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Pharmacochemistry and integrated pharmacokinetics of six alkaloids (groenlandicine, berberine, palmatine, epiberberine, jatrorrhizine, and columbamine) after oral administration of Huang-Lian-Jie-Du-Tang (HLJDT) decoction were investigated in this paper. The method of plasma pharmacochemistry was applied to predict the potential bioactive components in HLJDT decoction. Based on the accurate molecular weight, 10 components including 2 flavonoids (baicalin and wogonoside), 1 iridoid glycoside (geniposide), and 7 alkaloids (above-mentioned 6 alkaloids and coptisine) were structurally identified. Then, integrated pharmacokinetics of the alkaloids in Sprague–Dawley rats after oral administration of HLJDT decoction was investigated by HPLC method. The results showed that the pharmacokinetic behaviors of the alkaloids were different although their chemical structures were similar. This study developed a method to predict the potential bioactive components in HLJDT decoction and research the pharmacokinetic behaviors of the potential bioactive components. [ABSTRACT FROM PUBLISHER]

In this paper, the metabolites of four soy isoflavones, daidzein, daidzin, genistein, and genistin, on perfused rat intestine–liver model were investigated by high-performance liquid chromatography coupled with high-resolution mass spectrometer/tandem mass spectrometer. Totally 16 metabolites were detected and identified based on accurate mass, fragmentation patterns, and multiple-stage mass data (MSn). The metabolic site of dadzein-7-methyl ether (D-7-M) was further confirmed by nuclear magnetic resonance. Methylation, glucuronide conjugation, and sulfate conjugation were the primary metabolic processes. Among them, six metabolites, daidzin-4′,7-diglucoside, genistein-4′-glucoside, D-7-M, dadzein-4′,7-dimethyl ether, genistein-4′-methyl ether, and genistein-7-methyl ether were detected in rats for the first time and not reported in humans. The metabolic pathways of daidzein, daidzin genistein, and genistin in rats were postulated. The biological effects of these metabolites are worthy of further investigation. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the immunomodulatory effects of cinobufagin (CBG) isolated from Chan Su (Venenum Bufonis) in vitro. In this paper, our results show that CBG significantly stimulated cell proliferation of splenocytes and peritoneal macrophages (PMΦ) and markedly enhanced the phagocytic activation of PMΦ. CBG also significantly increased CD4+CD8+ double-positive T-cell populations and the percentage of S-phase cells of splenic lymphocytes. The levels of several Th1 cytokines, including interferon-γ and tumor necrosis factor-α, are significantly increased after CBG treatment, whereas the levels of the Th2 cytokine interleukin-4 and interleukin-10 are significantly decreased. As a result, the ratio of Th1/Th2 also increased. Taken together, these results indicated that CBG had potential immune system regulatory effects and suggested that this compound could be developed as a novel immunotherapeutic agent to treat immune-mediated diseases such as cancer. [ABSTRACT FROM AUTHOR]

Anticancer effect of tephrosin (1) has been documented; however, the molecular mechanisms underlying the cytotoxicity of tephrosin in cancer cells remain unclear. In the present paper, the proliferation inhibition rate of several cancer cells was tested using the MTT assay; cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were determined by flow cytometry; poly(ADP-ribose) polymerase (PARP) cleavage and heat shock protein 90 (Hsp90) expression were evaluated by Western blotting; autophagy was examined by confocal microscopy and light chain 3 (LC3) conversion assay. The results showed that exposure of the cells to tephrosin induced significant proliferation inhibition in a dose-dependent manner, especially on A549 with G2/M being arrested. Tephrosin was not found to induce cell apoptosis as PARP cleavage was not detected after 24 h treatment, but the formation of acidic vesicular organelle of autophagy character was found, and autophagy was further confirmed by the increase in the ratio of LC3-II to LC3-I. It was observed that tephrosin induced ROS generation and Hsp90 expression inhibition. These results indicate that tephrosin induces A549 cancer cell death via the autophagy pathway, and the roles of ROS generation and Hsp90 expression inhibition in this process need further study in the future. [ABSTRACT FROM AUTHOR]

The in vitro metabolism of two novel phosphate prodrugs of glycyrrhetic acid (GA) was studied by the method of incubation in the rat liver microsome and the in vivo plasma pharmacokinetics after injecting intravenously (i.v.) into six rats was investigated, respectively. The prodrugs diminished gradually with time and most of the parent drugs were released in 30 min in vitro. In this paper, the in vivo plasma concentration data were analyzed by compartmental modeling. Both the prodrugs and the corresponding released parent drugs could be described by a two-compartment model, which existed for 48 h in rats. The t1/2 increases remarkably after i.v. administration to rats when compared with injecting the parent drugs directly. [ABSTRACT FROM AUTHOR]

