Seventeen Cree anti-diabetic herbal medicines and eight Traditional Chinese Medicines have been examined for their potential to cause interactions with drugs, which is considered as a major reason for adverse drug effects. Specifically, the effect of these natural health products was examined on major Phase I drug metabolism enzymes including cytochrome P450, human carboxylesterase-1 and flavin-containing monooxygenases. Several of these natural health products have the potential to cause adverse drug effect through the inhibition of major drug metabolism enzymes. The results indicated that 7 Cree medicines plant extracts inhibited CYP3A4 activity, and 3 of them have been proven to cause potent mechanism-based inactivation of CYP3A4. Seven of eight Traditional Chinese Medicines have been identified as strong CYP3A4 inhibitors; the ethanol extract of Goji has identified as a potent inhibitor for CYP2C9 and 2C19. Goji juice showed universal inhibitory effects on most of the tested enzymes except flavin-containing monooxygenases 3.

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Seventeen Cree anti-diabetic herbal medicines and eight Traditional Chinese Medicines have been examined for their potential to cause interactions with drugs, which is considered as a major reason for adverse drug effects. Specifically, the effect of these natural health products was examined on major Phase I drug metabolism enzymes including cytochrome P450, human carboxylesterase-1 and flavin-containing monooxygenases. Several of these natural health products have the potential to cause adverse drug effect through the inhibition of major drug metabolism enzymes. The results indicated that 7 Cree medicines plant extracts inhibited CYP3A4 activity, and 3 of them have been proven to cause potent mechanism-based inactivation of CYP3A4. Seven of eight Traditional Chinese Medicines have been identified as strong CYP3A4 inhibitors; the ethanol extract of Goji has identified as a potent inhibitor for CYP2C9 and 2C19. Goji juice showed universal inhibitory effects on most of the tested enzymes except flavin-containing monooxygenases 3.

Made available in DSpace on 2015-05-14T12:56:06Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 3533467 bytes, checksum: bbf8bea9a32ae2311cd924bf8ad167bb (MD5) Previous issue date: 2010-01-12 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of this work was to identify through an Etnobotanic study the most used medicinal plants for health treatment of oral diseases and to evaluate the antibacterial activity and the potential for medicine interactions (antibiotics) during the use of medicinal plants. For this purpose the study was performed in the municipal districts of Cruz do Espírito Santo, Guarabira, Jacaraú, João Pessoa, Mamanguape, Santa Rita and Sapé, where 62 healers, 385 users and 197 dentists participated in an interview. They answered to subjects that involved socioeconomic and cultural variables and other factors relative to the use of medicinal plants for oral health. The antimicrobial activity of the most cited plants (n=5) was evaluated. To evaluate the antibacterial activity of the crude ethanolic extracts and decocts of the peels of Abarema cochliacarpos (Gomes) Barneby & J.W. Grimes (barbatimão), Anacardium occidentale L., (cashew tree-purple), Punica granatum L. (pomegranate), Schinus terebinthifolius Raddi (aroeira) and Ziziphus joazeiro Mart. (juá) were tested against strains of Streptococcus mutans (ATCC25175), Streptococcus mutans (ATCC700610), Streptococcus oralis (ATCC10557), Streptococcus salivarius (ATCC7073) and Staphylococcus aureus (ATCC6538), the Minimal Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (CBM) were determined for all strains through the diffusion method in solid medium, using disks of filter paper and using the microdilution method in broth, using plates of 96 wells. The interference of the crude extracts and decocts of the peels of the plants in the activity of the antibiotics Ampicillin 10μg/mL, Amoxicillin 10μg/mL and Cefalexina 30μg/mL was evaluated in an experimental model of microdiluição in broth. The results of the diffusion method evidenced that, except for the decoct of the Ziziphus joazeiro Mart., with activity just against Streptococcus mutans (ATCC25175) and the decot of Punica granatum L. against Streptococcus salivarius (ATCC7073), all the other tested products showed activity antimicrobial activity against all microorganisms. The diameters of halos varing from 12 to 28mm for the crude extracts and varying from 6 to18mm for the decocts. The MIC varying from 15 a 150 μg/mL and the 200 a 400 mg/mL, respectively, for the crude extracts and the decocts. The CBM for the crude extracts varying from 40 to 400 μg/mL and for the decocts