Cytochalasin Derivatives from the Endozoic Curvularia verruculosa CS-129, a Fungus Isolated from the Deep-Sea Squat Lobster Shinkaia crosnieri Living in the Cold Seep Environment.

A new cytochalasin dimer, verruculoid A (1), three new cytochalasin derivatives, including 12-nor-cytochalasin F (2), 22-methoxycytochalasin B6 (3), and 19-hydroxycytochalasin B (4), and 20-deoxycytochalasin B (5), a synthetic product obtained as a natural product for the first time, together with four known analogues (6-9), were isolated and identified from the culture extract of Curvularia verruculosa CS-129, an endozoic fungus obtained from the inner fresh tissue of the deep-sea squat lobster Shinkaia crosnieri, which was collected from the cold seep area of the South China Sea. Structurally, verruculoid A (1) represents the first cytochalasin homodimer containing a thioether bridge, while 12-nor-cytochalasin F (2) is the first 12-nor-cytochalasin derivative. Their structures were elucidated by detailed interpretation of the NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis and ECD calculations confirmed their structures and absolute configurations. Compound 1 displayed activity against the human pathogenic bacterium Escherichia coli (MIC = 2 µg/mL), while compounds 4, 8, and 9 showed cytotoxicity against three tumor cell lines (HCT-116, HepG-2, and MCF-7) with IC50 values from 5.2 to 12 µM. The structure-activity relationship was briefly discussed.

Antioxidant Hydroanthraquinones from the Marine Algal-Derived Endophytic Fungus Talaromyces islandicus EN-501.

Five new polyhydroxylated hydroanthraquinone derivatives, namely, 8-hydroxyconiothyrinone B (1), 8,11-dihydroxyconiothyrinone B (2), 4R,8-dihydroxyconiothyrinone B (3), 4S,8-dihydroxyconiothyrinone B (4), and 4S,8-dihydroxy-10-O-methyldendryol E (5), were isolated and identified from the culture extract of Talaromyces islandicus EN-501, an endophytic fungus obtained from the inner tissue of the marine red alga Laurencia okamurai. The structures of these compounds were established on the basis of detailed interpretation of their NMR and mass spectroscopic data, and the structures and absolute configurations of compounds 1 and 2 were confirmed by X-ray crystallographic analysis, while the absolute configurations of compounds 3-5 were determined by TDDFT calculations of the ECD spectra. The antimicrobial, antioxidant, and cytotoxic activities of compounds 1-5 were evaluated.

Three Diketopiperazine Alkaloids with Spirocyclic Skeletons and One Bisthiodiketopiperazine Derivative from the Mangrove-Derived Endophytic Fungus Penicillium brocae MA-231.

Four new diketopiperazines including spirobrocazines A-C (1-3) and brocazine G (4) were characterized from the mangrove-derived Penicillium brocae MA-231. Compounds 1 and 2 had a 6/5/6/5/6 cyclic system with a rare spirocyclic center at C-2. Their structures and absolute configurations were determined by spectroscopic analysis, TDDFT-ECD calculations, and X-ray diffraction. Compound 4 exhibited potent cytotoxicity against both sensitive and cisplatin-resistant human ovarian cancer cells and strong antimicrobial activity against pathogenic Staphylococcus aureus.

Preparation and Characterization of Folate Targeting Magnetic Nanomedicine Loaded with Gambogenic Acid.

To engineer multifunctional nanomedicines for simultaneous imaging and therapy of cancer cells, we have prepared Gambogenic acid (GNA) loaded folic acid (FA) armed MNPs (FA-GNA-MNPs) to target the folate receptor (FR) positive cancer cells. The FA-GNA-MNPs have been prepared by a facile method, which have been further characterized by SEM, TEM, IR and UV-vis spectra. And the cytotoxicity of FA-GNA-MNPs to HeLa and A549 cells was assessed using the MTT assay. The FA-GNA-MNPs (with loading efficiency of 4.35%) showed sustained liberation of GNA molecules (with 73.46% release in 96 h). The mean particle diameter (MD) of FA-GNA-MNPs and the polydispersity index (PDI) are 254.3 nm and 0.139, respectively. The cytotoxicity of free GNA and FA-GNA-MNPs toward HeLa cells showed that FA-GNA-MNPs was more cytotoxic than GNA. Based on these findings, it suggests that FA-GNA-MNPs would be as a novel multifunctional nanomedicine/theranostic for concurrent targeting, imaging and therapy of the FR-positive cancer cells.

[Roles of the cross talk between MAP kinases and Keap1-Nrf2-ARE signaling pathways in chronic obstructive pulmonary disease].

Chronic obstructive pulmonary disease (COPD), a common preventable and treatable disease, is characterized by airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways. Its main pathological manifestations include airway inflammation, mucus hypersecretion, oxidative stress and apoptotic epithelial cells. Recent research suggests that MAP kinases and Keap1-Nrf2-ARE signaling pathway are involved in the pathological process of inflammation and oxidative stress. This review explores the potential role of the cross talk of these signaling pathways in airway inflammation, mucus hypersecretion, oxidative stress and apoptotic epithelial cells. To clarify the roles of cross talk between MAP kinases and Keap1-Nrf2-ARE signaling pathway, we also focus on the drugs related to that in the treatment of COPD, and it provides ideas for more drug research in the treatment of COPD.

[Influence of huatanjiangqi prescription on multidrug resistance-associated protein 1 in human bronchial epithelial cells].

