ABSTRACT
Three new tricyclic cyclopiazonic acid (CPA) related alkaloids asperorydines N-P (1-3), together with six known compounds (4-9) were isolated and characterized from the fungus Aspergillus flavus SCSIO F025 derived from the deep-sea sediments of South China Sea. The structures including absolute configurations of 1-3 were deduced from spectroscopic data, X-ray diffraction analysis, and electronic circular dichroism (ECD). All compounds were evaluated for the antioxidative activities against DPPH, cytotoxic activities against four tumor cell lines (SF-268, HepG-2, MCF-7, and A549), and antimicrobial activities. Compound 9 showed significant radical scavenging activities against DPPH with an IC50 value of 62.23 µM and broad-spectrum cytotoxicities against four tumor cell lines with IC50 values ranging from 24.38 to 48.28 µM. Furthermore, compounds 4-9 exhibited weak antimicrobial activities against E scherichia coli, and compound 9 also showed antibacterial activity against Bacillus thuringiensis, Micrococcus lutea, Staphylococcus aureus, Bacillus subtilis, Methicillin resistant Staphylococcus aureus.
Subject(s)
Alkaloids/pharmacology , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Aspergillus flavus/chemistry , Indoles/pharmacology , Alkaloids/isolation & purification , Anti-Bacterial Agents/isolation & purification , Antineoplastic Agents/isolation & purification , Aquatic Organisms/chemistry , Bacillus/drug effects , Cell Line, Tumor , China , Escherichia coli/drug effects , Geologic Sediments/microbiology , Humans , Indoles/isolation & purification , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Micrococcus/drug effects , Molecular Structure , Seawater/microbiologyABSTRACT
To explore the potential application of enzymatic degraded polysaccharides from Enteromorpha prolifra (EEP) as antioxidant in fish oils, a stable fish oil emulsion system incorporating EEP was established. Effects of emulsifier (Tween 80, gum arabic and lecithin) and EEP concentration on the physical characteristics of fish oil emulsions were investigated. The results indicated that Tween 80 was the best choice, and 1% (w/w) of EEP was the optimum concentration for the preparation of fish oil emulsions. Influence of EEP on the oxidative stability and physical stability of fish oil emulsions was compared with that of antioxidants VE and TBHQ by determining the physical properties, lipid hydroperoxide formation, secondary reaction products formation, pH and long chain polyunsaturated fatty acid content, during storage at 45 °C. The results indicated that the fish oil emulsion system (5% oil, 1% EEP and 1% Tween 80, w/w) possessed good physical and oxidative stabilities.
Subject(s)
Emulsifying Agents/chemistry , Emulsions/chemistry , Fish Oils/chemistry , Polysaccharides/chemistry , Ulva/chemistry , Antioxidants/chemistry , Gum Arabic/chemistry , Lecithins/chemistry , Oxidation-Reduction , Polysorbates/chemistry , Rheology , Water/chemistryABSTRACT
A chemical investigation of the whole plant of Pronephrium megacuspe (Bak.) Holtt. led to the isolation of four flavonoids, pronephrones A-D (1-4), which were firstly reported. The chemical structures of four compounds were established using spectroscopic methods. These isolates were further evaluated for cytotoxicity to ovarian cells of Spodoptera litura Fabricius.
