Chelating decorporation agents for internal contamination by actinides: Designs, mechanisms, and advances.

During the wide utilization of the actinides in medicine, energy, military, and other fields, internal contaminations can profoundly endanger human health and public security. Chelating decorporation agents are the most effective therapies to reduce internal contamination that includes radiological and chemical toxicities. This review introduces the structures of chelating decorporation agents including inorganic salts, polyaminocarboxylic acids, peptides, polyphosphonates, siderophores, calixarenes, polyethylenimines, and fullerenes, and highlights ongoing advances in their designs and mechanisms. However, there are still numerous challenges that block their applications including coordination properties, pharmacokinetic properties, oral bioavailability, limited timing of administration, and toxicity. Therefore, additional efforts are needed to push novel decorporation agents with high efficiency and low toxicity for the treatment of internal contamination by actinides.

Purification of total flavonoids from Ginkgo biloba flowers with resin column chromatography and evaluation of antioxidant activities in vitro.

Purification of total flavonoids from Ginkgo biloba flowers (GBF) extracts were studied using six resins. Adsorption-desorption experiments indicated that polyamide resin is the most suitable resin. The optimal purification process of total flavonoids of GBF was as follows: a loading concentration of 5.85 mg/mL, a loading volume of 1 bed volume (BV), a loading flow rate of 2 BV/h, a water volume of 2.67 BV, and a desorption solution of 40% ethanol. Under these conditions, the maximum purity of total flavonoids was 37.1 ± 1.1%. The antioxidant activity of purified flavonoids was further evaluated in vitro. It showed that the 40% ethanol purified fraction (Fr. B) group had the strongest antioxidant activity of the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity concentration for 50% of maximal effect (EC50, 145.4 ± 13.8 µg/mL) and ferric reducing ability (2.5 ± 0.2 mM FeSO4 equivalent mg-1 Fr. B). In addition, at the concentration of 160 µg/mL, the Fr. B strikingly increased the viability rate of hydrogen peroxide stimulated PC-12 cells to normal levels (***p < 0.001). This method provides a basis for the application and development of GBF resources. It indicated that the purified GBF flavonoids can be used as a source of potential antioxidant.

Correction: Pentacyclic spermidine alkaloids with radioprotective and anti-inflammatory activities from Orychophragmus violaceus.

Correction for 'Pentacyclic spermidine alkaloids with radioprotective and anti-inflammatory activities from Orychophragmus violaceus' by Zan-Xin Xu et al., Org. Biomol. Chem., 2021, 19, 9844-9848, DOI: 10.1039/D1OB01973B.

Supercritical CO2 extraction of fermented soybean lipids against erastin-induced ferroptosis in rat pheochromocytoma cells.

The optimum supercritical carbon dioxide (SC-CO2) extraction of fermented soybean lipids (FSE-C) was as follows: 35 °C, 30 MPa, and 2.40 ± 0.19% moisture content using response surface methodology. The fatty acid composition of FSE-C contained more palmitic acid and α-linolenic acid and less linoleic acid than unfermented soybean lipids (SE-C). FSE-C had higher contents of minor active components (phytosterols, squalene, total flavonoid, and total polyphenol) than SE-C. The protective effects of FSE-C on erastin-induced ferroptosis were investigated to reveal the potential mechanisms of action characterized by increasing cell viability and glutathione concentrations, attenuating levels of intracellular Fe2+ ion, lipid peroxidation, and ROS, as well as modifying mRNA expression (GPx4, SLC7A11, ACSL4, and LPCAT3) and lipid metabolism. These findings suggest that FSE-C is a class of active ingredients against erastin-induced ferroptosis and warrants further exploration and utilization as a functional food.

Pentacyclic spermidine alkaloids with radioprotective and anti-inflammatory activities from Orychophragmus violaceus.

Two pairs of novel pentacyclic spermidine alkaloid enantiomers, (±)-orychoviolines A and B ((±)-1 and (±)-2), were isolated from the seeds of Orychophragmus violaceus and represented the first example of a 2-piperidinone-fused hydrodibenzofuran skeleton, constructed from a 6/5/6/6 tetracyclic system and an 18 atomic ring. The most unexpected novelty was the formation of one more piperidinone ring by a connection between C-6 and N-7. Their structures and absolute configurations were determined by spectroscopic analyses, X-ray crystallography, and ECD analysis. Compared to Ex-RAD (sodium salt of 4-carboxystyryl-4-chlorobenzylsulfone), (-)-1 exhibited a significant radioprotective effect on cell survival and DNA damage. (-)-1 also exhibited remarkable anti-inflammatory activity by inhibiting the production of NO in RAW 264.7 cells activated by lipopolysaccharide with an IC50 value of 20.3 ± 1.58 µM, which was equivalent to that of dexamethasone.