was >400mg/mL. It was observed synergism and antagonism effect of the extracts in the activity of the selected antibiotics. The results of this study indicate that the medicinal plants are frequently used as therapeutic source for oral health and that there is a potential association (synergic or antagonistic) of the plants and antibiotics in this experimental model. Therefore, the most used medicinal plants evaluated presented effective biological activity (antibacterial activity). However potential associations with medicines deserves attention among users and professionals of health. / O objetivo deste trabalho foi identificar através de estudo etnobotânico, as plantas medicinais mais utilizadas para tratamento de doenças bucais e, avaliar a atividade antimicrobiana e o potencial para interações medicamentosas com antibióticos. Para tanto, realizou-se estudo etnobotânico nos municípios de Cruz do Espírito Santo, Guarabira, Jacaraú, João Pessoa, Mamanguape, Santa Rita e Sapé, onde 62 raizeiros, 385 usuários e 197 cirurgiões-dentistas participaram de uma entrevista e responderam a questões que envolviam indicadores sócio-econômicos e culturais e, outras relativas ao uso de plantas medicinais para tratar doenças bucais. Avaliou-se a atividade antimicrobiana das cinco plantas mais citadas no estudo etnobotânico. Para o ensaio da atividade antibacteriana dos extratos etanólicos brutos e decoctos das cascas de Abarema cochliacarpos (Gomes) Barneby & J.W. Grimes (barbatimão), Anacardium occidentale L., (cajueiro-roxo), Punica granatum L. (romã), Schinus terebinthifolius Raddi (aroeira) e Ziziphus joazeiro Mart. (juá) em linhagens de Streptococcus mutans (ATCC25175), Streptococcus mutans (ATCC700610), Streptococcus oralis (ATCC10557), Streptococcus salivarius (ATCC7073) e Staphylococcus aureus (ATCC6538, determinou-se a Concentração Inibitória Mínima (CIM) e a Concentração Bactericida Mínima (CBM). Os ensaios foram realizados através do método de difusão em meio sólido, utilizando discos de papel de filtro e, pelo método de difusão em meio líquido, utilizando placas de 96 poços. A interferência dos extratos etanólicos brutos e dos decoctos das cascas das plantas na atividade dos antibióticos Ampicilina - 10 μg/mL, Amoxicilina 10 μg/mL e Cefalexina 30 μg/mL foram avaliados em modelo experimental de microdiluição em caldo. Os resultados evidenciaram que, com exceção do decocto do Ziziphus joazeiro Mart., com atividade apenas frente ao Streptococcus mutans (ATCC25175) e o da Punica granatum L., frente ao Streptococcus salivarius (ATCC7073), todos os demais produtos testados mostraram atividade antimicrobina frente aos microrganismos ensaiados. Os halos de inibição variaram de 12 a 28mm para os extratos e de 6 a 18mm para os decoctos ensaiados. A CIM variou de 15 a 150 μg/mL e de 200 a 400 mg/mL, respectivamente, para os extratos e decoctos testados. A CBM dos extratos estudados variou de 40 a 400 μg/mL e, a dos decoctos foi > 400 mg/mL. Observaram-se efeitos de sinergismo e de antagonismo nas associações entre as plantas medicinais e os antibióticos ensaiados, indicando interferência dos extratos testados na atividade dos antimicrobianos selecionados. Os resultados apresentados neste estudo indicam que as plantas medicinais são utilizadas popularmente como recurso terapêutico na área da Odontologia e que, a associação das plantas e antibióticos ensaiados, neste modelo experimental, apresentou potencial para promover interações medicamentosas sinérgicas ou antagônicas. Portanto, as plantas medicinais mais utilizadas pela população apresentaram atividade biológica antimicrobiana. No entanto, o uso simultâneo com medicamentos merece atenção dos usuários e dos profissionais de saúde.

Seventeen Cree anti-diabetic herbal medicines and eight Traditional Chinese Medicines have been examined for their potential to cause interactions with drugs, which is considered as a major reason for adverse drug effects. Specifically, the effect of these natural health products was examined on major Phase I drug metabolism enzymes including cytochrome P450, human carboxylesterase-1 and flavin-containing monooxygenases. Several of these natural health products have the potential to cause adverse drug effect through the inhibition of major drug metabolism enzymes. The results indicated that 7 Cree medicines plant extracts inhibited CYP3A4 activity, and 3 of them have been proven to cause potent mechanism-based inactivation of CYP3A4. Seven of eight Traditional Chinese Medicines have been identified as strong CYP3A4 inhibitors; the ethanol extract of Goji has identified as a potent inhibitor for CYP2C9 and 2C19. Goji juice showed universal inhibitory effects on most of the tested enzymes except flavin-containing monooxygenases 3.