Gelsemine is one of the major alkaloids from Gelsemium elegans Benth., which has been used as an antitumor remedy in clinic. In this paper, metabolism of gelsemine has been investigated in vitro in phenobarbital-treated rat liver microsomes. The metabolites of gelsemine were separated and evaluated using the flash silica gel column, preparative HPLC, using NMR and MS methods. According to the spectral data, two metabolites, M1 and M2, were identified as 4-N-demethylgelsemine and 21-oxogelsemine, respectively. By the MTT method in vitro, the antitumor activities between gelsemine and its metabolites were compared in the HepG2 and HeLa cell lines. Moreover, the main metabolic pathway was further proposed. [ABSTRACT FROM AUTHOR]

Sixty-nine 4-propargyloxybenzene sulfonamide derivatives with different amino acids as amino substituent were synthesized and evaluated for their insecticidal activity against third-instar Mythimna separate. The bioassay results revealed that some derivatives bearing amino acid ester group performed good insecticidal activity against third-instar M.separata, such as the LC50 values of D18 and D19 were 4.28 and 2.96 mg/ml after 48 h, in particular, the LC50 of D16 was 2.38 mg/ml and the activity was improved by 14 times compared to celangulin V (34.48 mg/ml). The above results provided theoretical and experimental basis for the discovery of novel insecticidal active compounds. [ABSTRACT FROM AUTHOR]

Two new glycosides of methyl everninate, rhodomollosides A (1) and B (2), were isolated from the aerial parts of a medicinal plant Rhododendron molle. The structures of 1 and 2 were elucidated on the basis of detailed spectroscopic analyses as well as HPLC analyses for thiazolidine derivatives of their sugar moieties. The sugar moiety of rhodomolloside A (1) was elucidated to be a rare monosaccharide, D-allose, while rhodomolloside B (2) was assigned as a D-glucoside of methyl everninate. Furthermore, they were evaluated for their cytotoxicity against RAW264.7 cells, and for their inhibitory effects with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW 264.7 cells model. [ABSTRACT FROM AUTHOR]

Two new sesquiterpene dimers, lappadimers A and B, were isolated from the roots of Saussurea lappa (Yunmuxiang). Their structures were established on the basis of spectroscopic methods. They were found to have potential anti-inflammatory activity at 10 µM and could reduce LPS-induced NO levels in murine macrophage, with inhibitory rates of 67% and 47%, respectively. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to examine the protective action and mechanisms of quercetin on the blood-brain barrier (BBB) in rats subjected to transient middle cerebral artery occlusion (tMCAO) and reperfusion. Quercetin (10, 30, 50mg/kg) was intraperitoneally administered at the onset of reperfusion. The results showed that quercetin significantly reduced cerebral infarct volume, neurological deficit, BBB permeability and ROS generation via Sirt1/Nrf2/HO-1 signaling pathway. Moreover, EX527, a selective inhibitor of Sirt1, reversed these neuroprotective effects. Our findings indicate that quercetin has neuroprotective effects against cerebral ischemia-reperfusion injury by protecting BBB through Sirt1 signaling pathway in MCAO rats. [ABSTRACT FROM AUTHOR]

A new lanostane triterpenoid (1) and two known (2, 3) analogues were isolated from Nothotsuga longibracteata. Their chemical structures were identified by spectral data including HR-ESI-MS, 1 D, and 2 D NMR. These lanostane triterpenoids showed no cytotoxic activities against three human tumour cell lines (A172, SHSY5Y, and Hela), but exhibited the activity of promoting the gastrointestinal motility of zebrafish treated with Nile red. [ABSTRACT FROM AUTHOR]

A new flavonol named 5,4'-dihydroxy-6,7-[(1''S,2''R)-1''-hydroxy-2''-(1-hydroxy-1-methylethyl)-furano]flavonol (1), together with eight known compounds (2–9), were isolated from the seeds of Psoralea corylifolia. Their chemical structures were elucidated on the basis of spectroscopic analyses. In addition, all compounds were firstly studied for their proliferation effects on osteoblastic-like UMR 106 cells. Results showed that compounds 1, 2, 5 and 8 possessed significant promoting effects on cell proliferation and increased osteoblastic cell numbers by 26.3%, 34.6%, 20.5% and 21.1% at concentrations of 10−8 M, 10−8 M, 10−10 M and 10−10 M, respectively. These data indicated that flavonoids may be the main constituents accounting for the bone protective effects of the seeds of P. corylifolia. [ABSTRACT FROM AUTHOR]

