Gigantol is a phenolic component of precious Chinese medicine Dendrobii Caulis, which has many pharmacological activities such as prevent tumor and diabetic cataract. This paper aimed to investigate the molecular mechanism of gigantol in transmembrane transport in human lens epithelial cells(HLECs). Immortalized HLECs were cultured in vitro and inoculated in the laser scanning confocal microscopy(LSCM) medium at 5 000 cells/mL. The fluorescence distribution and intensity of gigantol marked by fluorescence in HLECs were observed by LSCM, and the absorption and distribution of gigantol were expressed as fluorescence intensity. The transmembrane transport process of gigantol in HLECs were monitored. The effects of time, temperature, concentration, transport inhibitors, and different cell lines on the transmembrane absorption and transport of gigantol were compared. HLECs were inoculated on climbing plates of 6-well culture plates, and the ultrastructure of HLECs was detected by atomic force microscopy(AFM) during the transmembrane absorption of non-fluorescent labeled gigantol. The results showed that the transmembrane absorption of gigantol was in time and concentration-dependent manners, which was also able to specifically target HLECs. Energy and carrier transport inhibitors reduced gigantol absorption by HLECs. During transmembrane process of gigantol, the membrane surface of HLECs became rougher and presented different degrees of pits, indicating that the transmembrane transport of gigantol was achieved by active absorption of energy and carrier-mediated endocytosis.
Humans ; Lens, Crystalline/pathology* ; Cataract/prevention & control* ; Bibenzyls/pharmacology* ; Epithelial Cells ; Cells, Cultured ; Apoptosis

Eleven compounds were isolated from the 95% ethanol extract of the stems of Dendrobium officinale after water extraction by various modern chromatographic techniques, such as silica gel column chromatography(CC), octadecyl-silica(ODS) CC, Sephadex LH-20 CC, preparative thin layer chromatography(PTLC) and preparative high performance liquid chromatography(PHPLC). According to spectroscopic analyses(MS, 1D-NMR, 2D-NMR) combined with optical rotation data and calculated electronic circular dichroism(ECD), their structures were identified as dendrocandin Y(1), 4,4'-dihydroxybibenzyl(2), 3-hydroxy-4',5-dimethoxybibenzyl(3), 3,3'-dihydroxy-5-methoxybibenzyl(4), 3-hydroxy-3',4',5-trimethoxybibenzyl(5), crepidatin(6), alternariol(7), 4-hydroxy-3-methoxypropiophenone(8), 3-hydroxy-4,5-dimethoxypropiophenone(9), auriculatum A(10) and hyperalcohol(11). Among them, compound 1 was a new bibenzyl derivative; compounds 2 and 7-11 have not been previously reported from Dendrobium plants; compound 6 was reported from D.officinale for the first time. Compounds 3-6 exhibited potent antioxidant activity with IC_(50) values of 3.11-9.05 μmol·L~(-1) in ABTS radical scavenging assay. Compound 4 showed significant inhibitory effect on α-glucosidase, with IC_(50) value of 17.42 μmol·L~(-1), indicating that it boasted hypoglycemic activity.
Dendrobium ; Biological Assay ; Chromatography, High Pressure Liquid ; Chromatography, Thin Layer ; Bibenzyls

Fifteen bibenzyls were isolated and purified from the ethyl acetate extract of the stems of Dendrobium officinale by macroporous resin, MCI, silica gel, Sephadex LH-20, and ODS column chromatographies, as well as preparative thin-layer chromatography and preparative HPLC. The structures of compounds were identified according to the spectra data of ~1H-NMR, ~(13)C-NMR, and MS, and the physical and physiochemical properties: dendrocandin X(1), 3,4'-dihydroxy-4,5-dimethoxybibenzyl(2), 6″-de-O-methyldendrofindlaphenol A(3), 3,4-dihydroxy-4',5-dimethoxybibenzyl(4), dendrosinen B(5), 3,4,4'-trihydroxy-5-methoxybibenzyl(6), 3,3'-dihydroxy-4,5-dimethoxybibenzyl(7), 3,4'-dihydroxy-5-methoxybibenzyl(8), moscatilin(9), gigantol(10), 4,4'-dihydroxy-3,5-dimethoxybibenzyl(11), 3,4',5-trihydroxy-3'-methoxybibenzyl(12), 3-O-methylgigantol(13), dendrocandin U(14), and dendrocandin N(15). Compound 1 was a novel compound. Compound 2 was isolated from Dendrobium species for the first time. Compounds 3-7 were isolated from D. officinale for the first time.
Bibenzyls ; Chromatography, High Pressure Liquid ; Dendrobium ; Magnetic Resonance Spectroscopy

