ABSTRACT
Mineralocorticoid receptors (MRs), which are activated by mineralocorticoids and glucocorticoids, actively participate in mechanisms that affect the structure and function of blood vessels. Although experimental and clinical evidence shows that vascular damage in diabetes is associated with structural alterations in large and small arteries, the role of MR in this process needs further studies. Thus, we tested the hypothesis that MR, through redox-sensitive mechanisms, plays a role in diabetes-associated vascular remodelling. Male, 12-14-weeks-old db/db mice, a model of type 2 diabetes and their non-diabetic counterpart controls (db/+) were treated with spironolactone (MR antagonist, 50 mg/kg/day) or vehicle for 6 weeks. Spironolactone treatment did not affect blood pressure, fasting glucose levels or weight gain, but increased serum potassium and total cholesterol in both, diabetic and control mice. In addition, spironolactone significantly reduced serum insulin levels, but not aldosterone levels in diabetic mice. Insulin sensitivity, evaluated by the HOMA (homoeostatic model assessment)-index, was improved in spironolactone-treated diabetic mice. Mesenteric resistance arteries from vehicle-treated db/db mice exhibited inward hypertrophic remodelling, increased number of smooth muscle cells and increased vascular stiffness. These structural changes, determined by morphometric analysis and with a myography for pressurized arteries, were prevented by spironolactone treatment. Arteries from vehicle-treated db/db mice also exhibited augmented collagen content, determined by Picrosirius Red staining and Western blotting, increased reactive oxygen species (ROS) generation, determined by dihydroethidium (DHE) fluorescence, as well as increased expression of NAD(P)H oxidases 1 and 4 and increased activity of mitogen-activated protein kinases (MAPKs). Spironolactone treatment prevented all these changes, indicating that MR importantly contributes to diabetes-associated vascular dysfunction by inducing oxidative stress and by increasing the activity of redox-sensitive proteins.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Mineralocorticoid Receptor Antagonists/chemistry , Receptors, Mineralocorticoid/physiology , Aldosterone/blood , Animals , Blood Glucose/drug effects , Blood Pressure/drug effects , Body Weight/drug effects , Cholesterol/blood , Collagen/chemistry , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Type 2/blood , Ethidium/analogs & derivatives , Ethidium/chemistry , Glucocorticoids/metabolism , Insulin/blood , Male , Mice , Mineralocorticoids/metabolism , Potassium/blood , Reactive Oxygen Species/chemistry , Spironolactone/therapeutic useABSTRACT
O presente trabalho verificou a utilização de plantas medicinais encontradas no Cerrado mato-grossense para o tratamento de hiperlipidemias e obesidade. Entrevistas com 180 pessoas acima de 50 anos foram realizadas em Nova Xavantina-MT. O questionário abordou nome popular, parte utilizada, forma de preparo e uso das espécies citadas, além de informações gerais sobre o uso de plantas. As dez plantas mais citadas foram coletadas, identificadas e estudadas por meio de uma revisão bibliográfica. A maioria dos entrevistados (95,6 por cento) declarou utilizar plantas medicinais regularmente, sendo que 71,5 por cento deles herdaram o conhecimento sobre plantas dos pais e avós e 94,20 por cento relataram aconselhar o uso aos mais jovens. Além disso, 93,6 por cento atestaram que as plantas são mais eficazes que os medicamentos de farmácia e 57 por cento consideraram forte o efeito das mesmas, ou seja, sempre resolvem o problema de saúde. Quanto aos efeitos adversos, 95,9 por cento disseram nunca ter sentido após o uso de plantas. Dos entrevistados, 56,7 por cento conheciam ou já haviam utilizado plantas medicinais no tratamento de hiperlipidemias e obesidade, sendo citadas 54 espécies medicinais diferentes pertencentes a 53 gêneros e 38 famílias, com destaque para Fabaceae (13 por cento). As dez plantas mais citadas foram: guatambu (Aspidosperma tomentosum Mart.), quina-do-cerrado (Strychnos pseudoquina St. Hil.), ipê-roxo [Tabebuia impetiginosa (Mart. Ex DC.) Standl], embaúba (Cecropia pachystachya Trec.), calunga (Simaba sp.), pata-de-vaca [Bauhinia rufa (Bong.) Steud.], mangaba (Hancornia speciosa Gomez), batata-de-tiú [Jatropha elliptica (Pohl.) Muell. Arg.], folha-de-carne (Casearia sylvestris Sw.) e manacá (Spiranthera odoratissima A. St.-Hil.). A folha foi a parte mais utilizada (46 por cento) e o preparo das plantas ocorre principalmente por meio de infusão citado por 36,5 por cento dos entrevistados. Apesar do uso popular destas plantas no combate as hiperlipidemias e obesidade, há necessidade de estudos fitoquímicos e farmacológicos que comprovem estas atividades, com vistas ao desenvolvimento de um fitoterápico.
This study checked the use of medicinal plants found in the Cerrado mato-grossense for the treatment of hyperlipidemia and obesity. Interviews with 180 people over 50 years were held in Nova Xavantina-MT. The questionnaire addressed popular name, part used, type of preparation and use of the species mentioned, beyond general information about the use of plants. The ten plants most cited were collected, identified and studied through a literature review. Most respondents (95.6 percent) said using medicinal plants regularly, while 71.5 percent of them inherited the knowledge of plants of parents and grandparents and 94.20 percent reported the use to advise youngsters. Furthermore, 93.6 percent attested that the plants are more effective than the drugs from pharmacy and 57 percent considered the strong effect of the same, i.e., they always solved health problems. Regarding adverse effects, 95.9 percent said they have never felt them after the use of plants. Of the respondents, 56.7 percent knew or had used medicinal plants in the treatment of hyperlipidemias and obesity, being cited 54 medicinal species belonging to 53 different genera and 38 families, with emphasis on Fabaceae (13 percent). The ten most cited were: guatambu (Aspidosperma tomentosum Mart.), quina-do-cerrado (Strychnos pseudoquina St. Hil.), ipê-roxo [Tabebuia impetiginosa (Mart. Ex DC.) Standl], embaúba (Cecropia pachystachya Trec.), calunga (Simaba sp.), pata-de-vaca [Bauhinia rufa (Bong.) Steud.], mangaba (Hancornia speciosa Gomez), batata-de-tiú [Jatropha elliptica (Pohl.) Muell. Arg.], folha-de-carne (Casearia sylvestris Sw.) and manacá (Spiranthera odoratissima A. St.-Hil.). The leaf was the most used (46 percent) and the preparation of the plants occurs mainly through the infusion cited by 36,5 percent of respondents. Despite the popular use of these plants for treatment of obesity and hyperlipidemia, further chemical and pharmacological studies are required to demonstrate these activities, in order to develop a phytotherapic product.