Abstract

Diabetic retinopathy (DR), the most ordinary and specific microvascular complication of diabetes, is a disease of the retina. Zerumbone (ZER) is a monocyclic sesquiterpene compound, and based on reports, it is the predominant bioactive compound from the rhizomes of Zingiber zerumbet. The aim of the current study is to evaluate the protective effect of zerumbone against DR in streptozotocin (STZ)-induced diabetic rats. STZ-diabetic rats were treated with ZER (40 mg/kg) once a day orally for 8 weeks. ZER administration significantly (p < 0.05) lowered the levels of plasma glucose (32.5% ± 5.7% lower) and glycosylated hemoglobin (29.2% ± 3.4% lower) in STZ-diabetic rats. Retinal histopathological observations indicated that disarrangement and reduction in thickness of retinal layers were reversed in ZER-treated diabetic rats. ZER downregulated both the elevated levels of advanced glycosylated end products (AGEs) and the higher levels of the receptors for AGEs (RAGE) in retinas of diabetic rats. What’s more, ZER significantly (p < 0.05) ameliorated diabetes-induced upregulation of tumor necrosis factor-α, interleukin (IL)-1 and IL-6. ZER also attenuated overexpression of vascular endothelial growth factor and intercellular adhesion molecule-1, and suppressed activation of nuclear factor (NF)-κB and apoptosis in the retinas of STZ-diabetic rats. Our results suggest ZER possesses retinal protective effects, which might be associated with the blockade of the AGEs/RAGE/NF-κB pathway and its anti-inflammatory activity.

Highlights

  • Diabetes mellitus (DM) has been on the rise, resulting in serious economic, social, and health repercussions

  • Our results suggest ZER possesses retinal protective effects, which might be associated with the blockade of the advanced glycosylated end products (AGEs)/receptors for AGEs (RAGE)/nuclear factor (NF)-κB pathway and its anti-inflammatory activity

  • When STZ-diabetic rats were treated with ZER (32.5% ̆ 5.7%) for 8 weeks, it was obvious that the blood glucose lowered effect (Table 1)

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Summary

Introduction

Diabetes mellitus (DM) has been on the rise, resulting in serious economic, social, and health repercussions. The most common and serious complication of DM is diabetic retinopathy (DR), characterized by vascular alterations including endothelial cells dysfunction, breakdown of the blood-retinal barrier, retinal blood flow changes, ischemia, and neovascularisation [1,2,3]. If not properly treated, it is very likely that DR progresses to the advanced stage, during which severe pathologies often lead to irreversible blindness [3]. Factors like poor metabolic control and hyperglycemia play an important role in the development of DR since intensive glycemic control generally inhibits the progression of DR [4,5,6]. Even though blood glucose cannot be perfectly controlled, there is a need for the development of new drugs which help modulate the mechanism involved in DR

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