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Estrogen deficiency during menopause causes a variety of neurological symptoms, including depression. The edible Lion's Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (HE), is a medicinal mushroom that has the potential for a neuroprotective effect and ameliorating neurological diseases, such as depression, anxiety, and neurodegenerative diseases. HE contains phytoestrogens, including daidzein and genistein. However, the ameliorating effect of HE on menopausal symptoms is not well understood. Here we investigated the impact of methanol extract of the HE fruiting body on depressive-like behavior in postmenopausal model rats. The activation of estrogen receptor alpha (ERα) causes body weight loss and uterine weight gain. Body weight gain and uterine weight loss by estrogen deficiency in ovariectomized (OVX) rats were reversed with 17ß-estradiol (E2) but not with HE. Thus, the phytoestrogens in HE may hardly activate ERα. Estrogen receptor beta (ERß) is expressed in the brain, and activation of ERß ameliorates menopausal depressive symptoms. Notably, depressive-like behavior in OVX rats evaluated in forced swim test was reduced by administration of not only E2 but also HE for 92 d. Long-term activation of ERα increases the risk of breast and uterine cancers. HE, therefore, may be effective in treating menopausal depression without the risk of carcinogenesis caused by ERα activation.
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Agaricales , Fármacos Neuroprotetores , Animais , Estradiol/farmacologia , Receptor alfa de Estrogênio , Receptor beta de Estrogênio , Feminino , Genisteína , Hericium , Humanos , Metanol , Ovariectomia , Fitoestrógenos , Ratos , Aumento de PesoRESUMO
Fructans such as inulin and levan accumulate in certain taxonomic groups of plants and are a reserve carbohydrate alternative to starch. Onion (Allium cepa L.) is a typical plant species that accumulates fructans, and it synthesizes inulin-type and inulin neoseries-type fructans in the bulb. Although genes for fructan biosynthesis in onion have been identified so far, no genes for fructan degradation had been found. In this study, phylogenetic analysis predicted that we isolated a putative vacuolar invertase gene (AcpVI1), but our functional analyses demonstrated that it encoded a fructan 1-exohydrolase (1-FEH) instead. Assessments of recombinant proteins and purified native protein showed that the protein had 1-FEH activity, hydrolyzing the ß-(2,1)-fructosyl linkage in inulin-type fructans. Interestingly, AcpVI1 had an amino acid sequence close to those of vacuolar invertases and fructosyltransferases, unlike all other FEHs previously found in plants. We showed that AcpVI1 was localized in the vacuole, as are onion fructosyltransferases Ac1-SST and Ac6G-FFT. These results indicate that fructan-synthesizing and -degrading enzymes are both localized in the vacuole. In contrast to previously reported FEHs, our data suggest that onion 1-FEH evolved from a vacuolar invertase and not from a cell wall invertase. This demonstrates that classic phylogenetic analysis on its own is insufficient to discriminate between invertases and FEHs, highlighting the importance of functional markers in the nearby active site residues.
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Cebolas , beta-Frutofuranosidase , Frutanos/metabolismo , Glicosídeo Hidrolases/metabolismo , Inulina , Cebolas/genética , Cebolas/metabolismo , Filogenia , Vacúolos/metabolismo , beta-Frutofuranosidase/genética , beta-Frutofuranosidase/metabolismoRESUMO
The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.
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Vacinas Anticâncer , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Receptores de Imunoglobulina Polimérica , Anticorpos Antineoplásicos , Antígenos de Neoplasias , Cisplatino , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fluoruracila , Glucanos , Humanos , Imunoglobulina A , Imunoglobulina G , Proteínas de Membrana , PrognósticoRESUMO
BACKGROUND: In transfusion-related iron overload, haem-derived iron accumulation in monocytes/macrophages is the initial event. When iron loading exceeds the ferritin storage capacity, iron is released into the plasma. When iron loading exceeds transferrin binding capacity, labile, non-transferrin-bound iron (NTBI) appears and causes organ injury. Haemin-induced cell death has already been investigated; however, whether NTBI induces cell death in monocytes/macrophages remains unclear. MATERIAL AND METHODS: Human monocytic THP-1 cells were treated with haemin or NTBI, particularly ferric ammonium citrate (FAC) or ferrous ammonium sulfate (FAS). The intracellular labile iron pool (LIP) was measured using an iron-sensitive fluorescent probe. Ferritin expression was measured by western blotting. RESULTS: LIP was elevated after haemin treatment but not after FAC or FAS treatment. Reactive oxygen species (ROS) generation and cell death induction were remarkable after haemin treatment but not after FAC or FAS treatment. Ferritin expression was not different between the FAC and haemin treatments. The combination of an iron chelator and a ferroptosis inhibitor significantly augmented the suppression of haemin cytotoxicity (p = 0.011). DISCUSSION: The difference in LIP suggests the different iron traffic mechanisms for haem-derived iron and NTBI. The Combination of iron chelators and antioxidants is beneficial for iron overload therapy.
