RESUMO
Mangiferin (3) and genkwanin 5-O-ß-primeveroside (5) are the two major bioactive polyphenols with laxative property present in the extracts of agarwood (Aquilaria sinensis) leaves (AL). Here we developed an HPLC method to determine these bioactive components and four other major polyphenols in AL extracts and evaluated the pharmacological equivalence of organic and water extracts. Using mobile phase gradient conditions combined with UV detection at 330 nm, all six compounds were separated and we determined the relative extraction ratios of the six compounds present in A. sinensis extracts that were prepared under different conditions and compared the contents of the two laxative polyphenols present in the 60% ethanol extracts of A. sinensis and A. crassna. The polyphenols present in water extracts of 13 commercially cultivated A. crassna plants have also been analyzed. The laxative properties of 60% ethanol and four water extracts of A. crassna were evaluated by the frequency and weight of stools in loperamide-induced constipation model mice. The pharmacological equivalence of 60% ethanol extract and hot water (95°C) extract was identified in mice.
Assuntos
Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Polifenóis/análise , Thymelaeaceae/química , Animais , Cromatografia Líquida de Alta Pressão , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Etanol , Laxantes , Loperamida , Masculino , Camundongos , Extratos Vegetais/uso terapêutico , ÁguaRESUMO
The ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that directly contributes to high-density lipoprotein (HDL) biogenesis by regulating the cellular efflux of cholesterol. Since ABCA1 plays a pivotal role in cholesterol homeostasis and HDL metabolism, identification of a novel substance that is capable of increasing its expression would be beneficial for the prevention and therapy of atherosclerosis. In the present study, we studied the effects of ethanolic extracts of Brazilian red propolis (EERP) on ABCA1 expression and cholesterol efflux in THP-1 macrophages. EERP enhanced PPARγ and liver X receptor (LXR) transcriptional activity at 5-15µg/ml, which was associated with upregulation of PPARγ and LXRα expression. It was also found that EERP increase the activity of the ABCA1 promoter, which is positively regulated by LXR. Consistent with these findings, treatment with EERP increased both mRNA and protein expression of ABCA1. Finally, EERP upregulated ApoA-I-mediated cholesterol efflux. Our results showed that EERP promote ApoA-I-mediated cholesterol efflux from macrophages by increasing ABCA1 expression via induction of PPARγ/LXR.
Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Colesterol/metabolismo , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Própole/química , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Animais , Apolipoproteína A-I/efeitos dos fármacos , Apolipoproteína A-I/metabolismo , Transporte Biológico/efeitos dos fármacos , Bovinos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Receptores X do Fígado , Macrófagos/metabolismo , Modelos Biológicos , Receptores Nucleares Órfãos/efeitos dos fármacos , Receptores Nucleares Órfãos/genética , PPAR gama/efeitos dos fármacos , PPAR gama/genética , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Regiões Promotoras Genéticas/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Gênica/efeitos dos fármacosRESUMO
BACKGROUND: Agarwood (Aquilaria sinensis), well known as incense in Southeast Asia, has been used as a digestive in traditional medicine. We investigated the laxative effects of an ethanol extract of agarwood leaves (EEA) in a rat model of low-fiber diet-induced constipation. METHODS: A set of rats was bred on a normal diet while another set was placed on a low-fiber diet to induce constipation. The laxative effect of agarwood was then investigated on both sets of rats. RESULTS: Pretreatment of normal rats with single dose of EEA (600 mg/kg, p.o.) significantly increased frequency and weight of stools. Also, treatments with EEA (300 and 600 mg/kg, p.o.) for 14 days caused a significant increase in stool frequency and weight. Feeding of the animals with a low-fiber diet resulted in a decrease in stool weight, frequency, and water content and also delayed carmine egestion. A single treatment with EEA (600 mg/kg) or senna (150 and 300 mg/kg) significantly increased stool frequency, weight, and water content and also accelerated carmine egestion in the model rats. Once daily administrations of EEA (150 mg/kg), for 14 days, caused a significant increase in water content of stools. The higher doses of EEA (300 and 600 mg/kg) significantly increased frequency, weight, and water content of the stools while accelerating carmine egestion in the constipated rats. Senna (150 and 300 mg/kg) produced similar effect as the higher doses of EEA but, in addition, induced severe diarrhea. CONCLUSION: These findings indicate that EEA has a laxative effect, without causing diarrhea, in a rat model of low-fiber diet-induced constipation. These findings suggest that EEA may be highly effective on constipation as a complementary medicine in humans suffering from life style-induced constipation.
