Mechanism of Gardeniae Fructus in ameliorating rheumatoid arthritis based on metabolomics and intestinal microbiota / 中国中药杂志

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.

Glyphosate-resistant soybeans yield in function of glyphosate salts, doses and stadium phenological / Produtuvidade de cultivares de soja em função dos sais de glyphosate, doses e épocas de aplicação

Given the importance of soybean to the global economy and as a food source, improving crop management techniques is integral to obtaining higher yields. As such, this study aimed to assess the yield of soybean cultivars as a function of different glyphosate salt formulations, doses and application times. Two field experiments were conducted simultaneously using a randomized block design and 3x4x2 factorial scheme, with three repetitions. Factor A consisted of three glyphosate formulations: isopropylamine salt (Roundup Original®), ammonium salt (Roundup WG®), and potassium salt (Zapp Qi®), factor B four application times: 0, 14, 28, 42 days after planting (DAP), and factor C two doses: the recommended dose of 720 grams of acid equivalent per hectare and twice that (1440 grams of acid equivalent per hectare). There was no difference between the glyphosate salts for the BMX Ativa RR® cultivar, but yields of BMX Apolo RR® submitted to ammonium salt were 28% higher than those recorded for the other salts studied. Glyphosate potassium salt resulted in lower soybean yields. Potassium salt application between 14 and 28 DAP caused greater toxicity in both the soybean cultivars analyzed.

Diante da importância da cultura da soja tanto na economia mundial quanto para a alimentação, a melhoria das técnicas de cultivo torna-se um ponto fundamental na obtenção de maiores produtividades. Desta forma o objetivo do trabalho foi avaliar a produtividade de cultivares de soja sob a influência da aplicação de diferentes sais de glyphosate, doses e épocas de aplicação. Dois experimentos de campo foram realizados simultaneamente em delineamento de blocos casualizados com arranjo trifatorial (3x4x2) com três repetições. O fator A consistiu de três formulações de glyphosate: sal de isopropilamina (Roundup Original®), sal de amônio (Roundup WG®), sal de potássio (Zapp Qi®). O fator B consistiu de quatro épocas de aplicação: 0, 14, 28, 42 dias após a semeadura (DAS). O fator C consistiu em duas doses: a dose recomendada de 720 gramas de equivalente ácido por hectare e duas vezes a dose recomendada com 1440 gramas de equivalente ácido por hectare. Para a cultivar BMX Ativa RR® não se observou diferença quanto aos sais, porém a cultivar BMX Apolo RR® submetida a aplicação de sal de amônio demostrou uma produtividade 28% superior em relação aos demais sais. O glyphosate na formulação sal de potássio apresentou redução da produtividade da cultura da soja. Aplicações de glyphosate na formulação sal de potássio realizadas entre os 14 e 28 dias após a semeadura causam maior toxidez em ambas cultivares de soja utilizadas.

Avaliação dos efeitos da Suplementação do Ácido Graxo ômega 3 em modelo de tumor de mama murino e mucosite induzida por 5-Fluouracil / Evaluation of the effects of Omega 3 Fatty Acid Supplementation in a model of murine breast tumor and mucositis induced by 5-Fluouracil

O ômega 3 é um ácido graxo poliinsaturado utilizado como agente terapêutico no tratamento de diversas doenças. Evidências sugerem efeito anti-inflamatório com sua utilização. A escolha do tratamento eficiente que minimize os efeitos adversos do tratamento oncológico tem sido desafiadora para a prática clínica. Dessa forma, ele seria interessante na prevenção e / ou tratamento da mucosite, uma inflamação que acomete as mucosas da boca ao ânus, decorrente da utilização de quimioterápico e radioterápico. As consequências deste agravo vão desde a perda de peso, anorexia e odinofagia, ao aumento do risco de translocação bacteriana, em virtude do aumento da permeabilidade intestinal (PI). Tais complicações podem levar à interrupção do tratamento quimioterápico até que o paciente se restabeleça. Trabalhos anteriores do nosso grupos de pesquisa demonstraram que o ômega 3 foi capaz de atenuar a perda de peso e reduzir a PI pela regulação da apoptose de células intestinais. Entretanto, possíveis efeitos da suplementação do ômega 3 no tumor não foram investigados. O presente estudo avaliou o efeito deste composto na mucosite induzida por quimioterápico em modelo de tumor de mama murino. Para tanto, camundongos Balb/c foram divididos nos grupos controle (CTL), controle tumor (CTLTU), tumor ômega 3 (TUW3), tumor 5-fluouracil (TU5FU) e tumor 5-fluouracil ômega 3 (TU5FUW3). Nos animais dos grupos com tumor foi realizada a inoculação das células tumorais (dia 1) e, uma vez que os tumores já se encontravam palpáveis (dia10), os grupos TUW3 e TU5FUW3 iniciaram a suplementação com ômega 3 pela ração por 10 dias, enquanto os demais animais receberam ração controle. Ao final desse período, os animais dos grupos TU5FU e TU5FUW3 receberam injeção intraperitoneal de 5-FU (300mg/kg) para indução da mucosite, enquanto os demais animais receberam a injeção de solução salina. Após 72 horas, os animais foram eutanasiados para coleta de dados. A suplementação com ômega 3 não foi capaz de prevenir a perda de peso em decorrência da mucosite. Entretanto, os animais do grupo TU5FUW3 apresentaram redução da PI por meio da recuperação das junções firmes ZO-1 e ocludina, além da preservação da arquitetura dos vilos. Os animais do grupo CTLTU também apresentaram aumento da PI e redução da expressão das proteínas de junção, provavelmente pela liberação de citocinas TNF-α e IL-1ß, conforme dosagem destas no baço. Nos animais suplementados com ômega 3 foi observado redução do tamanho do tumor e do número de metástases tumorais, além de redução da proliferação de células tumorais e aumento da afinidade das células tumorais ao quimioterápico, levando à apoptose destas. Este processo de citotoxicidade seletiva foi observado pela redução da toxicidade hepática. Diante desses resultados, pode-se concluir que a suplementação de ômega 3, por período de dez dias, foi capaz de atenuar os efeitos da mucosite induzida por quimioterápico, sem causar prejuízo à sua atividade antitumoral.