Five new denudatine-type diterpenoid alkaloids (1–5), along with the known analogue aconicarmine (6), were isolated from an aqueous decoction of the lateral roots of Aconitum carmichaelii (fu-zi). Their structures were determined by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Compound 5 is the first denudatine-type diterpenoid alcohol iminium alkaloid, which could be partially transformed into the aza acetal form in pyridine-d5. Compound 5 inhibited mice writhing in an acetic acid-induced writhing assay. [ABSTRACT FROM AUTHOR]

A new oleanane type triterpene characterized as 3α, 24-diacetoxy-12-oleanene (1) together with known compounds 2-10, were isolated from Annona mucosa leaf extracts. Their structural elucidation was accomplished using physical and spectroscopic methods. The compounds showed weak to moderate insecticidal activities against stored maize insect pests Sitophilus zeamais and Prostephanus truncatus. [ABSTRACT FROM AUTHOR]

Four metabolites of mogrol were separated, identified and characterized. Their antitumor activity was evaluated, and the results showed side chain modification would probably enhance the cytotoxicity. Therefore, three types of amines, alcohols and rigid planar derivatives were synthesized. Compounds 20 and 21 containing a tetrahydro-β-carboline structure at the end of the side chain exhibited IC50 values around 2–9 μM against A549 and CNE1 cell comparing with 80–90 μM of mogrol. Structure analysis suggested that the perhydrocyclopentanophenanthrene moiety and the tetrahydro-β-carboline moiety could probably enhance the activity through an intramolecular synergistic effect. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of sulforaphane (SFN) on lipopolysaccharide (LPS)-induced liver failure, and to elucidate underlying mechanisms. SFN, a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. Mice were treated intravenously with SFN at 12 h after LPS treatment. LPS significantly increased mortality, serum levels of liver damage markers, and inflammatory cytokines, and toll-like receptor 4 (TLR4) protein expression, which were reduced by SFN. Our results suggest that SFN protects against LPS-induced liver damage, indicating its potential to treat liver diseases. [ABSTRACT FROM AUTHOR]

As our ongoing work on research of natural-product-based insecticidal agents, some 4α/β-acyloxypodophyllotoxin derivatives were synthesized, and were evaluated against the pre-third-instar larvae of B. mori, A. dissimilis and M. separate in vivo at the concentration of 1 mg ml−1, respectively. Among all derivatives, compounds 2 g, h and 4c, d showed more promising insecticidal activities than their precursors – podophyllotoxin and epipodophyllotoxin. Furthermore, derivatives 2 g, h and 4c, d exhibited more relative amicable activities than their precursors – podophyllotoxin and epipodophyllotoxin. This results indicated that 4β-acyloxy moiety in the podophyllotoxin derivatives was significant for obtaining the more potent compounds. [ABSTRACT FROM AUTHOR]

One new flavonoid derivative flavoside A (1), one new 5-hydroxyanthranilic acid derivative crassilin (2), along with the known angucyclinone PD116740 (3) and oxachelin (4), was isolated from the EtOAc extract of the fermentation broth of the sea urchin (Anthocidaris crassispina)-derived actinobacterium, Streptomyces sp. HD01. The structures of these compounds were established on the basis of their HR-ESI-MS and NMR spectroscopic data. All of these compounds were assessed for their antibacterial activity. [ABSTRACT FROM AUTHOR]

To compare the stimulation and binding characteristics of adenosine analogs including AMP, IMM-H007, and M1, to AMPK, and to explore the potential mechanism underlying the regulation effect of adenosine analogs on AMPK activity, [γ-32P]ATP assay, circular dichroism experiments and molecular docking test were performed. We found that the interactions with Thr86, Thr88, and His150 in site 1 are probably the reason why the affinities of IMM-H007, M1, and adenosine are comparable but their allosteric activation on AMPK varies greatly, partly interpreting the mechanism of AMPK activity regulated by adenosine analogs. [ABSTRACT FROM AUTHOR]

This study aimed at investigating the pharmacokinetics (PK) and acetylcholine (Ach) releasing effects of ginsenoside Rg1 in hippocampus (HIP) of soluble oligomeric assemblies of amyloid beta (ADDLs) induced Alzheimer's disease (AD) model rats. Extracellular fluid was collected by microdialysis technique. The concentrations of Rg1 and Ach in dialysates were detected by liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. The results showed, after administration, Rg1 was soon detected in the HIP of model rats and extracellular Ach concentrations in the HIP were significantly increased. [ABSTRACT FROM AUTHOR]