Advances in Supercritical Carbon Dioxide Extraction of Bioactive Substances from Different Parts of Ginkgo biloba L.

Ginkgo biloba L. has always been a popular area of research due to its various active ingredients and pharmacological effects. Ginkgo biloba is rich in ginkgo flavonoids, ginkgolides, and ginkgolic acid, with anti-inflammation, antioxidation, neuroprotection, anti-platelet agglutination, hypolipidemic effect, anti-cancer, and anti-radiation properties. There are many methods to extract and separate the active components of ginkgo. Among them, supercritical carbon dioxide fluid extraction (SFE-CO2) is known for its green, clean, and environment-friendly properties. In this paper, the pharmacological activities, the active components, and structures of different parts of ginkgo, the extraction methods of its effective ingredients, and the application of the SFE-CO2 method for the extraction and separation of active ingredients in Ginkgo biloba from leaves, seeds, pollen, and roots were reviewed, in order to make best use of ginkgo resources, and provide support and references for the development of SFE-CO2 of active components from Ginkgo biloba.

Lipidomics of Serum and Hippocampus Reveal the Protective Effects of Fermented Soybean Lipid on Rats of Microwave-Induced Cognitive Damage.

Fermented soybean lipids (FSE-C) is an extract enriched in active lipid classes. To explore whether FSE-C can alleviate cognitive damage triggered by the exposure to microwave radiation through regulating lipid metabolism, we employed lipidomic profiling based on a UPLC-MS to investigate differential lipid metabolites in the serum and hippocampus of rats. The results showed that orally administered FSE-C could protect from cognitive damage in microwave-induced rats. Serum lipidomics indicated that FSE-C effectively facilitated the recovery of 43 differential lipid metabolites including 6 phosphatidylcholines (PCs), 5 phosphatidylethanolamines (PEs), 1 phosphatidylinositol, 3 lysophosphatidylcholines (LPCs), 6 lysophosphatidylethanolamines (LPEs), and 22 triglycerides (TGs), which was consistent with the analysis of serum TG levels. Moreover, FSE-C positively coordinated hexacosanoic acid, 2 PCs, 4 sphingomyelins (SMs), and 11 TGs, through the hippocampal lipidomics. Collectively, these findings suggested that phospholipid and TG metabolisms were significantly modified in microwave-exposed rats. TGs may be regarded as potential biomarkers to further investigate and evaluate the roles and functions of FSE-C on the attenuation of cognitive damage induced by microwave radiation.

Antioxidant and anti-inflammatory constituents from Flos populi.

Investigation of the n-butanol extract of Flos populi led to the isolation of one new phenolic glycoside, 4'-hydroxybenzyl-2-hydroxybenzoate-1'-O-ß-D-glucopyranoside (1), together with twelve known compounds, which have been determined on the basis of spectroscopic analysis including UV, IR, HR-ESI-MS and 1D/2D NMR. The antioxidant capacity of all compounds were evaluated by ABTS radical-scavenging test and ferric reducing antioxidant power (FRAP) assay. And during a screening procedure for the anti-inflammatory activities among most compounds on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells, compound 13 exhibited remarkable inhibitory effects on nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß, suggesting that it might be a promising candidate as an anti-inflammatory agent.

New cyclopeptide alkaloids from the whole plant of Justicia procumbens L.

Three novel 14-membered cyclopeptide alkaloids, justicianenes B-D (1-3), were isolated from the EtOH extract of the whole plant of Justicia procumbens L., and their structures were determined on the basis of detailed NMR spectroscopic data and the absolute stereochemistry of the ring-bonded α-amino acids in the cyclopeptide alkaloids were determined by ECD spectra. The isolated compounds were evaluated for their in vitro cytotoxicity against human cancer cell lines, including brest cancer MCF-7, cervix carcinoma HeLa, lung cancer A549 and H460, and diphyllin (14) showed moderate cytotoxicity against the HeLa, A549 and H460 cells with IC50 of 9.13, 23.12, 42.34 µM, respectively, justicianene D showed weak cytotoxicity against the MCF-7 cell with inhibition rate of 50% at the concentration of 90 µM.