Subject(s)
Cytotoxins/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Flavonoids/isolation & purification , Plants, Medicinal/chemistry , Animals , Cytotoxins/chemistry , Cytotoxins/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Female , Flavonoids/chemistry , Flavonoids/pharmacology , Houseflies , Insecticides/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Ovary/cytology , Ovary/drug effects , Spodoptera/cytology , Spodoptera/drug effectsABSTRACT
Three new oleanane triterpenoids, 2α,3ß,29-trihydroxyolean-12-en-28-oic acid (1), 2α,3ß-dihydroxy-23-oxo-olean-12-en-28-oic acid (2) and 2α,3ß,21ß,22α-tetrahydroxyolean-12-en-28,29-dioic acid (3), and ten known ones, maslinic acid (4), arjunolic acid (5), oleanolic acid (6), 3-epi-oleanolic acid (7), stachlic acid A (8), serratagenic acid (9), gypsogenic acid (10), 2α,3ß-dihydroxyol-ean-13(18)-en-28-oic acid (11), mesembryanthemoidigenic acid (12) and 12α-hydroxy-δ-lactone (13), were isolated from the pericarps of Akebia trifoliata, a new valued fruit crop in China. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compounds 8, 10, 11 and 13 were isolated for the first time from the genus Akebia. All the compounds were tested for their antimicrobial activity against five bacterial strains. Compounds 4, 6 and 11 showed significant antibacterial activity toward all the assayed microorganisms with MIC values ranging from 0.9 to 15.6µg/mL, which were close or even more potent than the reference compound Kanamycin (MIC values ranging from 1.9 to 3.9µg/mL).
Subject(s)
Anti-Bacterial Agents/chemistry , Oleanolic Acid/chemistry , Plant Extracts/chemistry , Streptophyta/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Fruit/chemistry , Fruit/metabolism , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Conformation , Oleanolic Acid/isolation & purification , Oleanolic Acid/pharmacology , Plant Extracts/pharmacology , Streptophyta/metabolismABSTRACT
A new regioisomer of andrographolide, 17-hydro-9-dehydro-andrographolide (1), and five new sulfates of andrographolide (2-6) were isolated from Xiyanping, a China licensed anti-inflammatory drug derived from andrographolide through sulfation reaction. Their chemical structures were elucidated by spectroscopic and chemical methods. The inhibition effects of these compounds on angiogenesis were evaluated by rat aortic ring assay. Compounds 1 and 3 exhibited strong inhibitory activities on vascular endothelial cell tube formation in rat aorta ring at the concentration of 1 µM. Compounds 4 and 5 showed moderate suppression on angiogenesis at 10 µM.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Diterpenes/pharmacology , Drugs, Chinese Herbal/pharmacology , Sulfuric Acid Esters/pharmacology , Angiogenesis Inhibitors/chemistry , Animals , Aorta/drug effects , Cell Movement/drug effects , Diterpenes/chemistry , Drugs, Chinese Herbal/chemistry , Endothelial Cells/drug effects , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Rats , Stereoisomerism , Sulfuric Acid Esters/chemistryABSTRACT
Further investigation on the stems of Artocarpus nitidus subsp. lingnanensis led to the isolation and characterization of a new flavan-3-ol, named artoflavanocoumarin, along with three known compounds (+)-catechin, (+)-afzelechin 3-O-α-L-rhamnoside, and (+)-catechin 3-O-α-L-rhamnoside. Their structures were elucidated on the basis of spectroscopic data.
Subject(s)
Artocarpus/chemistry , Drugs, Chinese Herbal/isolation & purification , Flavonoids/isolation & purification , Drugs, Chinese Herbal/chemistry , Flavonoids/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Stems/chemistry , StereoisomerismABSTRACT
A novel sesquiterpene alcohol, named frabenol (1), was isolated from liquid cultures of Fimetariella rabenhorstii A20, an endophytic fungus of the agarwood-forming plant Aquilaria sinensis (Lour.) Gilg. The structure of the new compound was elucidated on the basis of spectroscopic methods. The finding of a sesquiterpenoid compound in F. rabenhorstii A20 implied that endophytic fungi of agarwood-producing plants could also contribute to the generation of fragrant chemicals during the agarwood formation processes.