Assuntos
Constipação Intestinal/tratamento farmacológico , Defecação/efeitos dos fármacos , Laxantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Senna , Thymelaeaceae , Animais , Carmim/análise , Constipação Intestinal/etiologia , Diarreia , Dieta , Fibras na Dieta/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fezes/química , Laxantes/farmacologia , Masculino , Extratos Vegetais/farmacologia , Folhas de Planta , Ratos , Ratos Sprague-Dawley , Água/análiseRESUMO
BACKGROUND: Bee pollen, a honeybee product, is the feed for honeybees prepared themselves by pollens collecting from plants and has been consumed as a perfect food in Europe, because it is nutritionally well balanced. In this study, we aimed to investigate the anti-inflammatory effect of bee pollen from Cistus sp. of Spanish origin by a method of carrageenan-induced paw edema in rats, and to investigate the mechanism of anti-inflammatory action and also to elucidate components involved in bee pollen extracted with ethanol. METHODS: The bee pollen bulk, its water extract and its ethanol extract were administered orally to rats. One hour later, paw edema was produced by injecting of 1% solution of carrageenan, and paw volume was measured before and after carrageenan injection up to 5 h. The ethanol extract and water extract were measured COX-1 and COX-2 inhibitory activities using COX inhibitor screening assay kit, and were compared for the inhibition of NO production in LPS-stimulated RAW 264.7 cells. The constituents of bee pollen were purified from the ethanol extract subjected to silica gel or LH-20 column chromatography. Each column chromatography fractions were further purified by repeated ODS or silica gel column chromatography. RESULTS: The bee pollen bulk mildly suppressed the carrageenan-induced paw edema and the water extract showed almost no inhibitory activity, but the ethanol extract showed relatively strong inhibition of paw edema. The ethanol extract inhibited the NO production and COX-2 but not COX-1 activity, but the water extract did not affect the NO production or COX activities. Flavonoids were isolated and purified from the ethanol extract of bee pollen, and identified at least five flavonoids and their glycosides. CONCLUSIONS: It is suggested that the ethanol extract of bee pollen show a potent anti-inflammatory activity and its effect acts via the inhibition of NO production, besides the inhibitory activity of COX-2. Some flavonoids included in bee pollen may partly participate in some of the anti-inflammatory action. The bee pollen would be beneficial not only as a dietary supplement but also as a functional food.
