Pharmacological activity of the hydroalcoholic extract from Hovenia dulcis thunberg fruit and the flavonoid dihydromyricetin during hypercholesterolemia induced in rats

No Brasil, o acidente vascular cerebral e a doença arterial coronariana constituem as principais causas de mortalidade cardiovascular, sendo os altos níveis de colesterol LDL um dos principais fatores de risco. Nesse contexto, diversos extratos vegetais e substâncias naturais isoladas têm se mostrado promissoras como hipocolesterolemiantes. O objetivo do trabalho foi avaliar o potencial do extrato hidroalcoólico dos frutos de Hovenia dulcis e do flavonóide diidromiricetina na redução do colesterol em ratos hipercolesterolêmicos. Quarenta e dois ratos Wistar machos, foram distribuídos em 7 grupos de 6 animais, que receberam dieta suplementada com 1% de colesterol e 0,3% de ácido cólico, à exceção do grupo controle, que recebeu ração convencional. Posteriormente, os animais foram tratados com suspensões orais contendo: atorvastatina 1,0 mg/kg; extrato de H. dulcis de 50,0 e 100,0 mg/kg; diidromiricetina de 25,0 e 50,0 mg/kg e veículo (grupo controle). Avaliaram-se os parâmetros bioquímicos: colesterol total, HDL-C, LDL-C, triglicérides, AST, ALT e fosfatase alcalina. A dieta hipercolesterolêmica foi efetiva na indução da hipercolesterolemia, aumentando o colesterol total em 112,7% em relação ao controle. Os tratamentos com as duas doses do extrato mostraram-se promissores como agentes hipocolesterolemiantes, já que foram capazes de reduzir substancialmente o colesterol total e LDL-C, sem alterar significativamente triglicérides, as transaminases hepáticas e a fosfatase alcalina, incentivando, assim, a continuidade de estudos com a planta H. dulcis. Já os grupos tratados com o flavonóide diidromiricetina, apesar de apresentarem redução significativa do colesterol total e de LDL-C, apresentaram elevações nos triglicérides e nos parâmetros hepáticos, resultado indesejável no âmbito das hipercolesterolemias.Cerebrovascular accidents and coronary artery disease are the leading causes of cardiovascular mortalities in Brazil and high levels of LDL cholesterol are one of the main risk factors. In this context, several plant extracts and natural substances have shown promise as cholesterol-lowering. The objective of this study was to evaluate the potential of the hydroalcoholic extract of the fruit of H. dulcis and of dihydromyricetin in cholesterol reduction in hypercholesterolemic rats. Forty-two Wistar male rats were distributed into seven groups of six animals that received diets supplemented with 1% cholesterol and 0.3% cholic acid, with the exception of the control group, which received conventional diets. Animals were treated with oral suspensions containing: atorvastatin 1.0 mg/kg; H. dulcis extract at 50.0 and 100.0 mg/kg and dihydromyricetin at 25.0 and 50.0 mg/kg vehicle (control group). The following biochemical markers were evaluated; total cholesterol, HDL-C, LDL-C, triglycerides, AST, ALT, and alkaline phosphatase. The hypercholesterolemic diet was effective in inducing hypercholesterolemia, increasing total cholesterol by 112.7% relative to the control group. The treatments with two doses of the extract proved to be promising hypocholesterolemic agents, as they were able to substantially reduce total cholesterol and LDL-C, without significantly altering triglycerides, hepatic transaminases, and alkaline phosphatase, thereby encouraging the studies with the plant H. dulcis. The groups treated with the flavonoid dihydromyricetin, although they showed a significant reduction in total cholesterol and LDL-C, and found increases in triglycerides and hepatic transaminases, which is unwanted in the context of hypercholesterolaemia

Evaluation of pre-clinical toxicity of Hovenia dulcis.

