RESUMO
The marine-derived Aspergillus protuberus MF297-2 and the terrestrial A. amoenus NRRL 35600 produce enantiomeric prenylated indole alkaloids. Investigation of biological activities of the natural and synthetic derivatives revealed that (-)-enantiomers of notoamides A and B, 6-epi-notoamide T, and stephacidin A inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenic differentiation of murine RAW264 cells more strongly than their respective (+)-enantiomers. Among them, (-)-6-epi-notoamide T was the most potent inhibitor with an IC50 value of 1.7µM.
Assuntos
Alcaloides Indólicos/química , Ligante RANK/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Fungos/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Concentração Inibidora 50 , Camundongos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Células RAW 264.7 , EstereoisomerismoRESUMO
The cholesterol ester accumulates in macrophages in the early stage of atherosclerotic lesions, leading to the formation of foam cells. We examined the inhibitory effects of the crude extracts of 22 edible plants on foam cell formation and isolated nine chlorophyll derivatives as potent inhibitors from Chinese cabbage. The results of the present study suggest that the chlorophyll derivatives contained in edible plants may be useful for the prevention and treatment of atherosclerosis.
Assuntos
Aterosclerose/dietoterapia , Brassica/química , Clorofila/farmacologia , Ésteres do Colesterol/antagonistas & inibidores , Aterosclerose/patologia , Linhagem Celular , Clorofila/análogos & derivados , Clorofila/isolamento & purificação , Células Espumosas/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacosRESUMO
Halenaquinone was isolated from the marine sponge Petrosia alfiani as an inhibitor of osteoclastogenic differentiation of murine RAW264 cells. It inhibited the RANKL (receptor activator of nuclear factor-κB ligand)-induced upregulation of TRAP (tartrate-resistant acid phosphatase) activity as well as the formation of multinuclear osteoclasts. In addition, halenaquinone substantially suppressed RANKL-induced IκB degradation and Akt phosphorylation. Thus, these results suggest that halenaquinone inhibits RANKL-induced osteoclastogenesis at least by suppressing the NF-κB and Akt signaling pathways.
Assuntos
Quinonas/química , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proteínas I-kappa B/metabolismo , Camundongos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Petrosia/química , Petrosia/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinonas/isolamento & purificação , Quinonas/farmacologia , Ligante RANK/toxicidade , Transdução de Sinais/efeitos dos fármacosRESUMO
Two new manzamine alkaloids, acantholactam (3) and pre-neo-kauluamine (4), were isolated from the marine sponge Acanthostrongylophora ingens along with manzamine A (1) and neo-kauluamine (2). Acantholactam contains a γ-lactam ring N-substituted with a (Z)-2-hexenoic acid moiety and is proposed to be biosynthetically derived from manzamine A by oxidative cleavage of the eight-membered ring. Compound 4 was converted to the dimer 2 during storage, suggesting nonenzymatic dimer formation. Among the four isolated compounds, 1, 2, and 4 showed proteasome inhibitory activity.
