RESUMO
A methanolic extract of Nepalese propolis yielded 10 new open-chain neoflavonoids (1-10), a new chalcone (11), and eight previously reported compounds (12-19). Their structures were determined on the basis of spectroscopic data and chemical conversion. The isolated compounds other than 5, 8, and 16 showed dose-dependent inhibitory activities on nitric oxide production in lipopolysaccharide-activated macrophage-like J774.1 cells and were more active than a positive control, N(G)-monomethyl-L-arginine (IC(50), 27.1 microM). The most potent activities, of 6 and 7 (IC(50), 0.5 microM), were greater than another positive control, caffeic acid phenethyl ester (IC(50), 4.8 microM).
Assuntos
Flavonoides/isolamento & purificação , Óxido Nítrico/antagonistas & inibidores , Álcool Feniletílico/análogos & derivados , Própole/química , Ácidos Cafeicos/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Estrutura Molecular , Nepal , Ressonância Magnética Nuclear Biomolecular , Álcool Feniletílico/farmacologia , ômega-N-Metilarginina/farmacologiaRESUMO
The effects of soft-shell turtle (Trionyx sinensis) powder (SST) on the proximal tibiae of ovariectomized (OVX) rats were investigated using peripheral quantitative computed tomography (pQCT) and examination of serum biochemical markers. Considering the relationship between the antioxidative property and antiosteoporotic activity, the synergistic effects of a mixture of SST and essential oil of the microalgae Haematococcus pluvialis (OHP) with strong antioxidant activity were also examined. Oral administration of SST (100, 200 mg/kg) or a mixture of SST (100, 200 mg/kg) and OHP (13, 26 mg/kg) three times weekly prevented the decrease in bone mineral content (BMC) in total bone, BMC and bone mineral density (BMD) in cortical bone, and bone strength indices induced by ovariectomy in a dose-dependent manner without uterine side effects. However, OHP alone showed no significant effects.
Assuntos
Densidade Óssea/efeitos dos fármacos , Eucariotos , Óleos Voláteis/uso terapêutico , Osteoporose/prevenção & controle , Tartarugas , Animais , Densidade Óssea/fisiologia , Quimioterapia Combinada , Eucariotos/isolamento & purificação , Feminino , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Ovariectomia , Pós , Ratos , Ratos WistarRESUMO
The MeOH and water extracts of the Netherlands propolis were tested for their inhibitory activity toward nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage-like J774.1 cells. Both of the extract possessed significant NO inhibitory activity with IC(50) values of 23.8 and 51.5 microg/ml, respectively. Then 13 phenolic compounds obtained from the MeOH extract showing stronger NO inhibition were examined on their NO inhibitory activities. Caffeic acid phenethyl ester (CAPE) analogues, i.e., benzyl caffeate, CAPE and cinnamyl caffeate, possessed most potent NO inhibitory activities with IC(50) values of 13.8, 7.64 and 9.53 microM, respectively, which were two- to four-fold stronger than the positive control N(G)-monomethyl-L-arginine (L-NMMA; IC(50), 32.9 microM). Further study on the synthetic analogues of CAPE revealed that both of 3-phenylpropyl caffeate (18; IC(50), 7.34 microM) and 4-phenylbutyl caffeate (19; IC(50), 6.77 microM) possessed stronger NO inhibitory activity than CAPE (10) and that elongation of alkyl side chain of alcoholic parts of caffeic acid esters enhance the NO inhibitory activity. In addition, it was found that CAPE analogues having longer carbon chain (>C(5)) in alcoholic part showed toxic effects toward J774.1 cells. This NO inhibitory effect may directly correlate with antiinflammatory properties of the Netherlands propolis.
Assuntos
Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Óxido Nítrico/antagonistas & inibidores , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Própole/análogos & derivados , Própole/farmacologia , Animais , Ácidos Cafeicos/isolamento & purificação , Linhagem Celular , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Camundongos , Países Baixos , Óxido Nítrico/biossíntese , Álcool Feniletílico/isolamento & purificação , Própole/isolamento & purificaçãoRESUMO
Two new flavonoids, 3-O-[(S)-2-methylbutyroyl]pinobanksin (1) and 6-cinnamylchrysin (2), were isolated from the EtOAc-soluble fraction of the MeOH extract of Chinese propolis, along with 12 known compounds (3-14). The structures of the isolated compounds were elucidated on the basis of spectroscopic and chemical analyses. The isolated compounds were tested for their antiproliferative activity toward five different cancer cell lines. Benzyl caffeate (13) and phenethyl caffeate (14) showed potent antiproliferative activity toward tested cell lines with a selective activity toward colon 26-L5 carcinoma cell line (EC(50) values: 13, 1.01; 14, 0.30 microM).
Assuntos
Antineoplásicos/isolamento & purificação , Flavonoides/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Álcool Feniletílico/análogos & derivados , Própole/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Compostos de Bifenilo , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , China , Cromatografia em Camada Fina , Neoplasias do Colo , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/química , Flavonoides/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Camundongos , Estrutura Molecular , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Picratos/química , Espectrofotometria Infravermelho , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
The MeOH extract of the Netherlands propolis showed promising antiproliferative activity toward highly liver-metastatic murine colon 26-L5 carcinoma with an EC(50) value of 3.5 microg/ml. Further, antiproliferative activity-guided purification of the MeOH extract led us to isolate four flavonoids (1-4), seven cinnamic acid derivatives (5-11) and two new glycerol derivatives (12, 13), whose structures were elucidated on the basis of spectral analysis. The isolated compounds were tested for their antiproliferative activity against murine colon 26-L5, murine B16-BL6 melanoma, human HT-1080 fibrosarcoma and human lung A549 adenocarcinoma cell lines. The benzyl (9), phenethyl (10) and cinnamyl caffeates (11) possessed potent antiproliferative activities with EC(50) values of 0.288, 1.76 and 0.114 microM, respectively, toward colon 26-L5 carcinoma. These caffeates were considered to be active constituents of the Netherlands propolis in their antiproliferative activity. The antioxidative activity of these caffeates may play an important role in their antiproliferative activities.