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柚皮素通过抗氧化应激和细胞损伤减少体内斑马鱼血管内皮生长因子的眼部干预。

Ophthalmic Intervention of Naringenin Decreases Vascular Endothelial Growth Factor by Counteracting Oxidative Stress and Cellular Damage in In Vivo Zebrafish.

机构信息

Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur 603203, India.

Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur 603203, India.

出版信息

Molecules. 2023 Jul 12;28(14):5350. doi: 10.3390/molecules28145350.

Abstract

Diabetes Mellitus is a metabolic disease that leads to microvascular complications like Diabetic retinopathy (DR), a major cause of blindness worldwide. Current medications for DR are expensive and report multiple side effects; therefore, an alternative medication that alleviates the disease condition is required. An interventional approach targeting the vascular endothelial growth factor (VEGF) remains a treatment strategy for DR. Anti-VEGF medicines are being investigated as the main therapy for managing vision-threatening complications of DR, such as diabetic macular oedema. Therefore, this study investigated the effect of flavonoid naringenin (NG) from citrus fruits on inhibiting early DR in zebrafish. When exposed to 130 mM glucose, the zebrafish larvae developed a hyperglycaemic condition accompanied by oxidative stress, cellular damage, and lipid peroxidation. Similarly, when adult zebrafish were exposed to 4% Glucose, high glucose levels were observed in the ocular region and massive destruction in the retinal membrane. High glucose upregulated the expression of VEGF. In comparison, the co-exposure to NG inhibited oxidative stress and cellular damage and restored the glutathione levels in the ocular region of the zebrafish larvae. NG regressed the glucose levels and cellular damage along with an inhibition of macular degeneration in the retina of adult zebrafish and normalized the overexpression of VEGF as a promising strategy for treating DR. Therefore, intervention of NG could alleviate the domestication of alternative medicine in ophthalmic research.

摘要

糖尿病是一种代谢疾病,会导致微血管并发症,如糖尿病视网膜病变(DR),这是全球范围内导致失明的主要原因。目前用于治疗 DR 的药物价格昂贵,并报告有多种副作用;因此,需要一种能够缓解疾病状况的替代药物。针对血管内皮生长因子 (VEGF) 的介入治疗仍然是治疗 DR 的一种策略。抗 VEGF 药物被作为治疗 DR 引起的视力威胁性并发症(如糖尿病性黄斑水肿)的主要疗法进行研究。因此,本研究探讨了来自柑橘类水果的黄酮类化合物柚皮苷(NG)抑制斑马鱼早期 DR 的作用。当暴露于 130mM 葡萄糖时,斑马鱼幼虫会出现高血糖状态,伴有氧化应激、细胞损伤和脂质过氧化。同样,当成年斑马鱼暴露于 4%葡萄糖时,眼部区域会出现高血糖水平,并导致视网膜膜的大量破坏。高血糖会上调 VEGF 的表达。相比之下,NG 的共同暴露抑制了氧化应激和细胞损伤,并恢复了眼部区域的谷胱甘肽水平,减轻了斑马鱼幼虫的葡萄糖水平和细胞损伤,并抑制了成年斑马鱼视网膜的黄斑变性,同时使 VEGF 的过表达正常化,这是治疗 DR 的一种很有前途的策略。因此,NG 的干预可能会减轻眼科研究中对替代药物的驯化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7682/10385844/d94aebb0efe6/molecules-28-05350-g001.jpg

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