Assuntos
Alcaloides/isolamento & purificação , Carbazóis/isolamento & purificação , Poríferos/química , Inibidores de Proteases/isolamento & purificação , Alcaloides/química , Alcaloides/farmacologia , Animais , Carbazóis/química , Carbazóis/farmacologia , Carbolinas , Indonésia , Macrófagos/efeitos dos fármacos , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oceanos e Mares , Inibidores de Proteases/química , Inibidores de Proteases/farmacologiaRESUMO
Sappanwood (Caesalpinia sappan Linn.) is used as an herbal medicine. It is sometimes used to treat skin damage or as a facial cleanser. In the present study, the methanol (MeOH) extract of sappanwood was found to inhibit melanin synthesis in cultured human melanoma HMV-II cells stimulated with forskolin, and six active compounds (1-5 and 7) were isolated from the extract along with a non-active compound (6). Compounds 2-7 were identified as sappanchalcone (2), 3'-deoxy-4-O-methylsappanol (3), brazilein, (4), brazilin (5), sappanol (6), and 4-O-methylsappanol (7). Compound 1 was a new compound, and its structure was determined to be (6aS,11bR)-7,11b-dihydro-6H-indeno[2,1-c]chromene-3,6a,10,11-tetrol by spectroscopic analyses. Among the six active compounds, brazilin (5) (EC50: 3.0 ± 0.5 µM) and 4-O-methylsappanol (7) (EC50: 4.6 ± 0.7 µM) strongly suppressed melanin synthesis in HMV-II cells. Bioactive compounds showed moderate cytotoxicities against HMV-II cells with IC50 values of 83.1 ± 4.0 µM (for 2), 72.0 µM ± 2.4 (for 3), 33.8 ± 1.1 µM (for 4), 18.4 ± 0.8 µM (for 5), and 20.2 ± 0.8 (for 7), respectively. Brazilin (5) selectively suppressed the expression of mRNAs for tyrosinase-related protein (TYRP) 2 and tyrosinase but did not influence the expression of TYRP1. These results suggest that brazilin (5) is a new class of melanin inhibitor and that sappanwood could be used as a cosmetic material.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Benzopiranos/farmacologia , Caesalpinia/química , Indenos/farmacologia , Melaninas/biossíntese , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Benzopiranos/análise , Relação Dose-Resposta a Droga , Humanos , Indenos/análise , Melaninas/análise , Melanoma/química , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Estrutura Molecular , Fenóis/química , Extratos Vegetais/análise , Neoplasias Cutâneas/química , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Células Tumorais CultivadasRESUMO
Peanut skin (Arachis hypogaea L., Fabaceae) is an abundant source for polyphenols, such as proanthocyanidin oligomers. To determine whether proanthocyanidin has beneficial effects on skin, we tested for inhibitory activity of proanthocyanidins isolated from peanut skin on inflammatory cytokine production and melanin synthesis in cultured cell lines. Administration of peanut skin extract (PSE, 200 µg/mL) decreased melanogenesis in cultured human melanoma HMV-II co-stimulated with phorbol-12-myristate-13-acetate. It also decreased production of inflammatory cytokines (PSE at 100 µg/mL), tumor necrosis factor-α and interleukin-6, in cultured human monocytic THP-1 cells in response to lipopolysaccharide. We isolated ten known proanthocyanidins and one new proanthocyanidin trimer from the PSE. The structure of the new compound (5) was determined by 1D- and 2D-NMR and mass spectrometry analyses, and was determined as epicatechin-(2ßâOâ7,4ßâ6)-epicatechin-(4ßâ6)-epicatechin. The other known proanthocyanidins were identified as proanthocyanidin monomers (1), dimers (6-9), trimers (3-5) and tetramers (2, 10, 11). They showed suppressive activities against melanogenesis and cytokine production at concentrations ranging from 0.1-10 µg/mL. Among the tested compounds, suppressive activities of proanthocyanidin dimers or trimers in two assay systems were stronger than those obtained with monomer or tetramers. These data indicate that proanthocyanidin oligomers from peanut skin have the potential to reduce dermatological conditions such as inflammation and melanogenesis.
Assuntos
Anti-Inflamatórios/farmacologia , Arachis , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Anti-Inflamatórios/química , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Indóis/metabolismo , Interleucina-6/metabolismo , Melaninas/metabolismo , Conformação Molecular , Extratos Vegetais/química , Proantocianidinas/química , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Fenugreek seed ( Trigonella foenum-graecum L.) is used as an herbal medicine for treating metabolic and nutritive dysfunctions. To determine if this plant has other beneficial effects, we tested the inhibitory activities of a methanol (MeOH) extract of fenugreek seed on the production of inflammatory cytokines and melanin synthesis in cultured cell lines in vitro. The MeOH extract inhibited the production of phorbol-12-myristate-13-acetate-induced inflammatory cytokines such as tumor necrosis factor (TNF)-α in cultured THP-1 cells, and also restrained the intracellular synthesis of melanin in murine melanoma B16F1 cells. We isolated three active constituents from fenugreek seed extracts. These were identified as the steroidal saponins 26- O-ß-D-glucopyranosyl-(25 R)-furost-5(6)-en-3 ß,22 ß,26-triol-3- O-α-L-rhamno-pyranosyl-(1'' â 2')-O-[ß-D-glucopyranosyl-(1''' â 6')- O]-ß-D-glucopyranoside 1, minutoside B 2, and pseudoprotodioscin 3. Compounds 1 and 2 strongly suppressed the production of inflammatory cytokines, whereas 3 showed a weaker suppressing effect. Melanogenesis in B16F1 cells was significantly suppressed by 1 and 3, and weakly suppressed by 2. All three compounds showed moderate cytotoxicities. These results indicate that fenugreek extract and its active constituents could protect against skin damage.
