A rapid, sensitive, and selective precolumn derivatization method for the simultaneous determination of eight thiophenols using 3-(2-bromoacetamido)-<i>N</i>-(9-ethyl-9<i>H</i>)-carbazol as a labeling reagent by high-performance liquid chromatography with fluorescence detection has been developed. The labeling reagent reacted with thiophenols at 50°C for 50 min in aqueous acetonitrile in the presence of borate buffer (0.10 mol/L, pH 11.2) to give high yields of thiophenol derivatives. The derivatives were identified by online postcolumn mass spectrometry. The collision-induced dissociation spectra for thiophenol derivatives gave the corresponding specific fragment ions at <i>m/z</i> 251.3, 223.3, 210.9, 195.8, and 181.9. At the same time, derivatives exhibited intense fluorescence with an excitation maximum at λ<sub>ex</sub> = 276 nm and an emission maximum at λ<sub>em</sub> = 385 nm. Excellent linear responses were observed for all analytes over the range of 0.033-6.66 μmol/L with correlation coefficients of more than 0.9997. Detection limits were in the range of 0.94-5.77 μg/L with relative standard deviations of less than 4.54%. The feasibility of derivatization allowed the development of a rapid and highly sensitive method for the quantitative analysis of trace levels of thiophenols from some rubber products. The average recoveries (<i>n</i> = 3) were in the range of 87.21-101.12%.
<br>Display Omitted<br>• 4′-Carbonyl chloride rosamine was synthesized and used for NTs by UHPLC-MS/MS. • <b>In situ</b> UA-DDLLME was reported for the simultaneous determination of AANTs and MANTs. • The method was sensitive, selective, low matrix effect, speedy and eco-friendly. • A new analytical tool in diagnosis of AD-related disease.<br>Neurotransmitters (NTs) may play an important role in neurodegenerative disorders such as Alzheimer’s disease (AD). In order to investigate the potential links, a new simple, fast, accurate and sensitive analytical method, based on <b>in situ</b> ultrasound-assisted derivatization dispersive liquid-liquid microextraction (<b>in situ</b> UA-DDLLME) coupled with ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), has been developed and validated. The quantitation of amino acid neurotransmitters (AANTs) and monoamine neurotransmitters (MANTs) in urine of AD rats were performed in this work. The <b>in situ</b> UA-DDLLME procedure involved the rapid injection of the mixture of low toxic 4-bromoanisole (extractant) and acetonitrile (dispersant), which containing the new designed and synthesized 4′-carbonyl chloride rosamine (CCR) as derivatization reagent, into the aqueous phase of real sample and buffer. Under the selected conditions, the derivatization and microextraction of analytes were simultaneously completed within 1 min. Good linearity for each analyte (R > 0.992) was observed with low limit of detections (LODs, S/N > 3). Moreover, the proposed method was compared with direct detection or other reported methods, and the results showed that low matrix effects and good recoveries results were obtained in this work. Taken together, <b>in situ</b> UA-DDLLME coupled with UHPLC-MS/MS analysis was demonstrated to be a good method for sensitive, accurate and simultaneous monitoring of AANTs and MANTs. This method would be expected to be highly useful in AD diseases’ clinical diagnostics and may have potential value in monitoring the efficacy of treatment.
The actinomycetes strain, lut0910, was isolated from polluted soil and identified as the Rhodococcus species with 99% similarity based on the sequence analysis of 16S recombinant DNA. The extract of this strain demonstrated in vivo and in vitro antitumor activity. The treatment of two human cancer cell lines, hepatocellular carcinoma HepG2 and cervical carcinoma Hela cells, with the lut0910 extract caused the delay in cell propagation in a dose-dependent manner with an IC50 of 73.39 and 33.09 µg/mL, respectively. Also, the oral administration of lut0910 extract to the mice with a solid tumor resulted in the inhibition of tumor growth in comparison with a placebo group. The thymus and spleen indexes were significantly increased in mice groups treated with the lut0910 extract. The histopathological changes of the tumor tissues showed that there were massive necrotic areas in the tumor tissues after treatment with different doses of the lut0910 extract. Our result would provide a new way and potent source for development of new anticancer agent from the polluted environment.
