卫矛水提取物通过介导血管生成来减轻糖尿病视网膜病变。
The water extracts of Euonymus alatus (Thunb.) Siebold attenuate diabetic retinopathy by mediating angiogenesis.
机构信息
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; Beijing Key Laboratory of TCM Syndrome and Formula, Beijing, China; Key Laboratory of TCM Syndrome and Formula (Beijing University of Chinese Medicine), Ministry of Education, Beijing, China.
Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
出版信息
J Ethnopharmacol. 2022 Feb 10;284:114782. doi: 10.1016/j.jep.2021.114782. Epub 2021 Oct 30.
ETHNOPHARMACOLOGICAL RELEVANCE
Euonymus alatus (Thunb.) Siebold (family Celastraceae) is a deciduous woody shrub that is recorded in ShenNong BenCaoJing. It has been widely used for diabetes in traditional Chinese medicine.
AIM OF THE STUDY
This study aimed to identify the most effective extract of Euonymus alatus (EA) against high glucose-induced endothelial cells in vitro, evaluate its pharmacological effect on retinopathy in diabetic mice and explore its underlying mechanism by RNA sequencing.
METHODS
Retinal vascular endothelial cells (RF/6A) were treated with normal glucose (5.5 mmol/L glucose), high glucose (25 mmol/L glucose) or high glucose plus methanol extracts of EA (MEA), ethyl acetate extracts of EA (EEA) or water extracts of EA (WEA). The cytotoxicity and cell viability were determined by Cell Counting Kit-8 (CCK-8) assay. Cell migration was examined using the Transwell assay, and tube formation ability was measured using the Matrigel assay. Then, the KK-Ay mice were administered WEA or water for 12 weeks. The velocities of ocular blood flow were determined by Doppler ultrasound. RNA sequencing and reverse transcription quantitative PCR (RT-qPCR) were performed on WEA-stimulated RF/6A cells to reveal the underlying mechanism.
RESULTS
The cytotoxicity assay found that 30 μg/mL MEA, 20 μg/mL EEA and 30 μg/mL WEA had no toxic effect on RF/6A cells. The cell viability results showed that MEA, EEA and WEA all decreased cell viability. Compared with the high-glucose group, both MEA and WEA decreased the number of migrated cells, while the inhibition rate of WEA was higher. The Matrigel results showed that 30 μg/mL WEA effectively reduced the total tube length. Moreover, WEA improved the haemodynamics of the central retinal artery. RNA sequencing coupled with RT-qPCR verified that WEA regulated angiogenesis-related factors in high glucose-stimulated RF/6A cells.
CONCLUSIONS
WEA inhibits the migration and tube formation of RF/6A cells and improves diabetic retinopathy (DR) by mediating angiogenesis.
药用植物学 relevance：卫矛（卫矛科）是一种落叶木本灌木，记录在《神农本草经》中。它在传统中药中被广泛用于糖尿病。
目的
本研究旨在鉴定卫矛（EA）对体外高葡萄糖诱导的内皮细胞最有效的提取物，评价其对糖尿病小鼠视网膜病变的药理作用，并通过 RNA 测序探讨其潜在机制。
方法
用正常葡萄糖（5.5mmol/L 葡萄糖）、高葡萄糖（25mmol/L 葡萄糖）或 EA 甲醇提取物（MEA）、EA 乙酸乙酯提取物（EEA）或 EA 水提取物（WEA）处理视网膜血管内皮细胞（RF/6A）。用细胞计数试剂盒-8（CCK-8）法测定细胞毒性和细胞活力。用 Transwell 测定细胞迁移，用 Matrigel 测定管形成能力。然后，KK-Ay 小鼠用 WEA 或水治疗 12 周。用多普勒超声测定眼血流速度。对 WEA 刺激的 RF/6A 细胞进行 RNA 测序和逆转录定量 PCR（RT-qPCR），以揭示潜在机制。
结果
细胞毒性试验发现，30μg/mL MEA、20μg/mL EEA 和 30μg/mL WEA 对 RF/6A 细胞无毒性作用。细胞活力结果表明，MEA、EEA 和 WEA 均降低细胞活力。与高糖组相比，MEA 和 WEA 均减少了迁移细胞的数量，而 WEA 的抑制率更高。Matrigel 结果表明，30μg/mL WEA 有效降低了总管长度。此外，WEA 改善了中央视网膜动脉的血液动力学。RNA 测序结合 RT-qPCR 验证了 WEA 调节高糖刺激 RF/6A 细胞中血管生成相关因子。
结论
WEA 通过调节血管生成抑制 RF/6A 细胞的迁移和管形成，改善糖尿病视网膜病变（DR）。
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