The stem and branch extract of Tripterygium wilfordii (Celastraceae) afforded seven new dihydroagarofuran sesquiterpene polyesters [tripterysines A-G (1-7)] and eight known ones (8-15). The chemical structures of these new compounds were established based on combinational analysis of HR-ESI-MS and NMR techniques. The absolute configurations of tripterysines A-C (1-3) and E-G (5-7) were determined by X-ray crystallographic analysis and circular dichroism spectra. All the compounds were screened for their inhibitory effect on inflammation through determining their inhibitory effect on nitric oxide production in LPS-induced RAW 264.7 cells and the secretion of inflammatory cytokines TNF-α and IL-6 in LPS-induced BV2 macrophages. Compound 9 exhibited significant inhibitory activity on NO production with an IC₅₀ value of 8.77 μmol·L^-1. Moreover, compound 7 showed the strongest inhibitory effect with the secretion of IL-6 at 27.36%.
Tripterygium/chemistry* ; Esters/pharmacology* ; Interleukin-6 ; Lipopolysaccharides/pharmacology* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/chemistry* ; Nitric Oxide/analysis* ; Sesquiterpenes/chemistry* ; Molecular Structure

A new hexaketide acid esterified by the 17-hydroxyl group of 16,17-dihydroxycyclooctatin, namely 17-[16,17-dihydroxycyclooctatinyl]-hexaketide ester (1), a member of the group of rare bacterial diterpenes with a fused 5-8-5 ring system was isolated from strain Streptomyces sp. SR107. The structure was determined on the basis of its spectral data (H NMR, C NMR, H-H COSY, HSQC, HMBC, NOESY, IR and HR-ESI-MS). The antibacterial activity was also evaluated in this paper.
Anti-Bacterial Agents ; chemistry ; pharmacology ; Bacteria ; drug effects ; Diterpenes ; chemistry ; metabolism ; pharmacology ; Esters ; chemistry ; pharmacology ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Streptomyces ; chemistry

OBJECTIVETo investigate the effect of Euphorbia fischeriana extract on latent HIV reactivation and the pathway involved in this process and discuss the value of Euphorbia fischeriana extract in eliminating HIV.

METHODSFresh tissues of Euphorbia fischeriana root were crushed into powder after quick freezing with liquid nitrogen and extracted with acetone followed by a three-day vacuum freeze-drying for dehydration of the extract. The extract (EFE) was separated using RP-C18 column with high-performance liquid chromatography (HPLC) and identified with mass spectrometry (MS). The activity of reactivated latent HIV was analyzed by fluorescence-activated cell sorting in a J-Lat 10.6 cell model treated with EFE (50 µg/mL) for 24 h, using TNF-α (10 ng/mL) as the positive control. The effect of a NF-κB pathway inhibitor (Bay 11-7082) on EFE activity was tested. The changes in P65 expression in the cell nuclei within 2 h and HIV protein p24 expression within 24 h were analyzed by Western blotting in cells treated with EFE.

RESULTSEFE was obtained by one-step acetone extraction, and the concentration of prostratin in the extract was around 0.53 mmol/L. About 50% of the cells showed HIV reactivation after treatment with 50 µg/mL EFE for 24 h accompanied by a significantly increased p24 expression. The activity of EFE in reactivating latent HIV was inhibited by Bay 11-7082 in a concentration-dependent manner, and p65 accumulation was detected in the cell nuclei within 2 h.

CONCLUSIONEFE we obtained contains the active compounds of prostratin and its analogues and shows a strong capacity to reactivate latent HIV through classical NF-κB pathway.

Euphorbia ; chemistry ; Flow Cytometry ; HIV ; drug effects ; HIV Infections ; Humans ; NF-kappa B ; metabolism ; Nitriles ; Phorbol Esters ; chemistry ; Plant Extracts ; pharmacology ; Signal Transduction ; Sulfones ; Tumor Necrosis Factor-alpha ; Virus Latency ; drug effects

The diethyl sulfate (DES) mutagenesis was chosen for the mutagenic treatment to Phellinus igniarius, and the relationship of mutagenesis time and death rate was investigated with 0.5% DES. The differences of mycelial growth speed, liquid fermentation mycelia biomass, morphology and pigment classes of secondary metabolites production speed and antioxidant activities of metabolite products were discussed. The study displayed that DES mutagenesis could change mycelial morphology without obvious effect on mycelium growth, and the DES mutagenesis improved antioxidant activities of the active ingredients of P. igniarius and had more antioxidant activity of hypoxia/sugar PC12 nerve cells than that of P. igniarius.
Basidiomycota ; drug effects ; genetics ; growth & development ; metabolism ; Mutagenesis ; Mutagens ; pharmacology ; Mycelium ; drug effects ; genetics ; growth & development ; metabolism ; Pigments, Biological ; analysis ; metabolism ; Secondary Metabolism ; drug effects ; Sulfuric Acid Esters ; pharmacology

