AIM: To investigate the chemical constituents and their biological activities of the aerial parts of Euphorbia tibetica. METHOD: Compounds were isolated and purified by various chromatographic methods, and their structures were elucidated through the use of extensive spectroscopic techniques including 2D-NMR, the structures of compounds 5 and 6 were confirmed by single-crystal X-ray crystallography. Bioactivities of all the isolated compounds were evaluated by the MTT method on A549 and anti-angiogenesis assay. RESULTS: One new compound, methyl 4-epi-shikimate-3-O-gallate (1), together with twenty-three known constituents (2-24) were isolated from the aerial parts of E. tibetica. CONCLUSION Compound 1 is new, and the other compounds were isolated from this plant for the first time. Compounds 5-7, 9, 11, 17, 18 and 20 exhibited inhibitory effects on the growth of human lung cancer cell A549 and compounds 5, 7, 12, 13, 17 and 19 showed anti-angiogenic effects in a zebrafish model.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Cell Line ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Euphorbia ; chemistry ; Growth Inhibitors ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Zebrafish

The dichloromethane extract of the air-dried leaves of Ardisia cf. elliptica (subgenus Tinus) afforded a mixture of bauerenol (1a), α-amyrin (1b) and β-amyrin (1c). Their structures were identified by NMR spectroscopy. Mixtures of the triterpenes (1a-1c) at ratios of 2 : 2 : 1, 2 : 2 : 3 and 1 : 1 : 1 were tested for their angio-suppressive effects on duck chorioallantoic membrane (CAM). All three ratios were found to be effective in restricting inter-capillary length, while 1a-1c (2 : 2 : 1) was most effective in reducing branch point density with 100% CAM viability and embryo survivability, suggesting a high impact angio-suppressive potential of 1a-1c (2 : 2 : 1).
Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Ardisia ; chemistry ; Chorioallantoic Membrane ; blood supply ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Ducks ; Plant Leaves ; chemistry ; Triterpenes ; chemistry ; pharmacology

Present study was focused on the chemical constituents of the stems and leaves of Salvia yunnanensis C . H. Wright and their anti-angiogeneic activities. The compounds were isolated by column chromatography over silica gel and Sephadex LH-20, and other isolation techniques. Their structures were elucidated on the basis of spectral analysis and chemical evidences. Their anti-angiogeneic activities were evaluated by the chicken chorioallantoic membrane (CAM) neovascularisation model. Seven compounds were separated and identified as ( + ) -spathulenol( 1), 5,7,4'-trihydroxyflavanone(2) , beta-amyrin(3), 3 beta-hydroxy-12-ursene(4), 2alpha,3 beta-dihydroxyursa-12-en-28-oic acid(5), ursolic acid (6) and 3-oxo-12-ursen-28-oic acid (7). Compounds 1, 2, 5 and 6 were obtained from this plant for the first time. Compounds 5 (an oleanane compound) and 6 (an ursane compound) could inhibit angiogenesis significantly in a dose-dependent manner.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Chorioallantoic Membrane ; drug effects ; metabolism ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Salvia ; chemistry

Alkaloids ; pharmacology ; Angiogenesis Inhibitors ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; Ginsenosides ; pharmacology ; Humans ; Lymphatic Metastasis ; prevention & control ; Pyrazines ; pharmacology ; Quinolizines

The ginseng family, including Panax ginseng (Asian ginseng), Panax quinquefolius (American ginseng), and Panax notoginseng (notoginseng), is commonly used herbal medicine. White ginseng is prepared by air-drying after harvest, while red ginseng is prepared by a steaming or heating process. The anticancer activity of red ginseng is significantly increased, due to the production of active anticancer ginsenosides during the steaming treatment, compared with that of white ginseng. Thus far, anticancer studies have been mostly focused on Asian ginseng. In this article, we review the research progress made in the anticancer activities of red Asian ginseng, red American ginseng and red notoginseng. The major anticancer mechanisms of red ginseng compounds include cell cycle arrest, induction of apoptosis/paraptosis, and inhibition of angiogenesis. The structure-function relationship analysis has revealed that the protopanaxadiol group ginsenosides have more potent effects than the protopanaxatriol group. Sugar molecules in ginsenosides inversely impact the antiproliferative potential of these compounds. In addition, ginsenoside stereoselectivity and double bond position also influence the anticancer activity. Future studies should focus on characterizing active red ginseng derivatives as potential anticancer drugs.
Angiogenesis Inhibitors ; pharmacology ; Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Ginsenosides ; pharmacology ; Humans ; Neoplasms ; drug therapy ; prevention & control ; Panax ; chemistry ; Panax notoginseng ; chemistry ; Phytotherapy ; Structure-Activity Relationship

AIMTo investigate the chemical constituents of the rhizomes of Beesia calthaefolia native to China in order to obtain a more comprehensive understanding of its effective components.