Two new carotane-type sesquiterpenes named trichocaranes E (1) and F (2), along with two known ones CAF-603 (3) and trichocarane C (4), were isolated from cultures of the insect pathogenic fungus Isaria fumosorosea. Their structures and relative configurations were elucidated by extensive spectroscopic analysis and X-ray crystallography. Compounds 1-3 showed potent cytotoxic activities against six tumor cell lines MDA, MCF-7, SKOV-3, Hela, A549, HepG2 with IC50 values in a concentration range of 0.1-6.0 μg/ml. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the absorption properties of isorhamnetin (IS), quercetin (QU), and kaempferol (KA) in total flavones of Hippophaë rhamnoides L. (TFH) by an in situ single-pass intestinal perfusion model. The results indicated that IS, QU, and KA in TFH were absorbed site-dependently, and both enterohepatic circulation and intestinal flora could participate in their absorption processes. The absorption mechanisms of IS, QU, and KA in TFH were involved in both passive diffusion and active transport, and the mediation of efflux transporter multidrug resistance-associated proteins (MRPs) should not be neglected. [ABSTRACT FROM AUTHOR]

A new highly oxygenated pregnane steroid, pregn-7-ene-2β,3α,15α,20-tetrol (1) and two new 5-hydroxymethylfurfural derivatives, (5-formylfuran-2-yl)methyl 2-hydroxypropanoate (2) and (5-formylfuran-2-yl)methyl 2-(4-hydroxyphenyl)acetate (3), together with four known compounds, were isolated from the water decoction of Poria cocos. Their structures were established on the basis of extensive spectroscopic analysis. Compound 1 showed moderate inhibitory activity and a known compound (3S,6S)-3-[(1R)-1-hydroxyethyl]-6-(phenylmethyl)-2,5-piperazinedione (5) showed weak inhibitory activity against α-glucosidase, respectively. [ABSTRACT FROM AUTHOR]

Two new phenolics, 1,3-di-O-p-coumaroyl-2′,6′-di-O-acetylsucrose (1) and quercetin 3-O-β-D-apiofuranoyl-(1→2)-α-L-rhamnopyranoside (2), along with nine known compounds (3-11), were isolated from the whole plants of Antenoron filiforme var. neofiliforme. Their chemical structures were characterized on the basis of various spectroscopic techniques. This is the first report of the isolation of phenylpropanoid sucrose (1, 3-4) from the genus Antenoron. The bioassay results showed that compound 11 exhibited antiviral activity against the Coxsackie virus B3 (CVB3). [ABSTRACT FROM AUTHOR]

Camellia oleifera C. Abel has been widely cultivated in China, and a group of bioactive constituents such as triterpeniod saponin have been isolated from C. oleifera C. Abel. In the current study, a new triterpeniod saponin was isolated from the EtOH extract of the roots of C. oleifera C. Abel, named as oleiferoside W, and the cytotoxic properties of oleiferoside W were evaluated in non-small cell lung cancer A549 cells. At the same time the inducing apoptosis, the depolarization of mitochondrial membrane potential (Δψ), the up-regulation of related pro-apoptotic proteins, such as cleaved-PARP, cleaved-caspase-3, and the down-regulation of anti-apoptotic marker Bcl-2/Bax were measured on oleiferoside W. Furthermore, the function, inducing the generation of reactive oxygen species (ROS) and apoptosis, of oleiferoside W could be reversed by N-acetylcysteine (NAC). In conclusion, our findings showed that oleiferoside W induced apoptosis involving mitochondrial pathway and increasing intracellular ROS production in the A549 cells, suggesting that oleiferoside W may have the possibility to be a useful anticancer agent for therapy in lung cancer. [ABSTRACT FROM AUTHOR]

To investigate the anti-oxidant activities and mechanism of rosmarinic acid (RA) on rat bone marrow mesenchymal stem cells (rBMSCs) from ischemia-induced apoptosis in vitro, which was established using H2O2-damage and analyzed for cell viability, cell apoptosis, ROS, morphological changes, and levels of apoptosis proteins. Pretreatment with RA significantly suppressed the generation of ROS, protected the morphological changes of cells, decrease the ratio of cell apoptosis, down-regulated the level of caspase-3, caspase-9, Bax/Bcl-2, and up-regulated the level of p-PI3K. These findings suggest that RA may protect rBMSCs from H2O2-induced apoptosis by partly regulating PI3K/Akt signaling pathway and can be developed as a potential anti-apoptotic agent for therapy in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Three new secoiridoids, nuezhenelenoliciside (1), isojaslanceoside B (2), 6′-O-trans-cinnamoyl-secologanoside (3), were isolated from the dried fruits of Ligustrum lucidum. Their structures were elucidated by comprehensive spectroscopic analysis. Among them, 1 featured a rare rearrangement product of secoiridoid, which underwent the cleavage of chemical bond between C-1 and O-2, and the reformation of a new iridoid ring between C-8 and O-2. In addition, all compounds were tested for their osteogenic activity on pre-osteoblastic MC3T3-E1 cells. As a result, 1 and 3 exhibited potent effects on promoting cell proliferation of pre-osteoblast cells. [ABSTRACT FROM AUTHOR]

