Made available in DSpace on 2015-05-14T12:59:28Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2717397 bytes, checksum: 9b595c87b494e8dd776ae15a3beac7f1 (MD5) Previous issue date: 2011-10-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Anxiety is an adaptive response of organism to situations that life presents, and driving performance with personal and psychological as well as physiological components. It is considered pathological when it causes suffering to the individual, bringing him damage in terms of injury avoidance behaviors and avoidance important situations in his academic, social and professional life. The pathological manifestations of anxiety are grouped as Anxiety Disorders. Several pharmacological classes are used to treat this group of disorders, especially benzodiazepines and antidepressants. However, the pattern of adverse reactions, the possibility of tolerance and dependence as well as abuse potential of benzodiazepines, added to slow response of antidepressant treatment, justify the search for new therapeutic possibilities. Preclinical studies have attested the anxiety-relieving activity of the roots extract of Panax ginseng C. A Meyer. Its ethnopharmacological use for anxiety is evident worldwide. The aim of this study was to test the therapeutic efficacy of the extract of the roots of P. ginseng in the acute treatment of experimentally induced anxiety in healthy volunteers and identify adverse effects caused by its use. The study population consisted of university students, aged between 18 and 30 years. We selected 60 healthy volunteers who met the study inclusion criteria. We developed a clinical double-blind, randomized, controlled, acute essay. The substances used were: P. ginseng (200 mg), diazepam (10 mg) and placebo. Anxiety was experimentally elicited through Simulation Test of Public Speaking, and evaluated through the use of physiological measures (blood pressure, heart pulse rate, ends temperature and skin electrical conductance) and psychometric scales (trait-state anxiety inventory and analog mood scale). The results were analyzed using several statistical, parametric and nonparametric methods. They showed that the extract of the roots of P. ginseng intensifies anxiety, especially during performance test and has a minor ability to reduce it in the final phase, with greater significance demonstrated through psychological measures. Although well tolerated, P. ginseng has not demonstrated effectiveness in controlling anxiety and subjective signs and symptoms associated with it. / A ansiedade é uma resposta adaptativa do organismo às situações que a vida apresenta, sendo propulsora do desempenho pessoal e com componentes psicológicos e fisiológicos. É considerada patológica quando provoca sofrimento ao indivíduo, trazendo-lhe prejuízo em função dos comportamentos de fuga e esquiva de situações importantes da vida acadêmica, social e profissional. As manifestações da ansiedade patológica são agrupadas nos transtornos de Ansiedade. Várias classes farmacológicas são utilizadas no tratamento deste grupo de transtorno, destacando-se os benzodiazepínicos e antidepressivos. Entretanto, o padrão de reações adversas, a possibilidade de dependência e tolerância e o potencial de abuso dos benzodiazepínicos, adicionado a lenta resposta terapêutica dos antidepressivos, justificam a busca de novas possibilidades terapêuticas. Estudos pré-clínicos atestaram a atividade ansiolítica do extrato das raízes do Panax ginseng C.A. Meyer. Seu uso etnofarmacológico para ansiedade é evidenciado em todo mundo. O objetivo deste estudo foi testar a eficácia terapêutica do extrato das raízes do P. ginseng no tratamento agudo da ansiedade induzida de maneira experimental em voluntários saudáveis e identificar os efeitos adversos provocados pelo seu uso. A população do estudo foi constituída por estudantes universitários, com idade entre 18 e 30 anos. Foram selecionados 60 voluntários saudáveis, que atenderam aos critérios de inclusão do estudo. Foi desenvolvido um ensaio clínico duplo-cego, randômico, controlado e agudo. As substâncias utilizadas foram: P. ginseng (200 mg), Diazepam (10 mg) e Placebo. A ansiedade foi produzida de modo experimental, através do Teste de Simulação de Falar em Público e avaliada mediante o uso de medidas fisiológicas (pressão arterial, frequência cardíaca, temperatura de extremidades e condutância elétrica da pele) e escalas psicométricas (Inventário de ansiedade traço-estado e escala analógica do humor). Os resultados foram analisados utilizando vários métodos estatísticos paramétricos e não-paramétricos. Eles demonstraram que o extrato das raízes de P. ginseng intensifica a ansiedade, principalmente na fase de performance do Teste e apresenta menor capacidade de reduzi-lá na fase final, demonstrado com maior significância através das medidas psicológicas. Embora bem tolerado, P. ginseng não demonstrou eficácia no controle subjetivo da ansiedade e de alguns sinais e sintomas a ela associados.

The purpose of the present study was to test the acute effects of a dietary supplement, having as its major ingredient an extract of ginseng, on grip strength, lower body power output, cardiovascular markers, metabolic markers, hormones, and mood state. Twelve experienced resistance-trained men (28.3 ± 5.7 yrs) were randomly administered placebo (P), single dose (SD) and double dose (DD) of the supplement on separate days. Diet and activity levels were kept constant across testing days. On each day, subjects began with the Profile of Mood States (POMSpre1), blood draws (BDpre1), blood pressure (BPpre1), and heart rate (HRpre1) assessments, then ingested the drink and sat quietly for 30 minutes. BDpre2, BPpre2, and HR pre1 were then taken. Subjects performed the grip strength and cycle ergometer tests followed immediately by BDpost, HRpost, and BPpost and POMSpost. The testing session ended with blood draws, heart rates, and blood pressures being taken 30 (post30), 60 (post60), 120 (post120) and 180 (post180) minutes post exercise. Grip strength did not differ between P, SD, or DD treatments. Cycle ergometry peak power (PP), average power (AP) and total work (TW) were significantly higher for the SD and DD than P; however, no significant difference existed between SD and DD treatments. For LH and T significant differences were found among all treatment conditions. There were no significant treatment effects for HR, BP, glucose, insulin, lactate, GH or PRL or for the POMS. There was a significant treatment*time interaction for ACTH (p < .05). Post hoc analysis indicated that at Tpost ACTH was significantly lower for D treatment vs P or S treatments (p < .05) and at Tpost60 ACTH was significantly lower for S and D treatments vs P treatment (p < .05). There was significant differences in C between the D treatment (260.45 ± 15.58 nmol•L-1) and the P (336.08 ± 27.59 nmol•L-1) and S (311.14 ± 21.01 nmol•L-1) treatments (p < .001). There was a significant difference for T:C ratio values among P (0.0810 ± 0.0090), S (0.0960 ± 0.0130) and D (0.1410 ± 0.0190) treatments (p < .001). Acute ingestion of a polynutrient supplement containing a standardized ginseng tract, was able to increase PP, AP, TW LH, and testosterone and decrease ACTH and cortisol. No significant effects were found for GH, PRL, insulin, glucose, lactate, HR, BP or POMS scores. Acute ingestion of a polynutrient supplement was able to increase performance and the anabolic environment in resistance trained men.