METHODSCompounds were isolated by column chromatography with silica gel. Their structures were elucidated by spectral analysis and chemical evidence. Compounds identified were subjected to pharmacological evaluation.

RESULTSTwo novel compounds were isolated and identified as (20S, 24S)-15 alpha-acetoxy-16 beta, 24; 20, 24-diepoxy-9, 19-cyclolanostane-3 beta, 25-diol-3-O-beta-D-xylopyranoside (I) and (20S, 24R)-15 alpha-acetoxy-9, 19-cyclolanostane-3 beta, 16 beta, 20, 24, 25-pentaol-3-O-beta-D-xylopyranoside (II), named beesioside O and beesioside P.

CONCLUSIONCompounds I and II are new compounds. Compounds I exhibited immunosuppressive activity and could inhibit angiogenesis as well as inhibit the proliferation of osteoblast. Compound II displayed remarkable inhibition activity against calcium channel receptor.

Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Calcium Channel Blockers ; chemistry ; pharmacology ; Immunosuppressive Agents ; chemistry ; pharmacology ; Mice ; Molecular Conformation ; Molecular Structure ; Plants, Medicinal ; chemistry ; Ranunculaceae ; chemistry ; Saponins ; chemistry ; isolation & purification ; pharmacology

We made fusion protein of fastatin and FIII 9-10, termed tetra-cell adhesion molecule (T-CAM) that can interact simultaneously with alphavbeta3 and alpha5beta1 integrins, both playing important roles in tumor angiogenesis. T-CAM can serve as a cell adhesion substrate mediating adhesion and migration of endothelial cells in alphavbeta3 and alpha5beta1 integrin-dependent manner. T-CAM showed pronounced anti-angiogenic activities such as inhibition of endothelial cell tube formation, endothelial cell proliferation, and induction of endothelial cell apoptosis. T-CAM also inhibited angiogenesis and tumor growth in mouse xenograft model. The anti-angiogenic and anti-tumoral activity of molecule like fastatin could be improved by fusing it with integrin-recognizing cell adhesion domain from other distinct proteins. The strategy of combining two distinct anti-angiogenic molecules or cell adhesion domains could facilitate designing improved anticancer agent of therapeutic value.
Angiogenesis Inhibitors/chemistry/*pharmacology ; Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Base Sequence ; Benzocaine/chemistry/*pharmacology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chloramphenicol/chemistry/*pharmacology ; DNA Primers ; Drug Combinations ; Factor VIII/chemistry/*pharmacology ; Humans ; Integrin alpha5beta1/*physiology ; Integrin alphaVbeta3/*physiology ; Male ; Mice ; Mice, Inbred BALB C ; Nitrofurazone/chemistry/*pharmacology ; Recombinant Fusion Proteins/chemistry/*pharmacology

Ursolic acid (UA) is a sort of pentacyclic triterpenoid carboxylic acid purified from natural plant. UA has a series of biological effects such as sedative, anti-inflammatory, anti-bacterial, anti-diabetic, antiulcer, etc. It is discovered that UA has a broad-spectrum anti-tumor effect in recent years, which has attracted more and more scholars' attention. This review explained anti-tumor actions of UA, including (1) the protection of cells' DNA from different damages; (2) the anti-tumor cell proliferation by the inhibition of epidermal growth factor receptor/mitogen-activated protein kinase signal or of FoxM1 transcription factors, respectively; (3) antiangiogenesis, (4) the immunological surveillance to tumors; (5) the inhibition of tumor cell migration and invasion; (6) the effect of UA on caspase, cytochromes C, nuclear factor kappa B, cyclooxygenase, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or mammalian target of rapamycin signal to induce tumor cell apoptosis respectively, and etc. Moreover, UA has selective toxicity to tumor cells, basically no effect on normal cells. With further studies, UA would be one of the potential anti-tumor agents.
Angiogenesis Inhibitors ; pharmacology ; therapeutic use ; Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Humans ; Immunologic Surveillance ; drug effects ; Neoplasms ; blood supply ; drug therapy ; immunology ; pathology ; Triterpenes ; chemistry ; pharmacology ; therapeutic use