A pair of unusual melibiose esters (1α/1β) and a pair of unusual raffinose esters (2α/2β), were isolated from Scrophularia ningpoensis. Structures of them were established by detailed spectroscopic analyses to be 6-O-(E)-cinnamoyl-α-d-galactopyranosyl-(1→6)-α(β)-d-glucopyranose (1α/1β) and 6-O-(E)/(Z)-cinnamoyl-α-d-galactopyranosyl-(1→6)-α-d-glucopyranosyl-(1→2)-β-d-fructofuranose (2α/2β), respectively. All these compounds were evaluated for antifouling activity against the settlement of Balanus amphitrite larvae, along with the cytotoxic effect against the proliferation of HeLa cell lines. [ABSTRACT FROM AUTHOR]

Oleuropein mediates most of the beneficial effects of olive products. This study examined the role of oxidative stress in the effects of oleuropein on lipid profile and blood glucose in rats with simultaneous renovascular hypertension and type 2 diabetes. Eight groups (n = 7–9 each) of male Sprague-Dawley rats including a control, a type 2 diabetic, a renovascular hypertensive, a sham, a simultaneously hypertensive diabetic receiving vehicle, and 3 simultaneously hypertensive-diabetic receiving 20, 40, or 60 mg/kg/day oleuropein were used. Four weeks after treatment, blood glucose, lipid profile, and biomarkers of oxidative stress were measured, and glucose tolerance test (GTT) was performed. Simultaneously hypertensive diabetic rats had significantly higher blood pressure, blood glucose, and serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and malondialdehyde. They also had lower serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and impaired glucose tolerance. Oleuropein significantly reduced blood pressure, blood glucose, and serum total cholesterol, LDL-C, triglyceride and malondoaldehyde. It also increased serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and improved glucose tolerance. The findings show that the model is associated with impaired glucose tolerance, and adverse lipid profile. They also show that oleuropein, partly by an antioxidant mechanism, improves glucose tolerance and changed lipid profile favorably. [ABSTRACT FROM AUTHOR]

The study was designed to evaluate the protective effect of α-mangostin and explore its mechanism in anin vitromodel of Parkinson’s disease (PD) induced by rotenone. SH-SY5Y cells were treated with rotenone and α-mangostin for 24 h. α-Mangostin significantly and concentration-dependently inhibited rotenone-induced cytotoxicity. The rotenone-induced aggregation of α-synuclein and loss of TH were alleviated by α-mangostin. α-Mangostin treatment also reversed the rotenone-induced overproduction of reactive oxygen species, activation of caspases (−8 and −3) and mitochondrial dysfunction, reflected by decrease in mitochondrial membrane potential and cellular ATP levels. These findings suggest that α-mangostin has neuroprotective effects against PD-related neuronal injury. [ABSTRACT FROM PUBLISHER]

The present study was undertaken to investigate whether hederacochiside C (HSC) possesses antischistosomal effects and anti-inflammatory response activities inSchistosoma japonicum-infected mice. Different concentrations of HSC were administrated to the mice infected by schistosomula or adult worm by intravenous injection twice a day for five consecutive days. The total worm burden, female worm burden, and the egg burden in liver of mice treated with 400 mg/kg HSC were fewer than those in non-treated ones. Murine immune responses following HSC treatment were investigated using enzyme-linked immunosorbent assays (ELISA). Our results indicated that 200 mg/kg HSC could reduce the expression of IgG, tumor necrosis factor (TNF)-α, interleukin (IL)-4 and IL-17 in comparison to infected group, exhibiting best immunomodulatory effects. In addition, scanning electron microscopical examination revealed that male worms treated with HSC lost their normal surface architecture since its surface showed extensive swelling, erosion, and peeling in tegumental regions. Remarkable amelioration was noticed in histopathological investigations, and 200 mg/kg HSC treatment could reduce the size of granulomatous inflammatory infiltrations in the liver which was reflected in nearly normalization of liver architecture. These results suggested that HSC had potential antischistosomal activity and provided a basis for subsequent experimental. [ABSTRACT FROM PUBLISHER]

