Effects of Rutin on Wound Healing in Hyperglycemic Rats.

Li-You Chen,Kai-Lin Yang,Kai-Jung Yen,Chih-Kai Liao,To-Jung Tseng,Chien-Ning Huang,Hsing-Chun Lin,Yu-Hsiang Kuan,Hung-Ming Chang

doi:10.3390/antiox9111122

Abstract

Long-term poor glycemic control negatively affects macrovascular and microvascular diseases, as well as wound restoration. Buckwheat is a good source of rutin (quercetin-3-O-rutoside) and has benefits in regulating blood sugar. This study was to evaluate the antioxidant and anti-inflammatory effects of rutin on wound healing in streptozotocin-induced hyperglycemic rats. Eighteen male Wistar rats were randomly divided into three groups: normal (NDM), hyperglycemic (DM), and hyperglycemic with rutin (DMR). After induction of hyperglycemia for 2 days, a 15 × 15 mm wound was induced on the back of each rat. Intraperitoneal injection of rutin significantly ameliorated diabetes-induced body weight loss and improved metabolic dysfunctions of hyperglycemic rats. Based on appearance and histopathological staining, rutin promotes wound healing and inhibits production of inflammatory cells. The immunoblotting data indicated that rutin promotes production of antioxidant enzymes induced by nuclear factor erythroid 2-related factor 2 (NRF2), inhibits the expression of matrix metalloproteinases (MMPs) regulated by NF-κB, and decreases the expression of vascular endothelial growth factor (VEGF). It also promotes the expression of neurogenic-related protein (UCH-L1). The aforementioned results indicated that rutin reduces oxidative stress and inflammatory response in hyperglycemic rats, promoting wound healing and subsequently reducing the risk of wound ulcers.

Highlights

According to an International Diabetes Federation (IDF) report published in 2019, diabetes has become one of the most important public health issues globally [1]
To explore the correlations of wound healing with oxidative stress and inflammation, we investigated the expressions of nuclear factor erythroid 2-related factor 2 (NRF2)-related antioxidant enzymes and inflammation-related proteins
Following STZ treatment, impaired liver and metabolic functions were clearly demonstrated by enhanced aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels together with incidences of hypertriglyceridemia and hyperlipidemia

Summary

Introduction

According to an International Diabetes Federation (IDF) report published in 2019, diabetes has become one of the most important public health issues globally [1]. Diabetes is a complex chronic disease that causes glucose induction, insulin secretion disorders, autoimmune-mediated beta cell destruction, or inadequate compensation of insulin secretion for insulin resistance. Complications such as macrovascular and microvascular diseases, neuropathy, and slow wound healing are common in diabetic patients [2]. Both diabetes and wounds can induce oxidative stress, especially hyperglycemia, which enhances the generation of free radicals and reduces anti-oxidation capabilities. Free radicals destroy the ability of β-cells to secrete insulin and increase the incidence of diabetes complications [3,4]. Oxidative stress and diabetes are mutually causal, resulting in a vicious cycle

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