This study presents an efficient strategy based on liquid-liquid extraction, high-speed counter-current chromatography, and preparative HPLC for the rapid enrichment, separation, and purification of four anthraquinones from Rheum tanguticum. A new solvent system composed of petroleum ether/ethyl acetate/water (4:2:1, v/v/v) was developed for the liquid-liquid extraction of the crude extract from R. tanguticum. As a result, emodin, aloe-emodin, physcion, and chrysophanol were greatly enriched in the organic layer. In addition, an efficient method was successfully established to separate and purify the above anthraquinones by high-speed counter-current chromatography and preparative HPLC. This study supplies a new alternative method for the rapid enrichment, separation, and purification of emodin, aloe-emodin, physcione, and chrysophanol.
In this paper, an efficient method was successfully established by the combination of macroporous resin (MR) and high-speed counter-current chromatography (HSCCC) for rapid enrichment and separation of aloe-emodin 8-O-β-D-glucoside, emodin 1-O-β-D-glucoside, emodin 8-O-β-D-glucoside and piceatannol 4'-O-β-D-(6″-O-gallate)-glucoside. Six kinds of macroporous resins were investigated in the first step and X-5 macroporous resin was selected for the enrichment of the target compounds. The recoveries of the target compounds reached 89.0, 85.9, 82.3 and 84.9% respectively after 40% ethanol elution. In the second step, the target compounds were separated by HSCCC with a two-phase solvent system composed of chloroform/ethyl acetate/methanol/water (8:1:6:5, v/v). The established method will be helpful for further characterization and utilization of Rheum tanguticum. The results demonstrate that MR coupled with HSCCC is a powerful technique for separation of bioactive compounds from natural products.
Abstract: In the present paper, the effect of the aqueous extract from aerial parts of Artemisia vestita (AV-ext), a traditional Tibetan medicine, on ear contact sensitivity was examined. AV-ext significantly reduced the ear swelling when administered during the induction phase of picryl-chloride (PCl)-induced ear contact sensitivity in mice. The extract also showed a dose-dependent inhibition on lymphocyte proliferation and IL-2 production in Con A-activated spleen cells. The proliferation inhibition was confirmed in the mixed lymphocytes reaction. Furthermore, the adhesion of the isolated spleen cells from PCl-sensitized mice to type IV collagen was significantly decreased in a dose-dependent manner by AV-ext. Such decrease was also seen in AV-ext-treated Jurkat T cells and the T cells purified from above spleen cells. The purified spleen T cells from PCl-sensitized mice produced more matrix metalloproteinase-9 (MMP-9) than naive T cells, and AV-ext remarkably reduced MMP-9 production both in vivo and in vitro. These results suggest that AV-ext may alleviate contact sensitivity through blocking the activation of T lymphocytes and decreasing their localization to the inflammatory sites via down-regulating the potential of cell adhesion and metalloproteinase production.
Biocompatible and bioresponsive microneedles (MNs) are emerging technology platforms for sustained drug release with a potential to be a key player in transdermal delivery of therapeutics. In this paper, an innovative biodegradable MNs patch for the sustained delivery of drugs using a polymer patch, which can adjust delivery rates based on its crosslinking degree, is reported. Gelatin methacryloyl (GelMA) is used as the base for engineering biodegradable MNs. The anticancer drug doxorubicin (DOX) is loaded into GelMA MNs using the one molding step. The GelMA MNs can efficiently penetrate the <i>stratum corneum</i> layer of a mouse cadaver skin. Mechanical properties and drug release behavior of the GelMA MNs can be adjusted by tuning the degree of crosslinking. The efficacy of the DOX released from the GelMA MNs is tested and the anticancer efficacy of the released drugs against melanoma cell line A375 is demonstrated. Since GelMA is a versatile material in engineering tissue scaffolds, it is expected that the GelMA MNs can be used as a platform for the delivery of various therapeutics.<br><b>A biocompatible and biodegradable microneedles patch</b> based on gelatin methacryloyl are developed for transcutaneous delivery of drugs. The microneedles can efficiently penetrate the <i>stratum corneum</i> layer in a mouse cadaver skin model and the drug release profile can be controlled by tuning the crosslinking degrees. The model drug doxorubicin keeps its anticancer efficacy after enzyme-mediated release from the patch.