An ongoing phytochemical investigation of the rhizomes ofAtractylodes lancearesulted in the isolation of four new C10-type polyacetylene glycosides (1−4). Their structures were elucidated on the basis of extensive spectroscopic data (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of compounds2−4were determined by comparing the specific rotations of their aglycones. Notably, compounds2and3exhibited significant hepatoprotective activities against APAP-induced HepG2 cell injury at a concentration of 10 μM. Compounds2and3showed weak anti-inflammatory effects on LPS-induced NO production in microglia BV2 cells at a concentration of 10 μM. [ABSTRACT FROM PUBLISHER]

A new lanostane-type triterpenoid, 3β-hydroxy-25-ethyl-lanost-9(11),24(24′)-diene (1), along with 3β-hydroxy-lanost-7-ene (2) and β-sitosterol-3-O-acetate (3) was isolated from the stem bark ofC. cumingianus. The chemical structure of the new compound was elucidated on the basis of spectroscopic data. All of the compounds were evaluated for their cytotoxic effects against P-388 murine leukemia cells. Compounds1-3showed cytotoxicity against P-388 murine leukemia cells with IC50values of 28.8 ± 0.10, 4.29 ± 0.03, and 100.18 ± 0.16 μg/ml, respectively. [ABSTRACT FROM PUBLISHER]

Eighteen terpenoids (1–18) were isolated fromIllicium merrillianum. Compound1was identified as new compound, and its structure was established by comprehensive spectroscopic analysis and single-crystal X-ray diffraction. All compounds were evaluated for nerve growth factor (NGF)-mediated neurite outgrowth activity using rat pheochromocytoma (PC12) cells as a model system of neuronal differentiation. Compounds1,3,18showed significant neurite outgrowth-promoting activity in the presence of 20 ng/ml NGF in a dose-dependent manner at concentrations of 1–100 μM after 24-h treatment. Subtle difference of functional groups at C-2 position in hopane-type triterpene resulted in enormous bioactivity difference, compound1was neurotrophic but2was cytotoxic. [ABSTRACT FROM AUTHOR]

A new brominated polyunsaturated lipid, methyl (E,E)-14,14-dibromo-4,6,13-tetradecatrienoate (1), along with three known related analogues (2–4), were isolated from the Et2O-soluble portion of the acetone extract of Chinese marine spongeXestospongia testudinariatreated with diazomethane. The structure of the new compound was elucidated by detailed spectroscopic analysis and by comparison with literature data. Compound3exhibited significant inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of type II diabetes and obesity, with an IC50value of 5.30 ± 0.61 μM, when compared to the positive control oleanolic acid (IC50 = 2.39 ± 0.26 μM). [ABSTRACT FROM PUBLISHER]

Two new sesquiterpenes, oligandrin (1) and oligandric acid (2), together with three analogues, tashironin A (3), tashironin (4), and oplodiol (5), were isolated from the roots ofIllicium oligandrum. The structures of new compounds were determined based on 1D and 2D NMR experiments and X-ray diffraction. Compound1represents a presumed biosynthetic precursor ofseco-prezizaane sesquiterpenes which consists of a novel 6/6/5 tricarbocyclic skeleton. Compound2is the first example of chamipinene-type sesquiterpene possessing a 6/4/6 tricyclic system from the genusIllicium. Compounds1–5were evaluatedin vitrofor their activity against coxsackie virus B3 (CVB3), influenza virus A/Hanfang/359/95 (H3N2), and influenza virus A/FM/1/47 (H1N1). Compound1showed selective antiviral activity against CVB3 with IC50value of 11.11 μM. [ABSTRACT FROM PUBLISHER]

A two-step release system (TSRS) for the compound Danshen, which has drug-release behavior that is in accordance with the circadian rhythms of cardiovascular disease, was developed by combining an effervescent osmotic pump tablet and a pulsed-released tablet into one hard capsule by our lab. Anin vivostudy indicated that after oral administration of TSRS, two peaks of the plasma concentration of both Danshensu (DS) and protocatechuic aldehyde (PA) were observed, which suggested that the drug plasma concentration–time curve could meet the requirements for chronotherapy of cardiovascular disease after the bed-time administration of such a device. High performance liquid chromatography using an ultraviolet (UV) detector was used to simultaneously determine the concentrations of DS and PA in plasma. This method was simple, convenient, and appropriate for the quality control of DS and PA. A linear correlation model was established based on the percent absorbant data and percentin vitrodissolution data. Because the drugs were released from the device in an osmotic pressure-dependent manner and absorbed rapidly, a reasonable linear regression relationship was observed between thein vitroandin vivoperformances. The current study highlights the potential use of such a device for chronopharmaceutical drug delivery. [ABSTRACT FROM AUTHOR]

