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Z-Ligustilide Ameliorates Diabetic Rat Retinal Dysfunction Through Anti-Apoptosis and an Antioxidation Pathway

Bing Yang, Guobin Ma, Yang Liu

Department of Endocrinology and Metabolism, 3201 Hospital, Xi’an Jiaotong University Health Science Center, Hanzhong, Shaanxi, China (mainland)

Med Sci Monit 2020; 26:e925087

DOI: 10.12659/MSM.925087

Available online: 2020-08-10

Published: 2020-10-04

BACKGROUND: Diabetic retinopathy (DR) is one of the major causes of vision impairment. Z-ligustilide (3-butylidene-4,5-dihydrophthalide; Z-LIG) is an important volatile oil from the Chinese herb Angelica sinensis (Oliv.) Diels. It has been extensively studied and reportedly has anti-inflammatory, antioxidant, antitumor, analgesic, vasodilatory, and neuroprotective effects. Its effects on DR, however, remain obscure. In this study, we attempted to explore the protective effects of Z-LIG on retinal dysfunction and the potential underlying mechanisms.
MATERIAL AND METHODS: A diabetic rat model was constructed with streptozotocin injection. Three study groups were constituted: control (CON), diabetic model (DM), and DM+Z-LIG. The DM+Z-LIG group was injected intraperitoneally with 10 mg/kg of Z-LIG. The other groups received the same volume of 3% solution of polysorbate 80. After a 12-week intervention, a series of assessments were performed, including tests for retinal function, morphology, and molecular biology.
RESULTS: Z-LIG treatment significantly elevated b-wave and OPs2-wave amplitude and thickened the inner layer of the nucleus of the retina, and the outer plexiform and nuclear layers (INL+OPL+ONL). Moreover, the rate of apoptosis and expression of bcl-2- associated X protein (BAX) and cleaved-Caspase-3 were clearly reduced, and the expression of bcl-2 was raised by Z-LIG in retinas of diabetic mice. In addition, the levels of retinal proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha were downregulated by Z-LIG. Furthermore, Z-LIG inhibited expression of vascular endothelial growth factor-alpha (VEGF-alpha) at the mRNA and protein levels.
CONCLUSIONS: Z-LIG can inhibit inflammatory response and cell apoptosis in retinas of diabetic rats by repressing the VEGF-alpha pathway. Therefore, it may serve as a potential therapeutic agent for DR.

Keywords: Apoptosis, Diabetic Retinopathy, Inflammation, Medicine, Chinese Traditional, Vascular Endothelial Growth Factor A