Submitted by Rafael Santana (rafael.silvasantana@ufpe.br) on 2018-03-16T17:55:36Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação HELLENCLEIA PEREIRA CUNHA.pdf: 1165835 bytes, checksum: abef97c86c02f2f00c033287fee3977e (MD5) / Made available in DSpace on 2018-03-16T17:55:36Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação HELLENCLEIA PEREIRA CUNHA.pdf: 1165835 bytes, checksum: abef97c86c02f2f00c033287fee3977e (MD5) Previous issue date: 2017-02-16 / CNPQ / A polifarmácia tem sido cada vez mais utilizada por pacientes idosos no tratamento de doenças crônicas. Além dos medicamentos prescritos por profissionais de saúde, muitos pacientes buscam a fitoterapia como medicina complementar. Entretanto, o uso concomitante de fitoterápicos com outros medicamentos pode trazer consequências ao paciente do ponto de vista clínico. O presente estudo teve por objetivo analisar a possível interferência do fitoterápico Panax ginseng sobre os efeitos farmacológicos da fluoxetina e da nimesulida, em modelos animais de depressão, memória e inflamação. Para isso, ratos Wistar adultos machos divididos em três grupos experimentais (n=8) foram submetidos ao regime de tratamento oral agudo (três doses em 24 horas) ou por 14 dias (estudo subcrônico) com veículo (água destilada 1,5 mL/kg, controle), fluoxetina (20 mg/kg) ou fluoxetina (20 mg/kg) + P. ginseng (100 mg/kg). Posteriormente, os animais foram avaliados nos testes da natação forçada ou campo aberto. Para os testes de inflamação aguda e crônica, os animais foram agrupados em quatro grupos experimentais (n=6): controle (água destilada, 1,5 mL/kg), nimesulida (10 mg/kg), P. ginseng (100 mg/kg) ou nimesulida (10 mg/kg) + P. ginseng (100 mg/kg), e submetidos ao modelo de edema de pata induzido por carragenina (estudo agudo, por 240 minutos) ou por Adjuvante de Freund (estudo crônico, por 40 dias). No teste da inflamação subcrônica, os animais foram divididos em três grupos (n=6): controle (água destilada, 1,5 mL/kg), nimesulida (10 mg/kg) ou nimesulida (10 mg/kg) + P. ginseng (100 mg/kg), sendo induzida a formação de granuloma por “pellets” de algodão. Os resultados mostraram que houve uma potencialização do efeito antidepressivo no grupo de animais tratados com P. ginseng + fluoxetina, com três doses em 24 horas, efeito este que não foi observado no tratamento subcrônico (14 dias). Verificou-se também que P. ginseng não modificou o efeito anti-inflamatório da nimesulida, nos estudos de inflamação aguda, subcrônica e crônica, e o mesmo apresentou um efeito anti-inflamatório semelhante ao da nimesulida. Conclui-se que o tratamento com P. ginseng modifica o efeito da fluoxetina em testes comportamentais de depressão e memória agudos, mas não modifica em testes subcrônicos e não interfere no efeito da nimesulida em testes de inflamação aguda, subcrônica e crônica em ratos. / Polypharmacy has been increasingly used by elderly patients in the treatment of chronic diseases. In addition to medicines prescribed by health professionals, many patients seek herbal medicine as complementary medicine. However, the concomitant use of herbal medicines with other medicinal products may have consequences for the patient from a clinical point of view. The present study aimed to analyze the possible interference of the phytotherapeutic Panax ginseng on the pharmacological effects of fluoxetine and nimesulide in animal models of depression, memory and inflammation. For this, adult male Wistar rats divided into three experimental groups (n = 8) underwent acute oral treatment (three doses in 24 hours) or 14 days (subchronic study) with vehicle (distilled water 1.5 mL/Kg, control), fluoxetine (20 mg/kg) or fluoxetine (20 mg/kg) + P. ginseng (100 mg/kg). Subsequently, the animals were evaluated in the forced swimming or open field tests. For the acute and chronic inflammation tests, the animals were grouped into four experimental groups (n = 6): control (distilled water, 1.5 mL/kg), nimesulide (10 mg/kg), P. ginseng (100 mg/Kg) or nimesulide (10 mg/kg) + P. ginseng (100 mg/kg) and submitted to the carrageenan-induced paw edema model (acute study, for 240 minutes) or by Freund's Adjuvant (chronic study, 40 days). In the subchronic inflammation test, the animals were divided into three groups (n = 6): control (distilled water, 1.5 mL/kg), nimesulide (10 mg/kg) or nimesulide (10 mg/kg) + P. ginseng (100 mg/kg), granuloma formation being induced by cotton pellets. The results showed that there was a potentiation of the antidepressant effect in the group of animals treated with P. ginseng + fluoxetine, with three doses in 24 hours, an effect that was not observed in the subchronic treatment (14 days). It was also found that P. ginseng did not modify the anti-inflammatory effect of nimesulide in acute, subchronic and chronic inflammation studies, and it had an anti-inflammatory effect similar to nimesulide. It is concluded that the treatment with P. ginseng modifies the effect of fluoxetine in behavioral tests of depression and acute memory, but does not modify in the subchronic tests and does not interfere in the effect of nimesulide in tests of acute, subchronic and chronic inflammation in rats.