Assuntos
Anti-Inflamatórios/uso terapêutico , Apiterapia , Cistus , Edema/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Abelhas , Carragenina , Linhagem Celular , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Edema/induzido quimicamente , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Membro Posterior , Mel , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Óxido Nítrico/biossíntese , Pólen , Ratos , Ratos WistarRESUMO
AIM OF THE STUDY: The aim of present study was to investigate the effects of ethanolic extracts of red propolis (EERP) on adipogenesis and evaluate the molecular basis for their anti-obesity effects. MATERIALS AND METHODS: We tested whether EERP alone could induce differentiation of 3T3-L1 cells, regulate the expression of adipocyte-specific genes and reverse inhibitory effects of TNF-α on their differentiation. Next, we performed a luciferase reporter gene assay to test whether EERP could enhance transcriptional activities of PPARγ and adiponectin promoter activities. RESULTS: EERP strongly induced differentiation of 3T3-L1 preadipocytes into adipocytes, and enhanced the PPARγ transcriptional activity and adiponectin promoter activity. In addition, EERP attenuated the inhibitory effect of TNF-α on adipocyte differentiation and adiponectin production in mature adipocytes. CONCLUSION: The present study indicates that EERP enhance differentiation of 3T3-L1 adipocytes in part by its potency of PPARγ activation and are capable of reversing inhibitory effects of TNF-α on adipocyte differentiation and adiponectin expression. These results suggest the value of EERP as a diet supplement for prevention and treatment of obesity and obesity-associated disorders.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adiponectina/metabolismo , Fármacos Antiobesidade/farmacologia , PPAR gama/metabolismo , Extratos Vegetais/farmacologia , Própole/farmacologia , Células 3T3-L1 , Adipócitos/citologia , Adiponectina/genética , Animais , Dalbergia/química , Camundongos , PPAR gama/genética , Extratos Vegetais/análise , Regiões Promotoras Genéticas , Própole/química , Ativação Transcricional/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Propolis, a honeybee product, has become popular as a food and alternative medicine. Its constituents have been shown to exert pharmacological effects, such as anticancer, antimicrobial, and anti-inflammatory effects. The present study was performed to investigate whether Brazilian green propolis exerts antihypertensive effects in spontaneously hypertensive rats (SHR) and which constituents are involved in its effects. Brazilian green propolis was extracted with ethanol and subjected to LH-20 column chromatography eluted with ethanol. The ethanol-eluted fractions at 10 mg/kg were administered orally to SHR for 14 d. Significant decreases in blood pressure were observed in fractions 6 and 7. The active constituents were purified and identified to be four flavonoids: dihydrokaempferide and isosakuranetin in fraction 6 and betuletol and kaempferide in fraction 7. These flavonoids at 10 mg/kg were administered orally to SHR for 28 d, and as a result, isosakuranetin, dihydrokaempferide and betuletol produced significant decrease in blood pressure, especially marked were the effects observed in the group that received isosakuranetin. Brazilian green propolis, fractions 6 and 7, and the 4 active constituents relaxed isolated SHR aorta in a concentration-dependent manner. Therefore, these finding suggest that the vasodilating action may be partly involved in the mechanism of antihypertensive effect. Hence, the ethanol extract of Brazilian green propolis and its main constituents may be useful for prevention of hypertension.
Assuntos
Anti-Hipertensivos/uso terapêutico , Flavonoides/uso terapêutico , Hipertensão/tratamento farmacológico , Própole/química , Administração Oral , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/isolamento & purificação , Baccharis/crescimento & desenvolvimento , Pressão Sanguínea/efeitos dos fármacos , Brasil , Flavonoides/química , Flavonoides/isolamento & purificação , Masculino , Estrutura Molecular , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Vasodilatação/efeitos dos fármacosRESUMO
We have previously reported that royal jelly (RJ) from honeybees (Apis mellifera) has weak estrogenic activity mediated by interaction with estrogen receptors that leads to changes in gene expression and cell proliferation. In this study, we isolated four compounds from RJ that exhibit estrogenic activity as evaluated by a ligand-binding assay for the estrogen receptor (ER) beta. These compounds were identified as 10-hydroxy-trans-2-decenoic acid, 10-hydroxydecanoic acid, trans-2-decenoic acid and 24-methylenecholesterol. All these compounds inhibited binding of 17beta-estradiol to ERbeta, although more weakly than diethylstilbestrol or phytoestrogens. However, these compounds had little or no effect on the binding of 17beta-estradiol to ERalpha. Expression assays suggested that these compounds activated ER, as evidenced by enhanced transcription of a reporter gene containing an estrogen-responsive element. Treatment of MCF-7 cells with these compounds enhanced their proliferation, but concomitant treatment with tamoxifen blocked this effect. Exposure of immature rats to these compounds by subcutaneous injection induced mild hypertrophy of the luminal epithelium of the uterus, but was not associated with an increase in uterine weight. These findings provide evidence that these compounds contribute to the estrogenic effect of RJ.
