RESUMO
The methanolic extract [inhibition (%): 61.2±3.8 (p<0.01) at 100 µg/mL] and its EtOAc-soluble fraction [inhibition (%): 82.5±1.7 (p<0.01) at 100 µg/mL1 from the sclerotia of Inonotus obliquus collected in Japan significantly inhibited invasion of human fibrosarcoma HT1080 cells through matrigel-coated filters. In addition, the methanolic extract significantly inhibited lung tumor formation fifteen days after injection of BI6F10 melanoma cells in mice [inhibition (%) 66.1 ± 12:8 (p < 0.05) at 500 mg/kg/d, p.o.]. Lanostane-type triterpenes were isolated as the common principal constituents from Japanese and Russian . obliquus. Furtheremore, we examine the inhibitory effects of the constituents on the invasion of HT 1080 cells. Interestingly, 3ß-hydroxylanosta-8,24-dien- 21-al [inhibition (%) 37.9 ± 3.0 (p < 0.05) at 30 µM] significantly inhibited the invasion, and no cytotoxic effect at 30 µM was observed.
Assuntos
Antineoplásicos/farmacologia , Basidiomycota/química , Triterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Feminino , Fibrossarcoma/tratamento farmacológico , Fibrossarcoma/patologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Invasividade NeoplásicaRESUMO
The methanolic extract from the pericarps of Sapindus rarak DC. was found to show pancreatic lipase inhibitory activity (IC50=ca. 614 microg/mL). From the extract, oleanane-type triterpene oligoglycosides, rarasaponins I-III (1-3), and raraoside A (4), were isolated together with 13 known saponins and four known sesquiterpene glycosides. Among them, several saponin constituents including rarasaponins I (1, IC50=131microM) and II (2, 172microM), and raraoside A (4, 151microM) inhibited pancreatic lipase activity, which were stronger than that of theasaponin E(1) (270microM).
Assuntos
Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Lipase/antagonistas & inibidores , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Pâncreas/enzimologia , Plantas Medicinais/química , Sapindus/química , Animais , Glicosídeos/química , Concentração Inibidora 50 , Estrutura Molecular , Ácido Oleanólico/química , Saponinas/farmacologia , SuínosRESUMO
The methanolic extracts from the wood and bark of Cotylelobium melanoxylon were found to inhibit plasma glucose elevation after sucrose loading in rats and triglyceride elevation after olive oil loading in mice. A new stilbene dimer, melanoxylin A, together with the known stilbene dimers [(+)-ampelopsin F, (+)-isoampelopsin F, and (+)-epsilon-viniferin] and a trimer (vaticanol G) and a lignan [(+)-lyoniresinol] were isolated from the wood extract, and a new stilbene trimer, melanoxylin B, together with the known stilbene dimers [(+)-epsilon-viniferin and cis-(+)-epsilon-viniferin] and trimers (vaticanols A, E, and G) were isolated from the bark extract of C. melanoxylon. The principal constituents, vaticanols A, E, and/or G, inhibited plasma glucose and triglyceride elevation after sucrose loading in rats and olive oil loading in mice, respectively. In addition, vaticanols A, E, and/or G inhibited the enzyme activities of rat intestinal alpha-glucosidase, porcine pancreatic lipase, and rat lens aldose reductase.
Assuntos
Dipterocarpaceae/química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Medicina Tradicional do Leste Asiático , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Espectroscopia de Ressonância Magnética , Masculino , Metanol/química , Camundongos , Estrutura Molecular , Pancrelipase/efeitos dos fármacos , Ratos , Ratos Wistar , Suínos , Tailândia , Madeira/química , alfa-Glucosidases/efeitos dos fármacosRESUMO
The methanolic extract and its saponin fraction (methanol-eluted fraction) of the pericarps of Sapindus rarak DC. were found to suppress plasma triglyceride elevation in olive oil-treated mice. From the active fraction, three new acylated oleanane-type triterpene saponins, rarasaponins IV (1), V (2), and VI (3), were isolated. The structures of 1-3 were elucidated on the basis of chemical and spectroscopic evidence. The principle saponin constituents, hederagenin 3-O-alpha-L-arabinopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside (4) and hederagenin 3-O-(3,4-di-O-acetyl-alpha-L-arabinopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside (5), showed inhibitory effects on plasma triglyceride elevation at a dose of 200 mg/kg, per os.