Made available in DSpace on 2015-05-14T12:59:41Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 679492 bytes, checksum: 3252c196788de3bae30bf110b0d94cce (MD5) Previous issue date: 2009-10-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Fibromyalgia is a chronic painful syndrome that affects up to 5% of the population worldwide. It may be associated with sleep or mood disorders and fatigue, and progresses with functional disability. Its pathogenesis consists of disorders of central pain modulation, involvement of the descending inhibitory system and substance P hyperactivity. The drug most commonly used for treatment of this syndrome is amitriptyline, which leads to an improvement in up to 50% of cases. Patients are interested in trying alternative or complementary medicine for the treatment of fibromyalgia. Panax ginseng C.A. Meyer is an herb that has been used for hundreds of years in oriental medicine. Preclinical studies have confirmed the antinociceptive effect of its active metabolites (ginsenosides) on substance P-induced pain, demonstrating an ability to inhibit calcium channels in dorsal medullary neurons. Clinical trials have shown an improvement in quality of life and fatigue with the use of ginseng. The study had as objective to evaluate the therapeutic efficacy of the extract of P. ginseng roots in controlling pain, fatigue, sleep quality, anxiety and quality of life in fibromyalgia. Fifty-two women of 21-60 years of age, who fulfilled the inclusion criteria of the study, were selected. A randomized, double-blind, controlled clinical trial was carried out over 12 weeks to compare the effect of P. ginseng (100 mg/day) with amitriptyline (25 mg/day) and placebo. Variables evaluated were pain, fatigue, sleep quality and anxiety using a visual analogue scale (VAS); pain was evaluated using a tender points count and quality of life using the Fibromyalgia Impact Questionnaire (FIQ). The patients were evaluated at six follow-up visits and results were expressed as means ± standard error (SE) of the mean using analysis of variation (ANOVA) and Tukey s post-hoc test. Thirty-eight women with a mean age of 43 years concluded the study. There were no statistically significant differences between the three groups with respect to baseline characteristics. VAS revealed a reduction in pain in the ginseng group (p<0.0001) with an improvement ≥ 30% from the sixth week of treatment onwards, an improvement in fatigue (p<0.0001) with a reduction ≥ 25% on the sixth week and ≥ 40% on the ninth week; and an improvement in sleep (p=0.0003) with a reduction ≥ 40% in the frequency of this complaint by the 6th week of treatment. The VAS evaluation of pain, fatigue and sleep detected an improvement compared to baseline values; however, there was no statistically significant difference between the three groups. With respect to anxiety, an improvement occurred in the ginseng group compared to baseline (p<0.0001); however, amitriptyline treatment resulted in a significantly greater improvement (p<0.05). Ginseng reduced the number of tender points and improved patients quality of life, as evaluated by the FIQ, compared to baseline in both cases (p<0.0001); however, no difference was found between the groups. Treatment with ginseng resulted in an improvement in all the parameters evaluated compared to baseline; however, there was no difference between this group of patients and those using placebo and amitriptyline, and this one was more effective than placebo or ginseng in improving anxiety. The beneficial effect on all parameters evaluated suggests that further studies should be performed with larger sample sizes and/or higher doses of ginseng to evaluate this herb for future use as a complementary therapy for fibromyalgia. / A fibromialgia é uma síndrome dolorosa crônica que afeta até 5% da população mundial. Pode associar-se com distúrbios do sono, do humor e fadiga, e cursar com incapacidade funcional. Sua patogênese envolve distúrbio de modulação central da dor, comprometimento do sistema inibitório descendente e hiperatividade da substância P. O fármaco mais utilizado na sua terapia farmacológica é a amitriptilina, com melhora em até 50% dos casos. Há muito interesse dos pacientes sobre a medicina alternativa e complementar na terapia da fibromialgia. O Panax ginseng C.A. Meyer é uma erva utilizada pela medicina oriental há centenas de anos. Estudos pré-clínicos comprovaram a ação antinociceptiva dos seus metabólitos ativos (ginsenosídeos) sobre a dor induzida pela substância P, e demonstraram sua capacidade de inibir canais de cálcio nos neurônios da região dorsal medular. Ensaios clínicos sugeriram melhora da qualidade de vida e da fadiga com uso do ginseng. O estudo teve como objetivos: avaliar a eficácia terapêutica do extrato das raízes do P. ginseng no controle da dor, fadiga, qualidade do sono e ansiedade, e qualidade de vida na fibromialgia. Foram selecionadas 52 mulheres, com idades entre 21 e 60 anos, após preencherem os critérios de inclusão para o estudo. Foi desenvolvido um ensaio clínico, randômico, duplo-cego, controlado, por 12 semanas, comparando a ação do P. ginseng (100 mg/dia) com amitriptilina (25 mg/dia) e placebo. Variáveis avaliadas: dor, fadiga, qualidade do sono e ansiedade, por escala visual analógica (EVA); dor, por contagem dos pontos dolorosos; e melhora da qualidade de vida, por meio do Fibromyalgia impact questionnaire (FIQ). As pacientes foram avaliadas em 6 visitas, e os resultados foram dados em média ± EPM, utilizando ANOVA e pós-teste de Tukey. Trinta e oito mulheres concluíram o estudo, com média de idade de 43 anos. Não houve diferença significante nas características basais médias nos três grupos. Na EVA, observou-se: redução da dor no grupo do ginseng (p<0,0001), com melhora ≥ 30% a partir da 6ª semana de terapia; melhora da fadiga (p<0,0001), com redução ≥ 25% a partir da 6ª semana, e ≥ 40% na 9ª semana; e melhora do sono (p= 0,0003), reduzindo ≥ 40% a partir da 6ª semana de terapia. Nas três variáveis avaliadas na EVA, houve melhora em relação ao período basal, mas não houve diferença entre os três grupos. Com relação à ansiedade, o ginseng mostrou-se melhor em relação ao período basal (p<0,0001), mas foi inferior à amitriptilina (p<0,05), na comparação entre os grupos. O ginseng reduziu o número de pontos dolorosos e melhorou a qualidade de vida das pacientes (FIQ), ambos em relação ao período basal (p<0,0001), mas não houve diferença entre os grupos. O ginseng foi capaz de melhorar todos os parâmetros avaliados em relação ao período basal, mas não foi diferente do placebo ou da amitriptilina, e esta foi superior ao placebo e ao ginseng na melhora da ansiedade. Sua atuação benéfica nos parâmetros avaliados sugere a realização de novos ensaios clínicos, com amostras maiores, e/ou com dose maior do ginseng, para uma futura indicação como terapia complementar na fibromialgia.