This work presents the metabolites of isocorynoxeine (ICOR), which is one of four bioactive tetracyclic oxindole alkaloids isolated fromUncariahooks used commonly in the traditional Chinese medicines and Kampo medicines. After oral administration of 40 mg kg− 1ICOR to rats, bile was drained and analyzed by LC-MS. Two phase I metabolites, namely 11-hydroxyisocorynoxeine (M1) and 10-hydroxyisocorynoxeine (M2), and two phase II metabolites, namely 11-hydroxyisocorynoxeine 11-O-β-d-glucuronide (M3) and 10-hydroxyisocorynoxeine 10-O-β-d-glucuronide (M4), were isolated from rat excreta and bile, respectively, whose structures were elucidated on the basis of CD, NMR, and MS. [ABSTRACT FROM AUTHOR]

Three new saikosaponin analogs, comastomasaponins I–K (1–3), were isolated from the aerial portions ofComastomapedunculatum. The structures of these compounds were elucidated on the basis of spectroscopic data analysis, and their nitric oxide production inhibitory activity was evaluatedinvitro. [ABSTRACT FROM AUTHOR]

Two new dopamine derivatives divesamides A (1) and B (2), along with six known N-containing compounds were isolated from the Chinese black ant (Polyrhachis dives). Their structures were determined on the basis of spectroscopic methods. Compound 1 is a racemate, and chiral HPLC separation yielded a pair of antipodes. The absolute configuration of (+)-1 was assigned by a computational method. The double signals in the 1H and 13C NMR spectra of 2 that resulted from the presence of a formamide group were discussed. The T- and B-lymphocytes proliferation assay showed that 2 has moderate immunosuppressive activity toward T- and B-lymphocytes proliferation at a concentration of 20 μM. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of ligustrazine on levels of amino acid transmitters in the extracellular fluid of striatum following cerebral ischemia/reperfusion (I/R) in male Sprague-Dawley rats. A microdialysis cannula guide was implanted into the right striatum. After recovery, animals underwent a sham operation or middle cerebral artery occlusion (MCAO). Those that developed cerebral ischemia after MCAO were randomized to receive propylene glycol salt water and ligustrazine respectively. Striatal fluid samples were collected from all animals at 15-min intervals after treatment and were subjected to HPLC analysis of aspartic acid, glutamic acid, taurine, and γ-amino butyric acid. Upon the last sample collection, animals were sacrificed and brain tissue specimens were collected for triphenyltetrazolium chloride staining and NeuN staining. Compared with the sham operation, MCAO induced significant neurological deficits and increased striatal concentrations of the four neurotransmitters assessed in a time-dependent manner (P < 0.01). Ligustrazine effectively attenuated the detrimental effects of MCAO on the brain. These observations suggest that ligustrazine as a novel cerebral infarction-protective agent may have potential clinical implications for I/R-related brain damage. [ABSTRACT FROM PUBLISHER]

The mechanism of oleuropein's antihypertensive effects was examined in rat model of simultaneous type 2 diabetes and renal hypertension (diabetic hypertensive). Five groups of male Sprague-Dawley rats including a control, a diabetic-hypertensive group receiving vehicle, and three diabetic-hypertensive groups receiving oleuropein at 20, 40, or 60 mg/kg/day were used. The duration of diabetes was 10 weeks; during the last 4 weeks of which, animals were hypertensive and received vehicle or oleuropein. Systolic blood pressure, glucose and malondialdehyde, heart rate, and maximal response to phenylephrine (PE) in the absence of nitro-l-arginine methyl ester (l-NAME) of oleuropein-treated groups were significantly lower than those of vehicle-treated group. Erythrocyte superoxide dismutase, maximal response to PE in the presence ofl-NAME, and maximal response to acetylcholine (Ach) of oleuropein-treated groups were significantly higher than those of vehicle-treated group. The findings indicate that antihypertensive effects of oleuropein might be partly mediated by improving the release of nitric oxide, and antioxidant and sympathoplegic activities. [ABSTRACT FROM PUBLISHER]

Two new flavonoid glycosides, named quercetin-3-O-(2″-O-tigloyl)-α-l-rhamnopyranoside (1) and quercetin-3-O-(3″-O-tigloyl)-α-l-rhamnopyranoside (2), together with 10 known flavonoids (3–12), were isolated from the whole plant of the halophyteLimonium franchetii. Their structures were elucidated on the basis of extensive spectroscopic analysis including 2D NMR and HR-EI-MS. In addition, primary bioassays showed that compound1had moderate cytotoxic activity against rat C6 glioma cell lines. [ABSTRACT FROM PUBLISHER]