Bibenzyl is a type of active compounds abundant in Dendrobium. In the present study, we investigated the inhibitory effects of six bibenzyls isolated from Dendrobium species on vascular endothelial growth factor (VEGF)-induced tube formation in human umbilical vascular endothelial cells (HUVECs). All those bibenzyls inhibited VEGF-induced tube formation at 10 micromol x L(-1) except tristin, and of which moscatilin was found to have the strongest activity at the same concentration. The lowest effective concentration of moscatilin was 1 micromol x L(-1). Further results showed that moscatilin inhibited VEGF-induced capillary-like tube formation on HUVECs in a concentration-dependent manner. Western blotting results showed that moscatilin also inhibited VEGF-induced phosphorylation of VEGFR2 (Flk-1/KDR) and extracellular signal-regulated kinase 1/2 (ERK1/2). Further results showed that moscatilin inhibited VEGF-induced activation of c-Raf and MEK1/2, which are both upstream signals of ERK1/2. Taken together, results presented here demonstrated that moscatilin inhibited angiogenesis via blocking the activation of VEGFR2 (Flk-1/KDR) and c-Raf-MEK1/2-ERK1/2 signals.
Angiogenesis Inhibitors ; administration & dosage ; isolation & purification ; pharmacology ; Animals ; Benzyl Compounds ; administration & dosage ; isolation & purification ; pharmacology ; Bibenzyls ; isolation & purification ; pharmacology ; Cell Count ; Cells, Cultured ; Dendrobium ; chemistry ; Dose-Response Relationship, Drug ; Human Umbilical Vein Endothelial Cells ; Humans ; MAP Kinase Kinase 1 ; metabolism ; MAP Kinase Kinase 2 ; metabolism ; MAP Kinase Signaling System ; drug effects ; Mice ; Mice, Inbred C57BL ; Neovascularization, Physiologic ; drug effects ; Phosphorylation ; drug effects ; Plants, Medicinal ; chemistry ; Proto-Oncogene Proteins c-raf ; metabolism ; Signal Transduction ; drug effects ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVETo isolate the bibenzyl derivatives from the tuber of Arundina graminifolia and evaluate the anti-tumor activity of these compounds in vitro.

METHODThe constituents have been extracted by 95% alcohol and then isolated by column chromatography on silica gel and Sephedax LH-20. The structures were determined by UV, IR, NMR and MS spectral analysis.

RESULTSix constituents have been isolated, and their structures have been established as 2,7-dihydroxy-1-(p-hydroxylbenzyl)-4-methoxy-9, 10-dihydrophenanthrene (1), 4,7-dihydroxy-1- (p-hydroxylbenzyl)-2-methoxy-9,10-dihydrophenanthrene (2), 3, 3'-dihydroxy-5-methoxybibenzyl (3), (2E) -2- propenoic acid-3-(4-hydroxy-3-methoxyphenyl) -tetracosyl ester (4), (2E) -2-propenoic acid-3- (4-hydroxy-3- methoxyphenyl) -pentacosyl ester (5) and pentadecyl acid (6), respectively.

CONCLUSIONAll compounds except for 3 were isolated from the tuber of A. graminifolia for the first time. Compound 3 with bibenzyl ring opening exhibits stronger anti-tumor activity than that of compounds 1 and 2 with bibenzyl ring closing.

Antineoplastic Agents ; chemistry ; isolation & purification ; pharmacology ; Bibenzyls ; chemistry ; immunology ; isolation & purification ; Cell Line, Tumor ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Humans ; Magnetic Resonance Spectroscopy ; Orchidaceae ; chemistry

OBJECTIVETo study the anti-cataract effect of gigantol combined with syringic acid and their action mechanism.

METHODH202-induced lens oxidative injury in vitro rat model was establish to observe the impact of gigantol combined with syringic acid on lens transparency under a dissecting microscope. D-galactose-induced cataract rat model was established to observe the impact of gigantol combined with syringic acid on lens transparency under a slit-lamp. UV spectrophotometry was adopted to detect the inhibitory activity of gigantol combined with syringic acid against AR. Molecular docking method was used to detect binding sites, binding types and pharmacophores of gigantol combined with syringic acid in prohibiting aldose reductase.

RESULTBoth in vitro and in vivo experiments showed a good anti-sugar cataract activity in the combination of gigantol and syringic acid and a better collaborative effect than single component-gigantol and syringic acid and positive control drug Catalin. Molecular docking and dynamic simulation showed their collaborative AR-inhibiting amino acid residue was Asn160 and the major acting force was Van der Waals' force, which formed common pharmacophores.