Omega 3 is a polyunsaturated fatty acid used as a therapeutic agent in the treatment of various diseases. It is widely accepted that its use can exert an anti-inflammatory effect. Thus, it would be interesting in the prevention and treatment of mucositis, which is described as an inflammation that affects mucosal membranes from the mouth to the anus, due to the use of chemotherapy and radiotherapy. Patients who suffer from this outcome, usually presents weight loss, anorexia and odynophagia,also there is an increased risk of bacterial translocation, due to the increase of the intestinal permeability (IP). Such complications can lead to the interruption of chemotherapy treatment until the patient is recovered. Previous work has shown that omega 3 was able to reduce weight loss and reduce IP by reducing intestinal cell apoptosis. However, the effects of omega 3 supplementation from the diet on the tumor remains unknown. This study aimed to investigate the effect of this compound on chemotherapy-induced mucositis in the murine breast tumor model. For that, BALB/ c mice were divided into the control (CTL), tumor control (CTLTU), omega 3 tumor (TUW3), 5-fluouracil tumor (TU5FU) and 5-fluouracil omega 3 tumor (TU5FUW3) groups. Tumor cells were inoculated (day 1) and, since they were already palpable (day 10), groups TUW3 and TU5FUW3 started receiving the chow supplemented with omega 3 for 10 days, while the other animals received control chow. At the end of this period, animals from groups TU5FU and TU5FUW3 received an intraperitoneal injection of 5-FU (300mg / kg) to induce mucositis, while the other animals received an injection of saline. After 72 hours, all animals were euthanized for data collection. Omega 3 supplementation was not able to prevent weight loss due to mucositis. However, animals from TU5FUW3 group showed a reduction in IP by recovering the tight-junctions ZO-1 and occludin, and by preventing the mucosal damage. Animals from CTLTU group also showed increased PI and reduced expression of tight-junction proteins, probably due to the release of cytokines TNF-α and IL-1ß, according to their dosage in the spleen. In addition, our results have demonstrated that animals supplemented with omega 3, have shown a reduction in the size of the tumor and the number of metastasis in lungs. We have found that the reduction was mediated through a reduction in the proliferation of tumor cells and also by an increased affinity of tumor cells to the chemotherapeutic drug, leading to their apoptosis. This selective cytotoxicity process leads to the reduction of liver toxicity. Given these results, we can conclude that omega 3 supplementation, for ten days, was able to attenuate the effects of chemotherapy-induced mucositis, without causing damage to its antitumor activity.

Ômega 3 na gestação e seus benefícios / Omega 3 during pregnancy and its benefits

O objetivo desta pesquisa é levantar a literatura científica sobre os benefícios do Ômega-3 na gestação, que se deu pelas bases de dados Scientifc Electronic Library Online (Scielo), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Literatura Internacional em Ciências de Saúde (Medline) e National Library of Medicine (Pubmed) e Cochrane em literaturas nacionais e internacionais. Nesta pesquisa pode-se verificar que o ácido docosahexaenoico (DHA) é considerado como o principal tipo de Ômega-3 pelo fato de proporcionar benefícios para a saúde, que vão desde o desenvolvimento do cérebro e da retina do bebê, os quais têm início a partir da suplementação da mãe já na gestação. O acúmulo do Ômega-3 ocorre no último trimestre da gestação e o transporte se dá através da placenta, sendo depositado no cérebro e na retina do concepto. Ocorre também um acúmulo simultâneo nas glândulas mamárias durante esta fase. O recomendado pelo consenso é de 200mg/dia, independentemente da fonte utilizada para suplementação. O adequado aporte de Ômega-3 na gestação e no pós-natal tem influência positiva no desenvolvimento visual e do sistema nervoso do recém-nascido, influenciando também na inteligência e na intelectualidade do indivíduo na vida adulta. O Ômega-3 é importante também na prevenção e tratamento de diversas doenças como obesidade, doenças cardiovasculares, imunológicas, câncer de cólon, entre outras.(AU)