Antecedentes y Objetivo Los adultos mayores exhiben mayor probabilidad de presentar Interacciones droga-droga (DDI) potencialmente graves. El objetivo del estudio fue identificar la frecuencia de las interacciones farmacológicas potencialmente graves en adultos mayores atendida en un hospital de referencia peruano, así como sus factores asociados. Materiales y Métodos Estudio transversal analítico en pacientes atendidos en consultorio externo de geriatría en el Hospital Centro Médico Naval durante noviembre del 2018 - marzo 2019. Se registraron los datos consignados en las historias clínicas y se evaluó la presencia de DDIs utilizando la herramienta Lexicomp®️. Se evaluó la asociación con los potenciales factores utilizando un modelo de Regresión de Poisson con varianzas robustas. Resultados Se analizaron 306 historias clínicas. La mediana fue de edad de 74 (68-82) años con predominancia masculina (63,40%). El 27,78% de la población presentó interacciones farmacológicas potencialmente graves. El 61,76% recibía de 5 o más fármacos. El 97,06% presentó multimorbilidad y el 56,21% presentó hipertensión arterial. En el análisis bivariado, los factores significativamente asociados a las interacciones farmacológicas potencialmente graves fueron el género femenino (PR:0,65; IC:0,45-0,93; p=0,018), la osteoartritis (PR:1,82; IC:1,28-2,56; p=0,001), la presencia de síntomas depresivos (PR:1,80; IC:1,14-2,87; p=0,012) y la polifarmacia (PR:8,15; IC:3,66-18,11; p<0,001). En el análisis multivariado, los factores significativamente asociados a DDIs potencialmente graves fueron la polifarmacia (PR:8,05; IC:3,61-17,92; p<0,001) y la osteoartritis (PR:1,76; IC:1,29-2,40; p<0,001). Conclusiones La polifarmacia es el principal factor de riesgo para la presencia de DDIs graves. Se debe evaluar rutinariamente las posibles interacciones medicamentosas en pacientes geriátricos polimedicados. / Background and Objectives Elderly are more likely to have potentially serious Drug-Drug Interactions (DDIs). The objective of the study was to identify the frequency of potentially serious drug interactions in the population of elderly treated at a Peruvian referral hospital, as well as their associated factors. Materials and Methods Analytical cross-sectional study in a population attended in the outpatient clinic of geriatrics at the Hospital Naval Medical Center during November 2018 - March 2019. The data recorded in the medical records were recorded and the presence of DDIs was evaluated using the Lexicomp®️ tool. The association with the potential factors was evaluated using a Poisson regression model with robust variances. Results We analyzed 306 clinical histories. The average age of 74 (68-82) years with male predominance (63,40%). 27,78% of the population had potentially serious drug interactions. Likewise, 61,76% consumed 5 to more drugs. 97,06% presented multimorbidity and 56,21% had arterial hypertension. In the bivariate analysis, the factors significantly associated with the potentially serious pharmacological interactions were the female gender (PR:0,65; CI:0,45-0,93; p=0,018), the presence of osteoarthritis (PR:1,82; CI:1,28-2,56; P=0,001), depressive symptoms (PR:1,80; CI:1,14-2,87; p=0,012), and polypharmacy (PR:8,15; CI:3,66-18,11; p<0,001). In the multivariate analysis, the factors significantly associated with potentially serious DDI were polypharmacy (PR:8,05; CI:3,61-17,92; P<0,001) and osteoarthritis (PR:1,76; CI:1,29-2,40; p<0,001). Conclusions Polypharmacy is the main risk factor for the presence of serious DDIs. Possible drug interactions should be routinely evaluated in polymedicated geriatric patients. / Tesis

Les patients admis aux soins intensifs (SI) souffrent de comorbidités qui affectent leur pronostic. Deux problèmes sont potentiellement associés aux sédatifs et compliquent le séjour de 35 à 50% des malades : le délirium, un état confusionnel aigu; et le coma ‘iatrogénique’, une altération de la conscience induite pharmacologiquement. L’importance de l’association entre clinique et médicaments a un intérêt pour prévenir ces syndromes cliniques morbides. Nous voulions étudier le délirium et le coma iatrogénique, les doses administrées de midazolam et de fentanyl, leurs niveaux plasmatiques, les variantes génétiques de métabolisme et de transport et les facteurs inflammatoires et ce, chez 100 patients admis aux soins intensifs. Nos données soulignent l’importance des interactions médicamenteuses dans l’incidence du coma iatrogénique, et réfutent l’association entre les benzodiazépines et le délirium. Ces résultats clarifient la pathophysiologie du délirium, corroborent le manque d’association délirium-benzodiazépines avec un marqueur biologique, c.