Site-Specific and Quantitative N-Glycan Heterogeneity Analysis of the Charge Isomers of an Anti-VEGF Recombinant Fusion Protein by High-Resolution Two-Dimensional Gel Electrophoresis and Mass Spectrometry.

Glycan modification prompts important concerns about the quality control of biopharmaceutical production. Conbercept is a multiglycosylated recombinant fusion protein drug approved for the treatment of age-related macular degeneration (AMD). With 14 N-glycosites in the molecule and 7 N-glycosites in the monomer, the charge isomer separation and characterization of conbercept pose great challenges due to its enormous heterogeneities. The batch-to-batch stability on the charge isomer distribution and the possible causation of the pattern necessitate the development of effective analytical approaches. Here, the immobilized pH gradient (IPG)-based two-dimensional gel electrophoresis (2-DE) approach was first optimized to achieve high-resolution, high-reproducible separation and preparation of charge isomers. Then, combined with the quantitative analysis strategy of site-specific N-glycan heterogeneity based on the diagnostic MS2 ion (peptides+GlcNAc, Y1 ions) of glycopeptides, an integrated approach for the quantitation of site-specific N-glycan heterogeneities among charge isomers was established. Finally, the quantitation of site-specific N-glycoforms in each of the 2-DE resolved spots were performed, and the results showed that the sialylation tends to increase for gel spots located in the acidic regions. This study provides an effective approach to separate the charge isomers of the heavily glycosylated protein drugs, and to quantitatively explore the site-specific N-glycans dynamics along with the different charge isomers.

The relationship between microwave radiation injury and abnormal lipid metabolism.

Microwave radiation can lead to some biological effects, mainly involving the nervous and reproductive systems. However, its lipid metabolic mechanism remains unclear. Here, we performed an untargeted metabolomics approach to analyze lipid metabolic changes caused by microwave radiation using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Then, multivariate analysis was used to reveal the different lipid metabolites and metabolic pathways. Compared with the sham group, biochemical parameters of the microwave group had significant changes in triglyceride (TG) and high-density lipoprotein (HDL) levels. Sixty-eight abnormal lipids were identified, which were mainly distributed in linoleic acid metabolism, glycerophospholipid metabolism, glycerolipid metabolism and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. Among them, phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC) and linoleic acid showed mainly upregulated expression, while sphingomyelin (SM), cholesterol esters (CE) and some free fatty acids (FFAs) showed downregulated expression. Phosphatidylcholine (PC) and triacylglycerol (TG) were increased or decreased. Furthermore, we obtained significant links between lipid metabolic changes and cognitive damage caused by microwave radiation. Together, our results suggested that microwave radiation could cause changes in lipid metabolism and provided a novel insight into the role of lipids in microwave radiation. Targeting lipid metabolism may provide a new therapeutic strategy for microwave radiation injury.

Anticancer Effects of Five Biflavonoids from Ginkgo Biloba L. Male Flowers In Vitro.

Ginkgo biloba L., an ancient dioecious gymnosperm, is now cultivated worldwide for landscaping and medical purposes. A novel biflavonoid-amentoflavone 7''-O-ß-D-glucopyranoside (1)-and four known biflavonoids were isolated and identified from the male flowers of Ginkgo. The anti-proliferative activities of five biflavonoids were evaluated on different cancer lines. Bilobetin (3) and isoginkgetin (4) exhibited better anti-proliferative activities on different cancer lines. Their effects were found to be cell-specific and in a dose and time dependent manner for the most sensitive HeLa cells. The significant morphological changes validated their anticancer effects in a dose-dependent manner. They were capable of arresting the G2/M phase of the cell cycle, inducing the apoptosis of HeLa cells dose-dependently and activating the proapoptotic protein Bax and the executor caspase-3. Bilobetin (3) could also inhibit the antiapoptotic protein Bcl-2. These might be the mechanism underlying their anti-proliferation. In short, bilobetin (3) and isoginkgetin (4) might be the early lead compounds for new anticancer agents.