Made available in DSpace on 2014-12-17T14:16:34Z (GMT). No. of bitstreams: 1 AnaLSAM_DISSERT.pdf: 1550415 bytes, checksum: caf1d01895bb5be79ca908c1ce3bf0f9 (MD5) Previous issue date: 2013-03-19 / Panax ginseng CA Meyer (Araliaceae) is a herbaceous plant widely used in China, South Korea, Japan and other Asian countries for the treatment of various diseases micro circulatory, cerebrovascular, among others, representing one of the drugs used by older man. It has over 30 biologically active ginsenosides with different pharmacological and behavioral effects and inhibitory effect on the NMDA receptor. The amino acid glycine is a co-agonist of the NMDA receptor, activating this receptor. At the cellular level, ketamine is widely known to be NMDA receptor antagonist. The aim of this study was to evaluate the general activity in the open field, and anxiety in elevated plus maze, mice treated with P. ginseng compared with the action of ketamine and glycine, to better understand the action of this herbal medicine at the NMDA receptor. We used 66 adult male rats were divided into six groups: a positive control, treated for 30 days with water by gavage, who received glycine (500mg/kg; po) on days 7, 14, 21 and 28 of treatment, one hour before of behavioral assessment, a negative control was treated for 30 days with water by gavage received ketamine (5mg/kg, ip) on days 7, 14, 21 and 28 of treatment, one hour prior to behavioral evaluation, three experimental groups, receiving 100, 200 or 300 mg / kg P. ginseng by gavage for 30 days and one group treated solely with white water, and is also administered 1 ml of water by gavage one hour prior to behavioral evaluation. Animal behavior in these three groups was also examined on days 7, 14, 21 and 28 of treatment. On day 30 of treatment, the animals were anesthetized with thiopental (70mg/kg) for blood collection and after euthanasia, withdrawal of various organs. There were no changes in weight and body weight gain and weight reasons in organ / body weight. However the consumption of water and food values showed a significant increase. Serum levels of AST was increased in a dose-dependently in the animals treated with doses of P. ginseng, glycine and ketamine as compared to the blank group. Unlike creatinine levels proved to be decreased in all treated groups when compared with white. However, the level of urea in these groups was reduced and no changes were observed in the ALT parameter. Histopathological examination revealed no changes in cell morphology in different tissues. There were no behavioral changes in the elevated plus maze and few changes were observed in the open field, animals treated with P. ginseng, glycine and ketamine when compared to white. These data suggest that the doses of P. ginseng employed were unable to induce general toxicity in rats treated for 30 days and also shows that the general behavior of mice treated with P. ginseng was slightly different from that observed in animals treated with ketamine and glycine. Finally, the study on the elevated plus maze showed that the extract of P. ginseng showed no anxiolytic or anxiogenic action / Panax ginseng C.A. Meyer (Araliaceae) ? uma planta herb?cea muito usada na China, Cor?ia do Sul, Jap?o e outros pa?ses da ?sia no tratamento de v?rias doen?as micro circulat?rias, vasculares cerebrais, entre outras. Possui mais de 30 ginsenos?deos, que inibem o receptor NMDA, provocando diferentes efeitos farmacol?gicos e comportamentais. O objetivo do presente estudo foi avaliar a atividade geral, no campo aberto, e a ansiedade, no labirinto em cruz elevado, de ratos tratados com P. ginseng. Ratos tratados com ketamina (antagonista do receptor NMDA) e com glicina (coagonista do receptor NMDA), foram tamb?m empregados para melhor entendimento do mecanismo de a??o desse fitoter?pico. Foram utilizados 66 ratos machos adultos, divididos em seis grupos: um controle positivo (n=12), tratado durante 30 dias com ?gua por gavagem, que recebeu glicina (500mg/kg; v.o.) nos dias 7, 14, 21 e 28 de tratamento, uma hora antes da avalia??o comportamental; um controle negativo (n=12), tratado durante 30 dias com ?gua por gavagem, que recebeu ketamina (5mg/kg; i.p.) nos dias 7, 14, 21 e 28 de tratamento, uma hora antes da avalia??o comportamental; tr?s grupos experimentais (n=12), que receberam 100, 200 ou 300 mg/kg de P. ginseng, por gavagem, durante 30 dias e um grupo branco (n=6) tratado exclusivamente com ?gua, sendo tamb?m administrado 1mL de ?gua por gavagem uma hora antes da avalia??o comportamental. O comportamento animal nesses grupos tamb?m foi analisado nos dias 7, 14, 21 e 28 de tratamento. No dia 30 de tratamento os animais foram anestesiados para coleta de sangue e retirada de ?rg?os diversos, que tiveram seus pesos anotados e por??es foram coletadas para estudo histopatol?gico. N?o foram observadas altera??es no peso e ganho de peso corporal entre os diversos grupos nem nas raz?es peso ?rg?o/peso corporal calculadas. Nos animais tratados com P. ginseng, ketamina e glicina o consumo de ?gua e de ra??o e as concentra??es s?ricas de AST revelaram estar aumentadas em compara??o com grupo branco. Entretanto, os animais tratados com as tr?s doses de P. ginseng, ketamina e glicina apresentaram n?veis reduzidos de creatinina e ureia quando comparados com o grupo branco. N?o foram observadas altera??es no par?metro ALT. O estudo histopatol?gico revelou aus?ncia de altera??es na morfologia celular nos diversos tecidos analisados. N?o foram encontradas altera??es comportamentais no labirinto em cruz elevado e poucas altera??es foram observadas nos animais tratados com P. ginseng, glicina e ketamina quando comparados com o grupo branco, no campo aberto. Esses dados sugerem que as doses de P. ginseng empregadas n?o foram capazes de provocar toxicidade geral em ratos tratados por 30 dias e revela tamb?m que o comportamento geral dos ratos tratados com P. ginseng foi pouco diferente daquele observado nos animais tratados com glicina e ketamina. Por fim, o estudo no labirinto em cruz elevado mostrou que o extrato de P. ginseng n?o apresentou a??o ansiog?nica nem ansiol?tica nas condi??es experimentais adotadas