Assuntos
Anti-Inflamatórios/farmacologia , Melaninas/antagonistas & inibidores , Plantas Medicinais/química , Saponinas/farmacologia , Trigonella/química , Animais , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Sequência de Carboidratos , Linhagem Celular Tumoral , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Humanos , Melaninas/biossíntese , Melanoma Experimental/metabolismo , Camundongos , Dados de Sequência Molecular , Estrutura Molecular , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Mieloma Múltiplo/metabolismo , Extratos Vegetais/farmacologia , Saponinas/isolamento & purificação , Sementes/química , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Two new phenyldihydronaphthalene-type lignan glucosides, vitecannasides A (1) and B (2) were isolated from the fruit of Vitex cannabifolia Sieb. et. Zucc. (Verbenaceae) along with the six known lignan derivatives (3-8), four known iridoid glucosides (9-12), three known flavonoids (13-15), and one known phenylbutanone glucoside (16). Their chemical structures were determined on the basis of spectroscopic data as well as chemical evidence. The scavenging effect of 1, 2, and 11-16 on the stable free radical 1,1-diphenyl-2-picrylhydrazyl was examined. Compounds 1, 2, 14, and 15 exhibited stronger activity than that of L: -cysteine. Especially, 14 and 15 showed more potent activity than that of alpha-tocopherol.
Assuntos
Flavonoides/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Glucosídeos/isolamento & purificação , Iridoides/isolamento & purificação , Lignanas/isolamento & purificação , Vitex/química , Compostos de Bifenilo , Cisteína/química , Flavonoides/química , Sequestradores de Radicais Livres/química , Frutas , Glucosídeos/química , Iridoides/química , Lignanas/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Picratos/química , alfa-Tocoferol/químicaRESUMO
Two new imidazole alkaloids, naamidines H ( 1) and I ( 2), were isolated from the marine sponge Leucetta chagosensis, collected in North Sulawesi, Indonesia. The compounds ( 1 and 2) showed cytotoxicity against HeLa cells with IC50 values of 5.6 and 15 microg/mL, respectively.
Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Imidazóis/isolamento & purificação , Imidazóis/farmacologia , Poríferos/química , Alcaloides/química , Animais , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Imidazóis/química , Indonésia , Concentração Inibidora 50 , Biologia Marinha , Estrutura MolecularRESUMO
OBJECTIVE: We performed the follow-up tests for three years for junior high school students by the quasi-experimental design to investigate the medium-term effect of smoking prevention education in the elementary school. METHODS: The intervention group consisted of 106 school students of three elementary schools and received a smoking prevention program in the elementary school. Moreover, the follow-up tests were conducted at each grade of junior high school, and the booster program was mailed. The comparison group consisted of 193 school students of another three elementary schools without the program. RESULTS: The intervention effects were recognized on knowledge up to the second grade of junior high school for boys and up to the third grade for girls, on awareness of the importance of not smoking at the second grade, and on the intention of smoking at the age of 20 for girls up to the first grade. On the other hand, the intervention effects were not recognized on smoking experience for boys and girls. However, increase of the rate of smoking experience was not significant in the intervention group, while it was significant in the comparison group. CONCLUSION: The effect of the program for three years was judged to be moderate.