The objective of this research is to raise the scientific literature on the benefits of omega-3 during pregnancy, which occurred in research in databases Scientifc Electronic Library Online (Scielo), Latin American and Caribbean Health Sciences (Lilacs) , International Literature in Health Sciences (MEDLINE) and national Library of Medicine (PubMed) and the Cochrane in national and international literature, which can be seen that docosahexaenoic acid (DHA) is considered as the main type of Omega-3, the fact provide health benefits ranging from brain development and the baby's retina, which begins from the mother during pregnancy supplementation already. The Omega-3 accumulation occurs in the last trimester of pregnancy and the transport is through the placenta being deposited in the brain and retina of the fetus. It is also a simultaneous accumulation in the mammary glands during this phase. The recommended by consensus is 200 mg / day, regardless of the source used for supplementation. Adequate intake of omega-3 during pregnancy and in the postnatal has positive influences on visual development and the nervous system of the newborn, influencing also the intelligence and the individual intellect in adulthood. The Omega-3 is also important in the prevention and treatment of various diseases as obesity, cardiovascular, immune disorders, colon cancer, among others.(AU)

α-Linolenic acid prevents hepatic steatosis and improves glucose tolerance in mice fed a high-fat diet

OBJECTIVES: Dietary omega-3 fatty acids have been efficacious in decreasing serum cholesterol levels and reducing the risk of cardiovascular disease. However, the metabolic and molecular changes induced by the omega-3 fatty acid α-linolenic acid (ALA), which is found in linseed oil, are not fully understood. In this study, we showed a correlation between ALA and insulin resistance, inflammation and endoplasmic reticulum stress (ERS). METHODS: We studied 40 male mice (C57/BL6) divided into 4 groups: a control (C) group, a control + omega-3/ALA (CA) group, a high-fat diet (HFD) (H) group and a high-fat diet + omega-3/ALA (HA) group. For 8 weeks, the animals in the H and HA groups were fed a high-fat (60%) diet, while the animals in the C and CA groups received regular chow. The diets of the CA and HA groups were supplemented with 10% lyophilized ALA. RESULTS: ALA supplementation improved glucose tolerance and reduced insulin resistance, as measured by intraperitoneal glucose tolerance tests and the homeostasis model assessment for insulin resistance, respectively. In addition, ALA reduced hepatic steatosis and modified the standard fat concentration in the liver of animals fed an HFD. Dietary ALA supplementation reduced the serum levels of interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1), increased the expression of important chaperones such as binding immunoglobulin protein (BIP) and heat shock protein 70 (HSP70) and reduced the expression of C/EBP-homologous protein (CHOP) and X-box binding protein 1 (XBP1) in hepatic tissues, suggesting an ERS adaptation in response to ALA supplementation. CONCLUSIONS: Dietary ALA supplementation is effective in preventing hepatic steatosis; is associated with a reduction in insulin resistance, inflammation and ERS; and represents an alternative for improving liver function and obtaining metabolic benefits.

Protective effects of perilla oil and alpha linolenic acid on SH-SY5Y neuronal cell death induced by hydrogen peroxide

BACKGROUND/OBJECTIVE: Oxidative stress plays a key role in neuronal cell damage, which is associated with neurodegenerative disease. The aim of present study was to investigate the neuroprotective effects of perilla oil (PO) and its active component, alpha-linolenic acid (ALA), against hydrogen peroxide (H₂O₂)-induced oxidative stress in SH-SY5Y neuronal cells. MATERIALS/METHODS: The SH-SY5Y human neuroblastoma cells exposed to 250 µM H₂O₂ for 24 h were treated with different concentrations of PO (25, 125, 250 and 500 µg/mL) and its major fatty acid, ALA (1, 2.5, 5 and 25 µ/mL). We examined the effects of PO and ALA on H₂O₂-induced cell viability, lactate dehydrogenase (LDH) release, and nuclear condensation. Moreover, we determined whether PO and ALA regulated the apoptosis-related protein expressions, such as cleaved-poly ADP ribose polymerase (PARP), cleaved caspase-9 and -3, BCL-2 and BAX. RESULTS: Treatment of H₂O₂ resulted in decreased cell viability, increased LDH release, and increase in the nuclei condensation as indicated by Hoechst 33342 staining. However, PO and ALA treatment significantly attenuated the neuronal cell death, indicating that PO and ALA potently blocked the H₂O₂-induced neuronal apoptosis. Furthermore, cleaved-PARP, cleaved caspase-9 and -3 activations were significantly decreased in the presence of PO and ALA, and the H₂O₂-mediated up-regulated BAX/BCL-2 ratio was blocked after treatment with PO and ALA. CONCLUSIONS: PO and its main fatty acid, ALA, exerted the protective activity from neuronal oxidative stress induced by H₂O₂. They regulated apoptotic pathway in neuronal cell death by alleviation of BAX/BCL-2 ratio, and down-regulation of cleaved-PARP and cleaved caspase-9 and -3. Although further studies are required to verify the protective mechanisms of PO and ALA from neuronal damage, PO and ALA are the promising agent against oxidative stress-induced apoptotic neuronal cell death.