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Sobrecarga de Ferro , Ferro , Morte Celular , Ferritinas , Hemina/farmacologia , Humanos , Ferro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transferrina/metabolismo , Transferrina/farmacologiaRESUMO
Under aquaculture conditions, Japanese eels (Anguilla japonica) produce a high percentage of males. However, females gain higher body weight and have better commercial value than males, and, therefore, a high female ratio is required in eel aquaculture. In this study, we examined the effects of isoflavones, genistein, and daidzein on sex differentiation and sex-specific genes of eels. To investigate the effects of these phytoestrogens on the gonadal sex, we explored the feminizing effects of soy isoflavones, genistein, and daidzein in a dose-dependent manner. The results showed that genistein induced feminization more efficiently than daidzein. To identify the molecular mechanisms of sex-specific genes, we performed a comprehensive expression analysis by quantitative real-time PCR and RNA sequencing. Phenotypic males and females were produced by feeding elvers a normal diet or an estradiol-17ß- or genistein-treated diet for 45 days. The results showed that female-specific genes were up-regulated and male-specific genes were down-regulated in the gonads, suggesting that genistein induces feminization by altering the molecular pathways responsible for eel sex differentiation.
Assuntos
Anguilla , Isoflavonas , Humanos , Animais , Masculino , Feminino , Genisteína/farmacologia , Anguilla/genética , Anguilla/metabolismo , Feminização/induzido quimicamente , Isoflavonas/metabolismo , FitoestrógenosRESUMO
Intervention studies have shown that n-3 polyunsaturated fatty acid (PUFA) supplementation is effective for the treatment of meibomian gland dysfunction (MGD). Ointment containing an analog of vitamin D has also been found to improve symptoms and signs of MGD. We have now evaluated the relation of MGD prevalence to dietary intake of fatty acids (FAs) and vitamin D among a Japanese population. Subjects comprised 300 adults aged 20 to 92 years residing on Takushima Island. MGD was diagnosed on the basis of subjective symptoms, lid margin abnormalities, and meibomian gland obstruction. Dietary FA and vitamin D intake was estimated with a brief-type self-administered diet history questionnaire. MGD prevalence was 35.3%. Multivariate adjusted odds ratios (95% confidence intervals) between extreme quintiles of intake for MGD prevalence were 0.40 (0.16-0.97) for total fat, 0.40 (0.17-0.97) for saturated FAs, 0.40 (0.17-0.97) for oleic acid, 0.52 (0.23-1.18) for n-3 PUFAs, 0.63 (0.27-1.49) for n-6 PUFAs, 1.32 (0.59-2.95) for the n-6/n-3 PUFA ratio, and 0.38 (0.17-0.87) for vitamin D. Total fat, saturated FA, oleic acid, and vitamin D intake may thus be negatively associated with MGD prevalence in the Japanese.
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OBJECTIVE: To evaluate the interaction between tear supplements and soft contact lenses (SCLs), we measured the contact angles (CAs) on the SCLs using commercially available tear supplements. METHODS: We used four daily disposable conventional hydrogel lenses (etafilcon A, etafilcon A+ polyvinylpyrrolidone, nelfilcon A, and omafilcon A containing 2-methacryloyloxyethyl phosphorylcholine [MPC]) and four silicone hydrogel lenses (narafilcon A, senofilcon A, delefilcon A, and stenfilcon A). The CAs on the SCLs were measured using a sessile drop technique and four different types of sessile drops, including saline, artificial tears, lubricants containing 2-MPC (MPC solution), and 0.1% hyaluronate acid (HA). RESULTS: The CA values associated with the silicone hydrogel lenses were significantly (P<0.001) lower than those associated with the conventional hydrogel lenses with all four solutions. The mean CA of 0.1% HA was significantly (P<0.01) higher than that of saline. The mean CA of the MPC solution was significantly (P<0.01) lower than that of saline with the conventional hydrogel lenses but significantly (P<0.05) higher than that of saline with the silicone hydrogel lenses. CONCLUSIONS: The CAs associated with the silicone hydrogel SCLs were higher with the use of the MPC solutions and HA in vitro. The measured CAs may depend on ingredient agents, surface treatment of the CLs, and components of the tear supplements.