Anti-inflammatory effects of chemical components from Ginkgo biloba L. male flowers on lipopolysaccharide-stimulated RAW264.7 macrophages.

Ginkgo biloba L., well known as living fossil, have various pharmacological activities. Eighteen compounds were isolated from Ginkgo male flowers including a novel matsutake alcohol glycoside, Ginkgoside A (1), and 17 known compounds-calaliukiuenoside (2), benzylalcohol O-α-l-arabinopyranosyl-(1 â†’ 6)-ß-d-glucopyranoside (3), amentoflavone (4), sciadopitysin (5), bilobetin (6), isoginkgetin (7), olivil 4-O-ß-d-glucopyranoside (8), dihydrodehydrodiconiferyl alcohol-4-O-ß-d-glucoside (9), (+)-cyclo-olivil-6-O-ß-d-glucopyranoside (10), (-)-isolariciresinol 4-O-ß-d-glucopyranoside (11), coniferin (12), trans-cinnamic acid-4-O-ß-d-glucopyranoside (13), p-coumaryl alchol glucoside (14), stroside B (15), methylconiferin (16), cis-p-coumaric acid 4-O-ß-d-glucopyranoside (17), and cis-coniferin (18). Thirteen of these compounds had not previously found in Ginkgo. All extractive fractions and isolated compounds were evaluated for their anti-inflammatory ability in the lipopolysaccharide-induced RAW264.7 macrophages. The ethanol extract of Ginkgo flowers and the chloroform and ethyl acetate fractions can significantly decrease nitric oxide (NO), interleukin-6 (IL-6), and prostaglandin E2 (PGE2 ) production at 100 µg/ml. The most effective compounds, bilobetin (6) and isoginkgetin (7), elevated the NO inhibition ratios to 80.19% and 82.37% at 50 µM, respectively. They also exhibited significant dose-dependent inhibitory effects on tumor necrosis factor-α, IL-6, PGE2 , inducible NO synthase mRNA, and cyclooxygenase-2 mRNA levels. So they can be promising candidates for the development of new anti-inflammatory agents.

A new triterpenoid saponin and a diterpene glucoside from the seeds of Orychophragmus violaceus.

One new triterpenoid saponin orychoside A (1) and one new diterpene glucoside orychoside B (12), together with eleven known compounds, were isolated from the seeds of Orychophragmus violaceus. The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The known compounds were identified by comparison with data reported in the literature. All compounds were tested for their cytotoxic activities against the HepG2 and A549 cell lines in vitro. The new compound 1 exhibited potent cytotoxicity against the two cell lines with IC50 values of 7.13 and 8.77 µM, respectively. Compounds 2, 5, 8 and 9 were found to possess obvious cytotoxicity.

Developing a robust LC-MS/MS method to quantify Zn-DTPA, a zinc chelate in human plasma and urine.

Quantitation of Zn-DTPA (zinc diethylenetriamene pentaacetate, a metal chelate) in complex biological matrix is extremely challenging on account of its special physiochemical properties. This study aimed to develop a robust and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of Zn-DTPA in human plasma and urine. The purified samples were separated on Proteonavi (250 × 4.6 mm, 5 µm; Shiseido, Ginza, Tokyo, Japan) and a C18 guard column. The mobile phase consisted of methanol-2 mm ammonium formate (pH 6.3)-ammonia solution (50:50:0.015, v/v/v), flow rate 0.45 mL/min. The linear concentration ranges of the calibration curves for Zn-DTPA were 1-100 µg/mL in plasma and 10-2000 µg/mL in urine. The intra- and inter-day precisions for quality control (QC) samples were from 1.8 to 14.6% for Zn-DTPA and the accuracies for QC samples were from -4.8 to 8.2%. This method was fully validated and successfully applied to the quantitation of Zn-DTPA in plasma and urine samples of a healthy male volunteer after intravenous infusion administration of Zn-DTPA. The result showed that the concentration of Zn-DTPA in urine was about 20 times that in plasma, and Zn-DTPA was completely (94.7%) excreted through urine in human.

Metabolomics analysis of serum reveals the effect of Danggui Buxue Tang on fatigued mice induced by exhausting physical exercise.

