Abstract
Infusions of murtilla leaves exhibit antioxidant, analgesic, and anti-inflammatory properties. Several compounds that are structurally similar to madecassic acid (MA), a component of murtilla leaf extract (ethyl acetate extract, EAE), have been shown to inhibit protein tyrosine phosphatase 1B (PTP1P). The aim of this study was to evaluate if EAE and two compounds identified in EAE (MA and myricetin [MYR]) could have a beneficial effect on systemic and vascular insulin sensitivity and endothelial function in a model of diet-induced obesity. Experiments were performed in 5-week-old male C57BL6J mice fed with a standard (LF) or a very high-fat diet (HF) for 4 weeks and treated with EAE, MA, MYR, or the vehicle as control (C). EAE significantly inhibited PTP1B. EAE and MA, but not MYR, significantly improved systemic insulin sensitivity in HF mice and vascular relaxation to Ach in aorta segments, due to a significant increase of eNOS phosphorylation and enhanced nitric oxide availability. EAE, MA, and MYR also accounted for increased relaxant responses to insulin in HF mice, thus evidencing that the treatments significantly improved aortic insulin sensitivity. This study shows for the first time that EAE and MA could constitute interesting candidates for treating insulin resistance and endothelial dysfunction associated with obesity.
Highlights
Ugni molinae Turcz, Myrtaceae (Myrtus ugni Mol.) is a Chilean native species commonly known as murtilla, murta or uñi that grows in the wild in southern Chile
We demonstrate for the first time that murtilla extract (EAE) inhibits protein tyrosine phosphatase 1B (PTP1B) activity and significantly improves i) systemic glucose tolerance, ii) endothelial function, and iii) vascular insulin sensitivity in a diet-induced obesity (DIO) model in mice
The amelioration of vascular function induced by treatment with ethyl acetate extract (EAE) in high-fat diet (HF) mice was found to be due to an increase in nitric oxide (NO) bioavailability
Summary
Ugni molinae Turcz, Myrtaceae (Myrtus ugni Mol.) is a Chilean native species commonly known as murtilla, murta or uñi that grows in the wild in southern Chile. Recent studies aimed at ameliorating cardiometabolic disorders associated with obesity have highlighted protein tyrosine phosphatase 1B (PTP1B) as a potential target to improve insulin sensitivity, and endothelial dysfunction[19]. In this regard, selective deficiency of PTP1B in the liver significantly improves insulin sensitivity, leading to complete protection against obesity-induced endothelial dysfunction[20]. The hypothesis of this study is that the EAE of murtilla leaves corresponding to genotype 19-1 (EAE) has a beneficial effect on insulin resistance through the inhibition of PTP1B and on endothelial dysfunction through an increase in NO availability in a murine DIO model. The aim of this study was to evaluate whether a 4-week treatment with either EAE, MA, or MYR modifies: i) body weight and adiposity, ii) systemic insulin sensitivity, iii) endothelial function, and iv) vascular insulin sensitivity
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