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多组分草药 UKGansan 诱导神经血管单元细胞治疗网络的相似性。

Similarity of therapeutic networks induced by a multi-component herbal remedy, Ukgansan, in neurovascular unit cells.

机构信息

Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea.

College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.

出版信息

Sci Rep. 2020 Feb 14;10(1):2658. doi: 10.1038/s41598-020-59537-8.

DOI:10.1038/s41598-020-59537-8
PMID:32060346
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7021700/
Abstract

The neurovascular unit, which includes neurons, glial cells, and vascular cells, plays crucial roles in the onset and progression of Alzheimer's disease (AD). Therefore, effective drugs against AD should be able to target the multi-cellular neurovascular unit and the therapeutic relationships among neurovascular cells should be defined. Here, we examined the therapeutic effects of Ukgansan (UGS), an herbal remedy with multi-targeting capabilities, using in vitro neurovascular unit models and an in vivo model of AD. In addition, we compared the therapeutic networks induced by UGS and its components in different neurovascular cell types. We found that UGS and its components protected neurovascular cells against diverse damaging agents and improved the behavioral patterns of AD model mice. A comparison of UGS- or its components-induced therapeutic networks, constructed from high-throughput data on gene expression, pathway activity, and protein phosphorylation, revealed similarities among neurovascular cell types, especially between BV-2 microglia and HBVP (human brain vascular pericytes). These findings, together with the functional connections between neurovascular cells, can explain the therapeutic effects of UGS. Furthermore, they suggest underlying similarities in the therapeutic mechanisms in different neurovascular cell types.

摘要

神经血管单元包括神经元、神经胶质细胞和血管细胞，在阿尔茨海默病（AD）的发病和进展中发挥着关键作用。因此，有效的 AD 治疗药物应该能够针对多细胞神经血管单元，并且应该明确神经血管细胞之间的治疗关系。在这里，我们使用体外神经血管单元模型和 AD 体内模型研究了 Ukgansan（UGS）的治疗效果，Ukgansan 是一种具有多靶向能力的草药疗法。此外，我们比较了 UGS 及其成分在不同神经血管细胞类型中诱导的治疗网络。我们发现，UGS 及其成分可保护神经血管细胞免受多种损伤剂的侵害，并改善 AD 模型小鼠的行为模式。比较 UGS 或其成分诱导的治疗网络，这些网络是基于基因表达、通路活性和蛋白质磷酸化的高通量数据构建的，揭示了神经血管细胞类型之间的相似性，尤其是 BV-2 小胶质细胞和 HBVP（人脑血管周细胞）之间。这些发现，以及神经血管细胞之间的功能联系，可以解释 UGS 的治疗效果。此外，它们表明不同神经血管细胞类型的治疗机制存在潜在的相似性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a37/7021700/692ee9c06d74/41598_2020_59537_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a37/7021700/692ee9c06d74/41598_2020_59537_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a37/7021700/c3f4f3bf1dc9/41598_2020_59537_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a37/7021700/05f8d307f1d9/41598_2020_59537_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a37/7021700/3df5f63d045f/41598_2020_59537_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a37/7021700/dd3339eea23e/41598_2020_59537_Fig4_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a37/7021700/a0d3f5f855f9/41598_2020_59537_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a37/7021700/692ee9c06d74/41598_2020_59537_Fig7_HTML.jpg

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