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

Bu-Yeo Kim,Hye-Sun Lim,Eunjin Sohn,Yu Jin Kim,Yun Hee Kim,Soo-Jin Jeong,Imhoi Koo

doi:10.1038/s41598-020-59537-8

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.

Highlights

The neurovascular unit, which includes neurons, glial cells, and vascular cells, plays crucial roles in the onset and progression of Alzheimer’s disease (AD)
We aimed to examine the therapeutic effects of UGS and its components using in vitro neurovascular unit models and an in vivo model of Aβ-induced AD
UGS is composed of 7 individual components including Uncaria sinensis (C1), Atractylodes japonica (C2), Poria cocos (C3), Bupleurum falcatum (C4), Angelica gigas (C5), Cnidium officinale (C6), and Glycyrrhiza uralensis (C7)

Summary

Introduction

The neurovascular unit, which includes neurons, glial cells, and vascular cells, plays crucial roles in the onset and progression of Alzheimer’s disease (AD). 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. Recent reports have suggested that the onset and progression of AD should be considered in terms of the neurovascular unit In this multicellular complex[8,9], neurons, glial cells, and vascular cells communicate with each other to tightly regulate the functional homeostasis of the brain[10]. Latin name Uncariae Ramulus et Uncus Atractylodis Rhizoma Alba Poria Sclerotium Bupleuri Radix Angelicae Gigantis Radix Cnidii Rhizoma Glycyrrhizae Radix et Rhizoma Mixture symbol Mix[1] Mix[2] Mix[3]

Objectives

Methods

Results

Conclusion