The biosynthesis of nanoparticles in bioreactors using microbial, plant, or animal cells is at the forefront of nanotechnology. We demonstrated for the first time that luminescent, water-soluble ZnO nanocrystals (bio-ZnO NCs) can be spontaneously biosynthesized in the mammalian blood circulation, not in cells, when animals were fed with Zn(CH3COO)2 aqueous solution. Serum albumin, rather than metallothioneins or glutathione, proved to play the pivotal role in biosynthesis. The bio-ZnO NCs were gradually taken up in the liver and degraded and excreted in the urine. Thus, we propose that in mammals such as rodents, bovinae, and humans, excess metal ions absorbed into the cardiovascular system via the intestine can be transformed into nanoparticles by binding to serum albumin, forming a "provisional metal-pool", to reduce the toxicity of free metal ions at high concentration and regulate metal homeostasis in the body. Furthermore, the bio-ZnO NCs, which showed favorable biocompatibility, were functionalized with the anticancer drug daunorubicin and effectively achieved controlled drug release mediated by intracellular glutathione in tumor xenograft mice.
Studies have revealed that bullying victimization was a risk factor for symptoms of depression, however, less is known about the underlying processes that may mediate or moderate this relationship. This study examined the mediating effect of resilience and moderating effect of mindfulness in the relation between bullying victimization and symptoms of depression. 448 Chinese children in grade 3 to grade 6 were recruited to complete the revised Bully/Victim Questionnaire, the Chinese version of Center for Epidemiologic Studies Depression Scale for Children, the Child and Youth Resilience Measure, as well as the Child and Adolescent Mindfulness Measure. Results showed that resilience partially mediated the relation between bullying victimization and depressive symptoms. Besides, both the effect of bullying victimization on depressive symptoms and the mediating effect of resilience were moderated by mindfulness, and both of the two effects were stronger for children with low mindfulness. The present study can contribute to a better understanding of how and when bullying victimization increases the risk of depression. It suggests that early intervention concerning diminishing negative effects of bullying victimization may start with increasing individual resilience and mindfulness.
Zuota is regarded as the king of Tibetan medicine. However, due to the confidentiality of this precious medicine, the scientific characterization of Zuota is very scarce, which limits the pharmacology and biosafety studies of Zuota. Herein, we collected four different Zuota samples from Tibet, Qinghai, Gansu, and Sichuan and characterized them by multiple techniques. Our results showed that Zuota was mainly an inorganic mixture of HgS, sulfur, and graphite. Morphologically, Zuota samples were composed of nanoparticles, which further aggregated into microsized particles. Chemically, the majorities of Zuota were S and Hg (in the forms of HgS and pure sulfur). All samples contained pure sulfur with orthorhombic crystalline. Zuota from Qinghai province had different HgS crystalline, namely, hexagonal crystalline. The others were all face-centered cubic crystalline. Carbon in Zuota NPs was in the form of graphite. The implication to future studies of Zuota was discussed.
Zuota is regarded as the king of Tibetan medicine. However, due to the confidentiality of this precious medicine, the scientific characterization of Zuota is very scarce, which limits the pharmacology and biosafety studies of Zuota. Herein, we collected four different Zuota samples from Tibet, Qinghai, Gansu, and Sichuan and characterized them by multiple techniques. Our results showed that Zuota was mainly an inorganic mixture of HgS, sulfur, and graphite. Morphologically, Zuota samples were composed of nanoparticles, which further aggregated into microsized particles. Chemically, the majorities of Zuota were S and Hg (in the forms of HgS and pure sulfur). All samples contained pure sulfur with orthorhombic crystalline. Zuota from Qinghai province had different HgS crystalline, namely, hexagonal crystalline. The others were all face-centered cubic crystalline. Carbon in Zuota NPs was in the form of graphite. The implication to future studies of Zuota was discussed.