Subject(s)
Alcohols/chemistry , Ascomycota/chemistry , Sesquiterpenes/chemistry , Thymelaeaceae/microbiology , Molecular StructureABSTRACT
Herpes simplex virus type 1 (HSV-1) is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypoglaucum (level) Hutch (Celastraceae) is a traditional Chinese medicine plant with many pharmacological activities such as anti-inflammation, anti-tumor and antifertility. The usual medicinal part is the roots which contain about a 1% yield of alkaloids. A crude total alkaloids extract was prepared from the roots of T. hypoglaucum amd its antiviral activity against HSV-1 in Vero cells was evaluated by cytopathic effect (CPE) assay, plaque reduction assay and by RT-PCR analysis. The alkaloids extract presented low cytotoxicity (CC(50) = 46.6 µg/mL) and potent CPE inhibition activity, the 50% inhibitory concentration (IC(50)) was 6.5 µg/mL, noticeably lower than that of Acyclovir (15.4 µg /mL). Plaque formation was significantly reduced by the alkaloids extract at concentrations of 6.25 µg/mL to 12.5 µg/mL, the plaque reduction ratio reached 55% to 75 which was 35% higher than that of Acyclovir at the same concentration. RT-PCR analysis showed that, the transcription of two important delayed early genes UL30 and UL39, and a late gene US6 of HSV-1 genome all were suppressed by the alkaloids extract, the expression inhibiting efficacy compared to the control was 74.6% (UL30), 70.9% (UL39) and 62.6% (US6) respectively at the working concentration of 12.5 µg/mL. The above results suggest a potent anti-HSV-1 activity of the alkaloids extract in vitro.
Subject(s)
Alkaloids/isolation & purification , Alkaloids/pharmacology , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Herpesvirus 1, Human/drug effects , Tripterygium/chemistry , Alkaloids/toxicity , Animals , Antiviral Agents/toxicity , Chlorocebus aethiops , Cytopathogenic Effect, Viral/drug effects , Gene Expression/drug effects , Inhibitory Concentration 50 , Microbial Viability/drug effects , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/toxicity , Plant Roots/chemistry , Transcription, Genetic/drug effects , Viral Plaque Assay , Viral Proteins/biosynthesisABSTRACT
ErbB-2 gene encodes tyrosine kinase receptor p185(neu). Overexpression of erbB-2 plays a key role in tumorigenesis or progression such as breast cancer and ovarian cancer. Our previous study showed that ON-III (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone) extracted from Traditional Chinese Medicine Cleistocaly xoperculatus dry flower could inhibit KDR tyrosine kinase phosphorylation and tumor growth in vivo. In this study, we reported that ON-III repressed tyrosine phosphorylation of erbB-2 without reduced erbB-2 receptor expression in MDA-MB-453 cells. Activation of mitogen-activated protein kinase (MAPK) and AKT, downstream molecules of erbB-2-mediated signal transduction pathway, was inhibited following exposure to ON-III. ON-III induced apoptosis in breast cancer cells as determined by caspase-3 and PARP cleavage. Also, ON-III upregulated the expression of proapoptotic BH3-only Bcl-2 family member Bim. Bim siRNA could inhibit ON-III-mediated apoptosis in MDA-MB-453 cells. It concludes that ON-III inhibits erbB-2 tyrosine kinase phosphorylation, shuts down its downstream pathway and triggered apoptosis via induction of Bim. These results suggest that ON-III is a potential novel anti-cancer agent for erbB-2-overexpressing cancer.
