Ursolic acid increases strength in mdx mice model and may decrease fibrosis deposition by tgf-ß downregulation / El ácido ursólico aumenta la resistencia en el modelo de ratones mdx y podría disminuir la deposición de fibrosis mediante la regulación decreciente de tgf-ß

SUMMARY: Dystrophin disfunction results in sarcolemma destabilization, leading muscle cell damage by continuous degeneration cycles and limited regeneration. In muscle dystrophy, caused by dystrophin dysfunction, inflammation, necrosis and fibrosis are pathophysiological muscle function loss characteristics. As a genetic disease, this muscle dystrophy has no cure, however, advances in drug therapy using glucocorticoids can decrease the disease progression. Subsequently, alternative therapies were studied, such as ursolic acid (UA), that inhibits muscle atrophy and increases muscle mass and strength. Herein, we used 10 mg/kg daily supplementation in mdx mice for 4 weeks to evaluate serum creatine phosphokinase (CPK), muscle strength (Kondziela test), muscular organization (histology) and expression of fibrosis related genes (TGF-ß, TNF-α, mstn and ostn). UA supplementation increased muscle morphological organization, motor strength and decreased muscular TGF-ß expression. Altogether, the gene expression profile, histological organization and strength could suggest that UA treatment did not stop the fibrogenesis but decreased its progress.

RESUMEN: La disfunción de la distrofina resulta en la desestabilización del sarcolema, llevando al daño de las células musculares por ciclos continuos de degeneración y regeneración limitada. En la distrofia muscular, debido a la disfunción de la distrofina, la inflamación, la necrosis y la fibrosis, son características fisiopatológicas de la pérdida de la función muscular. Como enfermedad genetica no es possible remediar esta distrofia muscular, sin embargo, los avances en la terapia de medicamentos con glucocorticoides pueden disminuir la progresión de la enfermedad. Se estudiaron terapias alternativas, como el ácido ursólico (UA), que inhibe la atrofia muscular y aumenta la masa y la fuerza muscular. En este estudio, utilizamos una suplementación diaria de 10 mg / kg en ratones mdx durante 4 semanas para evaluar la creatina fosfoquinasa (CPK) sérica, la fuerza muscular (prueba de Kondziela), la organización muscular (histología) y la expresión de genes relacionados con la fibrosis (TGF-ß, TNF- α, mstn y ostn). La suplementación con AU aumentó la organización morfológica muscular, la fuerza motora y la disminución de la expresión muscular de TGF-ß. El perfil de expresión génica, la organización histológica y la fuerza simultáneamente podrían sugerir que el tratamiento con AU no detuvo la fibrogénesis sino que disminuyó su progreso.

α, ß-Amyrin prevents steatosis and insulin resistance in a high-fat diet-induced mouse model of NAFLD via the AMPK-mTORC1-SREBP1 signaling mechanism

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,β-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.

Chikusetsu saponin Ⅳa ameliorates myocardial hypertrophy of rats through regulating expression of miR199a-5p/Atg5 / 中国中药杂志

The present study investigated the effects of chikusetsu saponin Ⅳa(CHS Ⅳa) on isoproterenol(ISO)-induced myocardial hypertrophy in rats and explored the underlying molecular mechanism. ISO was applied to establish a rat model of myocardial hypertrophy, and CHS Ⅳa(5 and 15 mg·kg~(-1)·d~(-1)) was used for intervention. The tail artery blood pressure was measured. Cardiac ultrasound examination was performed. The ratio of heart weight to body weight(HW/BW) was calculated. Morphological changes in the myocardial tissue were observed by HE staining. Collagen deposition in the myocardial tissue was observed by Masson staining. The mRNA expression of myocardial hypertrophy indicators(ANP and BNP), autophagy-related genes(Atg5, P62 and beclin1), and miR199 a-5 p was detected by qRT-PCR. Atg5 protein expression was detected by Western blot. The results showed that the model group exhibited increased tail artery blood pressure and HW/BW ratio, thickened left ventricular myocardium, enlarged myocardial cells, disordered myocardial fibers with widened interstitium, and a large amount of collagen aggregating around the extracellular matrix and blood vessels. ANP and BNP were largely expressed. Moreover, P62 expression was up-regulated, while beclin1 expression was down-regulated. After intervention by CHS Ⅳa at different doses, myocardial hypertrophy was ameliorated and autophagy activity in the myocardial tissue was enhanced. Meanwhile, miR199 a-5 p expression declined and Atg5 expression increased. As predicted by bioinformatics, Atg5 was a target gene of miR199 a-5 p. CHS Ⅳa was capable of preventing myocardial hypertrophy by regulating autophagy of myocardial cells through the miR-199 a-5 p/Atg5 signaling pathway.