A Hovenia dulcis, uva-do-japão, é uma planta exótica no Brasil originária do leste da Ásia e utilizada principalmente no tratamento de doenças do fígado e como agente detoxificante para intoxicação alcoólica. Com o objetivo de contribuir para o desenvolvimento de um medicamento fitoterápico este trabalho se propôs a elaborar uma revisão integrativa sobre a planta, determinar sua atividade antioxidante (método do DPPH) e avaliar a toxicidade pré-clínica (aguda e crônica) de uma formulação farmacotécnica à base do extrato hidroalcoólico dos frutos de Hovenia dulcis, previamente padronizado, de acordo com a RE no 90 de 2004. Para padronização foi determinado o teor de umidade, de acordo com a Farmacopéia Brasileira 4ed (perda por dessecação) e o doseamento do flavonóide dihidromiricetina no extrato (CLAE). No estudo toxicológico agudo, ratos Wistar (n=6 por dose e por sexo) foram tratados (v.o.) com a formulação na forma farmacêutica de suspensão na dose única de 6g/kg de peso corpóreo. Durante 14 dias após o tratamento foram observados: sinais tóxicos comportamentais, letalidade, variação ponderal, consumo de ração. Após esse período os animais foram eutanasiados e examinados os órgãos, aqueles que apresentaram alteração anatomopatológica foram coletados para análise histológica. No ensaio crônico os ratos (n=10 por dose e sexo) foram tratados com doses repetidas diariamente de 100, 200 e 300mg/kg de peso corporal durante 12 semanas. Durante o tratamento os sinais tóxicos comportamentais e letalidade foram avaliados diariamente e a variação ponderal semanalmente. Ao final do experimento os ratos foram eutanasiados para avaliação ponderal dos órgãos e análise dos parâmetros sanguíneos e histopatológicos. O extrato e a dihidromiricetina (400ppm) apresentaram atividade antioxidante de até 23,82%±1,60 e 82,53%±0,68, respectivamente, utilizou-se o BHA como padrão (50ppm) com atividade de até 76,97%± 0,96. O teor de umidade do extrato final foi de 21,4%, e o teor de dihidromiricetina foi 470,0±12,14 μg/grama de extrato. No estudo toxicológico agudo nenhum sinal comportamental foi atribuído ao tratamento, não houve morte dos animais e a variação ponderal e consumo de ração foram semelhantes ao grupo controle refletindo um comportamento normal e saudável dos animais de ambos os grupos. Na análise anatomohistopatológica pneumonia foi identificada em dois animais do grupo tratado e controle, não havendo relação com o tratamento. No ensaio crônico sinais de alterações comportamentais foram verificados eventualmente em alguns animais sem progressão e de forma dispersa e semelhante nos grupos, incluindo o controle. Dois animais do grupo tratado com a menor dose foram a óbito durante o experimento e os sintomas apresentados até o óbito caracterizaram falsa via de gavagem ou afecções não relacionadas ao tratamento. Nenhuma alteração hematológica, dos parâmetros bioquímicos do sangue e da histopatologia foram relacionadas à toxicidade. Os resultados da histomorfometria não apresentaram variações, estatisticamente significativas, comparando o grupo tratado com a maior dose ao controle. O fitopreparado desenvolvido a base do extrato hidroalcoólico dos frutos de Hovenia dulcis não apresentou evidencias de toxicidade aguda ou crônica em níveis comportamentais, ponderais, hematológicos, bioquímicos sorológicos e histológicos. Adicionalmente apresentou evidências, que corroboram a literatura, de efeitos benéficos em nível sanguíneo e histológico dos parâmetros hepáticos e renais.The Hovenia dulcis, oriental Raisin tree, is an exotic plant in Brazil originating from eastern Asia and is mainly used in the treatment of liver diseases and as a detoxication agent for alcohol intoxication. In order to further develop other a herbal drugs from this species this work presents an integrative review of the plant and their antioxidant activity (DPPH method). Herein a toxicity assessment in rats with the hydroalcoholic extract (formulation) from fruits of Hovenia dulcis according to Brazilian law ( ANVISA-RE 90/2004) is presented. The extract was standardized by water determination (Brazilian Pharmacopoeia methods Determination of loss on drying) and by dihydromyricetin (flavonoid) level determination (HPLC). In the acute toxicity test Wistar rats (n=6 per gender and dose) were treated (p.o.) with a pharmaceutical formulation in the form of extract suspension in a single dose of 6g/kg body weight. Each group was observed, for 14 days post treatment, in which certain indicators such as toxicity signs, lethality, body weight gain and food consumption were avaluated. After this period the animals were euthanized and the organs examined, those with visual changes were collected for histological analysis. In the chronic toxicity test rats were separated in to out on three experimental groups (100, 200 and 300mg/kg body weight). Each group (n=10 per gender and dose) was dosed daily by gavage for a period of 13 weeks. At the end of treatment the rats were euthanized for evaluation of organs weight and for biochemical, hematological and histopathologic analysis. The extract and dihydromyricetin (400ppm) showed antioxidant activity of up to 23.82%±1.60 and 82.53±0.68%, respectively. The standard BHA (50 ppm) showed antioxidant activity of up to 76.97%±0.96. The water determination of the extract was 21.4%, and the level of dihydromyricetin was 470.0±12.14 mg/g extract. The formulation developed with hydroalcoholic extract from fruits of Hovenia dulcis did not show evidence of acute or chronic toxicity, in which certain indicators such as toxicity signs, lethality, body weight gain, food consumption, organs weight biochemical, hematological and histopathologic analysis. Furthermore beneficial effects were found as determined by the blood levels and the histological parameters of liver and kidney.Coordenação de Aperfeiçoamento de Pessoal de Nível Superio

Estudo da Hovenia dulcis na diabetes e na cicatrização de feridas em coelhos.

