Li Xing, Ibrahim Khalid S, Baran Michal R, Tchivelekete Gabriel Mbuta, Zhou Xinzhi, Wu Yi, Reilly James, Tan Zhoujin, He Zhiming, Shu Xinhua
Pu Ai Medical School, Shaoyang University, Shaoyang, Hunan, 422000, P.R. China.
Department of Biology, Faculty of Science, University of Zakho, Kurdistan Region, Iraq.
Pharm Res. 2025 Jun 26. doi: 10.1007/s11095-025-03887-3.
Age-related macular degeneration (AMD) is the commonest cause of retinal disorders in the aged population. Ziyin-Mingmu decoction (ZD) has been widely used to treat AMD patients over thousands of years, however the underlying functional mechanisms of ZD are largely elusive. In this study, we aim to elucidate the therapeutic mechanisms of ZD in AMD models.
An in vivo AMD mouse model and an in vitro AMD model were established. Cholesterol level in mouse tissues was measured. Expression of antioxidant genes and proinflammatory cytokines in mouse tissues and in human retinal pigment epithelial (RPE) cells were detected using biochemical approaches. Gut microbiota community and functional pathways were analysed using bioinformatics approach. Compounds in ZD were identified using HPLC/MS.
High fat diet (HFD)-fed mice had significantly higher levels of cholesterol in the retina, RPE, liver and serum, and markedly decreased expression of cholesterol metabolism-associated genes in those tissues, compared to mice fed with normal diet. Similarly, expression of antioxidant and inflammation genes was dysregulated in HFD-fed mouse tissues. ZD treatment reversed these HFD-induced pathological effects. HFD also altered the composition of cecum bacterial communities and associated metabolic pathways, which returned to control levels by ZD. In vitro assays showed that HO significantly increased oxidative stress and enhanced expression of proinflammatory cytokines. Co-treatment with ZD significantly counteracted these changes. HPLC/MS identified 105 compound in water extracted ZD and most are polyphenols.
Our data suggests that protection of ZD against AMD is possibly through mitigating cholesterol level, oxidative stress and inflammation, and modulating gut microbiota by polyphenols.
年龄相关性黄斑变性（AMD）是老年人群中最常见的视网膜疾病病因。滋阴明目汤（ZD）数千年来一直被广泛用于治疗AMD患者，然而ZD的潜在功能机制在很大程度上仍不清楚。在本研究中，我们旨在阐明ZD在AMD模型中的治疗机制。
建立体内AMD小鼠模型和体外AMD模型。测量小鼠组织中的胆固醇水平。使用生化方法检测小鼠组织和人视网膜色素上皮（RPE）细胞中抗氧化基因和促炎细胞因子的表达。使用生物信息学方法分析肠道微生物群落和功能途径。使用HPLC/MS鉴定ZD中的化合物。
与正常饮食喂养的小鼠相比，高脂饮食（HFD）喂养的小鼠视网膜、RPE、肝脏和血清中的胆固醇水平显著更高，且这些组织中胆固醇代谢相关基因的表达明显降低。同样，HFD喂养的小鼠组织中抗氧化和炎症基因的表达失调。ZD治疗逆转了这些HFD诱导的病理效应。HFD还改变了盲肠细菌群落的组成和相关代谢途径，而ZD使其恢复到对照水平。体外实验表明，HO显著增加氧化应激并增强促炎细胞因子的表达。与ZD联合处理可显著抵消这些变化。HPLC/MS鉴定出ZD水提取物中的105种化合物，其中大多数是多酚。
我们的数据表明，ZD对AMD的保护作用可能是通过降低胆固醇水平、减轻氧化应激和炎症以及通过多酚调节肠道微生物群来实现的。
