Emblic Leafflower (Phyllanthus emblica L.) Fruits Ameliorate Vascular Smooth Muscle Cell Dysfunction in Hyperglycemia: An Underlying Mechanism Involved in Ellagitannin Metabolite Urolithin A.

Junxuan Zhou,Guo-Hua Zheng,Cong Zhang,Zhenpeng Qiu

doi:10.1155/2018/8478943

Abstract

Ellagitannins in Phyllanthus emblica L. (emblic leafflower fruits) have been thought of as the beneficial constituents for ameliorating endocrinal and metabolic diseases including diabetes. However, the effect of emblic leafflower fruits on diabetic vascular complications involved in ellagitannin-derived urolithin metabolites is still rare. In this study, acetylcholine-induced endothelium-independent relaxation in aortas was facilitated upon emblic leafflower fruit consumption in the single dose streptozotocin-induced hyperglycemic rats. Emblic leafflower fruit consumption also suppressed the phosphorylation of Akt (Thr308) in the hyperglycemic aortas. More importantly, urolithin A (UroA) and its derived phase II metabolites were identified as the metabolites upon emblic leafflower fruit consumption by HPLC-ESI-Q-TOF-MS. Moreover, UroA reduced the protein expressions of phosphor-Akt (Thr308) and β-catenin in a high glucose-induced A7r5 vascular smooth muscle cell proliferation model. Furthermore, accumulation of β-catenin protein and activation of Wnt signaling in LiCl-triggered A7r5 cells were also ameliorated by UroA treatment. In conclusion, our data demonstrate that emblic leafflower fruit consumption facilitates the vascular function in hyperglycemic rats by regulating Akt/β-catenin signaling, and the effects are potentially mediated by the ellagitannin metabolite urolithin A.

Highlights

Diabetes is an endocrine disease diagnosed by pathological blood glucose elevation which is caused by absolute (Type I) or relative (Type II) insulin insufficiency [1]
Diabetes is correlated with the superabundant production of reactive oxygen species (ROS) by hyperglycemia, which contributes to the elimination of endothelium-derived relaxing factor nitric oxide (NO) and the accumulation of endogenous vasoconstrictor substances, such as endothelin-1 [5, 6]
The protective effects of Emblic leafflower fruits (ELF) on STZinduced vascular smooth muscle cell (VSMC) dysfunction in rats were discovered for the first time

Summary

Introduction

Diabetes is an endocrine disease diagnosed by pathological blood glucose elevation which is caused by absolute (Type I) or relative (Type II) insulin insufficiency [1]. Diabetes is correlated with the superabundant production of reactive oxygen species (ROS) by hyperglycemia, which contributes to the elimination of endothelium-derived relaxing factor nitric oxide (NO) and the accumulation of endogenous vasoconstrictor substances, such as endothelin-1 [5, 6]. Both in vitro and in vivo evidence demonstrate that high glucose condition obstructs acetylcholine-mediated endothelium-dependent relaxation (EDR) and interdicts the generation of NO [7]. The vasomotor function may be implicated in hyperglycemia

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