Various chromatographic separations of the aerial parts of Scutellaria barbata afforded two new neoclerodane diterpenoids, scutebatas S and T (1 and 2), along with scutebata D (3). Their structures were elucidated by spectroscopic methods including high-resolution electrospray ionization mass spectrometry, 1D and 2D NMR and comparison with the literature values. Compounds 1 and 3 exhibited moderate cytotoxic activities against HL-60 (promyeloblast) human cancer cells. Weak cytotoxic effects toward four tested human cancer cell lines including KB (epidermoid carcinoma), LU-1 (lung adenocarcinoma), MCF7 (breast cancer), and Hep-G2 (hepatoma cancer) were observed for 1 and 3; whereas 2 was inactive on all five tested cell lines. [ABSTRACT FROM AUTHOR]

A new tetrahydrofuran-type lignan, episesaminone (1), was isolated from Asarum heterotropoides Fr. Schmidt var. mandshuricum (Maxim.) Kitag. Its structure was established by spectroscopic techniques (HR-MS, 1D NMR, 2D NMR, and circular dichroism). The anti-inflammatory activity in RAW 264.7 macrophages was carried out on 1 and other eight known compounds, the epimer of 1 (2) and seven known furofurans-type lignan (3–9) obtained from A. heterotropoides Fr. Schmidt var. mandshuricum. Compounds 1, 2, 3, 4, 5, 7, and 9 showed significant anti-inflammatory activity, particularly 50 μM compound 3 inhibited 69.2% NO production compared with the lipopolysaccharide group. [ABSTRACT FROM AUTHOR]

A new apiose-containing kaempferol trioside, kaempferol-3-O-α-l-rhamnosyl-(1‴ → 6″)-O-β-d-galactopyranosyl-7-O-β-d-apiofuranoside, along with 16 known compounds, were isolated from 50% acetone extract of Silphium perfoliatum L. Their structures were elucidated by acid hydrolysis and spectroscopic techniques including UV, IR, MS, 1H, 13C, and 2D-NMR. In addition, the pharmacological activity of compound 1 was tested with HepG2 and Balb/c mice (splenic lymphocytes and thymic lymphocytes) in vitro, and it exhibited inhibitory effect on the proliferation of HepG2 cells and showed the immunosuppressive activity. [ABSTRACT FROM AUTHOR]

Two new phenanthrene glycosides, dioscopposide A and dioscopposide B (1 and 2), were isolated from the rhizomes of Dioscorea opposita. Their structures were determined primarily on the basis of 1D and 2D NMR techniques, MS studies, and chemical methods. All the isolates were evaluated for their inhibitory effects on the lipopolysaccharide-induced nitric oxide production using murine macrophage RAW 264.7 cells. The IC50 values of dioscopposide A and dioscopposide B were 5.8 and 7.2 μM, respectively. [ABSTRACT FROM AUTHOR]

Bioassay-guided isolation of the aerial part of Scutellaria barbata yielded three new neo-clerodane diterpenoids scutebatas P–R (1–3), together with two known ones: scutebata E (4) and scutebarbatine B (5). The chemical structures of the isolated compounds were elucidated by spectroscopic methods (NMR and MS) and by comparison with the spectroscopic data reported in the literature. All compounds except 3 showed weak cytotoxicity with IC50 values ranging from 35.11 to 42.73 μM against K562 cell lines, and compounds 1, 2, and 5 also displayed weak activities against HL60 cell lines. [ABSTRACT FROM AUTHOR]

Three unusual sesquineolignans conchignans A (1), B (2), and C (3), together with two known compounds vanillin (4) and phloroglucinol (5), were isolated from the whole plants of Alpinia conchigera. Their structures were established by spectroscopic analysis, including 2D NMR spectroscopic techniques. [ABSTRACT FROM AUTHOR]

Three new guaiane sesquiterpene lactones (4S)-4-hydroxy-gweicurculactone (1), zedoalactone G (2), and (1R, 4R, 5S, 10S)-zedoalactone B (3), and three known guaiane sesquiterpene lactones, including zedoarolide B (4), zedoalactone B (5), and a new natural product (+)-zedoalactone A (6), were isolated from the rhizomes of Curcuma wenyujin Y.H. Chen et C. Ling. The structures were elucidated by spectroscopic methods including 1D and 2D NMR and HR-ESI-MS. The absolute configuration of 2 was determined via the calculated electronic circular dichroism (ECD), whereas the absolute configurations of 1 and 3 were determined via the ECD data of the [Rh2(OCOCF3)4] complex and [Mo2(OAc)4] complex, respectively. The inhibitory effects of compounds 1–6 on nitric oxide production in lipopolysaccharide-activated macrophages were evaluated. All of them exhibited weak anti-inflammatory activity. [ABSTRACT FROM AUTHOR]