Astragalosidic Acid: A New Water-Soluble Derivative of Astragaloside IV Prepared Using Remarkably Simple TEMPO-Mediated Oxidation.

There is an urgent need for a water-soluble derivative of astragaloside IV for drug R&D. In the present study, a remarkably simple method for the preparation of such a water-soluble derivative of astragaloside IV has been developed. This protocol involves oxidative 2,2,6,6-tetramethylpiperidine-1-oxyl free radical (TEMPO)-mediated transformation of astragaloside IV to its carboxylic acid derivative, which is a new compound named astragalosidic acid. The structure of astragalosidic acid was elucidated by means of spectroscopic analysis. Its cardioprotective activity was investigated using an in vitro model of cardiomyocyte damage induced by hypoxia/reoxygenation in H9c2 cells. The oxidative TEMPO-mediated transformation proposed in the present study could be applied to other natural saponins, offering an effective and convenient way to develop a new compound with greatly improved structure-based druggability.

Quick and selective extraction of Z-ligustilide from Angelica sinensis using magnetic multiwalled carbon nanotubes.

A facile and highly efficient magnetic solid-phase extraction method has been developed for Z-ligustilide, the major therapeutic agent in Angelica sinensis. The solid-phase adsorbent material used was prepared by conjugating carbon nanotubes with magnetic Fe3 O4 nanoparticles via a hydrothermal reaction. The magnetic material showed a high affinity toward Z-ligustilide due to the π-π stacking interaction between the carbon nanotubes and Z-ligustilide, allowing a quick and selective exaction of Z-ligustilide from complex sample matrices. Factors influencing the magnetic solid-phase extraction such as the amount of the added adsorbent, adsorption and desorption time, and desorption solvent, were investigated. Due to its high extraction efficiency, this method was proved highly useful for sample cleanup/enrichment in quantitative high-performance liquid chromatography analysis. The proposed method had a linear calibration curve (R(2) = 0.9983) over the concentration between 4 ng/mL and 200 µg/mL Z-ligustilide. The accuracy of the method was determined by the recovery, which was from 92.07 to 104.02%, with the relative standard deviations >4.51%.

Metabolic study of Angelica dahurica extracts using a reusable liver microsomal nanobioreactor by liquid chromatography-mass spectrometry.

Highly active and recoverable nanobioreactors prepared by immobilizing rat liver microsomes on magnetic nanoparticles (LMMNPs) were utilized in metabolic study of Angelica dahurica extracts. Five metabolites were detected in the incubation solution of the extracts and LMMNPs, which were identified by means of HPLC-MS as trans-imperatorin hydroxylate (M1), cis-imperatorin hydroxylate (M2), imperatorin epoxide (M3), trans-isoimperatorin hydroxylate (M1') and cis-isoimperatorin hydroxylate (speculated M2'). Compared with the metabolisms of imperatorin and isoimperatorin, it was found that the five metabolites were all transformed from these two major compounds present in the plant. Since no study on isoimperatorin metabolism by liver microsomal enzyme system has been reported so far, its metabolites (M1' and M3') were isolated by preparative HPLC for structure elucidation by (1) H-NMR and MS(2) analysis. M3' was identified as isoimperatorin epoxide, which is a new compound as far as its chemical structure is concerned. However, interestingly, M3' was not detected in the metabolism of the whole plant extract. In addition, a study with known chemical inhibitors on individual isozymes of the microsomal enzyme family revealed that CYP1A2 is involved in metabolisms of both isoimperatorin and imperatorin, and CYP3A4 only in that of isoimperatorin.

Selective extraction of berberine from Cortex Phellodendri using polydopamine-coated magnetic nanoparticles.