The effect of thymic stromal lymphopoietin (TSLP) on macrophage-derived foam cell formation and the underlying mechanism were studied. Macrophages isolated from C57BL/6 mice were co-cultured in vitro with different concentrations of TSLP or TSLPR-antibody in the presence of oxidized low density lipoprotein (ox-LDL). The effects of TSLP on macrophage-derived foam cell formation were observed by using oil red O staining and intracellular lipid determination. The expression levels of foam cell scavenger receptors (CD36 and SRA) as well as ABCA1 and TSLPR were detected by using RT-PCR and Western blotting. As compared with the control group, TSLP treatment significantly promoted lipid accumulation in macrophages, significantly increased protein expression of CD36 and TSLPR in a dose-dependent manner, and significantly reduced the expression of ABCA1 protein in a dose-dependent manner. No significant differences were noted between the TSLPR-antibody group and the control group. TSLP may down-regulate the expression of cholesterol efflux receptor ABCA1 and up-regulate scavenger receptor expression via the TSLPR signaling pathway, thereby promoting macrophage-derived foam cell formation.
ATP Binding Cassette Transporter 1 ; genetics ; metabolism ; Animals ; Antibodies ; immunology ; pharmacology ; Blotting, Western ; CD36 Antigens ; genetics ; metabolism ; Cells, Cultured ; Cholesterol ; metabolism ; Cholesterol Esters ; metabolism ; Cytokines ; pharmacology ; Dose-Response Relationship, Drug ; Foam Cells ; cytology ; drug effects ; metabolism ; Gene Expression ; drug effects ; Immunoglobulins ; immunology ; metabolism ; Lipoproteins, LDL ; pharmacology ; Macrophages ; cytology ; drug effects ; metabolism ; Mice ; Mice, Inbred C57BL ; Receptors, Cytokine ; immunology ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Scavenger Receptors, Class A ; genetics ; metabolism

To explore the anti-atherosclerotic mechanism of estrogen and especially observe the effect of estradiol on the content of cholesterol in J774a.1 mouse mononuclear/macrophage-derived foam cells which were incubated with oxidized low-density lipoproteins (ox-LDL). J774a.1 mouse mononuclear/macrophages were incubated with ox-LDL or with both ox-LDL and estradiol (1, 0.1 or 0.01 micromol x L(-1)). Oil red O staining was used to observe the formation of foam cells, and cholesterol oxidase fluorometric was used to determine the content of cellular cholesterol content. Western blotting and RTFQ-PCR were used to observe the expressions of scavenger receptor class B type I (SR-B I ) in J774a.1 foam cells. Compared with the control cells, J774a.1 mouse mononuclear/macrophage-derived foam cells showed significantly increased contents of total cholesterol and cholesterol ester (P < 0.001) and decreased SR-B I mRNA expression (P < 0.01). Estradiol treatment significantly lowered the contents of total cholesterol and cholesterol ester (P < 0.05), and increased SR-B I protein and mRNA expression (P < 0.01) in the foam cells in a dose-dependent manner. Estradiol can inhibit the formation of mononuclear/macrophage-derived foam cells by decreasing the contents of total cholesterol and cholesterol ester and up-regulating the expression of SR-B I in the foam cells.
Animals ; Cell Line ; Cholesterol ; metabolism ; Cholesterol Esters ; metabolism ; Estradiol ; pharmacology ; Foam Cells ; cytology ; metabolism ; Lipoproteins, LDL ; metabolism ; Macrophages ; drug effects ; metabolism ; Mice ; Scavenger Receptors, Class B ; metabolism

OBJECTIVETo investigate the inhibitory effect of arsenic trioxide (As₂O₃) combined with tetradecanoylphorbol acetate (TPA) on the proliferation of Kasumi-1 cell line and its mechanism.

METHODSKasumi-1 cells were treated with 200 nmol/L TPA, different concentrations of As₂O₃ alone and combined with 200 nmol/L TPA. The proliferative inhibition rates were determined with CCK-8. Annexin V was adopted to detect apoptosis. Colony formation assay was used to determine the cloning efficiency. Flow cytometry was used to detect the cell differentiation and cell cycle changes. Western blot was employed to detect the expression of P38 and p-P38.

