Procyanidin B2 improves endothelial progenitor cell function and promotes wound healing in diabetic mice via activating Nrf2.

Jiawei Fan,Xiaoping Yu,Hairong Liu,Peijian Wang,Wenlian Li,Zheng Yang,Jiang Zeng,Jinwu Wang,Yi Tan,Xiaozhen Dai,Yashu Wang

doi:10.1111/jcmm.16111

Abstract

One of the major reasons for the delayed wound healing in diabetes is the dysfunction of endothelial progenitor cells (EPCs) induced by hyperglycaemia. Improvement of EPC function may be a potential strategy for accelerating wound healing in diabetes. Procyanidin B2 (PCB2) is one of the major components of procyanidins, which exhibits a variety of potent pharmacological activities. However, the effects of PCB2 on EPC function and diabetic wound repair remain elusive. We evaluated the protective effects of PCB2 in EPCs with high glucose (HG) treatment and in a diabetic wound healing model. EPCs derived from human umbilical cord blood were treated with HG. The results showed that PCB2 significantly preserved the angiogenic function, survival and migration abilities of EPCs with HG treatment, and attenuated HG‐induced oxidative stress of EPCs by scavenging excessive reactive oxygen species (ROS). A mechanistic study found the protective role of PCB2 is dependent on activating nuclear factor erythroid 2‐related factor 2 (Nrf2). PCB2 increased the expression of Nrf2 and its downstream antioxidant genes to attenuate the oxidative stress induced by HG in EPCs, which were abolished by knockdown of Nrf2 expression. An in vivo study showed that intraperitoneal administration of PCB2 promoted wound healing and angiogenesis in diabetic mice, which was accompanied by a significant reduction in ROS level and an increase in circulating EPC number. Taken together, our results indicate that PCB2 treatment accelerates wound healing and increases angiogenesis in diabetic mice, which may be mediated by improving the mobilization and function of EPCs.

Highlights

The incidence of diabetes mellitus (DM) is rapidly growing worldwide
Our results indicate that Procyanidin B2 (PCB2) treatment accelerates wound healing and increases angiogenesis in diabetic mice, which may be mediated by improving the mobilization and function of Endothelial progenitor cells (EPCs)
We demonstrate the benefits of PCB2 in the angiogenic function of EPCs and wound healing in diabetic mice

Summary

| INTRODUCTION

The incidence of diabetes mellitus (DM) is rapidly growing worldwide. Foot ulceration is one of the most common complications in DM patients,[1] and emerging evidence shows that diabetic foot ulceration increases the mortality rate.[2,3] More than half of diabetic foot ulceration are infected and about 20% severe diabetic foot infections lead to amputation.[1]. PCB2 has been reported to have protective effects on diabetic nephropathy via inhibiting mesangial cells apoptosis[20] and ameliorating podocyte injury.[22] A previous study[23] showed that PCB2 protected against glycated low-density lipoproteins induced vascular endothelial cells apoptosis by up-regulation of L-isoaspartyl methyltransferase. It is not clear whether PCB2 could promote EPC function contributing to diabetic wound healing. We evaluated the therapeutic potential of PCB2 in a streptozotocin (STZ)-induced diabetic wound healing model

| MATERIALS AND METHODS

Findings

| DISCUSSION