Alpha-hederin induces the apoptosis of oral cancer SCC-25 cells by regulating PI3K/Akt/mTOR signaling pathway

BACKGROUND: Oral cancer is one of the common malignant tumors of the head and neck. However, current treatments have numerous side effects, and drugs from natural sources may have better therapeutic potential. This research investigated the induction of apoptosis by α-hederin (α-HN), a constituent of Pulsatilla chinensis (Bunge) Regel, in the oral cancer cell line SCC-25 and its underlying mechanism. RESULTS: SCC-25 cells were treated with 50, 100, and 200 µmol/L α-HN. Cell proliferation; extent of apoptosis; activities of caspases-3, 8, and 9; and the expression of Bcl-2, Bax, phosphorylated (p)-phosphoinositide 3-kinase (PI3K), p-Akt, and p-mammalian target of rapamycin (mTOR) proteins were determined using the 3-(4,5)-2-thiazole-(2,5)-diphenyl tetrazolium bromide, flow cytometry, caspase activity detection kits, and western blot assays, respectively. The results showed that the proliferation of SCC-25 cells in the α-HN-treated groups decreased significantly, and the inhibitory effect was time and concentration dependent. Compared with cells in the control group, the extent of apoptosis increased significantly, caspase-3 and -9 activities were significantly enhanced, and the Bcl-2 level was lowered and the Bax level was elevated significantly in SCC-25 cells treated with α-HN for 48 h (P b 0.05). The expression of p-PI3K, p-Akt, and p-mTOR was also significantly lower in SCC-25 cells treated with α-HN than that in the control group (P b 0.05). CONCLUSION: These results indicate that α-HN can inhibit proliferation and induce apoptosis of SCC-25 cells and may exert these effects by inhibiting the PI3K/Akt/mTOR signaling pathway.

Intervenção nas situações de crise psíquica: dificuldades e sugestões de uma equipe de atenção pré-hospitalar / Intervention in situations of psychic crisis: challenges and suggestions of a prehospital care staff / Intervención en situaciones de crisis psíquica: problemas y sugerencias de un equipo de atención prehospitalaria

Pesquisa descritiva, qualitativa, que objetivou conhecer como os profissionais de atenção pré-hospitalar percebem as intervenções nas pessoas em crise psíquica. O estudo foi realizado, no estado de Santa Catarina, com quatro equipes das Unidades de Suporte Básico do Serviço de Atendimento Móvel de Urgência, mediante entrevista, no período de abril a junho de 2011. Utilizou-se como método de análise o Discurso do Sujeito Coletivo. Dos resultados emergiram dois temas: Percepção das dificuldades no atendimento à pessoa em crise psíquica e Sugestões na busca por um atendimento mais próximo do desejado à pessoa em crise psíquica. As dificuldades apontadas se relacionam à falta de capacitação e de um local para encaminhamento e sugerem treinamento e sistematização do atendimento. Conclui-se que se faz necessário investir em processo de formação pautado em novas estratégias de cuidado norteadas pelos princípios do SUS e no paradigma psicossocial, além de rediscutir a estratégia de protocolos como sistemas norteadores e não padronizadores.