OBJECTIVE: To investigate the effect of Huatanjiangqi prescription (Sinapis Semen, Perillae Fructus, Cynanchi Stauntonii Rhizoma et Radix, Inulae Herba, Angelicae Sinensis Radix, Honey-fried Ephedrae Herba) on multidrug resistance-associated protein 1 (MRP1) in human bronchial epithelial cells. METHODS: The human bronchial epithelial cells line 16HBE140- was used to analyze the in vitro effect of Huatanjiangqi prescription on MRP1 transport. 5-CFDA was used as a model MRP1 substrate and was measured with flow cytometry. The mRNA expression of MRP1 was detected by real-time PCR. RESULTS: Huatanjiangqi prescription could promote the proliferation of human bronchial epithelial cells 16HBE140- in a certain range of concentration; Compared with the control group (5-CFDA), low, medium and high concentration (100, 1 000, 2 000 microg/mL) of Huatanjiangqi prescription on MRP1 function were increased by 22.59%, 47.14% and 68.36%, respectively; Huatanjiangqi prescription could concentration-dependently induce the expression of MRP1 mRNA, medium and high concentration could induce a significant difference. CONCLUSION: Huatanjiangqi prescription can improve MRP1 efflux function and mRNA levels in a concetration-dependent manner.

Ultra-high-performance liquid chromatography tandem mass spectrometry method for the determination of gambogenic acid in dog plasma and its application to a pharmacokinetic study.

A highly sensitive and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of gambogenic acid in dog plasma. Gambogic acid was used as an internal standard (IS). After a simple liquid-liquid extraction by ethyl acetate, the analyte and internal standard were separated on an Acquity BEH C18 (100 × 2.1 mm, 1.7 µm; Waters ) column at a flow rate of 0.2 mL/min, using 0.1% formic acid-methanol (10:90, v/v) as mobile phase. Electrospray ionization source was applied and operated in the positive ion mode. Multiple reaction monitoring mode with the transitions m/z 631.3 → 507.3 and m/z 629.1 → 573.2 was used to quantify gambogenic acid and the internal standard, respectively. The calibration curves were linear in the range of 5-1000 ng/mL, with a coefficient of determination (r) of 0.999 and good calculated accuracy and precision. The low limit of quantification was 5 ng/mL. The intra-and inter-day precisions (relative standard deviations) were <15%. The methodology recoveries were more than 66.63%. This validated method was successfully applied to a pharmacokinetic study after intravenous injection administration of gambogenic acid in dogs at a dose of 1 mg/kg.

Allyl isothiocyanate increases MRP1 function and expression in a human bronchial epithelial cell line.

Multidrug resistance-associated protein 1 (MRP1), a member of the ATP-binding cassette (ABC) superfamily of transporters, plays an important role in normal lung physiology by protecting cells against oxidative stress and toxic xenobiotics. The present study investigates the effects of allyl isothiocyanate (AITC) on MRP1 mRNA and MRP1 protein expression and transporter activity in the immortalised human bronchial epithelial cell line 16HBE14o-. MRP1 mRNA and MRP1 protein expression in 16HBE14o- cells that were treated with allyl isothiocyanate were analysed by real-time PCR assay and Western blotting. The transport of carboxyfluorescein, a known MRP1 substrate, was measured by functional flow cytometry to evaluate MRP1 activity. Treatment with AITC at concentrations of 5-40 µM increased MRP1 protein levels in a concentration-dependent manner. AITC treatments at concentrations of 1-40 µM caused concentration-dependent increases in MRP1 mRNA levels that were up to seven times greater than the levels found in control cells. Finally, AITC treatment at concentrations of 5-40 µM significantly increased MRP1-dependent efflux in 16HBE14o- cells. These results suggest that AITC can increase the expression and activity of MRP1 in 16HBE14o- cells in a concentration-dependent manner. The upregulation of MRP1 activity and expression by AITC could produce therapeutic effects in the treatment of lung disease.

Quantitative analysis of γ- and δ-lactones in wines using gas chromatography with selective tandem mass spectrometric detection.

RATIONALE: Aroma relevant γ- and δ-lactones are important flavor compounds in various foodstuffs. Their quantitative determination is essential for evaluating food sensory properties as well as food authenticity studies. METHODS: High-throughput head-space solid-phase microextraction as sample preparation, separation by capillary gas chromatography coupled with triple stage quadrupole mass spectrometry has been evaluated as the analytical method. RESULTS: Monitoring selected reaction mass fragments allowed sub-µg/L quantification of γ- and δ-lactones in complex wine matrices. CONCLUSIONS: Tandem mass spectrometry improves specific detection of γ- and δ-lactones, a prerequisite for reliable quantification at low-µg/L concentration levels in complex wine matrices.

Application of activated glassy carbon electrode for the detection of nuciferine in lotus leaves.

The electrochemical behavior of nuciferine has been studied for the first time. Nuciferine is irreversibly oxidized at high potentials, resulting in the formation of orthoquinone. The amount of the obtained orthoquinone is pH-dependent, and it demonstrates quasi-reversible electrochemical behavior at less positive potential. The concentration of nuciferine was successfully determined by using the redox character of the electrochemically obtained orthoquinone. A linear range between 8.7x10(-9) and 5.6x10(-7)mol/L and a detection limit of 5.0x10(-9)mol/L were obtained. The method has also been used to quantify nuciferine concentration in lotus leaves that obtained from the Slim West Lake, and the average result was 0.29% (w/w).