Assuntos
Hipertrigliceridemia/induzido quimicamente , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/química , Ácido Oleanólico/análogos & derivados , Sapindus/química , Saponinas/química , Saponinas/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Acetilação , Animais , Configuração de Carboidratos , Sequência de Carboidratos , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Hipertrigliceridemia/sangue , Hipolipemiantes/farmacologia , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Dados de Sequência Molecular , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Azeite de Oliva , Casca de Planta/química , Óleos de Plantas , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Ultravioleta , Triglicerídeos/sangueRESUMO
The methanolic extract from the flowers buds of Camellia japonica L. (Theaceae) were found to exhibit potent inhibitory activities on ethanol- or indomethacin-induced gastric mucosal lesions in rats. Through bioassay-guided separation, 28-noroleanane-type triterpene oligoglycosides, camelliosides A, B, and C, and an oleanane-type triterpene oligoglycoside, camellioside D, were isolated from the methanolic extract together with five known compounds. The absolute stereostructures of camelliosides were determined on the basis of chemical and physicochemical evidence, which included the structure revision of the nortriterpene aglycons (camellenodiol and camelledionol). The principal oligoglycosides, camelliosides A and B, showed platelet aggregation activity in addition to the gastroprotective effects on ethanol- or indomethacin-induced gastric mucosal lesions in rats.
Assuntos
Camellia/química , Flores/química , Glicosídeos/química , Inibidores da Agregação Plaquetária/farmacologia , Úlcera Gástrica/prevenção & controle , Triterpenos/química , Animais , Masculino , Modelos Moleculares , Estrutura Molecular , Inibidores da Agregação Plaquetária/química , Coelhos , Ratos , Ratos Sprague-Dawley , Análise Espectral/métodosRESUMO
The methanolic extract from the male flowers of Borassus flabellifer was found to inhibit the increase of serum glucose levels in sucrose-loaded rats at a dose of 250 mg/kg, p.o. From the methanolic extract, six new spirostane-type steroid saponins, borassosides A-F (1-6), were isolated together with 23 known constituents. The structures of borassosides (1-6) were elucidated on the basis of chemical and physicochemical evidences. In addition, the principal steroid saponin, dioscin (13), inhibited the increase of serum glucose levels in sucrose-loaded rats at a dose of 50 mg/kg, p.o.
Assuntos
Arecaceae/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/química , Plantas Medicinais/química , Saponinas/isolamento & purificação , Animais , Glicemia/metabolismo , Diosgenina/análogos & derivados , Diosgenina/química , Diosgenina/isolamento & purificação , Diosgenina/farmacologia , Relação Dose-Resposta a Droga , Masculino , Metanol/química , Estrutura Molecular , Ratos , Ratos Wistar , Saponinas/química , Saponinas/farmacologia , Fatores de TempoRESUMO
Principal rotenoids (deguelin, tephrosin, rotenone, and 12a-hydroxyrotenone) (3-30microM) isolated from the stems of Erycibe expansa significantly inhibited invasion of human fibrosarcoma HT1080 cells through Matrigel-coated filters and release of proMMPs-2 and 9. In addition, deguelin and tephrosin showed differentiation-inducing activity in human promyelocytic leukemia HL-60 cells. Furthermore, effects of various constituents isolated from the ethyl acetate-soluble fraction on proliferation of human leukemia U937 cells were examined. As a result, most of isoflavones and several flavans as well as rotenoids showed moderate or substantial anti-proliferative activities.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Convolvulaceae/química , Fibrossarcoma/tratamento farmacológico , Flavonoides/farmacologia , Invasividade Neoplásica/prevenção & controle , Rotenona/farmacologia , Precursores Enzimáticos/metabolismo , Fibrossarcoma/patologia , Gelatinases/metabolismo , Células HL-60/efeitos dos fármacos , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Metaloendopeptidases/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Rotenona/química , Células Tumorais Cultivadas/efeitos dos fármacos , Células U937/efeitos dos fármacosRESUMO