Made available in DSpace on 2015-05-14T13:00:02Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1170808 bytes, checksum: 7b299ea2ca71a584be9ecd4dbd10364c (MD5) Previous issue date: 2014-02-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The irritable bowel syndrome (IBS) is defined as the presence of continuing or recurrent abdominal pain or discomfort and it is associated with altered bowel habit. Its pathophysiology involves the following aspects: genetic variables, changes in gut motility and visceral sensitivity, psychosocial factors, in addition to inflammatory and infectious processes. The treatment is based on dietary guidance and change in lifestyle. The use of drugs is indicated in symptomatic stages of IBS. The growing interest of patients for complementary and alternative medicine has been observed in recent years. Panax ginseng C.A. Meyer has been used for centuries in oriental medicine. Experimental studies have demonstrated the antinociceptive action of this herbal medicine on calcium and sodium channels, as well as on primary sensory neurons. The study aimed to: conduct phase II clinical trial with Panax ginseng CA Meyer in patients with IBS; contribute to the study of the pharmacological effects of Panax ginseng C.A. Meyer; evaluate the therapeutic efficacy of Panax ginseng C.A. Meyer in abdominal pain control in patients with IBS; and observe the adverse effects. Twenty-six patients were selected by means of the inclusion criteria for the study and they were divided into two groups. A clinical double-blind, randomized, prospective and experimental trial was conducted for eight weeks, comparing the action of dry extract of Panax ginseng (300 mg / day) with trimebutine (600 mg / day). Abdominal pain was assessed using the Likert scale. Patients were assessed at four visits and the results were analyzed using the Mann-Whitney and Friedman tests, with a significance level of p < 0.05. Twenty- four patients completed the study, being 87.50% female and mean age of 47.41 years. There was a relative homogeneity among patients with regard to sex, age and duration of symptoms. All patients, before beginning treatment with Panax ginseng and trimebutine, had negative scores for the Likert scale values. There was improvement in abdominal pain, through this scale, in patients who used Panax ginseng. This group started from a median basal of -5 to 2.5, 3 and 5 in the 1st, 4th and 8th weeks of treatment, respectively, with a statistically significant difference. Similar results were achieved in the group that used the trimebutine. The only adverse effect observed was the occurrence of headache in two patients (16.66%) in the group that used the herbal. Panax ginseng C.A. Meyer was effective in the control of abdominal pain in IBS patients, analogous to trimebutine, and may be used in future studies, with the prospect of a phase III clinical trial. / A síndrome do intestino irritável (SII) é definida pela presença de dor ou desconforto abdominal contínuo ou recorrente, estando associada com alterações do hábito intestinal. Sua fisiopatologia envolve os seguintes aspectos: variáveis genéticas, alterações da motilidade intestinal e da sensibilidade visceral, fatores psicossociais, além de processos inflamatórios e infecciosos. O tratamento é baseado em orientação dietética e na mudança do estilo de vida. O uso de fármacos é indicado nas fases sintomáticas da SII. Tem sido observado o crescente interesse dos pacientes pela medicina alternativa e complementar, nos últimos anos. O Panax ginseng C.A. Meyer é utilizado há séculos pela medicina oriental. Estudos experimentais demonstraram a ação antinociceptiva desse fitoterápico sobre os canais de cálcio e de sódio, assim como sobre os neurônios sensoriais primários. O estudo teve como objetivos: realizar ensaio clínico de fase II com o Panax ginseng C.A. Meyer em pacientes com SII; contribuir para o estudo dos efeitos farmacológicos do Panax ginseng C.A. Meyer; avaliar a eficácia terapêutica do Panax ginseng C.A. Meyer no controle da dor abdominal em pacientes com SII; observar os efeitos adversos. Foram selecionados vinte e seis pacientes, através de critérios de inclusão para a pesquisa, sendo divididos em dois grupos. Foi realizado um estudo clínico, duplo cego, randômico, prospectivo e experimental por oito semanas, comparando a ação do extrato seco do Panax ginseng (300 mg/dia) com a trimebutina (600 mg/dia). A dor abdominal foi avaliada através da escala de Likert. Os pacientes foram avaliados em quatro consultas e os resultados foram analisados através dos testes de Mann-Whitney e Friedman, com nível de significância quando p<0,05. Vinte e quatro pacientes concluíram o estudo, sendo 87,50% do sexo feminino e média de idade de 47,41 anos. Ocorreu uma relativa homogeneidade nos grupos de estudo no que se refere ao sexo, idade e duração dos sintomas. Todos os pacientes, antes do início dos tratamentos com Panax ginseng e trimebutina, apresentavam os valores negativos para os escores na escala de Likert. Houve melhora da dor abdominal, nos pacientes que utilizaram o Panax ginseng. Esse grupo partiu de uma mediana basal de -5 para 2,5, 3 e 5, na 1ª., 4ª. e 8ª. semanas de tratamento, respectivamente, com diferença estatisticamente significativa. O efeito adverso observado foi a ocorrência de cefaleia em dois pacientes (16,66%), no grupo que usou o fitoterápico. O Panax ginseng C.A. Meyer foi eficaz no controle da dor abdominal em pacientes com SII, de modo análogo à trimebutina, podendo ser utilizado em novos estudos, com a perspectiva de um ensaio clínico de fase III.