Assuntos
Lentes de Contato Hidrofílicas , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato , Lubrificantes Oftálmicos , Silicones , Lágrimas , MolhabilidadeRESUMO
Sialidase cleaves sialic acid residues from a sialoglycoconjugate: oligosaccharides, glycolipids and glycoproteins that contain sialic acid. Histochemical imaging of the mouse pancreas using a benzothiazolylphenol-based sialic acid derivative (BTP3-Neu5Ac), a highly sensitive histochemical imaging probe used to assess sialidase activity, showed that pancreatic islets have intense sialidase activity. The sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA) remarkably enhances glutamate release from hippocampal neurons. Since there are many similar processes between synaptic vesicle exocytosis and secretory granule exocytosis, we investigated the effect of DANA on insulin release from ß-cells. Insulin release was induced in INS-1D cells by treatment with 8.3 mM glucose, and the release was enhanced by treatment with DANA. In a mouse intraperitoneal glucose tolerance test, the increase in serum insulin levels was enhanced by intravenous injection with DANA. However, under fasting conditions, insulin release was not enhanced by treatment with DANA. Calcium oscillations induced by 8.3 mM glucose treatment of INS-1D cells were not affected by DANA. Blood insulin levels in sialidase isozyme Neu3-deficient mice were significantly higher than those in WT mice under ad libitum feeding conditions, but the levels were not different under fasting conditions. These results indicate that DANA is a glucose-dependent potentiator of insulin secretion. The sialidase inhibitor may be useful for anti-diabetic treatment with a low risk of hypoglycemia.
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Glucose/fisiologia , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Ácido N-Acetilneuramínico/análogos & derivados , Neuraminidase/antagonistas & inibidores , Animais , Benzotiazóis/química , Sinalização do Cálcio/efeitos dos fármacos , Corantes/análise , Avaliação Pré-Clínica de Medicamentos , Jejum/sangue , Teste de Tolerância a Glucose , Hipoglicemiantes/farmacologia , Injeções Intravenosas , Insulina/sangue , Secreção de Insulina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácido N-Acetilneuramínico/farmacologia , Neuraminidase/fisiologia , Ácidos Siálicos/químicaRESUMO
Women with estrogen deficiency are at the risk of suffering from neurological symptoms such as memory impairment. In the present study, we investigated the effect of garlic, Allium sativum L. (Asparagales: Amaryllidaceae), treated with subcritical water on memory impairment in ovariectomized (OVX) rats. OVX rats were administered garlic powder for 84 d. Hippocampus-dependent spatial memory was assessed using the Morris water maze test. Escape latency of the OVX rats increased compared with that of sham-operated rats. The prolonged escape latency of the OVX rats decreased to the level of that of sham-operated rats upon the administration of garlic powder (0.5% in feed). The weights of the body, uterus, and brain were not affected by the garlic powder administration. These results suggest that garlic powder treated with subcritical water mitigates memory impairment in OVX rats.
Assuntos
Estrogênios/deficiência , Alho , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Ovariectomia/efeitos adversos , Extratos Vegetais/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Memória/efeitos dos fármacos , RatosRESUMO
Outcomes of treatment for malignant pediatric tumors including leukemia are improving by conventional multimodal treatment with strong chemotherapy, surgical resection, radiotherapy, and bone marrow transplantation. However, patients with advanced neuroblastoma, metastatic Ewing's sarcoma family of tumor (ESFT), and metastatic osteosarcoma continue to have an extremely poor prognosis. Therefore novel therapeutic strategies are urgently needed to improve their survival. Apoptotic cell death is a key mechanism for normal cellular homeostasis. Intact apoptotic mechanisms are pivotal for embryonic development, tissue remodeling, immune regulation, and tumor regression. Genetic aberrations disrupting programmed cell death often underpin tumorigenesis and drug resistance. Moreover, it has been suggested that apoptosis or cell differentiation proceeds to spontaneous regression in early stage neuroblastoma. Therefore apoptosis or cell differentiation is a critical event in this cancer. We extracted many compounds from natural plants (Angelica keiskei, Alpinia officiarum, Lycaria puchury-major, Brassica rapa) or synthesized cyclophane pyridine, indirubin derivatives, vitamin K3 derivatives, burchellin derivatives, and GANT61, and examined their effects on apoptosis, cell differentiation, and cell cycle in neuroblastoma and ESFT cell lines compared with normal cells. Some compounds were very effective against these tumor cells. These results suggest that they may be applicable as an efficacious and safe drug for the treatment of malignant pediatric tumors.
