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整合网络药理学和实验模型以研究黄芩苷对青光眼的治疗作用。

Integrating network pharmacological and experimental models to investigate the therapeutic effects of baicalein in glaucoma.

作者信息

Yang Jiawei, Zhang Mingxu, Song Qiuyi, Li Siqi, Zhao Xiulan, Kan Liping, Zhu Siquan

机构信息

Eye School, Chengdu University of Traditional Chinese Medicine, 37 Shi Er Qiao Road, Chengdu, 610075, China.

Ineye Hospital of Chengdu University of TCM, Chengdu, China.

出版信息

Chin Med. 2021 Nov 25;16(1):124. doi: 10.1186/s13020-021-00537-9.

Abstract

BACKGROUND

Traditional Chinese medicine (TCM) has a long history of treating glaucoma with remarkable effects, but there is no clear conclusion on its mechanism.

METHODS

Network pharmacology and molecular docking were used to analyze the mechanism and targets of TCM in the treatment of glaucoma, and baicalein was used to treat chronic ocular hypertension animal models rats for observation.

RESULTS

The results of animal experiments showed that baicalein could significantly reduce intraocular pressure (IOP) in a rat model of chronic ocular hypertension and protect the structure of the retina and optic nerve, as shown by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM). Reducing the apoptosis of retinal ganglion cells (RGCs) by upregulating the expression of the antiapoptotic protein BCL-2 is basically consistent with the results of molecular docking. In the network pharmacology analysis, many key proteins of biological pathways involved in the herbal therapeutic processes in glaucoma, such as threonine kinase 1 (AKT1, core protein of PI3K/AKT signaling), tumor protein p53 (TP53, a tumor suppressor gene coding tumor protein P53), signal transducer and activator of transcription 3 (STAT3, core protein of JAK/STAT signaling), interleukin 6 (IL-6) and interleukin 17 (IL-17, proinflammatory factors), were identified. Their interactions built complicated chain reactions in the process of glaucoma.

CONCLUSION

By combining the analysis of network pharmacology and animal experimental results, baicalein could effectively improve the symptoms of glaucoma and reduce RGC apoptosis, suggesting that the potential mechanism of TCM in treating glaucoma is related to regulating inflammation and cellular immunity and reducing apoptosis.

摘要

背景

中医治疗青光眼历史悠久,疗效显著,但作用机制尚无明确结论。

方法

采用网络药理学和分子对接技术分析中药治疗青光眼的作用机制及靶点,并采用黄芩苷治疗慢性高眼压动物模型大鼠进行观察。

结果

动物实验结果显示,黄芩苷可显著降低慢性高眼压大鼠模型的眼压,并保护视网膜和视神经结构,苏木精-伊红(H&E)染色和透射电子显微镜(TEM)观察结果表明了这一点。上调抗凋亡蛋白BCL-2的表达以减少视网膜神经节细胞(RGCs)的凋亡,这与分子对接结果基本一致。在网络药理学分析中,鉴定出了许多参与青光眼中药治疗过程的生物途径关键蛋白,如苏氨酸激酶1(AKT1,PI3K/AKT信号通路的核心蛋白)、肿瘤蛋白p53(TP53,编码肿瘤蛋白P53的肿瘤抑制基因)、信号转导和转录激活因子3(STAT3,JAK/STAT信号通路的核心蛋白)、白细胞介素6(IL-6)和白细胞介素17(IL-17,促炎因子)。它们之间的相互作用在青光眼发病过程中形成了复杂的连锁反应。

结论

结合网络药理学分析和动物实验结果,黄芩苷可有效改善青光眼症状并减少RGC凋亡,提示中医治疗青光眼的潜在机制与调节炎症和细胞免疫以及减少细胞凋亡有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a10/8613988/bb6a463d980d/13020_2021_537_Fig1_HTML.jpg

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