RESUMO
Renin is the rate limiting enzyme in the renin-angiotensin (RA) system that regulates blood pressure and electrolyte balance. In this study, we investigated the renin inhibitory effect of a royal jelly (RJ)-derived peptide. A dipeptide YY was isolated from the digested fraction of RJ proteins by proteases and was found to inhibit human renin activity. The inhibition constant (Ki) of YY was estimated to be 10 microM when the Km was 0.16 microM using sheep angiotensinogen as the substrate. The peptide was observed to lower blood pressure in spontaneously hypertensive rats.
Assuntos
Dipeptídeos/farmacologia , Ácidos Graxos/química , Proteínas de Insetos/química , Renina/metabolismo , Angiotensinogênio/genética , Angiotensinogênio/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Células CHO , Cromatografia Líquida de Alta Pressão , Cricetinae , Cricetulus , DNA Complementar/genética , Dipeptídeos/química , Dipeptídeos/metabolismo , Ensaio de Imunoadsorção Enzimática , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/metabolismo , Feminino , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Humanos , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Proteínas de Insetos/isolamento & purificação , Proteínas de Insetos/metabolismo , Estrutura Molecular , Peptídeo Hidrolases/metabolismo , Ratos , Ratos Endogâmicos SHR , Proteínas Recombinantes/metabolismo , Renina/genética , Sistema Renina-Angiotensina/efeitos dos fármacos , OvinosRESUMO
We studied the protective effects of Echinacea purpurea against radiation by evaluating changes in the peripheral blood cell count and peripheral blood antioxidant activity. E. purpurea administration had a suppressive effect on radiation-induced leukopenia, especially on lymphocytes and monocytes, and resulted in a faster recovery of blood cell counts. Mouse peripheral blood antioxidant activity was increased by E. purpurea, and a relationship between the suppressive effect on radiation-induced leukopenia and the antioxidant effect was suggested. Furthermore, we reviewed the evidence of augmentation of found in this study humoral immunity. The effects of immune activation by E. purpurea were investigated by measuring total immunoglobulin (IgG, IgM). The radioprotective effects of immune activation by E. purpurea were investigated by measuring T lymphocyte subsets in the peripheral blood of mice following whole-body irradiation. E. purpurea activates macrophages to stimulate IFN-gamma production in association with the secondary activation of T lymphocytes, resulting in a decrease in IgG and IgM production. Cytokines released from macrophages in mouse peripheral blood after E. purpurea administration activated helper T cells to proliferate. In addition, it is reported that activated macrophages in association with the secondary T lymphocyte activation increases IFN-gamma production and stimulates proliferation of cytotoxic T cells and suppressor T cells. We think that CD 4 and CD 8 subsets were more immunologically enhanced by E. purpurea than helper T cells and suppressor T cell these results reflect activation. In addition, we think that these results reflect cell-mediated immune responses.
Assuntos
Adjuvantes Imunológicos/farmacologia , Antioxidantes/farmacologia , Echinacea , Adjuvantes Imunológicos/isolamento & purificação , Animais , Antioxidantes/isolamento & purificação , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Estruturas VegetaisRESUMO
A cell growth inhibitory effect of drupanin and baccharin, ingredients of propolis, was found in human cancer cell lines. These compounds induced apoptosis in the cells characterized by morphological and nucleosomal DNA fragmentation analysis. Their effects were less potent compared with that of artepillin C, which is a known anticancer compound from propolis. Importantly, HL60 cells were more sensitive to drupanin than were Con A-stimulated peripheral blood lymphocytes, whereas the potency of artepillin C was the opposite of that of drupanin.