-à-d. les niveaux sériques, et ouvrent le débat quant aux agents les plus utiles pour traiter l’anxiété et le délirium. Finalement, plusieurs caractéristiques pharmacocinétiques des benzodiazépines administrées aux soins intensifs publiées récemment complètent les données de notre étude quant à la sédation en soins critiques. Un chapitre sur l’importance de la pharmacogénomique en soins intensifs et un débat publié quant au pro et con de l'utilisation des benzodiazépines aux SI, sont soumis en complément de l’étude clinique décrite ci-haut effectuée dans le cadre de cette maîtrise. / Critically ill patients suffer from co-morbid conditions that impact on their prognosis. Two problems complicate Intensive Care Unit (ICU) stay in 35-50% of patients and are potentially associated with sedatives: delirium, an acute confusional state, and 'iatrogenic' coma, when consciousness is altered pharmacologically. Establishing the association between these clinical syndromes and administering sedatives is key in planning effective prevention of these morbid complications. We studied iatrogenic delirium and coma in 100 ICU patients given midazolam and/or fentanyl, and tallied drug doses, measured plasma levels, genetic variations in metabolism and transport and inflammatory factors. Our data highlight the role drug-drug interactions play in iatrogenic coma, and refute the association between benzodiazepines and delirium. These results clarify the pathophysiology of delirium, corroborate the lack of delirium-benzodiazepine association with a benzodiazepine biological marker, i.e. serum levels, and open the debate as to which agents are useful for treating anxiety and delirium. Recent publications addressing benzodiazepine pharmacokinetics in critical care complement our data in the field of critical care sedation. A chapter on the importance of pharmacogenomics in intensive care, and a published pro-con debate as to benzodiazepine use in critical care are submitted in addition to the clinical study mentioned above as part of this master’s thesis.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Treatment with neuroleptic drugs has been associated to side effects like tardive diskynesia and hepatic damage. In spite of the several reports of hepatotoxicity after neuroleptic administration, few data are available in the literature about these effects and the precise mechanisms by which neuroleptics induce hepatotoxicity remain unclear. In the same way, there are few studies about the effects of neuroleptics on kidney. In this way, the first aim of the present work was to assess the effects of chronic exposure to fluphenazine in liver and kidney of rats, as well as the protective effect of diphenyl diselenide on the fluphenazine-induced damage (article 1). Long-term treatment with fluphenazine caused an increase in lipid peroxidation levels in liver and kidney homogenates, a decrease in hepatic SOD activity, and an increase in hepatic CAT activity. Diphenyl diselenide was able to protect liver and kidney from lipid peroxidation, ameliorate SOD activity in liver, and prevent the increase in hepatic CAT activity. Diphenyl diselenide treatment did not affect δ-ALA-D activity, but fluphenazine and/or in combination with diphenyl diselenide showed an inhibitory effect on δ-ALA-D activity in liver and kidney. The second objective of this study was to determine whether the treatment with haloperidol (HP), valerian or both in association impairs liver or kidney functions (article 2). Valerian did not affect oxidative stress parameters in the liver or kidney of rats. HP only increased glutathione (GSH) depletion in liver, but not in kidney. However, when HP was associated with valerian, an increase in lipid peroxidation levels and reactive species production was observed in the hepatic tissue. HP and valerian when administered independently did not affect the activity of hepatic and renal δ-ALA-D, however, these drugs administered concomitantly provoked an inhibition of hepatic δ-ALA-D activity. Serum aspartate aminotransferase (AST) activity was not altered by any treatment. However, serum alanine aminotransferase (ALT) activity was higher in the HP group and HP plus valerian group. Taken together, these results indicate the relationship between the treatment with flufenazine and the oxidative stress, and