<p><em>Panax ginseng</em> is a traditional herb that has been used for over 2000 years to promote health and longevity. Active components of ginseng include ginsenosides, polysaccharides, flavonoids, polyacetylenes, peptides, vitamins, phenols and enzymes, of which the ginsenosides are considered to be the major bioactive constituents. Although widely used, the exact mechanisms of ginseng and its compounds remain unclear. In this thesis we use melanophores from <em>Xenopus laevis</em> to investigate the effects of <em>Panax ginseng</em> extract G115 and its constituents on organelle transport and signalling. Due to coordinated bidirectional movement of their pigmented granules (melanosomes), in response to defined chemical signals, melanophores are capable of fast colour changes and provide a great model for the study of intracellular transport. The movement is regulated by alterations in cyclic adenosine 3’:5’-monophosphate (cAMP) concentration, where a high or low level induce anterograde (dispersion) or retrograde (aggregation) transport respectively, resulting in a dark or light cell. Here we demonstrate that <em>Panax ginseng</em> and its constituents ginsenoside Rc and Rd and flavonoid quercetin induce a concentration-dependent anterograde transport of melanosomes. The effect of ginseng is shown to be independent of cAMP changes and protein kinase A activation. Upon incubation of melanophores with a combination of Rc or Rd and quercetin, a synergistic increase in anterograde movement was seen, indicating cooperation between the ginsenoside and flavonoid parts of ginseng. Protein kinase C (PKC) inhibitor Myristoylated EGF-R Fragment 651-658 decreased the anterograde movement stimulated by ginseng and ginsenoside Rc and Rd. Moreover, ginseng, but not ginsenosides or quercetin, stimulated an activation of 44/42-mitogen activated protein kinase (MAPK), previously shown to be involved in both aggregation and dispersion of melanosomes. PKC-inhibition did not affect the MAPK-activation, suggesting a role for PKC in the ginseng- and ginsenoside-induced dispersion but not as an upstream activator of MAPK.</p> / <p><em>Panax ginseng </em>är ett av de vanligaste naturläkemedlen i världen och används traditionellt för att öka kroppens uthållighet, motståndskraft och styrka. Ginseng är ett komplext ämne bestående av ett antal olika substanser, inklusive ginsenosider, flavonoider, vitaminer och enzymer, av vilka de steroidlika ginsenosiderna anses vara de mest aktiva beståndsdelarna. Flavonoider (som finns i till exempel frukt och grönsaker) och ginseng har genom forskning visat sig motverka bland annat hjärt-och kärlsjukdomar, diabetes, cancer och demens. Trots den omfattande användningen är dock mekanismen för hur ginseng verkar fortfarande oklar. I den här studien har vi använt pigmentinnehållande celler, melanoforer, från afrikansk klogroda för att undersöka effekterna av <em>Panax ginseng</em> på pigment-transport och dess maskineri. Melanoforer har förmågan att snabbt ändra färg genom samordnad förflyttning av pigmentkorn fram och tillbaka i cellen, och utgör en utmärkt modell för studier av intracellulär transport. Förflyttningen regleras av förändringar i halten av cykliskt adenosin-monofosfat (cAMP) i cellen, där en hög eller låg koncentration medför spridning av pigment över hela cellen (dispergering) eller en ansamling i mitten (aggregering), vilket resulterar i mörka respektive ljusa celler. Här visar vi att <em>Panax ginseng</em>, ginsenosiderna Rc och Rd samt flavonoiden quercetin stimulerar en dispergering av pigmentkornen. När melanoforerna inkuberades med en kombination av ginsenosid Rc eller Rd och quercetin, kunde en synergistisk ökning av dispergeringen ses, vilket tyder på en samverkan mellan ginsenosid- och flavonoid-delarna av ginseng. Ett protein som tidigare visats vara viktigt för pigmenttransporten är mitogen-aktiverat protein kinas (MAPK), och här visar vi att också melanoforer stimulerade med ginseng, men dock inte med ginsenosider eller quercetin, innehåller aktiverat MAPK. Genom att blockera enzymet protein kinas C (PKC) (känd aktivator av dispergering), minskade den ginseng- och ginsenosid-inducerade dispergeringen, medan aktiveringen av MAPK inte påverkades alls. Detta pekar på en roll för PKC i pigment-transporten men inte som en aktivator av MAPK.</p>

Panax ginseng is a traditional herb that has been used for over 2000 years to promote health and longevity. Active components of ginseng include ginsenosides, polysaccharides, flavonoids, polyacetylenes, peptides, vitamins, phenols and enzymes, of which the ginsenosides are considered to be the major bioactive constituents. Although widely used, the exact mechanisms of ginseng and its compounds remain unclear. In this thesis we use melanophores from Xenopus laevis to investigate the effects of Panax ginseng extract G115 and its constituents on organelle transport and signalling. Due to coordinated bidirectional movement of their pigmented granules (melanosomes), in response to defined chemical signals, melanophores are capable of fast colour changes and provide a great model for the study of intracellular transport. The movement is regulated by alterations in cyclic adenosine 3’:5’-monophosphate (cAMP) concentration, where a high or low level induce anterograde (dispersion) or retrograde (aggregation) transport respectively, resulting in a dark or light cell. Here we demonstrate that Panax ginseng and its constituents ginsenoside Rc and Rd and flavonoid quercetin induce a concentration-dependent anterograde transport of melanosomes. The effect of ginseng is shown to be independent of cAMP changes and protein kinase A activation. Upon incubation of melanophores with a combination of Rc or Rd and quercetin, a