Sageretia thea fruit extracts rich in methyl linoleate and methyl linolenate downregulate melanogenesis via the Akt/GSK3β signaling pathway

BACKGROUND/OBJECTIVES: Sageretia thea is traditionally used as a medicinal herb to treat various diseases, including skin disorders, in China and Korea. This study evaluated the inhibitory effect of Sageretia thea fruit on melanogenesis and its underlying mechanisms in B16F10 mouse melanoma cells. The active chemical compounds in anti-melanogenesis were determined in Sageretia thea. MATERIALS/METHODS: Solvent fractions from the crude extract were investigated for anti-melanogenic activities. These activities and the mechanism of anti-melanogenesis in B16F10 cells were examined by determining melanin content and tyrosinase activity, and by performing western blotting. RESULTS: The n-hexane fraction of Sageretia thea fruit (HFSF) exhibited significant anti-melanogenic activity among the various solvent fractions without reducing viability of B16F10 cells. The HFSF suppressed the expression of tyrosinase and tyrosinase-related protein 1 (TRP1). The reduction of microphthalmia-associated transcription factor (MITF) expression by the HFSF was mediated by the Akt/glycogen synthase kinase 3 beta (GSK3β) signaling pathway, which promotes the reduction of β-catenin. Treatment with the GSK3β inhibitor 6-bromoindirubin-3'-oxime (BIO) restored HFSF-induced inhibition of MITF expression. The HFSF bioactive constituents responsible for anti-melanogenic activity were identified by bioassay-guided fractionation and gas chromatography-mass spectrometry analysis as methyl linoleate and methyl linolenate. CONCLUSIONS: These results indicate that HFSF and its constituents, methyl linoleate and methyl linolenate, could be used as whitening agents in cosmetics and have potential for treating hyperpigmentation disorders in the clinic.

Insufficient intake of alpha-linolenic fatty acid (18:3n-3) during pregnancy: and associated factors / Ingestão insuficiente de ácido graxo alfa-linolênico (18:3n-3) durante a gestação: e fatores associados

ABSTRACT Objective: To analyze alpha-linolenic fatty acid intake in two cohorts of pregnant women, and to identify factors associated with alpha-linolenic acid intake. Methods: This is a cohort study involving pregnant women with low obstetric risk (N=353) in public health system from a municipality of São Paulo state, Brazil. In each trimester, two 24-hour food recalls were collected. Descriptive analyses of dietary lipid profiles were performed, followed by a multiple comparison test. According to the trimester of pregnancy, differences were assessed using the mean difference test. To evaluate the adequacy of linoleic fatty acid and alpha-linolenic acid intake, the adequate intake test was used. The association between alpha-linolenic acid intake adequacy and maternal characteristics was investigated using a binary logistic regression model. Results: Total lipids intake and the percentage contribution to dietary energy met recommended levels. One-third of the diets demonstrated a lower than daily recommended intake of alpha-linolenic acid. Overweight pregnant women were twice as likely to have inadequate alpha-linolenic acid intake. Pregnant women from a more disadvantaged socioeconomic situation had greater risks of inadequate intake. Conclusion: Over-intake of lipids is not problematic, but quality is an issue, with one third of the pregnant women and their fetuses exposed to adverse effects due to low intake of omega-3 fatty acids, indicating important nutritional vulnerability in this population.

RESUMO Objetivo: Analisar a ingestão ácidos graxos alfa-linolênico e identificar fatores associados à ingestão inadequada em duas coortes de gestantes acompanhadas trimestralmente. Métodos: Estudo de coorte com gestantes de baixo risco obstétrico (N=353) representativas das usuárias da rede pública de saúde de um município paulista. Nos três trimestres gestacionais foram coletados dois recordatórios alimentares de 24 horas. Análises descritivas do perfil lipídico da dieta foram processadas seguidas do teste de comparações múltiplas. As diferenças, segundo trimestre gestacional, foram avaliadas pelo teste de diferença de médias. Para avaliação da adequação do consumo foi utilizada a ingestão recomendável. A associação entre a adequação da ingestão de ácido alfa-linolênico e características maternas foi investigada por meio de modelo de regressão logística binária. Resultados: A contribuição percentual de lipídeos totais mostrou-se adequada;1/3 das gestantes não alcançou a recomendação de ingestão diária de ácido alfa-linolênico. Gestantes com excesso de peso apresentam o dobro de chances de consumo inadequado de ácido alfa-linolênico. Comparadas às gestantes das classes D/E, as pertencentes a classe C têm menores chances de consumo inadequado. Conclusão: Não há um problema de excesso de consumo de lipídeos e sim da qualidade destes, cerca de 1/3 das gestantes acompanhadas e seus conceptos estão expostos aos efeitos adversos do baixo consumo de ácidos graxos de cadeia ômega-3 na gestação, indicando importante vulnerabilidade nutricional nessa população.