Danggui Buxue Tang (DBT), believed to invigorate 'Qi' (vital energy) and nourish 'Blood' (body circulation), is a traditional Chinese medicine formula. In this study, a metabolomics approach with gas chromatography coupled to mass spectrometry combined with pattern recognition was adopted to investigate the underlying mechanism of the antifatigue effect of DBT on fatigue of mice induced by weight-loaded forced swimming. Fourteen endogenous metabolites, up-regulated or down-regulated, were identified in the model mice by analysis tools of partial least-squares discriminant analysis (PLS-DA) and XCMS online software. Furthermore, the metabolites were reversed by DBT treatment, offering evidence for the antifatigue effect. In addition, intervention of DBT changed the levels of biochemical parameters. DBT showed obvious efficacy on the fatigued mice possibly by regulating the pathways of phenylalanine, tyrosine and tryptophan metabolism, glycine, serine, and threonine metabolism, glyoxylate and dicarboxylate metabolism, pyruvate metabolism, and TCA cycle. This study demonstrated that DBT has a good antifatigue effect and that metabolomics is a powerful means to gain insights into the therapeutic effect of traditional Chinese medicine formulas.

Isocoumarin derivatives and monoterpene glycoside from the seeds of Orychophragmus violaceus.

Five new compounds, including four new isocoumarin derivatives [orychophramarin A-D (1-4)] and a new monoterpene glycoside [orychovioside A (5)], together with fourteen known compounds were isolated from the seeds of Orychophragmus violaceus. Their structures were established on the basis of chemical evidence and spectroscopic analysis. Compound 1 showed significant cytotoxicity against HCT-116 and Hela cell lines compared with the positive control group (Cisplatin) with IC50 values of 5.10 and 8.91µM, respectively. Compound 1 exhibited evident cell cycle retardation that arrested HCT-116 cells at G2 phase and induced apoptosis in HCT-116 cells in the further mechanism study.

Orychophragines A-C, Three Biologically Active Alkaloids from Orychophragmus violaceus.

Orychophragines A-C (1-3), three new alkaloids with an novel 2-piperazinone-fused 2,4-dioxohexahydro-1,3,5-triazine skeleton, were isolated from the seeds of Orychophragmus violaceus. Their structures were established on the basis of spectroscopic analysis and X-ray crystallographic analysis. Orychophragines A (1) exhibited remarkable cytotoxicity against HepG2, A549, Hela, and HCT-116 cells with IC50 values of 7.73, 10.79, 11.91, and 9.93 µM, respectively. Orychophragines C (3) showed moderate 60Co γ radiation protection activity in HUVEC cells. A plausible biosynthetic pathway for 1-3 was proposed.

Drug-loaded pH-responsive polymeric micelles: Simulations and experiments of micelle formation, drug loading and drug release.

pH-responsive drug nanocarriers are widely applied for cancer treatment. However, the mechanistic details of drug loading and drug release from these micelles are unknown. Here, we reveal the mechanistic details of micelle formation, drug loading and drug release from pH-responsive polymeric micelles using computer simulations and experiments. A triblock amphiphilic copolymer, methoxy-poly(ethylene glycol) 2000-poly(2-(N,N-diethylamino)ethyl methacrylate)-polycaprolactone (mPEG-PDEA-PCL, PDC), was used to load paclitaxel (PTX), a hydrophobic anticancer agent, using an injection method. The micelles showed strong pH-responsive behavior, where the sizes and zeta potentials ranged from 51nm and 19mV at pH 4.5, respectively, to 22nm and -5.5mV at pH 8, respectively, with greater PTX release at pH 6.5 than that at pH 7.4. Furthermore, the PTX-loaded PDC micelles showed higher cytotoxicity to MCF-7 cells at pH 6.5 than that at pH 7.4 due to differential drug release. Molecular dynamics and the coarse-grained dissipative particle dynamic method were used to mimic micelle formation, drug loading and drug release. The pH-responsive segment, PDEA, transforms to its protonated form, PDEAH+, in an acidic environment. PTX and PDC form micelles based on hydrophobic interactions, where PTX inserts into the hydrophobic PDEA-PCL core in a neutral environment. An acidic transition of the environment leads to rapid PTX release from the micelles due to the hydrophobic-hydrophilic transition of PDEA to PDEAH+, though some PTX molecules still remain in the PCL core. The pH-responsive PDC micelles are suitable for triggered drug release in an acidic tumor microenvironment. The PDC micelle is, therefore, a promising nanocarrier of anticancer agents for cancer treatment.