A diabetes é uma doença crônica não transmissível, que apresenta alterações nos níveis de glicose, triacilglicerol, substâncias cetônicas, colesterol, aldose redutase e glicoproteínas acídicas na circulação sanguínea, dentre outras. Diabetes foi induzida em coelhos por aloxano e no final de 28 dias, após tratamentos, foram avaliados parâmetros plasmáticos e hematológicos. As feridas de pele ocorrem por ataque de vírus, bactérias, fungos, choques mecânicos, na diabetes ou por alteração da microcirculação periférica , dentre varias causas. Feridas foram induzidas por HCl 20% em etanol, e após tratamento, foram avaliados parâmetros plasmáticos, hematológicos e histológicos. A Hovenia dulcis, uva-do-Japão, é uma árvore da família Rhamnaceae utilizada na medicina tradicional chinesa contra intoxicação alcoólica e para tratar diabetes, dentre outras utilizações. Formulações à base dos seus frutos e um flavonóide foram utilizadas no tratamento de diabe tes e à base de suas cascas e ácido tânico, no tratamento das feridas. De acordo com os resultados obtidos, o extrato dos frutos e o flavonóide reduziram a glicemia em 25% e 47%, aumentaram os níveis de insulina em 55% e 126% e reduziram os de triacilglicerol em 28% e 43%, respectivamente. Na cicatrização o ácido tânico acelerou o processo cicatricial de forma equivalente à sulfadiazina de prata (controle) e o extrato das cascas retardou o processo possívelmente pela presença de substâncias irritativas ou formação de corpo estranho.Diabetes is not transmissible a chronic illness, it modify the glucose levels, triacilglicerol, ketonics substances, cholesterol, aldose redutase, acidics glycoproteins, the sanguineous circulation. Diabetes was induced in rabbits for alloxan. It had been treated during 28 days and evaluated plasmáticos and hematológicos parameters. The skin wounds occur for attack of virus, bacteria, fungos, mechanical shocks, diabetes, modification of the peripheral microcirculation. Wounds had been induced for HCl 20% in rabbits. It had been evaluated plasmáticos, hematológicos and histológicos parameters. The Hovenia dulcis, japonese raisintree (Rhamnaceae) is used in Chinese traditional medicine to treat liver diseases and diabetes. Its fruits and flavonóide, had been used in the treatment of diabetes. Its root bark and acid tanic had been used in the treatment of the skin wounds. The extract of the fruits and flavonóide had reduced the glicemy in 25% and 47%. They had increased insulina in 55% and 126% and reduced triacilglicerol in 28% and 43%, respectively. The acid tanic accelerated healing of skin wounds equal Sulfadiazina de Prata (Control) and the root bark harmed the healing because of irritatives substances or stranges bodies

Pharmacological activity of the hydroalcoholic extract from Hovenia dulcis thunberg fruit and the flavonoid dihydromyricetin during hypercholesterolemia induced in rats

Cerebrovascular accidents and coronary artery disease are the leading causes of cardiovascular mortalities in Brazil and high levels of LDL cholesterol are one of the main risk factors. In this context, several plant extracts and natural substances have shown promise as cholesterol-lowering. The objective of this study was to evaluate the potential of the hydroalcoholic extract of the fruit of H. dulcisand of dihydromyricetin in cholesterol reduction in hypercholesterolemic rats. Forty-two Wistar male rats were distributed into seven groups of six animals that received diets supplemented with 1% cholesterol and 0.3% cholic acid, with the exception of the control group, which received conventional diets. Animals were treated with oral suspensions containing: atorvastatin 1.0 mg/kg; H. dulcisextract at 50.0 and 100.0 mg/kg and dihydromyricetin at 25.0 and 50.0 mg/kg vehicle (control group). The following biochemical markers were evaluated; total cholesterol, HDL-C, LDL-C, triglycerides, AST, ALT, and alkaline phosphatase. The hypercholesterolemic diet was effective in inducing hypercholesterolemia, increasing total cholesterol by 112.7% relative to the control group. The treatments with two doses of the extract proved to be promising hypocholesterolemic agents, as they were able to substantially reduce total cholesterol and LDL-C, without significantly altering triglycerides, hepatic transaminases, and alkaline phosphatase, thereby encouraging the studies with the plant H. dulcis. The groups treated with the flavonoid dihydromyricetin, although they showed a significant reduction in total cholesterol and LDL-C, and found increases in triglycerides and hepatic transaminases, which is unwanted in the context of hypercholesterolaemia

Elaboration and characterization of Japanese Raisin Tree (Hovenia dulcis Thumb.) pseudofruits fermented alcoholic beverage

<div><p>Abstract Hovenia dulcis pseudofruits have underexplored properties for food purposes, despite their pleasant sensory characteristics and therapeutic benefits. The aim of this study was the elaboration and chemical characterization of the alcoholic fermented beverage of H. dulcis, using selected strain of Saccharomyces cerevisiae (CCMA 0200). The resulting fermented beverage presented high content of phenolic compounds and antioxidant activity when compared to other fruits and beverages (DPPH and ABTS assay). The alcohol content was 12.9 oGL and total sugars 3.57g/L. By the GC-MS analysis, 39 compounds were identified including metabolites with therapeutic potential such as eugenol, trans-farnesol salicylates. The flavonoid dihidromyricetin was identified and quantified (75.17 mg/L) by HPLC-DAD and UPLC-MS/MS. The results reinforce the interest on nutraceutical and functional properties of this beverage and opens perspectives for new studies that value this underexplored pseudofruit.</p></div

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)