Zuota is regarded as the king of Tibetan medicine. However, due to the confidentiality of this precious medicine, the scientific characterization of Zuota is very scarce, which limits the pharmacology and biosafety studies of Zuota. Herein, we collected four different Zuota samples from Tibet, Qinghai, Gansu, and Sichuan and characterized them by multiple techniques. Our results showed that Zuota was mainly an inorganic mixture of HgS, sulfur, and graphite. Morphologically, Zuota samples were composed of nanoparticles, which further aggregated into microsized particles. Chemically, the majorities of Zuota were S and Hg (in the forms of HgS and pure sulfur). All samples contained pure sulfur with orthorhombic crystalline. Zuota from Qinghai province had different HgS crystalline, namely, hexagonal crystalline. The others were all face-centered cubic crystalline. Carbon in Zuota NPs was in the form of graphite. The implication to future studies of Zuota was discussed.
Graphical abstract The introduction of chiral enantiomers generated chiral β-HgS QDs, which showed chirality inversion compared with the corresponding chiral ligands. Their chiroptical activity, good cytocompatibility, near-infrared optical absorption, near-infrared fluorescence emission and high-performance photothermal conversion implied that these chiral β-HgS quantum dots have potential to be applied in biotechnology and bio-medicine. Abstract β-HgS quantum dots (QDs) have drawn enormous attention due to the size-tunable bandgap and the lowest quantum state in conduction band which have been applied to semiconductor transistor and photodetector. Though β-HgS is the essential component of Tibetan medicine, the potential toxicity of β-HgS limits its applications, especially in bio-application. Herein, chiral biomolecule enantiomers N -isobutyryl- L (D)-cysteine (L (D)-NIBC) and L (D)-cysteine (L (D)-Cys) were introduced into HgCl 2 and Na 2 S aqueous solution to synthesize chiral β-HgS QDs in one-pot, which significantly improved their water-solubility and cytocompatibility. Notably, all chiral β-HgS QDs showed none cytotoxicity even at high concentration (20 mg·L−1), and the cytocompatibility of D -β-HgS QDs was better than corresponding L -β-HgS QDs at the concentration of 20 mg·L−1. This cytotoxicity discrimination was associated with the chirality inversion of chiral β-HgS QDs compared with the corresponding chiral ligands. In-situ real-time circular dichroism (CD) monitoring indicated that the chirality of β-HgS QDs originated from the asymmetrical arrangement of chiral ligands on the achiral core surface. Their chiroptical activity, near-infrared optical absorption (800 nm), fluorescence emission (900–1000 nm), high-performance photothermal conversion and good cytocompatibility, implied chiral β-HgS QDs could be used as a candidate material for photothermal therapy or a near-infrared fluorescent probe in organism, which brings a novel insight for bio-application of β-HgS QDs. [ABSTRACT FROM AUTHOR]
Cirsilineol (4′,5-dihydroxy-3′,6,7-trimethoxyflavone) is a compound isolated from the herb of <i>Artemisia vestita</i> Wall (Compositae). In this study, we aimed at examining the anti-proliferative activity of cirsilineol against multiple types of cancer cells and the underlying mechanisms. Cirsilineol significantly inhibited proliferation of Caov-3, Skov-3, PC3 and Hela cells in a concentration-dependent manner. The compound also dose-dependently induced apoptosis in Caov-3 cells, as determined by annexin V/propidium iodide staining. Besides, cirsilineol induced a remarkable change in mitochondrial membrane potential and caused release of cytochrome <i>c</i> to cytosol. Furthermore, the compound caused a marked activation of capase-3, caspase-9 and poly (ADP-ribose) polymerase (PARP). These results suggested that the induction of apoptosis via the mitochondrial pathway was involved in the anti-proliferative activity of cirsilineol against cancer cells.