A new extraction agent featuring dopamine self-polymerized on magnetic Fe3 O4 nanoparticles has been successfully synthesized and evaluated for the SPE of berberine from the extract of the traditional Chinese medicinal plant, Cortex Phellodendri. The nanoparticles prepared possessed a core-shell structure and showed super-paramagnetism. It was found that these polydopamine-coated nanoparticles exhibited strong and selective adsorption for berberine. Among the chemical components present in C. Phellodendri, only berberine was adsorbed by the nanoparticles and extracted by a following SPE procedure. Various conditions such as the amount of polydopamine-coated nanoparticles, desorption solvent, desorption time and equilibrium time were optimized for the SPE of berberine. The purity of berberine extracted from C. Phellodendri was determined to be as high as 91.3% compared with that of 9.5% in the extract. The established SPE protocol combined advantages of highly selective enrichment with easy magnetic separation, and proved to be a facile efficient procedure for the isolation of berberine. Further, the prepared polydopamine-coated magnetic nanoparticles could be reused for multiple times, reducing operational cost. The applicability and reliability of the developed SPE method were demonstrated by isolating berberine from three different C. Phellodendri extracts. Recoveries of 85.4-111.2% were obtained with relative standard deviations ranging from 0.27-2.05%.

Vesicular gold assemblies based on host-guest inclusion and its controllable release of doxorubicin.

We have developed a kind of gold nanoparticle (AuNP) in which polyethylene glycol (PEG) and poly(N-isopropylacrylamide) (PNIPAM) are attached on the surface of a gold nanocrystal through the host-guest inclusion between adamantane groups (ADA) and ß-cyclodextrin (ß-CD). The resulting AuNPs become amphiphilic in water above body temperature and self-assemble into vesicles. It is found that these vesicles can load doxorubicin (Dox) effectively. With a decrease in temperature, the PNIPAM shifted from hydrophobic to hydrophilic, causing Au vesicles to disassemble into stable small AuNPs, triggering the release of Dox. These hybrid vesicles, combining polymer functionality with the intriguing properties of AuNPs, can first release free Dox and AuNP/Dox at a site of a tumor through the application of either simple ice packs or deeply penetrating cryoprobes, then the AuNP/Dox can be taken in by tumor cells and destroy them like miniature munitions. Furthermore, these vesicles showed other therapeutic possibilities due to the presence of gold. We believe that the development of such multi-functional vesicles will provide new and therapeutically useful means for medical applications.

Synthesis of biocompatible hybrid magnetic hollow spheres based on encapsulation strategy.

A kind of novel magnetic hollow spheres was prepared by encapsulating magnetofluid into polymeric hollow spheres. Polymeric hollow nanospheres were constructed by self-assembly of rod-coil complexes, in which the rod-like segments were formed by inclusion of α-cyclodextrins (α-CD) and grafting poly(ethylene glycol) (PEG) chains of chitosan-graft-PEG (CS-g-PEG). Structural characteristics of CS-g-PEG/α-CD hollow spheres were investigated in detail by NMR, XRD, TEM, etc. Furthermore, those hollow spheres showed a pH responsive property which induced a considerable change of their radius. Magnetofluid was physically entrapped into the empty domain while hollow spheres were formed, it was found that the hollow spheres can encapsulate large quantities of magnetofluid and the encapsulated magnetofluid still possess magnetic responsiveness properties. We expect that this strategy may be served as a novel and more straightforward approach to obtain magnetic hollow spheres for biomedical application.

A new dimeric iridal triterpenoid from Belamcanda chinensis with significant molluscicide activity.

An unprecedented dimeric triterpenoid, designated dibelamcandal A, with a six-membered ring linking two iridal type triterpenoid nuclei, was isolated from the rhizome of Belamcanda chinensis. Its structure was determined by extensive spectroscopic measurements, including IR, ESI-MS, HR-ESI-MS, and 1D and 2D NMR. It demonstrated significant molluscicide activity against Pomacea canaliculata.

Chemical constituents from the aerial parts of Artemisia minor.

Four new compounds including three bicoumarins, arteminorins A-C (1-3), and one neolignan, arteminorin D (4), together with 31 known ones were isolated from the aerial parts of Artemisia minor. Their structures were established on the basis of spectroscopic data and comparison with those of the related known compounds. Ethyl caffeate (27) showed in vitro cytotoxicity against the HepG2 cancer cell line. Arteminorin C (3) and luteolin (19) showed inhibitory activity on xanthine oxidase (XOD), and caffeic acid (28) exhibited inhibitory activity on protein tyrosine phosphatase 1B (PTP1B).

A false positive F-FDG PET/CT scan caused by breast silicone injection.