RESULTSThe proliferation inhibition rates of Kasumi-1 cells by TPA combined with different concentrations of As₂O₃ (0.2, 2.0 and 20.0 mmol/L)for 48 h were (25.56 ± 7.29)%, (60.63 ± 6.64)%, and (73.37 ± 2.15)%, the apoptosis rates were (61.65 ± 2.62)%, (75.39 ± 1.04)%, and (89.95 ± 1.46)%, and the colony formation rates were (76.17 ± 2.06)%, (38.50 ± 1.87)%, and (18.53 ± 2.20)%, respectively, compared with the different concentrations of As₂O₃ alone groups, the difference was statistically significant (P<0.05). Cells treated with both TPA and As₂O₃ expressed more CD11b antigens compared with the cells exposed to As₂O₃ alone. TPA treated Kasumi-1 cells were arrested at G1 phase compared with the control group, while As₂O₃ increased the percentage of Kasumi-1 cells in the G2 phase. Combination treatment increased the expression of p-P38 of Kasumi-1 cells compared with the cells exposed to As₂O₃ alone.

CONCLUSIONTPA can enhance the effect of As₂O₃ on inducing apoptosis and regulating cell cycle, thereby enhancing its anti-leukemia effect.

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Oxides ; pharmacology ; Phorbol Esters ; pharmacology

Five compounds (tenuifoliside C, tenuifoliside D, telephiose A, telephiose C and polygalaxanthone III) from polygala tenuifolia wild were incubated together with CYP probe substrate in human liver microsomes to investigate the inhibitory effect towards CYP450 enzyme. Phenacetin (CYP1A2), coumarin (CYP2A6), paclitaxel (CYP2C8), diclofenac (CYP2C9), S-mepheriytoin (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A) were selected as the isoforfn specific substrate. And the formation of paracetamol, 7-hydroxycoumarin, 6alpha-hydroxy paclitaxel, 4'-hydroxydiclofenac, dextrorphan, 6-hydroxychlorzoxazone, 1'-hydroxymidazolam, 4'-hydroxymephenytoin were detected respectively to measure the effect towards CYP450 by high-pressure liquid chromatography (HPLC). The result shows that five compounds from polygala tenuifolia willd significantly inhibit chlorzoxazone 6-hydroxylation catalyzed by CYP2E1, while showed no effect towards CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A. And IC50 value was 38.73, 54.14, 61.77, 62.22, 50.56 micromol x L(-1), respectively.
Cytochrome P-450 Enzyme System ; metabolism ; Esters ; pharmacology ; Glycosides ; pharmacology ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; Oligosaccharides ; pharmacology ; Polygala ; chemistry ; Xanthones ; pharmacology

We previously proposed the processing theory of "reducing ketone and dryness, and increasing ester and effect" for bran-fried atractylodes, and made a preliminary study. To further verify the science and rationality of the theory, we determined the changes in the content of atractylenolide I, II, III and atractylon in atractylodes after and before being fried with bran, in order to compare the effect of raw and bran-fried atractylodes on the water intake and urination in rats in this study. The effect of raw and bran-fried atractylodes on the content of four gastrointestinal hormones and two neurotransmitters in serum was observed in an attempt to verify the science and rationality the processing theory of "reducing ketone and dryness, and increasing ester and effect" for bran-fried atractylodes.
Animals ; Atractylodes ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Esters ; chemistry ; Ketones ; chemistry ; Lactones ; chemistry ; isolation & purification ; pharmacology ; Male ; Pharmacology ; methods ; Rats ; Rats, Sprague-Dawley ; Sesquiterpenes ; chemistry ; isolation & purification ; pharmacology

A series of valproic acid salicylanilide esters were designed and synthesized based on the principle of prodrug. The structures of the target compounds were confirmed by MS, 1H NMR and 13C NMR. Anti-tumor activities of these compounds against K562, A549, A431 cells in vitro were investigated by MTT assay and SRB assay. The results indicated that the compounds 6h-6j were found to have stronger cell growth inhibitory action than gefitinib, and comparable to niclosamide, which are worth to be intensively studied further.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Design ; Esters ; Humans ; Inhibitory Concentration 50 ; K562 Cells ; Molecular Structure ; Prodrugs ; chemical synthesis ; chemistry ; pharmacology ; Salicylanilides ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Valproic Acid ; chemical synthesis ; chemistry ; pharmacology