The methanolic extract and its alkaloid fraction from the rhizomes of Nuphar pumilum showed cytotoxic effects on human leukemia cell (U937), mouse melanoma cell (B16F10), and human fibroblast (HT1080). Dimeric sesquiterpene thioalkaloids with the 6-hydroxyl group (6-hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, 6-hydroxythionuphlutine B) showed substantial cytotoxic activity at a concentration of 10 microM, but dimeric sesquiterpene thioalkaloids lacking the 6-hydroxyl group (thiobinupharidine, thionuphlutine B, 6'-hydroxythionuphlutine B, neothiobinupharidine, thionuphlutine B beta-sulfoxide, and neothiobinupharidine beta-sulfoxide) and monomeric sesquiterpene alkaloids (nupharidine, 7-epideoxynupharidine, and nupharolutine) showed weak activity. Next, apoptosis-inducing activity of a principal active constituent, 6-hydroxythiobinupharidine, on U937 was examined using morphological observation and DNA fragmentation assay (TUNEL method). Apoptosis of U937 was immediately observed within 1 h after treatment of 6-hydroxythiobinupharidine at 2.5-10 microM.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Nuphar , Sesquiterpenos/farmacologia , Alcaloides/isolamento & purificação , Animais , Antineoplásicos/isolamento & purificação , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Marcação In Situ das Extremidades Cortadas , Leucemia/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Camundongos , Rizoma , Sesquiterpenos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
The methanolic extract and its alkaloid fraction from the rhizomes of Nuphar pumilum inhibited invasion of B16 melanoma cells across collagen-coated filters in vitro. Dimeric sesquiterpene thioalkaloids with the 6-hydroxyl group, 6-hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, and 6-hydroxythionuphlutine B, showed potent activity with IC(50) values of 0.029, 0.087, and 0.36 microM, respectively, but dimeric sesquiterpene thioalkaloids lacking the 6-hydroxyl group (thiobinupharidine, neothiobinupharidine, syn-thiobinupharidine sulfoxide, thionuphultine B beta-sulfoxide, and neothiobinupharidine beta-sulfoxide) and monomeric sesquiterpene alkaloids (nupharidine, deoxynupharidine, 7-epideoxynupharidine, and nupharolutine) showed weak activity. The alkaloid fraction (20 mg/kg/d, po) and the principal dimeric sesquiterpene thioalkaloid 6-hydroxythiobinupharidine (5 mg/kg/d, po) significantly inhibited lung tumor formation by more than 90% 10 days after injection of B16 melanoma cells in mice.
Assuntos
Alcaloides/farmacologia , Antineoplásicos/isolamento & purificação , Metástase Neoplásica/prevenção & controle , Nuphar , Rizoma , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Alcaloides/isolamento & purificação , Animais , Antineoplásicos/química , Dimerização , Feminino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos , Modelos Moleculares , Invasividade Neoplásica , Relação Estrutura-AtividadeRESUMO
The effects of polygodial isolated from the leaves of Tasmannia lanceolata on necrotizing agents-induced gastric lesions in rats were compared with capsaicin. Polygodial markedly inhibited the gastric mucosal lesions induced by several necrotizing agents, such as ethanol (ED(50)=0.029 mg/kg, p.o.), 0.6 M HCl (ED(50)=0.26 mg/kg, p.o.), and aspirin (ED(50)=0.38 mg/kg, p.o.), and partly inhibited the gastric mucosal lesions induced by indomethacin, but showed no significant effect on acid output in pylorus-ligated rats at doses of 0.05-0.5 mg/kg. The gastroprotection of polygodial was attenuated by pretreatment with indomethacin (10 mg/kg, s.c.), N(G)-nitro-L-arginine methyl ester (70 mg/kg, i.p.), N-ethylmaleimide (10 mg/kg, s.c.) and ruthenium red (3.5 mg/kg, s.c.). Polygodial (0.2 mg/kg, p.o.) increased the amount of reduced glutathione in gastric mucosa of ethanol-treated group. These results suggested that endogenous prostaglandins, nitric oxide, sulfhydryl compounds and vanilloid receptor-mediated effects are involved in the protective effect of polygodial.