A qualitative and descriptive research, aimed at knowing how the pre-hospital care professionals perceive the interventions towards people in mental crisis. The study was developed in Santa Catarina with four teams of basic life support units of the Department of Mobile Emergency Care, during April to June 2011. The Collective Subject Discourse was used as the method of analysis. Two themes emerged: Awareness of the difficulties in meeting a person in mental crisis and Suggestions in the search for a closer attention to the person in mental crisis. The difficulties mentioned were related to the lack of training and a local to forward the patients, suggesting a better training and systematization of care. We conclude that it is necessary to invest in the educational process, based on new care strategies guided by the principles of SUS and of the psychosocial paradigm, and revisit the strategy of protocols as guidelines and not as standardizing systems.

Investigación descriptivo-cualitativa, que objetivó conocer como los profesionales de la atención pre-hospitalaria perciben las intervenciones en personas con crisis mental. El estudió fue realizado en Santa Catarina con cuatro equipos de las Unidades de Soporte Vital Básico, mediante entrevista realizada de abril a junio de 2011. El Discurso del Sujeto Colectivo fue utilizado como método de análisis; surgiendo dos temas: Percepción de las dificultades en la atención a la persona en crisis mental y Sugerencias en la búsqueda de una mejor atención a la persona en crisis mental. Las dificultades mencionadas se relacionan con la falta de capacitación y lugar para la atención, sugiriendo un mejor entrenamiento y sistematización de la atención. Se resalta la necesidad de invertir en el proceso de formación basado en nuevas estrategias de atención guiadas por los principios del SUS y el paradigma psicosocial, y revisar la estrategia de protocolos como nortes no estandarizados.

Compositional studies and Biological activities of Perovskia abrotanoides Kar. oils

BACKGROUND: Current study has been designed to evaluate the chemical composition of essential and fixed oils from stem and leaves of Perovskia abrotanoides and antioxidant and antimicrobial activities of these oils. RESULTS: GC-MS analysis of essential oil identified 19 compounds with (E)-9-dodecenal being the major component in stem and hexadecanoic acid in leaves. In contrast, GC-MS analysis of fixed oil showed 40 constituents with α-amyrin the major component in stem and α-copaene in leaves. The antioxidant activity showed the highest value of 76.7% in essential oil from leaves in comparison with fixed oil from stem (45.9%) through inhibition of peroxidation in linoleic acid system. The antimicrobial assay tested on different microorganisms (e.g. E. coli, S. aureus, B. cereus, Nitrospira, S. epidermis, A. niger, A. flavus and C. albicans) showed the higher inhibition zone at essential oil from leaves (15.2 mm on B. cereus) as compared to fixed oil from stem (8.34 mm onS. aureus) and leaves (11.2 mm on S. aureus). CONCLUSIONS: The present study revealed the fact that essential oil analyzed from Perovskia abrotanoides stem and leaves could be a promising source of natural products with potential antioxidant and antimicrobial activities, as compared to fixed oil.

Pesticidal and pest repellency activities of a plant derived triterpenoid 2α, 3ß, 21ß, 23, 28-penta hydroxyl 12-oleanene against Tribolium castaneum

BACKGROUND: Tribolium castaneum (Herbst) is a major pest of stored grain-based products, and cause severe damage to cereal grains throughout the world. The present investigation was aimed to determine the pesticidal and pest repellent activities of 2α,3ß,21ß,23,28-penta hydroxyl 12-oleanene against T. castaneum. The compound 2α,3ß,21ß,23,28-penta hydroxyl 12-oleanene is a triterpenoid which was isolated from the roots of Laportea crenulata Gaud. Surface film technique was used for pesticidal screening, whereas, pest repellency property of the triterpenoid was determined by filter paper disc method. RESULTS: At 24 hours of exposure duration, significant mortality records (80% and 86%) were observed at doses 0.88 and 1.77 mg/cm². No significant change in mortality records was observed when duration of exposure was increased up to 48 hours. The triterpenoid showed significant repellency activity at doses 0.47 and 0.94 mg/cm². CONCLUSION: These data suggest that the triterpenoid 2α,3ß,21ß,23,28-penta hydroxyl 12-oleanene possess both pesticidal and pest repellency activities against T. castaneum and can be used in controlling the pest of grain-based products.