Vascular disrupting agents (VDAs) have presented a new kind of anti-cancer drug in recent years. VDAs take advantage of the weakness of established tumor endothelial cells and their supporting structures. In contrast to anti-angiogenic therapy, which inhibits the outgrowth of new blood vessels, vascular targeting treatments selectively attack the existing tumor vasculature. Here we summarized the anti-tumor activities, mechanisms and clinical applications of small molecule VDAs.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; therapeutic use ; Animals ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Bibenzyls ; chemistry ; pharmacology ; therapeutic use ; Diphosphates ; chemistry ; pharmacology ; therapeutic use ; Endothelial Cells ; drug effects ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; pathology ; Neovascularization, Pathologic ; Oligopeptides ; chemistry ; pharmacology ; therapeutic use ; Organophosphorus Compounds ; chemistry ; pharmacology ; therapeutic use ; Serine ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Stilbenes ; chemistry ; pharmacology ; therapeutic use ; Tubulin Modulators ; chemistry ; pharmacology ; therapeutic use ; Xanthones ; chemistry ; pharmacology ; therapeutic use

Arg-Gly-Asp (RGD)-toxin protein Lj-RGD3 of Lampetra japonica shares homologous with a Histidine-rich glycoprotein (HRG), and both RGD-toxin protein and HRG have antiangiogenic activities with different targets. To study the relationship between the function and the structure of Lj-RGD3, we studied the anti-angiogenic characteristics of both Lj-RGD3 and the mutation named Lj-112 of which three RGD motifs of Lj-RGD3 were deleted. We synthesized the gene of Lj-112, constructed it to the plasmid pET23b, and expressed the recombinant proteins in Escherichia coli BL21. Both recombinant proteins with the C-terminal his-tag were 15 kDa soluble proteins. Then we purified rLj-RGD3 and rLj-112 using the His-Bind affinity chromatography. To examine the effect of both proteins on bFGF-induced proliferation of ECV304 cell, we carried out the 3-(4,5)-dimethylthiahiazo (-z-yl)-3,5-di-phenytetrazoliumromide (MTT) assays. For cell migration and invasion assays, we used Transwell containing insert filter and Matrigel to imitate the in vivo environment. To examine whether both proteins were capable of interrupting the angiogenesis in vivo, we used the chick chicken embryonic chorioallantoic membrane (CAM) as an angiogenesis model. We used Integrin-linked kinase1 (ILK1) ELISA method to study functionary mechanisms of rLj-RGD3 and rLj-112. Both rLj-RGD3 and rLj-112 inhibited bFGF-induced proliferation of ECV304 cells in a dose-dependent manner with IC50 at 0.889 micromol/L and 0.160 micromol/L, respectively. The results of migration and invasion assays revealed that both rLj-RGD3 and rLj-112 showed significant inhibition on bFGF induced migration and invasion of ECV304; and rLj-112 was more active than rLj-RGD3. The result of CAM angiogenesis assay demonstrated that both proteins inhibited the angiogenesis in chick CAM, and rLj-112 was more active than rLj-RGD3. ELISA assay of ILK1 showed that both rLj-RGD3 and rLj-112 down-regulated ILK1 expression of ECV304 cell. The fact of rLj-112 was more active than rLj-RGD3 on anti-angiogenesis indicate that rLj-112 was likely with histidine-rich glycoprotein (HRG), and the factor of sequence homologous between rLj-RGD3 and HRG cannot enhance antiangiogenic activities of rLj-RGD3, the signal pathway of anti-angiogenesis of rLj-RGD3 and rLj-112 are differently.
Amino Acid Sequence ; Angiogenesis Inhibitors ; pharmacology ; Animals ; Base Sequence ; Cell Line ; Fish Venoms ; biosynthesis ; genetics ; isolation & purification ; pharmacology ; Humans ; Lampreys ; metabolism ; Molecular Sequence Data ; Mutant Proteins ; chemistry ; pharmacology ; Oligopeptides ; biosynthesis ; genetics ; isolation & purification ; pharmacology