One new compound, Colletotrichine A (1), was produced by the fungal Colletotrichum gloeosporioides GT-7. The structure was established by 1D and 2D NMR spectra. Monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitory activity of 1 was also evaluated. Compound 1 showed AChE-inhibiting activity with IC50 value of 28 μg/mL.
One new compound, colletotrichine B (1), was produced by the fungal Colletotrichum gloeosporioides GT-7. The structure of 1 was elucidated on the basis of spectroscopic analysis and X-ray crystallographic analysis. Monoamine oxidase (MAO), acetylcholinesterase (AChE) and phosphoinositide 3-kinase (PI3Kα) inhibitory activity of 1 was also evaluated. Compound 1 showed only AChE inhibiting activity with IC50 value of 38.0 ± 2.67 μg/mL.
Four novel lactams, colletotrilactam A-D (1-4), along with six known compounds (5-10) were isolated from the culture broth of Colletotrichum gloeosporioides GT-7, a fungal endophyte of Uncaria rhynchophylla. The structures of these compounds were elucidated by comprehensive NMR spectroscopy. Isolates were tested for monoamine oxidase (MAO) inhibitory activity and compound 9 showed potent MAO inhibitory activity with IC50 value of 8.93±0.34μg/mL, when the IC50 value of iproniazid as a standard was 1.80±0.5μg/mL.
Four novel lactams, colletotrilactam A-D (1-4), along with six known compounds (5-10) were isolated from the culture broth of Colletotrichum gloeosporioides GT-7, a fungal endophyte of Uncaria rhynchophylla. The structures of these compounds were elucidated by comprehensive NMR spectroscopy. Isolates were tested for monoamine oxidase (MAO) inhibitory activity and compound 9 showed potent MAO inhibitory activity with IC50 value of 8.93±0.34μg/mL, when the IC50 value of iproniazid as a standard was 1.80±0.5μg/mL.
[Objectives] To explore the mechanism for the attenuate-synergistic effect of Zuota to Renqing Mangue, a contrasted study on the tissue distribution of Tibetan medicines Renqing Mangue compatible with Zuota was carried out. [Methods] The SD rats gastric ulcer model were made successfully, and then respectively were given Renqing Mangue compatible with Zuota or not according to the dose of 0.144 g/kg and normal saline by gavage administration, once a day. After 14 d of administration, various organs and tissue were isolated, including brain, heat, liver, spleen, lung, kidney, jejunum, skeletal muscle, fat, skin, submandibular gland, uterus and ovary (or testicle and epididymis). The LC-MS/MS methods were used for determining the contents of brucine and strychnine in various organs and tissue, and significant difference analysis, main target site analysis and clustering analysis were implemented. [Results] Between the Zuota group and non-Zuota group, there was extremely significat diference in the content of brucine in the liver, kidney, muscle, lung, ovary, and heart (P < 0.01), significant difference in the jeeunum (P <0.05), and no significant diference in the epididymis, testis, brain, skin and uterus (P > 0.05); the content of brucine in the submadibular gland, spleen, liver and ovary increased significantly, but significanty reduced in the kidney, muscle, jeeunum, lung and heart. And there was extremely significant diference in the content of strychnine in the liver, kidney, ovary, brain and heat (P <0.01), and no significat difference in the uterus (P > 0.05); the strychnine content increased significantly in the liver, spleen and ovary, and significanty decreased in the kidney, muscle, testis, lung, brain and heart. [Conclusions] Compatibility of Zuota can afect the distribution of brucine and strychnine in some tissue and organs, so a to achieve attenuate-synergistic effect of Zuota to Renqing Mague. [ABSTRACT FROM AUTHOR]
ETHNOPHARMACOLOGICAL RELEVANCE: Tibetan medicine get used to use the flowers of Gentiana straminea Maxim. to cure inflammation of stomach and intestines, hepatitis, cholecystitis, etc. The flowers of Gentiana macrophylla Pall. have been traditionally treated as an anti-inflammatory agent to clear heat in Mongolian medicine. In traditional Chinese medicine, Gentiana macrophylla Pall. and Gentiana straminea Maxim. have also been used under the name "Gentianae Macrophyllae Radix" and prescribed for the treatment of pain and inflammatory conditions.AIM OF STUDY: The present study evaluated the pharmacological effects of two species of "Radix Gentianae Macrophyllae" in experimental inflammation and pain models, and determined the chemical compounds that may correlate with their pharmacological activities. The comparison is needed to identify whether the two related plants can be used interchangeably.