Conjugated linoleic acid supplementation does not maximize motor performance and abdominal and trunk fat loss induced by aerobic training in overweight women / Suplementação de ácido linoléico conjugado não maximiza o desempenho motor e a perda de gordura de tronco e abdominal induzida pelo treinamento aeróbio em mulheres com excesso de peso

ABSTRACT Objective: To analyze the effect of eight weeks of conjugated linoleic acid supplementation on physical performance, and trunk and abdominal fat in overweight women submitted to an aerobic training program. Methods: Twenty-eight overweight women (body mass index ³25 kg/m2) were divided randomly and double-blindly to receive conjugated linoleic acid or placebo, both associated with an aerobic exercise program (frequency = three times a week, duration=30 min/session, intensity=80% of maximum heart rate). Conjugated linoleic acid (3.2 g) and placebo (4.0 g) supplements were consumed daily (four capsules) for eight weeks. Maximum speed and time to exhaustion were determined in incremental treadmill test. Trunk fat was estimated by dual-energy X-Ray absorptiometry. Waist circumference was used as indicator of abdominal fat. Results: Main effect of time (p<0.05) showed increased maximum speed (conjugated linoleic acid=+6.3% vs. placebo=+7.5%) and time to exhaustion (conjugated linoleic acid=+7.1% vs. placebo=+8.6%) in the incremental treadmill test, with no differences between the groups (p>0.05). Similarly, significant reductions (p<0.05) in trunk fat (conjugated linoleic acid=-1.7% vs. placebo=-1.5%) and abdominal fat (conjugated linoleic acid=-4.7% vs. placebo=-4.0%) were found after eight weeks of intervention, with no differences between the groups (p>0.05). Conclusion: The results of this study suggest that conjugated linoleic acid supplementation does not maximize motor performance, and loss of body and abdominal fat induced by aerobic training in overweight women.

RESUMO Objetivo: Analisar o efeito de oito semanas de suplementação de ácido linoleico conjugado sobre o desempenho físico, a gordura de tronco e abdominal em mulheres com excesso de peso submetidas a um programa de treinamento aeróbio. Métodos: Vinte e oito mulheres com excesso de peso (índice de massa corporal ³ 25 kg/m2) foram separadas aleatoriamente por meio de um delineamento duplo cego para receber suplementação de ácido linoleico ou placebo associado a um programa de exercícios aeróbios (frequência = três sessões semanais, duração=30 min/sessão, intensidade=80% da frequência cardíaca máxima). A suplementação de ácido linoleico (3,2 g) ou de placebo (4,0 g) foi consumida diariamente (quatro cápsulas), durante oito semanas. As variáveis velocidade máxima atingida e tempo de permanência até a exaustão foram determinadas em teste incremental em esteira. A gordura de tronco foi estimada por absortometria radiológica de dupla energia. A circunferência de cintura foi utilizada como indicador de gordura abdominal. Resultados: Efeito principal do tempo (p<0,05) revelou aumento da velocidade máxima atingida (suplementação de ácido linoleico=+6,3% versus placebo=+7,5%) e tempo de duração até a exaustão (suplementação de ácido linoleico=+7,1% versus placebo=+8,6%) em teste incremental em esteira, sem diferenças entre os grupos (p>0,05). De forma similar, uma redução significante (p<0,05) na gordura relativa de tronco (suplementação de ácido linoleico=-1,7% versus placebo=-1,5%) e na gordura abdominal (suplementação de ácido linoleico=-4,7% versus placebo=-4,0%) foi encontrada após oito semanas de intervenção, sem diferenças entre os grupos (p>0,05). Conclusão: Os resultados do presente estudo sugerem que a suplementação de ácido linoleico não maximiza o desempenho motor e a redução da gordura de tronco e abdominal induzida pelo treinamento aeróbio em mulheres com excesso de peso.

Efecto del extracto de maíz morado sobre la expresión génica de srebp-1, A5d y A6d en glándula mamaria de ratas nodrizas suplementadas con aceite de chía (Salvia Hispánica L) / Effect of purple corn extract on gene expression of srebp-1, A5d y A6d in mammary gland of nursing rats supplemented with chia oil (Salvia Hispánica L)

The effect of the dietary intake of purple-corn extract (EMM) as a source of anthocyanins and the oral supplementation of chia oil (CH), rich in α-linolenic acid on the lipid metabolism of the mammary glands were evaluated by gene expression SREBP-1, Δ6D Δ5D in 36 nursing rats distributed in olive oil (OL), chia oil (CH), olive oil - EMM (EMM OL +) or chia oil - EMM (CH + EMM) treatments. Gene expression of SREBP-1 was similar in OL and CH, increasing in presence of EMM; suggesting that under this conditions, CH and OL oils have similar effect on SREBP-1, while anthocyanins upregulate the gene expression. ALA inhibited the expression of desaturases, and the anthocyanins imaaproved Δ5D expression at control levels similar or higher in the case of Δ6D.