We present here the case of a 40-year-old woman with a greater than 10 year prior history of bilateral breast silicone injection and saline bag implantation. Bilateral palpable breast nodules were observed, but the ultrasound scan was suboptimal and the magnetic resonance imaging showed no gadolinium-enhanced tumor. The (18)F-FDG PET/CT scan showed a hypermetabolic nodule in the left breast with a 30% increase of (18)F-FDG uptake on the delayed imaging, and this mimicked breast cancer. She underwent a left partial mastectomy and the pathology demonstrated a siliconoma.

[Chemical constituents of aerial part of Acalypha australis].

OBJECTIVE: To study the chemical constituents in the aerial part of Acalypha australis. METHOD: The aerial part of Acalypha australis were extracted with EtOH at room temperature. The compounds were separated by various kinds of chromatographic methods and their structures were identified on the basis of spectroscopic techniques. RESULT: Eleven compounds have been isolated and identified: emodin (1), beta-sitosterol (2), loliolide (3), 2,6-dimethoxy-1,4-benzoquinone (4), nicotinic acid (5), protocatechuic acid (6), daucosterol (7), gallic acid (8), rutin (9), succinic acid (10), brevifolin (11). CONCLUSION: Compounds 1, 3-5, 10 and 11 were obtained from A. australis for the first time.

Verticillium infection--a rare cause of hepatosplenic abscesses.

We report a rare case of hepatosplenic abscesses caused by Verticillium spp. in a 40-year-old female leukemic patient. Identification of the microorganism was based on amplification of the D1-D2 region of the large-subunit RNA gene from DNA extracted from paraffin sections of liver tissue, followed by sequencing of the amplified polymerase chain reaction product.

Semi-permeable nanocapsules of konjac glucomannan-chitosan for enzyme immobilization.

Carboxymethyl konjac glucomannan-chitosan (CKGM-CS) nanocapsules, spontaneously prepared under very mild conditions by electrostatic complexation, were used for immobilizing L-asparaginase. The matrix has semi-permeability to allow the substrate and product to pass through and to keep L-asparaginase in the matrix to prevent leaking. The cell-like hydrogel matrix was prepared in aqueous system without organic solvents and reagents. The process of the preparation does not denature the enzyme and the activity of the immobilized and native enzyme is very similar. The activity, stability, and characters of the enzyme-loaded nanocapsules were studied. The results indicated the immobilized enzyme has better stability and activity in contrast to the native enzyme. These studies may supply a new material for the immobilization of pH and temperature-sensitive enzyme.

Two new triterpenoid saponins from Gymnema sylvestre.

Two new oleanane-type triterpenoid saponins, gymnemoside-W1 and W2, together with seven known compounds were isolated from the leaves of Gymnema sylvestre R. Br. By means of spectral and chemical analysis, the structures of the new compounds were elucidated as 16 beta-hydroxyl olean-12-en-3-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl]-28-O-beta-D-glucopyranoside(1) and 16 beta,21 beta,28-trihydroxyl-olean-12-ene-3-O-glucoronopyranoside (2). The EtOH/H(2)O extracts of this plant were shown to be able to inhibit glucose absorption in rats.

Minor iridoids from the roots of Valeriana wallichii.

Four new iridoids, valeriotetrates B and C (1 and 2), 8-methylvalepotriate (3), and 1,5-dihydroxy-3,8-epoxyvalechlorine A (4), together with three known iridoids, were isolated from the roots of Valeriana wallichii. The structures of the new compounds were elucidated by analysis of 1D and 2D NMR and HRESIMS data. Compound 4 is an unusual iridoid bearing a C-10 chloro group and an oxo bridge connecting C-3 and C-8, resulting in a rigid skeleton.