synergistic increase in anterograde movement was seen, indicating cooperation between the ginsenoside and flavonoid parts of ginseng. Protein kinase C (PKC) inhibitor Myristoylated EGF-R Fragment 651-658 decreased the anterograde movement stimulated by ginseng and ginsenoside Rc and Rd. Moreover, ginseng, but not ginsenosides or quercetin, stimulated an activation of 44/42-mitogen activated protein kinase (MAPK), previously shown to be involved in both aggregation and dispersion of melanosomes. PKC-inhibition did not affect the MAPK-activation, suggesting a role for PKC in the ginseng- and ginsenoside-induced dispersion but not as an upstream activator of MAPK. / Panax ginseng är ett av de vanligaste naturläkemedlen i världen och används traditionellt för att öka kroppens uthållighet, motståndskraft och styrka. Ginseng är ett komplext ämne bestående av ett antal olika substanser, inklusive ginsenosider, flavonoider, vitaminer och enzymer, av vilka de steroidlika ginsenosiderna anses vara de mest aktiva beståndsdelarna. Flavonoider (som finns i till exempel frukt och grönsaker) och ginseng har genom forskning visat sig motverka bland annat hjärt-och kärlsjukdomar, diabetes, cancer och demens. Trots den omfattande användningen är dock mekanismen för hur ginseng verkar fortfarande oklar. I den här studien har vi använt pigmentinnehållande celler, melanoforer, från afrikansk klogroda för att undersöka effekterna av Panax ginseng på pigment-transport och dess maskineri. Melanoforer har förmågan att snabbt ändra färg genom samordnad förflyttning av pigmentkorn fram och tillbaka i cellen, och utgör en utmärkt modell för studier av intracellulär transport. Förflyttningen regleras av förändringar i halten av cykliskt adenosin-monofosfat (cAMP) i cellen, där en hög eller låg koncentration medför spridning av pigment över hela cellen (dispergering) eller en ansamling i mitten (aggregering), vilket resulterar i mörka respektive ljusa celler. Här visar vi att Panax ginseng, ginsenosiderna Rc och Rd samt flavonoiden quercetin stimulerar en dispergering av pigmentkornen. När melanoforerna inkuberades med en kombination av ginsenosid Rc eller Rd och quercetin, kunde en synergistisk ökning av dispergeringen ses, vilket tyder på en samverkan mellan ginsenosid- och flavonoid-delarna av ginseng. Ett protein som tidigare visats vara viktigt för pigmenttransporten är mitogen-aktiverat protein kinas (MAPK), och här visar vi att också melanoforer stimulerade med ginseng, men dock inte med ginsenosider eller quercetin, innehåller aktiverat MAPK. Genom att blockera enzymet protein kinas C (PKC) (känd aktivator av dispergering), minskade den ginseng- och ginsenosid-inducerade dispergeringen, medan aktiveringen av MAPK inte påverkades alls. Detta pekar på en roll för PKC i pigment-transporten men inte som en aktivator av MAPK.

Submitted by Reginaldo Soares de Freitas (reginaldo.freitas@ufv.br) on 2016-11-11T16:46:37Z No. of bitstreams: 1 texto completo.pdf: 682521 bytes, checksum: 869569e287896b20f5fe279b28aee120 (MD5) / Made available in DSpace on 2016-11-11T16:46:37Z (GMT). No. of bitstreams: 1 texto completo.pdf: 682521 bytes, checksum: 869569e287896b20f5fe279b28aee120 (MD5) Previous issue date: 2006-11-06 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Com o apelo da mudança para hábitos saudáveis, observa-se o aumento do consumo de fruta fresca em todo o mundo, que se estende aos sucos processados. Bebidas com novos sabores e aromas estão sendo elaboradas, sendo as bebidas mistas de frutas mais uma opção para os consumidores e uma tendência do mercado internacional. A adição de componentes funcionais também vem sendo feita, e os extratos de Ginkgo biloba e Panax ginseng vêm como uma nova opção, por apresentarem inúmeros benefícios à saúde, agregando valor aos produtos de frutas. Diante do exposto, o presente trabalho objetivou a elaboração de néctares mistos à base de caju, manga e acerola, adicionados de extratos de Ginkgo biloba e Panax ginseng e a mistura dos dois extratos, além de estudar a estabilidade dos produtos por um período de seis meses. Foram formulados néctares mistos de frutas tropicais, a partir de 35% de polpa e sólidos solúveis totais padronizados a 11 °Brix. Os teores de polpas variaram segundo um delineamento de misturas: caju (12,25%-21,00%); acerola (1,75%-10,50%); e manga (12,25%-21,00%). A formulação com 12,25% de caju, 21,00% de manga e 1,75% de acerola foi a mais aceita pelos provadores, e apresentou 49,9 mg de vitamina C/100mL de néctar. As respostas sensoriais também foram avaliadas através de análise de agrupamento e os grupos obtidos foram submetidos à análise de componentes principais, revelando a existência de três grupos distintos entre os provadores, indicando claramente a segmentação dos consumidores que preferiam formulações diferenciadas. A adição de extratos de Ginkgo biloba, Panax ginseng e a mistura de ambos em concentrações 15, 20, 25 e 30mg/100mL de néctar foi testada nos néctares, observando-se diminuição das notas de aceitação com o aumento da concentração dos extratos. Foram selecionados os néctares com adição de 15 mg de extrato de Ginkgo biloba/100 mL, 20 mg de extrato de Panax ginseng / 100 mL e a mistura com 10 mg de extrato de Ginkgo biloba e 10 mg de extrato de Panax ginseng/100 mL para avaliação da estabilidade durante 180 dias de armazenamento em condições similares às de comercialização. O tratamento térmico de 90 oC / 60s, conjuntamente com a adição de benzoato de sódio e metabissulfito foram suficientes para garantir a estabilidade microbiológica dos néctares formulados à temperatura ambiente. Os valores de pH, sólidos solúveis, acidez, e açúcares redutores apresentaram pouca variação ao longo dos 180 dias de armazenamento a temperatura