Se evaluó el efecto dietario de un extracto de maíz morado (EMM) como fuente de antocianinas y la suplementación oral de aceite de chía (CH), rico en ácido α-linolénico sobre la expresión génica de SREBP-1, Δ5D y Δ6D en en glándula mamaria de 36 ratas nodrizas distribuidas en cuatro tratamientos: aceites de oliva (OL), CH, OL + EMM o CH + EMM. La expresión de SREBP-1 fue similar en OL y CH, incrementándose en presencia de EMM. La expresión de Δ5D y Δ6D fue mayor en OL que en CH, donde incrementó en presencia de EMM, sugiriendo que bajo estas condiciones los aceites CH y OL tienen efectos similares sobre la expresión de SREBP-1 mientras las antocianinas regulan al alza dicha expresión. ALA inhibió la expresión de las desaturasas y la presencia de antocianinas aumentó la de Δ5D a niveles similares al control, o superiores en el caso de Δ6D.

Diet high in alpha-linolenic acid up-regulate PPAR-gamma gene expression in the liver of goats

Background There is little information on the effects of diets containing high α-linolenic acid (C18:3n-3) on liver lipid composition and lipogenic gene expressions. In this study fourteen goats (Capra aegagrus hircus) were fed either a flaxseed oil (FSO) supplemented diet containing high α-linolenic acid or a control diet without added flaxseed oil (CON) for 100-d to evaluate the effects on liver lipid composition and the gene expression of peroxisome proliferator-activated receptors (PPAR-α) and stearoyl-CoA-desaturase (SCD) in the liver. Results An increase in the levels of C18:3n-3 and C20:5n-3, C22:5n-3, C22:6n-3 was observed in the liver of FSO-treated goats. There was a significant (P < 0.05) up-regulation of PPAR-α gene expression and downregulation of SCD gene in the liver of goats fed the high α-linolenic acid diet. Conclusions In conclusion, genes associated with the control of fatty acid (FA) conversion (SCD and PPAR) were affected by the α-linolenic acid supplementation in the goat diet. It is suggested that PPAR-α is the key messenger responsible for the translation of nutritional stimuli into changes in hepatic gene expression.

Low Plasma Proportion of Omega 3-Polyunsaturated Fatty Acids Predicts Poor Outcome in Acute Non-Cardiogenic Ischemic Stroke Patients / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Alterations in blood fatty acid (FA) composition are associated with cardiovascular diseases. We investigated whether plasma FA composition was related to stroke severity and functional outcome in acute ischemic stroke patients. METHODS: We prospectively enrolled 156 patients with first-episode cerebral infarction, within 7 days of symptom onset. The proportion of FAs was analyzed using gas chromatography, and the summation of the omega-3 polyunsaturated fatty acids (omega3-PUFA), 18:3 omega3 alpha-linolenic acid, 20:3 omega3 eicosatrienoic acid, 20:5 omega3 eicosapentaenoic acid (EPA), and 22:6 omega3 docosahexaenoic acid (DHA) was reported as Sigmaomega3-PUFAs. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score on admission. Poor functional outcome was defined by modified Rankin scale (mRS) > or =3 at three months after the index stroke. RESULTS: Lower proportions of EPA (beta=-0.751), DHA (beta=-0.610), and Sigmaomega3-PUFAs (beta=-0.462) were independently associated with higher NIHSS score, after adjusting for stroke subtype, hemoglobin, high density lipoprotein, high sensitivity C-reactive protein, fasting glucose, 16:0 palmitic acid, and Sigmasaturated fatty acids. Moreover, a lower proportion of DHA (odds ratio [OR]: 0.20, 95% confidence interval [CI]: 0.04-0.88), and Sigmaomega3-PUFAs (OR: 0.22, 95% CI: 0.05-0.84) showed an independent relationship with poor functional outcome after adjusting for age, sex, smoking status, NIHSS score, stroke subtype, and 16:0 palmitic acid. CONCLUSIONS: Our results demonstrate that omega3-PUFAs correlated with stroke severity on admission and functional outcomes at 3 months. omega3-PUFAs are potential blood biomarkers for prognosis of acute non-cardiogenic ischemic stroke patients.

Modulatory effects of α- linolenic acid on generation of reactive oxygen species in elaidic acid enriched peritoneal macrophages in rats.

Fatty acids are known to influence the ability of macrophages to generate reactive oxygen species (ROS). However the effect of elaidic acid (EA, 18:1 trans fatty acid) on ROS generation is not well studied. Rat peritoneal macrophages were enriched with elaidic acid by incubating the cells with 80 µM EA. The macrophages containing EA generated higher amounts of superoxide anion (O2·-), hydrogen peroxide (H2O2) and nitric oxide (NO˙) by 54, 123 and 237%, respectively as compared to control cells which did not contain EA. To study the competition of other C18 fatty acids with EA macrophages were incubated with EA along with stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2) and α- linolenic acid (ALA, 18:3). ALA significantly reduced the incorporation of EA into macrophage lipids. This also significantly reduced the generation of O2· -, H2O2, NO˙ by macrophages. Studies were also conducted by feeding rats with diet containing partially hydrogenated vegetable fat (PHVF) as a source for EA and linseed oil (LSO) as a source for ALA. The rats were fed AIN-93 diet containing PHVF with 17% EA and incremental amounts of linseed oil for 10 weeks. The peritoneal macrophages from rats fed partially hydrogenated vegetable fat generated higher levels of O2·-, H2O2, NO˙ by 46, 161 and 76% respectively, when compared to rats fed control diets containing ground nut oil. Macrophages from rats fed PHVF with incremental amounts of LSO produced significantly lower levels ROS in a dose dependent manner. Thus ALA reduces the higher levels of ROS generated by macrophages containing EA.