also point to the protective role of diphenyl diselenide on the oxidative damage induced by fluphenazine in liver. Our data also suggest adverse interactions between haloperidol and valerian treatments causing hepatic damage related to oxidative stress. / O tratamento com drogas neurolépticas tem sido associado a efeitos colaterais como a discinesia tardia (DT) e o dano hepático. Apesar dos inúmeros casos de hepatotoxicidade após a administração de neurolépticos, são escassos os dados na literatura a respeito desses efeitos e o mecanismo exato pelo qual neurolépticos induzem hepatotoxicidade permanece incerto. Da mesma forma, existem poucos estudos relatando os efeitos dos neurolépticos sobre o rim. Dessa forma, o primeiro objetivo deste trabalho foi avaliar os efeitos da exposição crônica à flufenazina em fígado e rim de ratos bem como o efeito protetor do disseleneto de difenila sobre o dano induzido por flufenazina (artigo 1). O tratamento prolongado com flufenazina causou um aumento na peroxidação lipídica no fígado e no rim, uma diminuição na atividade da SOD hepática, e um aumento na atividade da CAT hepática. O disseleneto de difenila foi capaz de proteger o fígado e o rim da peroxidação lipídica, melhorou a atividade da SOD no fígado, e preveniu o aumento na atividade da CAT no fígado. O tratamento com disseleneto de difenila não afetou a atividade da δ-ALA-D, mas a flufenazina e/ou em combinação com disseleneto de difenila demonstrou ter efeito inibitório sobre a atividade da δ-ALA-D no fígado e no rim. O segundo objetivo deste estudo foi determinar se o tratamento com haloperidol (HP), valeriana ou a associação de ambas as drogas pode alterar as funções hepáticas e renais (artigo 2). A valeriana não afetou nenhum parâmetro de estresse oxidativo no fígado e no rim dos ratos. O HP apenas aumentou a depleção de glutationa (GSH) no fígado, mas não no rim. Entretanto, quando o HP foi associado com a valeriana, um aumento na peroxidação lipídica e produção de espécies reativas foram observados no tecido hepático. HP e valeriana quando administrados independentemente não afetaram a atividade da δ-ALA-D hepática e renal, contudo, quando estas drogas foram administradas concomitantemente provocaram uma inibição da atividade da δ-ALA-D hepática. A atividade da aspartato aminotransferase (AST) do soro não foi alterada por nenhum dos tratamentos. No entanto, a atividade da alanina aminotransferase (ALT) do soro estava aumentada nos grupos tratados com HP e HP mais flufenazina. Juntos estes resultados indicam uma relação entre o tratamento com flufenazina e o estresse oxidativo, e também apontam para o papel protetor do disseleneto de difenila no dano oxidativo induzido por flufenazina no fígado. Nossos dados também sugerem interações adversas no tratamento com haloperidol e valeriana, ocasionando dano hepático associado ao estresse oxidativo.

This thesis examines the cytochrom P450 (CYP) drug metabolizing enzyme inhibition and antimicrobial properties of 46 common food plants available in the Canadian Market and the inhibitory properties of 17 traditional Cree antidiabetic medicines on aldose reductase. Inhibitory activity profiles of CYP 3A4, 3A5, 3A7 and 2D6 were created for the 46 samples. The most active plants in the CYP inhibition assay were the spices, belonging to the Apiaceae and Lamiaceae. Similarly, the most active plants in the antimicrobial assay were also the Apiaceae and Lamiaceae. Swine lens homogenate was tested as a novel model for the aldose reductase inhibition assay. Several Cree plants selected for the aldose reductase study showed a high activity, primarily in samples which also contained high levels of phenolics. A positive correlation was observed between total phenolics content and aldose reductase inhibition r2=0.44, p=0.05. Crude extracts of Rhododendron groenlandicum exhibited inhibitory activities of 35.11 ± 0.16 %. The subfractionation and HPLC analysis of R. groenlandicum revealed high levels of phenolics compounds including, catechin, epicatechin, quercetin and quercetin glycosides. This study found that medicinal and food plants contain phytochemicals that may have both beneficial and detrimental biological effects. / Nous avons étudié dans cette thèse les capacités de 46 plantes comestibles, disponibles sur le marché canadien, à inhiber le cytochrome P450 (CYP), enzyme responsable du métabolisme des médicaments, les propriétés antimicrobiennes, et les propriétés inhibitrices de l'aldose réductase à partir de 17 médicaments