Traditional Chinese Medicine, Ziyin-Mingmu Decoction, Regulates Cholesterol Metabolism, Oxidative Stress, Inflammation and Gut Microbiota in Age-related Macular Degeneration Models.

IF 3.5 3区 医学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Xing Li, Khalid S Ibrahim, Michal R Baran, Gabriel Mbuta Tchivelekete, Xinzhi Zhou, Yi Wu, James Reilly, Zhoujin Tan, Zhiming He, Xinhua Shu
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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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 H2O2 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.

Conclusion: 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.

中药紫银明目汤调节老年性黄斑变性模型的胆固醇代谢、氧化应激、炎症和肠道微生物群
背景:年龄相关性黄斑变性(AMD)是老年人视网膜疾病最常见的原因。紫银明目汤(ZD)已被广泛用于治疗AMD患者数千年,但其潜在的作用机制在很大程度上是未知的。在本研究中,我们旨在阐明ZD在AMD模型中的治疗机制。方法:建立AMD小鼠体内模型和体外模型。测定小鼠组织中的胆固醇水平。采用生化方法检测小鼠组织和人视网膜色素上皮细胞中抗氧化基因和促炎细胞因子的表达。采用生物信息学方法分析肠道菌群群落和功能途径。采用高效液相色谱/质谱法对ZD中的化合物进行了鉴定。结果:与正常饮食小鼠相比,高脂饮食小鼠视网膜、RPE、肝脏和血清中的胆固醇水平显著升高,且这些组织中胆固醇代谢相关基因的表达显著降低。同样,饲喂hfd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诱导的病理作用。HFD还改变了盲肠细菌群落的组成和相关的代谢途径,通过ZD恢复到控制水平。体外实验表明,H2O2显著增加氧化应激和促炎细胞因子的表达。与ZD联合治疗显著抵消了这些变化。HPLC/MS鉴定出105个化合物,其中多酚类化合物居多。结论:我们的数据表明,ZD对AMD的保护可能是通过降低胆固醇水平、氧化应激和炎症,以及通过多酚调节肠道微生物群。
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来源期刊
Pharmaceutical Research
Pharmaceutical Research 医学-化学综合
CiteScore
6.60
自引率
5.40%
发文量
276
审稿时长
3.4 months
期刊介绍: Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.
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