Lv Xiao-Min, Li Na, Chen Lin-Wei, Sun Cheng
Department of Pharmacy, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China.
Department of Pharmacy, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Front Pharmacol. 2025 Jul 11;16:1615910. doi: 10.3389/fphar.2025.1615910. eCollection 2025.
Resveratrol is a natural polyphenolic compound that shows great potential in neuroprotection, anti-inflammation,and antioxidation. Previous studies have demonstrated that resveratrol can effectively treat various animal models of retinal diseases.
The aim of the research was to use an animal experimental model to assess the effectiveness of resveratrol in treating retinal-related diseases in various animal models of retinal diseases such as ischemia-reperfusion injury, diabetic retinopathy, glaucoma, chronic ocular hypertension, optic neuritis, age-related macular degeneration, and retinopathy of prematurity. Furthermore, this study aims to reveal the underlying mechanisms of resveratrol related to the treatment of retina-related diseases.
A search was conducted across several databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and OVID. The search time was from the establishment of the database to October 2024 to collect studies on resveratrol intervention in animal models of retinal diseases. The studies included in this paper adopted the SYRCLE's risk of bias tool. Stata 16.0 and RevMan 5.4 software were used to analyze and visualize the results.
Our meta-analysis comprises 26 studies and 365 animals demonstrates the following effects of resveratrol compared to the control group: a significant increase in the number of retinal ganglion cells (SMD = 3.91, 95% Cl = [2.97, 4.86], 0.00001) and superoxide dismutase activity (SMD = 3.14, 95% Cl = [0.96, 5.33], 0.005). Moreover, a decrease in malondialdehyde (SMD = -9.29,95% Cl = [-12.84, -5.74], 0.00001), reactive oxygen species level (SMD = -4.29,95% Cl = [-6.25, -2.32], 0.0001), cyclooxygenase-2 (SMD = -2.66, 95% Cl = [-4.01, -1.30], 0.0001), tumour necrosis factor-α(SMD = -3.96,95% Cl = [-6.27, -1.65], = 0.0008) and interleukin-6 (SMD = -3.32,95% Cl = [-4.20, -2.44], 0.00001) was observed. The A-wave amplitude and B-wave amplitude showed an increase respectively (MD = 105.92,95% Cl = [58.99, 152.84], 0.00001); (MD = 158.00,95% Cl = [86.35, 229.65], 0.0001), along with an increase in inner retinal thickness (SMD = 6.33, 95% CI = [5.10, 7.56], 0.00001) and total retinal thickness (SMD = 2.70, 95%Cl = [0.77, 4.83], 0.01). Subgroup analysis showed that different doses of resveratrol were associated with an increase in the number of RGCs ( 0.05). Resveratrol improves retinal diseases through multiple mechanisms: i) Neuroprotection: it activates the SIRT1/NF-κB and Nrf2 pathways, inhibits Caspase-3 expression, and promotes the survival of RGCs and ii) Antioxidation: it upregulates SOD activity, reduces the levels of MDA and ROS, and alleviates oxidative damage and iii) Anti-inflammation: it inhibits the COX-2, TNF-α, IL-6, and NF-κB pathways, alleviating the inflammatory response. These mechanisms resulted in enhanced amplitude of A/B waves, improved retinal thickness and visual function.
Resveratrol has neuroprotective, anti-inflammatory and antioxidant effects through multiple mechanisms, thereby reducing retinal damage and maintaining the structure and function of the retina. This provides preclinical support for its possible therapeutic uses in the management of retinal diseases.
白藜芦醇是一种天然多酚化合物，在神经保护、抗炎和抗氧化方面具有巨大潜力。先前的研究表明，白藜芦醇可有效治疗各种视网膜疾病的动物模型。
本研究旨在利用动物实验模型评估白藜芦醇在治疗多种视网膜疾病动物模型中的视网膜相关疾病的有效性，这些疾病包括缺血再灌注损伤、糖尿病性视网膜病变、青光眼、慢性高眼压、视神经炎、年龄相关性黄斑变性和早产儿视网膜病变。此外，本研究旨在揭示白藜芦醇治疗视网膜相关疾病的潜在机制。
在多个数据库中进行检索，包括PubMed、EMBASE、Cochrane对照试验中央注册库、Web of Science和OVID。检索时间从数据库建立至2024年10月，以收集白藜芦醇干预视网膜疾病动物模型的研究。本文纳入的研究采用SYRCLE偏倚风险工具。使用Stata 16.0和RevMan 5.4软件分析并可视化结果。
我们的荟萃分析纳入了26项研究和365只动物，结果表明，与对照组相比，白藜芦醇具有以下作用：视网膜神经节细胞数量显著增加（标准化均数差=3.91，95%可信区间=[2.97, 4.86]，P<0.00001）和超氧化物歧化酶活性增加（标准化均数差=3.14，95%可信区间=[0.96, 5.33]，P=0.005）。此外，丙二醛（标准化均数差=-9.29，95%可信区间=[-12.84, -5.74]，P<0.00001）、活性氧水平（标准化均数差=-4.29，95%可信区间=[-6.25, -2.32]，P=0.0001）、环氧化酶-2（标准化均数差=-2.66，95%可信区间=[-4.01, -1.30]，P=0.0001）、肿瘤坏死因子-α（标准化均数差=-3.96，95%可信区间=[-6.27, -1.65]，P=0.0008）和白细胞介素-6（标准化均数差=-3.32，95%可信区间=[-4.20, -2.44]，P<0.00001）水平均降低。A波振幅和B波振幅分别增加（均数差=105.92，95%可信区间=[58.99, 152.84]，P<0.00001）；（均数差=158.00，95%可信区间=[86.35, 229.65]，P=0.0001），同时视网膜内层厚度增加（标准化均数差=6.33，95%可信区间=[5.10, 7.56]，P<0.00001）和视网膜总厚度增加（标准化均数差=2.70，95%可信区间=[0.77, 4.83]，P=0.01）。亚组分析表明，不同剂量的白藜芦醇与视网膜神经节细胞数量增加相关（P<0.05）。白藜芦醇通过多种机制改善视网膜疾病：i）神经保护：激活SIRT1/NF-κB和Nrf2通路，抑制Caspase-3表达，促进视网膜神经节细胞存活；ii）抗氧化：上调超氧化物歧化酶活性，降低丙二醛和活性氧水平，减轻氧化损伤；iii）抗炎：抑制环氧化酶-2、肿瘤坏死因子-α、白细胞介素-6和NF-κB通路，减轻炎症反应。这些机制导致A/B波振幅增强、视网膜厚度改善和视觉功能提高。
白藜芦醇通过多种机制具有神经保护、抗炎和抗氧化作用，从而减少视网膜损伤，维持视网膜的结构和功能。这为其在视网膜疾病管理中的可能治疗用途提供了临床前支持。