Subject(s)
Apoptosis Regulatory Proteins/metabolism , Apoptosis/drug effects , Breast Neoplasms/pathology , Chalcones/pharmacology , Membrane Proteins/metabolism , Proto-Oncogene Proteins/metabolism , Receptor, ErbB-2/antagonists & inhibitors , Signal Transduction/drug effects , Apoptosis Regulatory Proteins/antagonists & inhibitors , Apoptosis Regulatory Proteins/genetics , Bcl-2-Like Protein 11 , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Cell Proliferation/drug effects , Humans , Immunoblotting , Immunoprecipitation , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/genetics , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation/drug effects , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering/pharmacology , Receptor, ErbB-2/metabolism , Tumor Cells, CulturedABSTRACT
Antiangiogenesis is a promising strategy of cancer treatment. Vascular endothelial growth factor receptor [fetal liver kinase/kinase-inserting domain-containing receptor (KDR)] is a tyrosine kinase receptor and has been strongly implicated in tumor angiogenesis. In this study, we report that 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (ON-III), extracted from the dried flower Cleistocalyx operculatus, used in traditional Chinese medicine, reversibly inhibited KDR tyrosine kinase phosphorylation, but epidermal growth factor receptor tyrosine kinase phosphorylation was unaffected under the same concentrations of ON-III. ON-III also inhibited mitogen-activated protein kinase (MAPK) and AKT activation of KDR signal transduction in downstream molecules without reduced total MAPK and AKT. The results in vitro showed that ON-III inhibited growth of human vascular endothelial HDMEC cells in the presence of VEGF preferentially, compared with epidermal growth factor. Systemic administration of ON-III at nontoxic doses in nude mice resulted in inhibition of subcutaneous tumor growth of human hepatocarcinoma Bel7402 and lung cancer GLC-82 xenografts. The tumor vessel density decreased, as determined by immunohistochemical staining, for CD31 after ON-III treatment. These results indicated that ON-III inhibited KDR tyrosine kinase, shut down KDR-mediated signal transduction, and inhibited tumor growth of human xenografts in vivo.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Chalcone/analogs & derivatives , Chalcone/pharmacology , Drugs, Chinese Herbal/pharmacology , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Signal Transduction/drug effects , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Chalcones , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Receptors, Vascular Endothelial Growth Factor/metabolism , Signal Transduction/physiology , Xenograft Model Antitumor Assays/methodsABSTRACT
The human bronchial epithelial cells are the primary sites of influenza virus infection. In this study, the effect of indirubin on the expression of the chemokine regulated on activation, normal T cell expressed and secreted (RANTES) by the influenza virus-infected H292 human epithelial cell line was examined. The expression of RANTES mRNA was analyzed using reverse transcription polymerase chain reaction and the concentration of RANTES production was determined by the enzyme-linked immunosorbent assay. At the non-cytotoxic concentrations, indirubin was found to reduce both the expression and production of RANTES in influenza A/NWS/33-infected H292 cells. Inhibition was also observed in influenza virus B/Lee-infected cells. Significant reduction of the expression of IL-8 was not observed after the infection. Indirubin-3'-oxime, a recently developed derivative with kinase inhibitory activity, also mediates a potent inhibitory effect on the expression of RANTES. The influenza virus infection-induced phosphorylation of the nuclear transcription NF-kB regulatory molecule IkBalpha and the p38 MAP kinase were also found to be inhibited by indirubin-3'-oxime. This finding suggests that indirubin is one of the components in the Chinese medicinal herbs Isatis indigotica and Strobilanthes cusia with immunomodulatory activity on the expression of RANTES.
Subject(s)
Chemokine CCL5/biosynthesis , Epithelial Cells/drug effects , Gene Expression Regulation/drug effects , Indoles/pharmacology , Orthomyxoviridae/physiology , Bronchi/cytology , Chemokine CCL5/genetics , Epithelial Cells/metabolism , Epithelial Cells/virology , Humans , I-kappa B Proteins/biosynthesis , Indigo Carmine , Indoles/chemistry , Interleukin-8/biosynthesis , Interleukin-8/genetics , Isatin/pharmacology , Mitogen-Activated Protein Kinases/biosynthesis , RNA, Messenger/biosynthesis , RNA, Messenger/drug effects , p38 Mitogen-Activated Protein KinasesABSTRACT
AIM: To study the inhibition of oxygen consumption by annonaceous acetogenins (ACG) and their structure-activity relationship (SAR). METHODS: The inhibition of oxygen consumption in chicken liver cell respiration by different structural ACG was studied by using oxygen electrode technique. RESULTS: Six ACG showed potent inhibitory effects like rotenone which was a classical inhibitor of mitochondrial complex I, and was more potent than complex IV inhibitor KCN. The IC50 values of six ACG for inhibiting oxygen consumption suggested that bistetrahydrofuran (THF) ACG was 7-11 times more active than non-THF ACG, and A1-type ACG was more potent than A2-type ACG. CONCLUSION: The terminal gamma-lactone was crucial for the inhibition of oxygen consumption. The distance between THF and gamma-lactone, the hydroxyl groups in the alkyl chain, were the important factors of SAR, but the 4-OH group possibly played some negative role in the exhibit of potent activity.