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Desenvolvimento de Medicamentos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Apoptose , Diferenciação Celular , Criança , Pré-Escolar , Genes Supressores de Tumor , Humanos , Lactente , Leucemia/tratamento farmacológico , Leucemia/patologia , Neoplasias/patologia , Extratos Vegetais , PrognósticoRESUMO
Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required. We have demonstrated the therapeutic potential of bacteriophage ΦEF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains of E. faecalis Phage ΦEF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with E. faecalis-related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 × 104 cells) into the vitreous. The number of viable bacteria in the eye increased to >1 × 107 CFU, and neutrophil infiltration into the eye was detected as an increase in myeloperoxidase activity at 24 h after infection. A clinical score based on loss of visibility of the fundus as well as the number of viable bacteria and the level of myeloperoxidase activity in the eye were all significantly decreased by intravitreous injection of ΦEF24C-P2 6 h after injection of EF24 or VRE2. Whereas histopathologic analysis revealed massive infiltration of inflammatory cells and retinal detachment in vehicle-treated eyes, the number of these cells was greatly reduced and retinal structural integrity was preserved in phage-treated eyes. Our results thus suggest that intravitreous phage therapy is a potential treatment for endophthalmitis caused by vancomycin-sensitive or -resistant strains of E. faecalis.
Assuntos
Bacteriófagos/genética , Endoftalmite/terapia , Endoftalmite/virologia , Enterococcus faecalis/virologia , Infecções Oculares Bacterianas/terapia , Resistência a Vancomicina/genética , Vancomicina/farmacologia , Animais , Antibacterianos/farmacologia , Modelos Animais de Doenças , Endoftalmite/microbiologia , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/virologia , Injeções , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana/métodos , Terapia por Fagos/métodosRESUMO
PURPOSE: Oral L-citrulline (Cit) increases plasma L-arginine (Arg) concentration and the production of nitric oxide (NO). NO dilates blood vessels and potentially improves sports performance. The combination of oral Arg and Cit (Arg + Cit) immediately and synergistically increases plasma Arg and nitrite/nitrate (NOx) concentrations more than either Cit or Arg alone. This prompted us to assess the effects of oral Arg + Cit on 10-min cycling performance in a double-blind, randomized, placebo-controlled crossover trial. METHODS: Twenty-four male soccer players ingested either Cit + Arg or placebo (both 1.2 g/day each) for 6 days. On day 7, they ingested Cit + Arg 1 h before performing a 10-min full-power pedaling test on a bicycle ergometer. Plasma NOx and amino acid levels were measured before and after the test, as well as the participants' subjective perception of physical exertion. RESULTS: Power output was significantly greater with Cit + Arg than in the placebo group (242 ± 24 vs. 231 ± 21 W; p < 0.05). Plasma concentrations of post-exercise NOx (p < 0.05), Cit (p < 0.01) and Arg (p < 0.01) were significantly higher in the Cit + Arg than in the placebo group, whereas exercise upregulated plasma NOx concentrations in both groups (p < 0.05). Cit + Arg also gave improved post-exercise subjective perception of "leg muscle soreness" and "ease of pedaling" (both p < 0.05). CONCLUSION: Seven days of oral Citrulline (1.2 g/d) and Arginine (1.2 g/d) ingestion improved 10-min cycling performance and the perception of physical exertion in male collegiate soccer players.
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Arginina/farmacologia , Citrulina/farmacologia , Tolerância ao Exercício/efeitos dos fármacos , Administração Oral , Adolescente , Adulto , Arginina/administração & dosagem , Citrulina/administração & dosagem , Combinação de Medicamentos , Humanos , Masculino , Futebol/fisiologiaRESUMO
Recent studies have shown that aronia (black chokeberry) and haskap fruits (contain anthocyanins) have beneficial health effects in animals and humans. However, some reports have shown that anthocyanin is poorly absorbed in the small intestine. In this study, we compared the intestinal absorption of aronia and haskap anthocyanins by using rats with a ligated small intestinal loop and cannulated portal vein. Our results clearly showed that the intestinal absorption of aronia anthocyanins was significantly lower than that of haskap anthocyanins, suggesting that the intestinal absorption of anthocyanins is influenced by the glycoside type (galactoside or glucoside). In addition, we also examined the effects of capsaicin and capsiate on intestinal anthocyanin absorption. The amount of aronia anthocyanins in portal blood was much higher when they were co-administered with capsaicin or capsiate. Our study is the first to show that the intestinal absorption of aronia anthocyanins is promoted by capsaicin and capsiate.
