Department of Ophthalmology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
Department of Retinology, Shanxi Eye Hospital, Taiyuan, 030001, China.
Appl Biochem Biotechnol. 2022 Dec;194(12):6407-6422. doi: 10.1007/s12010-022-04012-5. Epub 2022 Aug 6.
Diabetic retinopathy (DR) is a diabetes mellitus (DM) complication that causes visual acuity impairment and loss of sight in the working population, mainly in developed countries. According to the WHO, DR accounts for 5% of the world's 37 million blind people. The prevalence of diabetic retinopathy was highest in Africa, followed by North America and the Caribbean and South and Central America. Hyperglycemia can generate excessive ROS that activates multiple pathways, which can damage the cells. Oxidative stress and inflammatory process are intricate in the DR pathological mechanism. Bilobalide is the main bioactive compound isolated from the Ginkgo biloba, a plant utilized in folklore medicine. Bilobalide, a sesquiterpene trilactone, exhibits excellent antioxidant activity. But the molecular mechanisms associated with such effects, especially the antioxidant-related mechanism, have not been documented. Hence, this investigation explored whether bilobalide may attenuate DR in streptozotocin (STZ)-prompted diabetic rats. The effects of bilobalide on parameters of antioxidant content, oxidative stress, and inflammatory factors in the retinal tissues were evaluated by ELISA, RT-PCR, and immunohistochemistry methods. Bilobalide improved caloric management by reducing food consumption and increasing body weight. Furthermore, the administration of bilobalide decreases the blood glucose level and glycosylated (HbA1c) hemoglobin. The anti-retinopathy activity of bilobalide was established by the increase in the total retina thickness (TRT), inner nuclear layer (INL), and outer nuclear layer (ONL) in diabetic rats. Additionally, the serum level of MDA was decreased. In contrast, the antioxidant enzyme (SOD and CAT) levels were increased with TAC plus lower Keap1 and higher Nrf2 expression in the retina when associated with the DM rats. Moreover, bilobalide increased the nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1) expression level and inflammatory mediators (NF-κβ p65, TNF-α, IL-1β, and VEGF), thus inhibiting oxidative stress. Bilobalide can be effective against DR, and the possible mechanism may be relatively elucidated by decreasing oxidative stress and anti-inflammatory activities. But the further investigation should be directed to expose the precise mechanism.
糖尿病视网膜病变（DR）是一种糖尿病（DM）并发症，会导致工作人群视力受损和失明，主要发生在发达国家。根据世界卫生组织的数据，DR 占全球 3700 万盲人的 5%。在非洲，糖尿病视网膜病变的患病率最高，其次是北美和加勒比地区以及南美和中美洲。高血糖会产生过多的活性氧（ROS），激活多条通路，从而损害细胞。氧化应激和炎症过程在 DR 的病理机制中错综复杂。白果内酯是从银杏中分离出来的主要生物活性化合物，银杏是民间医学中使用的一种植物。白果内酯，一种倍半萜三内酯，具有出色的抗氧化活性。但是，与这些作用相关的分子机制，特别是与抗氧化相关的机制，尚未有记录。因此，本研究探讨了白果内酯是否可能减轻链脲佐菌素（STZ）诱发的糖尿病大鼠的 DR。通过 ELISA、RT-PCR 和免疫组织化学方法评估了白果内酯对视网膜组织中抗氧化含量、氧化应激和炎症因子参数的影响。白果内酯通过减少食物消耗和增加体重来改善热量管理。此外，白果内酯降低血糖水平和糖化（HbA1c）血红蛋白。白果内酯的抗视网膜病变活性通过增加糖尿病大鼠的总视网膜厚度（TRT）、内核层（INL）和外核层（ONL）来建立。此外，血清 MDA 水平降低。相反，与 DM 大鼠相关时，抗氧化酶（SOD 和 CAT）水平升高，TAC 增加，Keap1 降低，Nrf2 表达增加。此外，白果内酯增加了核因子红细胞 2 相关因子 2（Nrf2）和血红素加氧酶-1（HO-1）的表达水平以及炎症介质（NF-κβ p65、TNF-α、IL-1β 和 VEGF），从而抑制氧化应激。白果内酯可以有效对抗 DR，其可能的机制可能是通过降低氧化应激和抗炎活性来相对阐明。但是，应该进一步研究以揭示确切的机制。