Effect of bioactive compounds extracted from euphorbious plants on hematological and biochemical parameters of Channa punctatus / Efeito de compostos bioativos extraídos de plantas eufórbicas sobre os parâmetros hematológicos e bioquímicos da Channa punctatus

Channa punctatus was exposed to four different concentrations of Rutin, Taraxerol and Apigenin. Changes in some hematological parameters of Channa punctatus were assessed to determine the influence of these compounds on test fish. Fish were exposed to sublethal concentrations (80 percent of LC50 of 24h) of these compounds for one week. Control fish were also administered for one week. Thereafter, blood samples were obtained from the control and experimental fish. Blood was assayed for selected hematological parameters (hematocrit, hemoglobin, red blood cell count, white blood cell count total plasma protein and plasma glucose concentration). The derived hematological indices of mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) were calculated. Sublethal concentrations of these compounds caused a dose dependent decrease in hemoglobin values coupled with a decrease in hematocrit values and red blood cell counts are an obvious indication of anemia. The total white blood cell counts and the differential white blood cell counts were decreased except for the lymphocytes, where there was a slight increase. Plasma protein and glucose were also lower in exposed fish when compared with control. The hematological indices MCH, MCHC, MCV were also lowered. The result from this study reveals high mortality rate and deleterious consequences on the health of fish subjected to acute exposure of Rutin, Taraxerol and Apigenin and therefore, should not be used directly in aquaculture without having the proper knowledge.

Channa punctatus foi exposta a quatro diferentes concentrações de Rutina, Taraxerol e Apigenina. Alterações de alguns parâmetros hematológicos da Channa punctatus foram acessados para determinar a influência destes compostos no peixe teste. Peixes foram expostos a concentrações sub-letais (80 por cento 0f LC50 em 24h) destes compostos por uma semana. Os peixes controles foram também expostos durante uma semana. A seguir, amostras de sangue foram obtidas do peixe controle e do experimental. O sangue foi estudado por parâmetros hematológicos selecionados (hematócrito, hemoglobina, contagem de células vermelhas e brancas, proteína plasmática total e concentração de glucose plasmática). Os índices hematológicos derivados da média da concentração corpuscular da hemoglobina (MCHC), a média de hemoglobina corpuscular (MCH) e a média de volume corpuscular (MCV), foram calculados. Concentrações sub-letais destes compostos causaram decréscimo dose-dependente dos valores da hemoglobina unidos a decréscimo de valores de hematócrito e das contagens de células sanguíneas vermelhas o que caracteriza indicação óbvia de anemia. As contagens totais de células brancas e a contagem diferencial destas células estavam diminuídas exceto pelos linfócitos que mostraram leve aumento. A proteína plasmática e a glicose estavam também baixas nos peixes expostos quando comparados com o controle. Os índices hematológicos MCH, MCHC, MCV estavam também diminuídos. Os resultados deste estudo revelam alto percentual de mortalidade e conseqüências deletérias à saúde de peixes submetidos à exposição aguda de Rutina, Talaxerol e Apigenina e portanto eles não devem ser usados diretamente em aquacultura sem conhecimento apropriado.

Impact of Taraxerol in combination with extract of Euphorbia tirucalli plant on biological parameters of Lymnaea acuminata / Impacto do Taraxerol em combinação com o extrato da planta de Euphorbia tirucalli nos parâmetros biológicos da Lymnaea acuminata

The present work was carried out to evaluate the molluscicidal activity of active ingredient Taraxerol with the acetone extract of Euphorbia tirucalli against Lymnaea acuminata snail. The (fecundity, hatchability and survivability) of snail L. acuminata exposed to this extract was studied. The effects of the tested extracts on life-history traits of harmful snail L. acuminata have also been evaluated, and this study also expounds the inhibitory effects of these extracts singly as well as in binary combination (1:1 ratio). It concluded that these herbal products act as a potential source of molluscicides, and that they would also have the advantage of easy availability, low cost, biodegradability and greater acceptance amongst users than synthetic pesticide.

