Loranthus regularis Ameliorates Neurodegenerative Factors in the Diabetic Rat Retina

Mohammad Ola,Mohammed Ahmed,Abdul Malik,Ahmed Alanazi,Ajamaluddin Malik,Abdullah Alhomida,Salim Al-Rejaie

doi:10.3390/app12062875

Abstract

Diabetic retinopathy remains a primary source of blindness with the growing pandemic of diabetes. Numerous studies have shown that early neurodegeneration caused by elevated oxidative stress may initiate microvascular damage in the diabetic retina during the last few decades. A variety of preventive and treatment strategies using phytochemicals that possess high antioxidants have shown great promise in reducing diabetes-induced neurodegeneration retinal damage. In this investigation, we employed an extract of Loranthus regularis, a traditional medicinal herb which is found to improve diabetes and associated complications in experimental studies. We orally treated STZ-induced diabetic rats with L. regularis and analyzed the neurodegenerative factors in the retina. After treatments, we used Western blotting techniques to analyze the protein content of neurotrophic factors (NGF, BDNF, TrkB), apoptotic factors (cytochrome c, Bcl-2, Bax), and phosphorylation of AKT in the diabetic retina. Additionally, we used ELISA methods to measure the contents of BDNF and the activity of Caspase-3 and biochemical procedures to determine the levels of glutathione and lipid peroxidation (TBARS). Our findings show that L. regularis treatments resulted in a considerable increase in neurotrophic factors and a decrease in apoptotic factors in the diabetic retina. Furthermore, in diabetic retina treated with L. regularis, the level of Bcl-2 protein increased, while the phosphor-AKT signaling improved. As a result, L. regularis may protect against diabetic-induced retinal neuronal damage by increasing neurotrophic support and reducing oxidative stress and apoptosis. Therefore, this study suggests that in diabetic retinopathy, L. regularis could be a potential therapy option for preventing neuronal cell death.

Highlights

Diabetic retinopathy (DR) remains a significant impediment to diabetes and a primary source of blindness and vision loss in adults
The levels of brain-derived neurotrophic factor (BDNF) in the retinal of L. regularis-treated and untreated control and diabetic rats were determined by the ELISA method
L. regularis treatments resulted in a considerable rise in BDNF levels in the diabetic retina (30.3 ± 5.2 vs. 60.4 ± 7.4%; p < 0.05)

Summary

Introduction

Diabetic retinopathy (DR) remains a significant impediment to diabetes and a primary source of blindness and vision loss in adults. With an increasing worldwide prevalence of diabetes, which is predicted to be 700 million by 2045, the suffering of DR on both people and the burden on the healthcare system is projected to be extremely high [1,2]. Despite significant laboratory and clinical investigations, the primary etiology of diabetes-related vision loss and blindness remains unknown. Many functional tests and molecular data have demonstrated early neurodegeneration in the diabetic retina, which might contribute to microvascular damage, the classical hallmark of DR [3–5]. Numerous reports established that diabetes increases apoptosis and oxidative stress, while decreasing neurotrophic factors, interestingly, all of these are critical markers of neurodegeneration in the diabetic retina [3,6–10]

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