Creosote Bush (Larrea tridentata) Improves Insulin Sensitivity and Reduces Plasma and Hepatic Lipids in Hamsters Fed a High Fat and Cholesterol Diet.

Georgina Del Vecchyo-Tenorio,Maricela Rodríguez-Cruz,Adolfo Andrade-Cetto,René Cárdenas-Vázquez

doi:10.3389/fphar.2016.00194

Abstract

Creosote bush, Larrea tridentata (Sesse y Moc. Ex DC, Zygophyllaceae) is a shrub found in the deserts of Northern Mexico and Southwestern United States. In traditional medicine, it is used to treat a variety of illnesses including type 2 diabetes. The present study aims to investigate the effects of creosote bush ethanolic extract on plasma and liver parameters associated with the metabolic syndrome in hamsters fed a high fat and cholesterol diet (HFD), comparing them with those induced by ezetimibe (EZ). Seven groups of six hamsters each were formed. Six groups were fed HFD for 2 weeks. The following 2 weeks, the HFD groups received: (1) only HFD, (2) HFD + 3 mg% EZ, (3) HFD + 0.2% creosote bush ethanolic extract, (4) only standard diet (Std Diet), (5) Std Diet + 3 mg% EZ, (6) Std Diet + 0.2% creosote bush ethanolic extract. The beneficial effects of creosote bush ethanolic extract in the HFD hamster model were a reduction of insulin resistance, associated with lower serum insulin and leptin, lower hepatic lipid peroxidation and higher liver antioxidant capacity. Plasma and liver lipids tended or were reduced to values closer to those of animals fed standard diet. A similar effect on lipids was induced by EZ, although with even lower hepatic cholesterol and total lipids concentrations. In general, the change from HFD to standard diet plus ethanolic extract induced the same but deeper changes, including a reduction in plasma glucose and an increase in the percentage of HDL cholesterol. Unlike creosote bush extract, EZ increased food consumption and neutral fecal steroids, with no significant effect on body weight, epididymal fat pads, liver peroxidation or antioxidant capacity. Also EZ did not modify serum insulin and leptin. However, insulin sensitivity improved to values similar to those induced by the extract. This suggests that the mechanism of action of creosote bush ethanolic extract is different to inhibition of cholesterol absorption or increase excretion. The ethanolic extract of L. tridentata could be useful in the treatment of the metabolic syndrome.

Highlights

The aim of the present work was to study the effects of creosote bush ethanolic extract on the Syrian golden hamster fed a high fat and cholesterol diet that expresses some components of the MS, in order to determine its possible use in the treatment of this alteration
Groups with EZ, creosote bush ethanolic extract and those changed from high fat and cholesterol diet (HFD) to Std diet with or without EZ were not significantly different from the heaviest HDF group nor from the lighter one that receiving only Std diet for 4 weeks
The present study shows that a diet based on lard and cholesterol is effective in inducing some of the MS parameters, such as increased body weight, high plasma and hepatic lipids and low sensitivity to insulin

Summary

Introduction

Larrea tridentata (Sesse y Moc. Ex DC, Zygophyllaceae) is a shrub found in the deserts of Northern Mexico and Southwestern United States. The resin that covers the leaves contains flavonoid aglycones, as well as several lignans, notably including the antioxidant NDGA (Konno et al, 1990). Other lignans present are the linear ones, guaiaretic acid and meso-dihydroguaiaretic acid, and the cyclolignans, norisoguaiacin and it’s 3 methyl derivative (Gnabre et al, 2015). L. tridentata contains about 0.1% of dry weight as volatile oils, mainly monoterpenoids and aromatic sesquiterpenoids (Mabry and Bohnstedt, 1981; Xue et al, 1988). The ethanol extraction of leaves and twigs of L. tridentata, at room temperature, yields 10% resin in a dry weight basis, containing 26% NDGA (Belmares et al, 1981)

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