O presente trabalho foi levado a efeito para avaliar a atividade moluscicida do ingrediente ativo Taraxerol junto com o extrato de acetona da Euphorbia tirucalli contra o caramujo Lymnaea acuminata. Foram estudados a fecundidade, o desenvolvimento e sobrevivência do caramujo Lymnaea acuminata exposto a estes extratos. Os efeitos danosos destes extratos testados na vida do caramujo L. acuminata foram também avaliados e este estudo demonstra os efeitos inibidores destes extratos isolados ou em combinação binária (relação l:1). Concluiu-se que estes produtos vegetais agem como fontes potenciais de moluscicidas e que eles também têm a vantagem de obtenção fácil, baixo custo, biodegradabilidade e maior aceitação entre os usuários do que os pesticidas sintéticos.

Protective effect of total aralosides of Aralia elata (Miq) Seem (TASAES) against diabetic cardiomyopathy in rats during the early stage, and possible mechanisms

Total aralosides of Aralia elata (Miq) Seem (TASAES) from Chinese traditional herb Longya Aralia chinensis L was found to improve cardiac function. The present study was to determine the protective effects of TASAES on diabetic cardiomyopathy, and the possible mechanisms. Therefore, a single dose of streptozotocin was used to induce diabetes in Wister rats. Diabetic rats were immediately treated with low, medium and high doses of TASAES at 4.9, 9.8 mg/kg and 19.6 mg/kg body weight by gavage, respectively, for eight weeks. Cardiac function was evaluated by in situ hemodynamic measurements, and patch clamp for the L-type Ca2+ channel current (ICa2+-L) and transient outward K+ channel current (Ito). Histopathological changes were observed under light and electron microscope. The expression of pro-fibrotic factor, connective tissue growth factor (CTGF) was monitored using immunohistochemistry staining. Compared with diabetic group, medium and high doses, but not low dose, of TASAES showed a significant protection against diabetes-induced cardiac dysfunction, shown by increased absolute value of left ventricular systolic pressure (LVSP) and maximum rates of pressure development (+/-dp/dt(max)), and enhanced amplitude of ICa2+-L (P < 0.05). Histological staining indicated a significant inhibition of diabetes-caused pathological changes and up-regulation of CTGF expression (P < 0.05). The results suggest that TASAES prevents diabetes-induced cardiac dysfunction and pathological damage through up-regulating ICa2+-L in cardiac cells and decreasing CTGF expression.

Studies on the chemical constituents of the roots of Rhododendron molle G. Don / 华中科技大学学报（医学）（英德文版）

The compounds from the root of Rhododendron molle G. Don were isolated, purified by various chromatographic techniques, and their structures were identified according to the physical and chemical features and spectral data. Three compounds were separated from the root of Rhododendron molle G. Don and identified as Rhodojaponin-III, taraxerol, beta-sitosterol for the first time.

A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure.

The efficacy of the interferon stimulator named Stronger Neo Minophagen-C (SNMC) derived form the plant G. glabra was studied at a dose of 40 or 100 ml daily for 30 days followed by thrice weekly intravenously for 8 wk in 18 patients of subacute hepatic failure due to viral hepatitis. The survival rate amongst these patients was 72.2 per cent, as compared to the earlier reported rate of 31.1 per cent in 98 patients who received supportive therapy (P < 0.01). Death in four of the five patients was due to associated infections leading to hepatorenal failure and terminal coma. Further studies are necessary to standardize the dose and duration of therapy with SNMC in subacute hepatic failure.