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Cedrela odorata 内皮的水醇提取物毒性低,可降低蔗糖和葡萄糖过载引起的高血糖。

Hydroethanolic extract of the inner stem bark of Cedrela odorata has low toxicity and reduces hyperglycemia induced by an overload of sucrose and glucose.

机构信息

Department of Chemistry, Biochemistry Laboratory, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil.

Natural Products Research Laboratory, Faculty of Medicine, Federal University of Tocantins (UFT), Av. NS15, Palmas, CEP: 77020-210, Palmas, Tocantins, Brazil.

出版信息

J Ethnopharmacol. 2015 Mar 13;162:352-61. doi: 10.1016/j.jep.2014.12.059. Epub 2015 Jan 3.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Cedrela odorata L. (Meliaceae) is a native plant of the Amazon region and its inner stem bark is used in the treatment of diabetes in the form of maceration in Brazilian popular medicine. Until now, there is no scientific study on this activity. The present study was aimed at evaluating the anti-hyperglycemic activity, anti-diabetic, toxicity, antioxidant and potential mechanism of action of hydroethanolic extract of the inner stem bark of Cedrela odorata.

MATERIAL AND METHODS

The inner stem bark extract of Cedrela odorata was prepared by maceration in 70% ethanol for 7 days to obtain hydroethanolic extract of Cedrela odorata (HeECo). The preliminary phytochemical analysis was performed according to procedures described in the literature. Selected secondary metabolites detected were quantified by high performance liquid chromatography (HPLC). Acute toxicity of HeECo was investigated in male and female mice with oral administration of graded doses of HeECo from 10 to 5000 mg/kg. Subchronic oral toxicity study was done by oral administration of HeECo (500 mg/kg) and vehicle for 30 days to both sexes of Wistar rats. Clinical observations and toxicological related parameters were determined. Blood was collected for biochemical and hematological analyses, while histological examinations were performed on selected organs. Anti-hiperglycemic and antidiabetic effects were evaluated in streptozotocin-induced diabetic rats. In acute evaluation, the animals received pretreatment with 250 and 500 mg/kg of HeECo, before carbohydrate overload. For subchronic effect, the antidiabetic activity of HeECo was evaluated using the same doses for 21 days. At the end of the treatments, the levels of triacylglycerols, malondialdehyde, total antioxidant status, superoxide dismutase and glutathione peroxidase activities were evaluated in the plasma.

RESULTS

The extract showed low acute toxicity. HeECo exhibited inhibitory activity against α-glucosidase and caused a lowering in the peak levels of blood glucose in animals that received glucose overload by 36.7% and 24.1% in the area under the glucose curve (AUC). When the overload was sucrose, HeECo reduced the blood glucose level by 44.4% without affecting AUC. Treatment with HeECo of the blood glucose of the diabetic animals for 21 days did not lead to improvement in weight gain and regularization of the blood glucose level, but reduced the triacylglycerol and malondialdehyde levels by 36.6% and 48.1%, respectively. The activity of the antioxidant enzymes, superoxide dismutase and glutathione peroxidase were significantly increased when compared to diabetic control rats. HPLC analysis showed the presence of polyphenols, such as gallic acid, (-)- gallocatechin and (+)- catechin, the latter is present in higher quantity.

CONCLUSIONS

Collectively, these data showed that HeECo could blunt the postprandial glycemic surge in rats; possibly through inhibition of alpha-glucosidase and positive modulation of antioxidant enzymes. Our findings confirmed the anti-hiperglycemic activity of HeECo in STZ- diabetic rats. Cedrela odorata is effective in diminishing glucose levels in vitro and in vivo and in ameliorating oxidative damage that occurs in diabetes and/or due to hyperglycemia in rats. According to our results, the efficacy of Cedrela odorata preparation could be due to the presence of active principles with different mode of actions at the molecular level, including α-glycosidases and glucose transporter inhibitors and antioxidant property.

摘要

植物药的相关性

Cedrela odorata L.(楝科)是亚马逊地区的原生植物,其内皮在巴西民间医学中被用于治疗糖尿病,方法是浸泡在 70%乙醇中。到目前为止,尚未对此种活性进行科学研究。本研究旨在评估 Cedrela odorata 内皮的水醇提取物的抗高血糖活性、抗糖尿病、毒性、抗氧化作用和潜在作用机制。

材料和方法

采用 70%乙醇浸泡 Cedrela odorata 的内皮,制备 Cedrela odorata 的水醇提取物(HeECo)。根据文献中描述的程序进行初步的植物化学分析。选择的次级代谢物通过高效液相色谱法(HPLC)进行定量检测。通过口服给予 10-5000mg/kg 的 HeECo 对雄性和雌性小鼠进行急性毒性研究。通过口服给予 500mg/kg 的 HeECo 和载体对雄性和雌性 Wistar 大鼠进行 30 天的亚慢性毒性研究。测定临床观察和毒理学相关参数。采集血液进行生化和血液学分析,同时对选定的器官进行组织学检查。在链脲佐菌素诱导的糖尿病大鼠中评估抗高血糖和抗糖尿病作用。在急性评估中,动物在碳水化合物过载前接受 250 和 500mg/kg 的 HeECo 预处理。对于亚慢性作用,使用相同剂量的 HeECo 评估 21 天的抗糖尿病活性。在治疗结束时,评估血浆中三酰甘油、丙二醛、总抗氧化状态、超氧化物歧化酶和谷胱甘肽过氧化物酶活性的水平。

结果

提取物表现出低急性毒性。HeECo 对α-葡萄糖苷酶表现出抑制活性,并使接受葡萄糖过载的动物的血糖峰值降低 36.7%和 24.1%(AUC)。当使用蔗糖过载时,HeECo 使血糖水平降低 44.4%,而不影响 AUC。HeECo 治疗糖尿病动物 21 天不能改善体重增加和血糖水平的规律,但降低了 36.6%和 48.1%的三酰甘油和丙二醛水平。与糖尿病对照大鼠相比,抗氧化酶超氧化物歧化酶和谷胱甘肽过氧化物酶的活性显著增加。HPLC 分析表明存在多酚,如没食子酸、(-)-表儿茶素和(+)-儿茶素,后者的含量更高。

结论

综上所述,这些数据表明 HeECo 可以抑制大鼠的餐后血糖激增;可能通过抑制α-葡萄糖苷酶和正向调节抗氧化酶。我们的研究结果证实了 HeECo 在 STZ-糖尿病大鼠中的抗高血糖作用。Cedrela odorata 在体外和体内均能有效降低血糖水平,并能改善糖尿病和/或高血糖大鼠发生的氧化损伤。根据我们的结果,Cedrela odorata 制剂的功效可能是由于存在具有不同作用模式的活性成分,包括α-糖苷酶和葡萄糖转运体抑制剂以及抗氧化特性。

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