antidiabétiques traditionnellement utilisés par les Cris. Les profils de l'activité inhibitrice du CYP 3A4, 3A5, 3A7 et 2D6 ont été réalisés pour les 46 plantes à l'étude. Les plantes les plus actives dans le test d'inhibition du CYP furent les épices, plantes appartenant aux familles des Apiaceae et Lamiaceae. De même, les plantes les plus actives dans le bioessai antimicrobien furent aussi les plantes de ces deux mêmes familles. Un homogénat de cristallin de porc a été utilisé comme modèle nouveau pour le test d'inhibition de l'aldose réductase. Plusieurs plantes, utilisées par la nation Cri, qui ont été sélectionnées pour l'étude ont montré une forte activité inhibitrice de l’aldose réductase, principalement dans les échantillons qui contenaient des teneurs élevées en composés phénoliques. Une corrélation positive a été observée entre la teneur totale en composés phénoliques et l'inhibition de l'aldose réductase (r2 = 0.44, p = 0.05). Des extraits bruts de Rhododendron groenlandicum ont montré des activités inhibitrices de 35.11 ± 0.16%. Le sous-fractionnement et l'analyse HPLC de R. groenlandicum ont aussi révélé des teneurs élevées des composés phénoliques, incluant la catéchine, l'épicatéchine, la quercétine et les glycosides de quercétine. Cette étude a montré que les plantes médicinales et alimentaires contiennent des composés phytochimiques qui peuvent avoir à la fois des effets biologiques bénéfique et préjudiciable.

This thesis examines the cytochrom P450 (CYP) drug metabolizing enzyme inhibition and antimicrobial properties of 46 common food plants available in the Canadian Market and the inhibitory properties of 17 traditional Cree antidiabetic medicines on aldose reductase. Inhibitory activity profiles of CYP 3A4, 3A5, 3A7 and 2D6 were created for the 46 samples. The most active plants in the CYP inhibition assay were the spices, belonging to the Apiaceae and Lamiaceae. Similarly, the most active plants in the antimicrobial assay were also the Apiaceae and Lamiaceae. Swine lens homogenate was tested as a novel model for the aldose reductase inhibition assay. Several Cree plants selected for the aldose reductase study showed a high activity, primarily in samples which also contained high levels of phenolics. A positive correlation was observed between total phenolics content and aldose reductase inhibition r2=0.44, p=0.05. Crude extracts of Rhododendron groenlandicum exhibited inhibitory activities of 35.11 ± 0.16 %. The subfractionation and HPLC analysis of R. groenlandicum revealed high levels of phenolics compounds including, catechin, epicatechin, quercetin and quercetin glycosides. This study found that medicinal and food plants contain phytochemicals that may have both beneficial and detrimental biological effects. / Nous avons étudié dans cette thèse les capacités de 46 plantes comestibles, disponibles sur le marché canadien, à inhiber le cytochrome P450 (CYP), enzyme responsable du métabolisme des médicaments, les propriétés antimicrobiennes, et les propriétés inhibitrices de l'aldose réductase à partir de 17 médicaments antidiabétiques traditionnellement utilisés par les Cris. Les profils de l'activité inhibitrice du CYP 3A4, 3A5, 3A7 et 2D6 ont été réalisés pour les 46 plantes à l'étude. Les plantes les plus actives dans le test d'inhibition du CYP furent les épices, plantes appartenant aux familles des Apiaceae et Lamiaceae. De même, les plantes les plus actives dans le bioessai antimicrobien furent aussi les plantes de ces deux mêmes familles. Un homogénat de cristallin de porc a été utilisé comme modèle nouveau pour le test d'inhibition de l'aldose réductase. Plusieurs plantes, utilisées par la nation Cri, qui ont été sélectionnées pour l'étude ont montré une forte activité inhibitrice de l’aldose réductase, principalement dans les échantillons qui contenaient des teneurs élevées en composés phénoliques. Une corrélation positive a été observée entre la teneur totale en composés phénoliques et l'inhibition de l'aldose réductase (r2 = 0.44, p = 0.05). Des extraits bruts de Rhododendron groenlandicum ont montré des activités inhibitrices de 35.11 ± 0.16%. Le sous-fractionnement et l'analyse HPLC de R. groenlandicum ont aussi révélé des teneurs élevées des composés phénoliques, incluant la catéchine, l'épicatéchine, la quercétine et les glycosides de quercétine. Cette étude a montré que les plantes médicinales et alimentaires contiennent des composés phytochimiques qui peuvent avoir à la fois des effets biologiques bénéfique et préjudiciable.