CONCLUSIONGigantol combined with syringic acid shows good anti-cataract, their action mechanism is reflected in their good collaborative inhibitory effect on AR.

Aldehyde Reductase ; antagonists & inhibitors ; Animals ; Bibenzyls ; Cataract ; drug therapy ; enzymology ; Drug Synergism ; Female ; Gallic Acid ; analogs & derivatives ; pharmacology ; Guaiacol ; analogs & derivatives ; pharmacology ; Humans ; In Vitro Techniques ; Lens, Crystalline ; drug effects ; enzymology ; Male ; Rats ; Rats, Wistar

Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) have poor prognosis and rare incidence compared to well differentiate thyroid cancer. Since the original description of PDTC in 1983, PDTC was introduced as a separate entity in the 2004 WHO Classification of Endocrine Tumors. PDTC was defined as a thyroid cancer with thyroglobulin-producing non-follicular non-papillary growth pattern and high-grade features, having an intermediate behavior between well differentiated thyroid cancer (WDTC) and ATC. But the criteria of PDTC are still controversial and heterogeneously applied in the diagnostic practice. Also the modalities of treatment, such as the extent of thyroid surgery, the use of radioiodine therapy and external radiation therapy are still controversial. ATC is rapidly progressing human carcinoma with a median survival of 4 to 12 months after diagnosis. Although the complete resection combined with external radiation therapy was reported to be effective recently and multimodality treatment has been recommended, current treatment of ATC has not been adequate for controlling the diseases. Therefore there are new attempts for treatment, such as chemotherapy with paclitaxel, clinical trials of combretastatin 4 phosphate and CS-7107 and multitargeted therapy of bevacizumab with doxorubicin, sorafenib, sunitinib etc. PDTC and ATC are an unexplored field like this, therefore, the studies for molecular pathology and therapeutic approach are necessary for improving survival and quality of life of patients.
Antibodies, Monoclonal, Humanized ; Bevacizumab ; Bibenzyls ; Doxorubicin ; Humans ; Incidence ; Indoles ; Niacinamide ; Paclitaxel ; Pathology, Molecular ; Phenylurea Compounds ; Prognosis ; Proline ; Pyrroles ; Quality of Life ; Thiocarbamates ; Thyroid Gland ; Thyroid Neoplasms

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

OBJECTIVETo study the chemical constituents of Dendobium crystallinum.

METHODCompounds were isolated and purified by silica gel and Sephadex LH-20 column chromatography. Their structures were identified by physicochemical properties and spectral analyses.

RESULTNine compounds were obtained and identified as: 4, 4'-dihydroxy-3, 5-dimethoxybi-benzyl (1), gigantol (2), naringenin (3) , p-hydroxybenzoic acid (4), n-tetracosyl trans-p-cou-marate (5), n-octacosy trans-p-coumarate (6), n-hexacosyl trans-ferulate (7), stigmasterol (8), daucosterol (9).

CONCLUSIONAll these compounds were obtained from this plant for the first time, compounds 1 and 4 were isolated firstly from the genus.

Bibenzyls ; Chromatography ; Dendrobium ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Flavanones ; chemistry ; Guaiacol ; analogs & derivatives ; chemistry ; Magnetic Resonance Spectroscopy ; Parabens ; chemistry ; Sitosterols ; chemistry ; Stigmasterol ; chemistry

OBJECTIVETo analyse the 1H-NMR finger-print of the stem of Dendrobium loddigesii.

METHODSilica gel column chromatography was used to separate the chemical constituents of SCE A of the stem of D. loddigesii. The characteristic signals of the H-NMR finger-print were analysed after determining the structures of the compounds isolated from SCE A.

RESULT1H-NMR finger-prints of the samples of D. loddigesii collected from different regions showed highly characteristic features and reproducibility. Four compounds predominant in SCE A were isolated and their structures were determined by spectral analysis as 1, 2, 3 and 4, respectively.

CONCLUSIONCompound 3 and 4 were isolated from D. loddigesii for the first time. The 1H-NMR finger-print of CGE A of the stem of D. loddigesii showed mainly the characteristic signals of the above four compounds and might be utilized for the original authentication of this plant.

Benzyl Compounds ; chemistry ; isolation & purification ; Bibenzyls ; Dendrobium ; chemistry ; classification ; Guaiacol ; analogs & derivatives ; chemistry ; isolation & purification ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry ; Species Specificity