Assuntos
Antocianinas/farmacocinética , Capsaicina/análogos & derivados , Capsaicina/farmacocinética , Glicosídeos/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Photinia/química , Animais , Frutas/química , Intestino Delgado/metabolismo , Masculino , Extratos Vegetais/farmacocinética , Ratos , Ratos Sprague-DawleyRESUMO
L-Carnitine (LC) plays an important role in the metabolism of fatty acids, and LC deficiency is associated with a feeling of weakness or general fatigue. Cancer patients receiving chemotherapy often develop LC deficiency, which is considered to be a factor contributing to general fatigue. The aim of the present study was to evaluate the efficacy of LC supplementation as a treatment for general fatigue in cancer patients during chemotherapy. A total of 11 cancer patients who were suffering from general fatigue during chemotherapy in our hospital between September 2014 and December 2015 were examined (6 cases involved adjuvant chemotherapy and 5 cases involved chemotherapy for unresectable or recurrent disease). The patients were administered 1,500 mg/day of levocarnitine per os, and the change in mean daily fatigue from the baseline to 8 weeks was assessed using the Brief Fatigue Inventory. The change in the plasma levels of albumin and the lymphocyte counts from the baseline to 8 weeks were also assessed. LC supplementation reduced general fatigue in all cases. Moreover, LC supplementation maintained the plasma levels of albumin and lymphocyte counts during chemotherapy, and enabled patients to continue chemotherapy sequentially without dose reduction. Therefore, LC supplementation improved general fatigue in all the examined cancer patients during chemotherapy. This treatment may make improve the tolerability of chemotherapy in cancer patients by reducing general fatigue and improving the nutritional status.
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BACKGROUND: Neuroblastoma is one of the most commonly encountered malignant solid tumors in the pediatric age group. We examined the antitumor effects of five burchellin derivatives against human neuroblastoma cell lines. MATERIALS AND METHODS: We evaluated cytotoxicity by the MTT assay for four human neuroblastoma and two normal cell lines. We also performed analysis of the apoptotic induction effect by flow cytometry, and examined the expression levels of apoptosis- and cell growth-related proteins by western blot analysis. RESULTS: We found that one of the burchellin derivatives (compound 4) exerted cytotoxicity against the neuroblastoma cell lines. Compound 4 induced caspase-dependent apoptosis via a mitochondrial pathway. The apoptosis mechanisms induced by compound 4 involved caspase-3, -7 and -9 activation and poly (ADP-ribose) polymerase cleavage. In addition, compound 4 induced cell death through inhibition of the cell growth pathway (via extracellular signal-regulated kinase 1 and 2, AKT8 virus oncogene cellular homolog, and signal transducer and activator of transcription 3). CONCLUSION: Compound 4 exerted cellular cytotoxicity against neuroblastoma cells via induction of caspase-dependent apoptosis, and may offer promise for further development as a useful drug for the treatment of advanced neuroblastoma.
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Antineoplásicos Fitogênicos/farmacologia , Benzofuranos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neuroblastoma/tratamento farmacológico , Benzofuranos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , HumanosRESUMO
Young coconut (Cocos nucifera Linn.) juice (YCJ) has traditionally been consumed to alleviate symptoms associated with the menopause. Recently, the authors demonstrated that short-term (6-week) YCJ supplementation to ovariectomized rats resulted in increased bone mass and bone formation parameter, suggesting that YCJ consumption has a positive effect on bone metabolism and may represent an intervention to help slow the bone loss during menopause transition. The present study sought to determine how long-term (12-week) YCJ supplementation affects bone metabolism in ovariectomized rats, to investigate whether such supplementation may be helpful to in osteoporosis treatment. Ten-week-old female Wistar rats were subjected to either a sham operation (Sham) or bilateral ovariectomy (Ovx). The Ovx+YCJ group received 5X-concentrated YCJ at a dose of 15 ml/kg/day for 12 weeks. Rats in the Ovx group had significantly lower femur bone mineral density than those in the Sham group. YCJ supplementation did not significantly affect this difference. However, YCJ prevented the increase in bone area of the mid third of the femur, a site high in cortical bone, and body weight gain observed following Ovx. Our findings indicate that long-term YCJ intake does not alter bone loss, but rather alleviates body weight gain following menopause.
