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

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.