MATERIALS AND METHODS: We evaluated the pharmacological effects of the flowers of Gentiana macrophylla Pall. and Gentiana straminea Maxim. in experimental inflammation and pain models. An HPLC-MS method was developed to analyze the chemical composition. The effects of Gentiana macrophylla Pall. and Gentiana straminea Maxim. on the p65 and p50 phosphorylation were examined by immunblotting. NF-κB transcriptional activity was measured using the luciferase assay, in vitro kinase assay and Griess reaction.
RESULTS: The extracts of Gentiana macrophylla Pall. and Gentiana straminea Maxim. possessed significant antinociceptive and anti-inflammatory activities. Flavonoids, secoiridoid glycosides and triterpines were determined in the extracts and may be the basis of the observed pharmacological effects. Nuclear translocation of p65, p50 and NF-κB transcriptional activity induced by LPS were suppressed by Gentiana macrophylla Pall. and Gentiana straminea Maxim.
CONCLUSION: The results clearly demonstrated that the chemical composition and pharmacological activities of the two herbs were similar, which support the interchangeability among the two herbs when using them in folk medicine.
To provide insights into the mechanism for the attenuate-synergistic effect of Zuota to Tibetan medicine Renqing Mangjue, a contrasted study was carried out on the pharmacokinetics of brucine and strychnine in mice plasm, which are active and toxicant ingredient in the Tibetan medicine Renqing Mangjue. LC-MS/MS was used to detect simultaneously the concentrations of brucine and strychnine in mice plasm at-different time intervals after administration parallelly and randomly, and the pharmacokinetic software Kinetica 5. 0 was selected to non-compartmental analysis (NCA) for data, and statistical analysis software SPSS 19. 0 was used for significance test on the pharmacokinetic parameters. A reliable LC-MS/MS method was established for the determination of brucine and strychnine in blood plasma, which are consistent with the requirements of the preclinical pharmacokinetic study confirmed by the methodology. The linear concentration ranges of brucine and strychnine were 0.301-104.4 µg · L(-1) (r = 0.999 5) and 0.305-106 µg · L(-1) (r = 0.999 7), respectively; The intra-day and inter-day variable coefficients were both less than 10.0% with good precision; The average extraction recoveries of brucine and strychnine were 116.23% and 112.82%, and RSD were 3.2% and 2.3% separately;The average matrix effects of brucine and strychnine were 122.48% and 116.36%, and RSD were 7.7% and 4.4%, respectively. The pharmacokinetic results showed that AUCtot of brucine and strychnine in Zuota group were both increased remarkably (P < 0.05), and the Cmax of brucine in Zuota group was about 5.25-fold higher than that of brucine in non-Zuota group (P < 0.05). The Tmax of brucine and strychnine reduced to one-eighth and one-quarter respectively compared with those in Non-Zuota group. In addition, the eliminations of brucine and strychnine in vivo were accelerated after the compatibility of Zuota. A significant difference (P < 0.05) occurred at the MRT0-t, of brucine, while the MRT0-∞ and Lz of strychnine were statistically significant upon the inspection level α = 0.1. It was found that the absorption degree of brucine and strychnine in Zuota group increased in the range of the safe dose (or concentration), while their elimination rates were accelerated, which may be one of the mechanisms for attenuate-synergistic effect of Zuota to Tibetan medicine Renqing Mangjue.
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