Negative electrospray ionization tandem mass spectrometric investigation of ent-kaurane diterpenoids from the genus Isodon.

ent-Kaurane diterpenoids are a class of natural compounds isolated from genus Isodon, which have been found to have important bioactivities. Negative electrospray ionization tandem mass spectrometry ((-)ESI-MS(n)) was used to investigate the fragmentation pattern of C-20-nonoxygenated ent-kauranes and two subtypes of C-20-oxygenated ent-kauranes by using an ion trap instrument and accurate mass measurement on an ESI-Q-time-of-flight (TOF) mass spectrometer. The analysis revealed that loss of CH(2)O or CO(2) is the predominant process for 7, 20-epoxy and 7, 20 : 14, 20-diepoxy subgroup of C-20-oxygenated ent-kauranes. In addition, compounds of C-20-nonoxygenated ent-kauranes with a conserved core structure but different substituent groups, such as a hydroxyl, aldehyde, carboxyl, and acetyl moiety, resulted in diagnostic product ions through losses of H(2)O, CO, CO(2), and AcOH, respectively. This work clearly demonstrates the utility of tandem mass spectrometry for studies on the rationalization of the diagnostic fragmentation of a series of compounds from two main types of the ent-kaurane diterpenoids.

Phenyl and phenylethyl glycosides from Picrorhiza scrophulariiflora.

A new phenyl glycoside, scrophenoside D (1) and a new phenylethyl glycoside, scroside F (2), together with three known phenylethyl glycosides, scroside A (3), plantainoside D (4), and plantamajoside (5), were isolated from the stems of Picrorhiza scrophulariiflora. Their structures were elucidated by spectroscopic and chemical methods.

[Studies on chemical constituents of Eriophyton wallichii].

OBJECTIVE: To study the chemical constituents of Eriophyton wallichii. METHOD: The constituents were isolated and purified by silica gel column and Sephadex LH-20 chromatography. Their structures are elucidated by physicochemical properties and spectral analysis. RESULT: Seven compounds were obtained and identified as beta-sitosterol (1), marrubiin (2), ursolic acid (3), cimigoside (4), 5-deoxyantirrhinoside (5), 8-epiloganic acid (6) and apigenin 7-(6"-p-coumaroyl) glucoside (7). CONCLUSION: Compounds 1-7 were isolated from this plant for the first time.

Multistage electrospray ionization mass spectrometric analyses of sulfur-containing iridoid glucosides in Paederia scandens.

Paederia scandens is a traditional Chinese herbal medicine that possesses important bioactive sulfur-containing iridoid glucosides. This study reports the investigation of the fragmentation behavior of four sulfur-containing iridoid glucosides isolated from P. scandens by ion trap electrospray ionization tandem mass spectrometry (ESI-MSn). Both multistage electrospray ionization (ESI-MSn) experiments in an ion trap instrument and high-resolution and accurate mass measurement in an ESI-Q-TOF mass spectrometer in positive mode were used to elucidate the main fragmentation pathways of these compounds. These experiments yielded essentially the same product ions in both ion trap and Q-TOF instruments, and their fragmentation patterns were found useful for their characterization, which were applied to elucidate a trace compound in the extracts of P. scandens by on-line LC/ESI-MSn. Major and diagnostic product ions have been identified and their origins are proposed.

ent-Abietane diterpenoids from Isodon rubescens var. rubescens.

ent-Abietane diterpenoids, hebeiabinins A-F (1-5), together with seven known diterpenoids were isolated from leaves of Isodon rubescens var. rubescens. The structures of 1-5 were established on the basis of spectroscopic analyses, including application of 2D NMR spectroscopic techniques. The diterpenoids isolated were evaluated for the cytotoxicity against A549, HT-29, and K562 tumor cells. Compound 5 was the most active with IC(50) value of 0.91 microM against A549 cells.

[Studies on chemical constituents of Paederia scandense].

OBJECTIVE: To study the chemical constituents of Paederia scandense. METHOD: The constituents were isolated and purified by silica gel and Sephadex LH - 20 column chromatography. Their structures were elucidated by physicochemical properties and spectral analysis. RESULT: 20 compounds were obtained and identified as rubiadin-1-methylether (1), diadzein (2), cleomiscosin B (3), cleomiscosin D (4), isolariciresinol (5), linarin (6), isoscopoletin (7), caffic acid (8), coumarinic acid (9), p-hydroxyl-benzoic acid (10), oleanolic acid (11), ursolic acid (12), beta-sitosterol (13), daucosterol (14), paederoside (15), paederosidic acid (16), paederosidic acid methyl ester (17), saprosmoside E (18), paederoscandoside (19), caffeic acid 4-O-beta-D-glucopyranoside (20). CONCLUSION: Compounds 1-10, and 20 were isolated from this plant for the first time.