Premenstrual syndrome: clinical assessment of treatment outcomes following Borago officinalis extract therapy / Síndrome da tensão pré-menstrual: avaliação clínica dos resultados de tratamento após terapia com extrato de Borago officinalis

With the objective of evaluating the use of Borago officinalis oil in the treatment of premenstrual syndrome (PMS) symptoms, we assessed 180 patients who presented a clinical diagnosis of PMS and who were treated with one daily 900mg borage oil capsule. Efficacy and safety assessments were performed based on data obtained prior to the start of treatment (Pretreatment), and after each menstrual cycle (Assessment 2 - first menstrual cycle after the start of treatment; Assessment 3 - second menstrual cycle; Assessment 4/Final Assessment - third menstrual cycle). Efficacy assessments included a PMS questionnaire evaluating emotional and physical PMS symptoms and the Patient and Physician Assessments, in which both the subject and the physician rated the patient's overall condition on a scale of 1-10 points. The primary safety and tolerability measures included any changes in vital signs and physical exam in relation to pretreatment, changes in laboratory exams, and the occurrence of adverse events after the first dose of study medication. We observed a statistically significant reduction in the total scores of the PMS assessment (p<0.0001), with 95.4% of all patients displaying some reduction in scores at Assessment 4 in relation to Pretreatment values. The emotional symptoms and physical symptoms scores also decreased significantly from Pretreatment to Assessment 4 (p<0.0001 for both)...

The Stimulatory Effect of Essential Fatty Acids on Glucose Uptake Involves Both Akt and AMPK Activation in C2C12 Skeletal Muscle Cells

Essential fatty acid (EFA) is known to be required for the body to function normally and healthily. However, the effect of EFA on glucose uptake in skeletal muscle has not yet been fully investigated. In this study, we examined the effect of two EFAs, linoleic acid (LA) and alpha-linolenic acid (ALA), on glucose uptake of C2C12 skeletal muscle cells and investigated the mechanism underlying the stimulatory effect of polyunsaturated EFAs in comparison with monounsaturated oleic acid (OA). In palmitic acid (PA)-induced insulin resistant cells, the co-treatment of EFAs and OA with PA almost restored the PA-induced decrease in the basal and insulin-stimulated 2-NBDG (fluorescent D-glucose analogue) uptake, respectively. Two EFAs and OA significantly protected PA-induced suppression of insulin signaling, respectively, which was confirmed by the increased levels of Akt phosphorylation and serine/threonine kinases (PKCtheta and JNK) dephosphorylation in the western blot analysis. In PA-untreated, control cells, the treatment of 500 microM EFA significantly stimulated 2-NBDG uptake, whereas OA did not. Phosphorylation of AMP-activated protein kinase (AMPK) and one of its downstream molecules, acetyl-CoA carboxylase (ACC) was markedly induced by EFA, but not OA. In addition, EFA-stimulated 2-NBDG uptake was significantly inhibited by the pre-treatment of a specific AMPK inhibitor, adenine 9-beta-D-arabinofuranoside (araA). These data suggest that the restoration of suppressed insulin signaling at PA-induced insulin resistant condition and AMPK activation are involved at least in the stimulatory effect of EFA on glucose uptake in C2C12 skeletal muscle cells.

Effects of C18 Fatty Acids on Intracellular Ca2+ Mobilization and Histamine Release in RBL-2H3 Cells

To investigate the underlying mechanisms of C18 fatty acids (stearic acid, oleic acid, linoleic acid and alpha-linolenic acid) on mast cells, we measured the effect of C18 fatty acids on intracellular Ca2+ mobilization and histamine release in RBL-2H3 mast cells. Stearic acid rapidly increased initial peak of intracellular Ca2+ mobilization, whereas linoleic acid and alpha-linolenic acid gradually increased this mobilization. In the absence of extracellular Ca2+, stearic acid (100 microM) did not cause any increase of intracellular Ca2+ mobilization. Both linoleic acid and alpha-linolenic acid increased intracellular Ca2+ mobilization, but the increase was smaller than that in the presence of extracellular Ca2+. These results suggest that C18 fatty acid-induced intracellular Ca2+ mobilization is mainly dependent on extracellular Ca2+ influx. Verapamil dose-dependently inhibited stearic acid-induced intracellular Ca2+ mobilization, but did not affect both linoleic acid and alpha-linolenic acid-induced intracellular Ca2+ mobilization. These data suggest that the underlying mechanism of stearic acid, linoleic acid and alpha-linolenic acid on intracellular Ca2+ mobilization may differ. Linoleic acid and alpha-linolenic acid significantly increased histamine release. Linoleic acid (C18:2: omega-6)-induced intracellular Ca2+ mobilization and histamine release were more prominent than alpha-linolenic acid (C18:3: omega-3). These data support the view that the intake of more alpha-linolenic acid than linoleic acid is useful in preventing inflammation.

