Antidiabetic effects of Olea europaea L. leaves in diabetic rats induced by high-fat diet and low-dose streptozotocin

https://doi.org/10.1016/j.jep.2019.02.001Get rights and content

Highlights

  • Diabetes mellitus is a widespread disease worldwide.

  • It is associated with high rates of mortality and morbidity due to its complications.

  • Medicinal plants possess bioactive constituents that are important in diseases prevention and treatment.

  • Olive leaves has important biological activities that may be useful in the treatment of diabetes mellitus.

Abstract

Ethnopharmacological relevance

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, insulin resistance, and dyslipidemia. It has broad occurrence worldwide, affecting millions of people, and can cause serious complications. The olive (Olea europaea L.) has important pharmacological functions, including anti-inflammatory, antioxidant, and hypoglycemic activities. Olive leaves are used in traditional medicine for diabetes and hypertension.

Aim of the study

To evaluate the effect of the ethanolic extract of olive leaves (EEOL) on the metabolism of rats with diabetes induced by a high-fat diet and low dose of streptozotocin (STZ).

Materials and methods

Male Wistar rats were either given normal feed or a high-fat diet (70% standard laboratory feed, 15% sucrose, 10% lard and 5% yolk powder) for four weeks, followed by administration of STZ (35 mg/kg, via ip). Animals with fasting glucose levels above 200 mg/dL were considered diabetic. Animals were divided into 5 groups, which received ethanol (10 mL/kg), metformin (250 mg/kg), or EEOL at doses of 200 and 400 mg/kg during 10 weeks by oral gavage. Blood samples were used to measure hematological and biochemical parameters, and kidneys were removed for posterior analysis. Body weight was recorded weekly.

Results

A significant decrease in body weight was observed among diabetic animals treated with ethanol and EEOL compared to the control group. Moreover, animals treated with EEOL showed an improvement in glucose levels and in levels of inflammatory and metabolic markers when compared to diabetic animals.

Conclusions

The results indicate a potential anti-diabetic activity of olive leaves, however more studies are needed to validate clinical effects.

Introduction

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, resulting in defects in insulin secretion and/or action, and dyslipidemia. DM can be classified into two main classes: type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), with T2DM affecting about 5% of the population (Wang et al., 2009). T2DM is associated with long-term organ damage, dysfunction and failure, and is currently one of the costliest chronic diseases in the world (American Diabetes Association (ADA), 2011, Constantino et al., 2013). This disease is also linked to obesity, insulin resistance, and defects in pancreatic β-cell function and mass (Skovsø, 2014). The increase of diabetic patients has been partly associated with the consumption of a high-calorie diet, sedentary lifestyle and obesity (Klein et al., 2007).

Many drugs have been used for the treatment of diabetes. However, their high cost and adverse effects have increased the search for alternative therapies. Recently, evidence on complementary treatments for T2DM using plants and their bioactive compounds has increased (Mirmiran et al., 2014). About 80% of people with diabetes in the world depend on medicinal plants for a successful treatment (Oloyede et al., 2015). Among these plants is Olea europaea L. This species belongs to the Oleaceae family and is popularly known as the olive tree, holding a history of commercial, medicinal and nutritional use of its fruit, leaves and oil (Soni et al., 2006). Olive leaves are considered low-cost raw materials and have been widely used in traditional remedies in European and Mediterranean countries (Abd El-Rahman, 2016). Moreover, olive leaves have been used as a medical herb to treat diabetic hyperglycemia, hypertension and infectious diseases, being especially recognized in Europe as a folk medicine for diabetes and hypertension (El and Karakaya, 2009). A study conducted by Candar et al. (2018) demonstrated that olive leaves, black cumin and cinnamon were the most commonly preferred herbal products among diabetic patients. Its bioactive compounds such as oleuropein, verbascoside, rutin, tyrosol and hydroxytyrosol may be responsible for the biologic activities of this plant (Rahmanian et al., 2015).

Due to its hypoglycemic activity and popular use for treating diabetes, new studies regarding olive leaves and their potential treatment for DM play an important role in the field of health sciences. Therefore, the aim of this study was to investigate the effect of ethanolic extract of olive leaves (EEOL) on the metabolism of rats with diabetes induced by a high-fat diet and streptozotocin.

Section snippets

Chemicals and reagents

Streptozotocin (STZ) was purchased from Sigma–Aldrich (St Louis, MO, USA). All chemicals were of analytical grade. Gallic acid, chlorogenic acid, (+)-catechin, vanillic acid, 6-hydroxycoumarin, p-coumaric acid, rutin, 4-hydroxycoumarin, rosmarinic acid, quercitrin, myricetin, fisetin, resveratrol, trans-cinnamic acid, quercetin, luteolin, apigenin, kaempferol, 3–6 dihydroxyflavone, chrysin, galangin, 3-acetyl coumarin and acetic acid were obtained from Sigma Aldrich (St. Louis, MO, USA).

UHPLC-MS/MS analysis

The ethanolic extract of Olea europaea leaves was analyzed by UHPLC/MS. The Table 1 represents the compounds identified in EEOL: resveratrol, 6-hydroxycoumarin, quercetin, ferulic acid, p-coumaric acid, vanillic acid, quercitrin, caffeic acid, apigenin, rutin and luteolin.

Body weight

Body weight of animals during the treatment showed a normal trend during the first weeks of treatment, however there was a significant decrease in diabetic animals treated with vehicle and EEOL compared to the control group (

Discussion

Diabetes mellitus is a highly prevalent disease worldwide and is associated with high rates of mortality and morbidity. When this disease is not treated properly, it can trigger serious complications such as neuropathy, nephropathy, cardiovascular diseases, etc. (ADA, 2011). In this study, DM was induced through a high-fat diet associated with a low dose of streptozotocin in rats. This model was chosen because it can reflect the clinical symptoms observed in humans diagnosed with the disease (

Conclusion

In summary, this study demonstrated that the ethanolic extract of olive leaves has an important influence on DM, promoting benefits to blood glucose and adipokine concentrations in diabetic animals. This extract was also able to attenuate inflammatory markers, which are important in the pathogenesis of DM. However, more studies are needed to validate the clinical improvement of olive extracts in experimental models of DM.

Acknowledgements

The authors thank Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Universidade Federal de Santa Maria (UFSM) and Bioclin/Quibasa for the financial assistance.

Conflict of interest

The authors declare that there are no conflicts of interest.

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