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We studied the anti-inflammatory activity of twelve 5,7-dihydroxyflavone analogues in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. We found that chrysin (1) and 4'-methoxytricetin (9) showed relatively significant anti-inflammatory activity and low cytotoxicity. Moreover, 1 and 9 recovered the expression levels of iNOS and COX2, as well as those of the intracellular inflammatory mediators IL-1ß and IL-6, which were upregulated by LPS stimulation. In addition, 1 and 9 actively regulated the phosphorylation of IκBα, leading to the activation of NFκB. Phosphorylation of Akt and ERK5 (upstream of NFκB) by LPS stimulation was significantly regulated by 1 and 9, as well as by BIX 02189 and LY 294002, which are phosphorylation inhibitors of ERK5 and Akt, respectively. The results suggest that compounds 1 and 9 may suppress the levels of iNOS and COX2 by regulating phosphorylation of Akt, ERK5, and IκBα and thus NFκB-related signaling pathways, resulting in anti-inflammatory effects in the cells. Because 1 and 9 showed low cytotoxicity and regulated both PGE2 and NO production caused by inflammatory responses, they may hold promise as natural anti-inflammatory agents.
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Eleutherococcus sieboldianus (Makino) Koidz. is a local product from the area in and around Yonezawa City in Yamagata Prefecture, Japan. It has been used as a medicinal plant for a long time. We isolated and identified four types of flavonoid glycosides [astragalin (1), isoquercetin (2), rhamnocitrin 3-O-glucoside (3), and nicotiflorin (4)], a triterpene [methyl hederagenin (5)], and three types of triterpene glycosides [δ-hederin (6), echinocystic acid 3-O-arabinoside (7), and cauloside B (8)] from the methanol extract of E. sieboldianus, which regulates lipid accumulation in 3T3-L1 preadipocytes. Among the compounds isolated, 2 and 8 up- and down-regulated lipid accumulation and insulin induced adipocyte differentiation in 3T3-L1 preadipocytes. Compound 2 induced up-regulation of lipid accumulation and decreased adipocyte size, while 8 down-regulated lipid accumulations without decreasing cell size. Additionally, 2 increased adipogenic proteins [peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and fatty-acid-binding protein 4 (FABP4)]. In contrast, 8 decreased the levels of all adipogenic proteins and glucose transporter type 4 (GLUT4), but increased adiponectin.
Assuntos
Fármacos Antiobesidade/farmacologia , Eleutherococcus/química , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Triterpenos/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Metabolismo dos Lipídeos/efeitos dos fármacos , CamundongosRESUMO
Toll-like receptor 4 (TLR4) plays an essential role in innate immunity through inflammatory cytokine induction. Recent studies demonstrated that the abnormal activation of TLR4 has a pivotal role in obesity-induced inflammation, which is associated with several diseases, including hyperinsulinemia, hypertriglyceridemia, and cardiovascular disease. Here we demonstrate that (-)-epigallocatechin-3-O-gallate, a natural agonist of the 67-kDa laminin receptor (67LR), suppressed TLR4 expression through E3 ubiquitin-protein ring finger protein 216 (RNF216) up-regulation. Our data indicate cyclic GMP mediates 67LR agonist-dependent RNF216 up-regulation. Moreover, we show that the highly absorbent 67LR agonist (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3â³Me) significantly attenuated TLR4 expression in the adipose tissue. EGCG3â³Me completely inhibited the high-fat/high-sucrose (HF/HS)-induced up-regulation of tumor necrosis factor α in adipose tissue and serum monocyte chemoattractant protein-1 increase. Furthermore, this agonist intake prevented HF/HS-induced hyperinsulinemia and hypertriglyceridemia. Taken together, 67LR presents an attractive target for the relief of obesity-induced inflammation.
Assuntos
Catequina/análogos & derivados , Regulação da Expressão Gênica/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Receptores de Laminina/metabolismo , Chá/química , Receptor 4 Toll-Like/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Catequina/farmacologia , Células Cultivadas , Hiperinsulinismo/metabolismo , Hiperinsulinismo/prevenção & controle , Hipertrigliceridemia/metabolismo , Hipertrigliceridemia/prevenção & controle , Inflamação/etiologia , Inflamação/prevenção & controle , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Obesidade/etiologia , Obesidade/prevenção & controle , Receptores de Laminina/agonistas , Receptores de Laminina/genética , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Ativação Transcricional , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitina-Proteína Ligases/genética , Regulação para CimaRESUMO
We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.