in vivo.

[Effect of calcium supplement on superoxide dismutase and malonaldehyde of disuse osteoporosis in young rats].

Effects of Ca supplement on the bone mineral density(BMD), red blood cell superoxide dismutase(SOD), plasma malonaldehyde(MDA) of disused osteoporosis were studied in this paper. Twenty five healthy pregnant SD rats were randomly divided into 5 groups, groups 2-5 were reproduced with patterns of animal osteoporosis. The diet in groups 1-2 was the basic diet, while the groups 3-5 experiment diets were supplemented with Ca. Selected 3 young rats, live with the mother rate each brood. The BMD, red blood cell SOD, plasma MDA were measured 37 d later. The results showed that BMD level of young rats in Ca supplement groups is higher than vigorous groups (P < 0.05). The MDA in vigorous group was higher than Ca supplement, groups(P < 0.01) and SOD was lower than high biologic calcium group(P < 0.05). It was suggested that Ca supplemented certain effect on red blood cell SOD, plasma MDA of disused osteoporosis.