Fatty acid analysis and regulatory effects of citron (Citrus junos Sieb. ex TANAKA) seed oil on nitric oxide production, lipid accumulation, and leptin secretion / 한국영양학회지

PURPOSE: Citron seed oil (CSO) has been reported to have high antioxidant activity. However, the composition and other biologically activities of CSO have not been reported. In this study, we confirmed the fatty acid composition of CSO, which may be beneficial to vascular disease and obesity. METHODS: We investigated the oil composition of CSO using gas chromatography coupled with mass spectrometry (GC-MS) analysis, and cytotoxicity was confirmed by Cell Counting Kit-8 (CCK-8) assay. Nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) was measured using Griess reagent, and lipid accumulation and leptin secretion in 3T3-L1 cells were measured by Oil-Red O staining and commercial ELISA kit, respectively. RESULTS: GC-MS analysis indicated that CSO contains several components, including linoleic acid, oleic acid, palmitic acid, stearic acid, linolenic acid, palmitoleic acid, and arachidic acid. In physiological activity analysis, CSO did not induce cytotoxic effects in HUVECs and 3T3-L1 cells. Further, CSO significantly induced nitric oxide and leptin secretion as well as inhibited lipid accumulation. CONCLUSION: CSO increased NO release, inhibited lipid accumulation, and induced leptin secretion, suggesting it may be useful for the management of vessels and weight gain. Although further studies are required to investigate the safety and mechanism of action of CSO, our results show that the composition and physiological activity of CSO are sufficient for its use as functional edible oil.

Protective effect of eicosapentaenoic acid-docosahexaenoic acid and α–linolenic acid rich phytosterol ester on brain antioxidant status and brain lipid composition in hypercholesterolemic rats.

With a view to investigate the ameliorative effects of sitosterol esters against degenerative effects of hypercholesterolemia brain antioxidant enzyme assays, brain lipid profile, brain phospholipid compositional change and brain neurotransmitter concentrates (glutamic acid, asparctic acid, glycine) were measured in hypercholesterolemic rats. The results indicated that phytosterol esters have a role in countering hypercholesterolemia-related changes in the brain by decreasing the cholesterol levels, increasing the phospholipid levels and increasing the level of antioxidant enzymes. The results suggest that phytosterol esters may be of therapeutic significance and may offer new and effective options for the treatment of hypercholesterolemia-induced changes in the brain.

Direct Analysis in Real Time Mass Spectrometry (DART-MS) Analysis of Skin Metabolome Changes in the Ultraviolet B-Induced Mice

Ultraviolet (UV) radiation is a major environmental factor that leads to acute and chronic reactions in the human skin. UV exposure induces wrinkle formation, DNA damage, and generation of reactive oxygen species (ROS). Most mechanistic studies of skin physiology and pharmacology related with UV-irradiated skin have focused on proteins and their related gene expression or single- targeted small molecules. The present study identified and analyzed the alteration of skin metabolites following UVB irradiation and topical retinyl palmitate (RP, 5%) treatment in hairless mice using direct analysis in real time (DART) time-of-flight mass spectrometry (TOF-MS) with multivariate analysis. Under the negative ion mode, the DART ion source successfully ionized various fatty acids including palmitoleic and linolenic acid. From DART-TOF-MS fingerprints measured in positive mode, the prominent dehydrated ion peak (m/z: 369, M+H-H2O) of cholesterol was characterized in all three groups. In positive mode, the discrimination among three groups was much clearer than that in negative mode by using multivariate analysis of orthogonal partial-least squares-discriminant analysis (OPLS-DA). DART-TOF-MS can ionize various small organic molecules in living tissues and is an efficient alternative analytical tool for acquiring full chemical fingerprints from living tissues without requiring sample preparation. DART-MS measurement of skin tissue with multivariate analysis proved to be a powerful method to discriminate between experimental groups and to find biomarkers for various experiment models in skin dermatological research.

Effects of perilla oil on plasma concentrations of cardioprotective (n-3) fatty acids and lipid profiles in mice

The aim of this study was to examine the effects of perilla oil as well as several vegetable oils, including flaxseed oil, canola oil, and rice bran oil on plasma levels of cardioprotective (n-3) polyunsaturated fatty acids in mice by feeding each vegetable oil for a period of eight weeks. Concentrations of docosapentaenoic acid (DHA) and eicosapentaenoic acid (EPA), fish-based (n-3) polyunsaturated fatty acids, showed an increase in the plasma of mice fed perilla and flaxseed oils compared to those of mice in the control group (P < 0.05), whereas rice bran and canola oils did not alter plasma DPA and EPA concentrations. Arachidonic acid concentration was increased by feeding rice bran oil (P < 0.05), but not canola, flaxseed, or perilla oil. In addition, oleic acid, linoleic acid, and docosahexaenoic acid concentrations were altered by feeding dietary rice bran, canola, perilla, and flaxseed oils. Findings of this study showed that perilla oil, similar to flaxseed oil, is cardioprotective and could be used as an alternative to fish oil or even flaxseed oil in animal models.