ambiente. Os teores de vitamina C foram os que apresentaram maiores variações em todos os néctares mistos de frutas no decorrer de armazenamento. O tempo de armazenamento não afetou a qualidade sensorial dos produtos; sendo que a adição de extrato de Ginkgo biloba ao néctar misto de frutas alterou a aceitação pelos consumidores, sendo a aceitação destes produtos menores. Os resultados sensoriais foram avaliados através da metodologia de Mapa de Preferência Interno, que permitiu identificar a segmentação dos consumidores no aroma, sabor e impressão global, podendo ser feita uma identificação e caracterização de preferências e grupos consumidores. Os néctares sem adição de extrato (controle) e com adição de Panax ginseng foram os mais aceitos pelos consumidores em todos os atributos testados. / With the appealing of changes to healthy habits, it is observed that the consumption of fresh fruit has increased all over the world, and processed juices are an extension of that. Beverages presenting new flavors and aromas are being elaborated; being the mixed fruit drinks one more option to consumers and a trend to international market. The addition of functional components can also be noticed, and extracts of Ginkgo biloba e Panax ginseng are new options, once they present large benefits to human s health and aggregate value to fruit products. According to what was quoted, the actual work had as objective to develop mixed nectars based on cashew apple, mango and acerola, added to extracts of Ginkgo biloba e Panax ginseng and the mix of both extracts, as well as to study the stability of the developed products for six months. They were developed mixed nectars of tropical fruit formulated with at least 35% of pulp and total soluble solids, with 11°Brix. The values of pulp varied according to design of the mixtures: cashew apple (12.25%-21.00%); acerola (1.75%-10.50%); and mango (12.25%-21.00%). The formulation containing 12.25% of cashew apple, 21.00% of mango and 1.75% of acerola was best accepted among the panelists, and it showed 49.9mg of vitamin C/100mL of nectar. The sensorial responses were also evaluated trough cluster analyses and the obtained groups were submitted to main components analyses, showing the existence of three distinct groups among the panelists, indicating clearly consumer s segmentation that preferred different formulations. The addition of Ginkgo biloba and Panax ginseng extracts and the mixture of both in concentrations of 15, 20, 25 and 30mg/100ml nectar were tested at nectars; it was observed that values decreased as the concentration of the extract was being enhanced. They was selected the nectars with addition of 15mg of Ginkgo biloba extract/100 mL, 20 mg of Panax ginseng extract/100 mL and the mixture containing 10 mg of de Ginkgo biloba extract and 10 mg of Panax ginseng extract/100 mL for stability evaluation for the period of 180 days of storage in similar conditions of commercialization. The thermal treatment of 90 o C / 60s, combined to the addition of sodium benzoate and sodium metabisulfite were sufficient to guarantee microbiological stability of the formulated nectars at room temperature. The values of pH, soluble solids, acidity and reducing sugar showed little variation during 180 days of storage at room temperature. The contents of vitamin C were the ones that presented the highest variations in all mixed fruit nectars during the storage. The storage period did not affect the sensorial quality of the products, besides that, the addition of Ginkgo biloba extract to the mixed fruit nectar altered the consumers acceptance, being these products acceptance the lowest ones. The sensorial results were evaluated trough internal preference mapping methodology, which allowed an identification of the consumers segmentation of aroma, flavor and global impression, being possible an identification of characterization of preferences and consumers groups. The nectars without the addition of extract (control) and addition of Panax ginseng were preferred by consumers in all tested attributes.

Esta Dissertação apresenta informações gerais sobre os medicamentos fitoterápicos e os aspectos toxicológicos de uma amostra de dez plantas medicinais comercializadas como medicamentos fitoterápicos no Brasil, pesquisados junto aos principais bancos de dados e fontes públicas de informação. A análise dos medicamentos fitoterápicos cobre as dimensões histórica, econômica e farmacêutica. No tocante aos aspectos toxicológicos, foram avaliados os dados de toxicidade pré-clínica de dez plantas selecionadas, e realizado um levantamento das informações publicadas para Hypericum perforatum e Piper methysticum, relacionadas ao termo toxicidade, segundo três importantes bancos de dados. Adicionalmente, este trabalho aborda as propostas para realização de ensaios de toxicidade pré-clínica para os fitoterápicos segundo a OMS e legislação brasileira, e as normas para avaliação de substâncias químicas segundo a OECD. / This thesis presents general information on herbal medicines and on the toxicological aspects of a sample of ten medicinal plants traded as herbal medicines in Brazil. The survey was carried out in the main databases and public sources of information. The analysis on the herbal medicines encompasses the historical, economic and pharmaceutical dimensions. In what concerns toxicological aspects, data on pre-clinical toxicity were evaluated for Hypericum perforatum and Piper methysticum, these keywords being related to toxicity in three important databases. In addition, this study discusses the proposals for pre-clinical toxicity trials on herbal medicines according to WHO and the Brazilian legislation, and the standards for evaluation of chemical substances according to OECD.