Xueshuantong Improves Functions of Lymphatic Ducts and Modulates Inflammatory Responses in Alzheimer’s Disease Mice

Recent studies have revealed significant contributions of lymphatic vessels (LVs) to vital functions of the brain, especially related to clearance of waste from the brain and immune responses in the brain. These studies collectively indicate that enhancing the functions of LVs may improve brain func...

Full description

Bibliographic Details
Main Authors: Rui Zheng, Yang-mei Huang, Qiang Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.605814/full
_version_ 1818438995489587200
author Rui Zheng
Yang-mei Huang
Qiang Zhou
author_facet Rui Zheng
Yang-mei Huang
Qiang Zhou
author_sort Rui Zheng
collection DOAJ
description Recent studies have revealed significant contributions of lymphatic vessels (LVs) to vital functions of the brain, especially related to clearance of waste from the brain and immune responses in the brain. These studies collectively indicate that enhancing the functions of LVs may improve brain functions during brain aging and in Alzheimer’s disease (AD) where LV functions are impaired. However, it is currently unknown whether this enhancement can be achieved using small molecules. We have previously shown that a widely used Chinese herbal medicine Xueshuantong (XST) significantly improves functions and reduces pathology in AD transgenic mice associated with elevated cerebral blood flow (CBF). Here, we show that XST partially rescues deficits in lymphatic structures, improves clearance of amyloid-β (Aβ) from the brain, and reduces the inflammatory responses in the serum and brains of transgenic AD mice. In addition, we showed that this improvement in the lymphatic system occurs independently of elevated CBF, suggesting independent modulation and limited interaction between blood circulation and lymphatic systems. Moreover, XST treatment leads to a significant increase in GLT-1 level and a significantly lower level of MMP-9 and restores AQP4 polarity in APP/PS1 mice. These results provide the basis for further exploration of XST to enhance or restore LV functions, which may be beneficial to treat neurodegenerative diseases or promote healthy aging.
first_indexed 2024-12-14T17:49:25Z
format Article
id doaj.art-d123e6b87913405fb64b571ce4f050c2
institution Directory Open Access Journal
issn 1663-9812
language English
last_indexed 2024-12-14T17:49:25Z
publishDate 2021-09-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj.art-d123e6b87913405fb64b571ce4f050c22022-12-21T22:52:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-09-011210.3389/fphar.2021.605814605814Xueshuantong Improves Functions of Lymphatic Ducts and Modulates Inflammatory Responses in Alzheimer’s Disease MiceRui ZhengYang-mei HuangQiang ZhouRecent studies have revealed significant contributions of lymphatic vessels (LVs) to vital functions of the brain, especially related to clearance of waste from the brain and immune responses in the brain. These studies collectively indicate that enhancing the functions of LVs may improve brain functions during brain aging and in Alzheimer’s disease (AD) where LV functions are impaired. However, it is currently unknown whether this enhancement can be achieved using small molecules. We have previously shown that a widely used Chinese herbal medicine Xueshuantong (XST) significantly improves functions and reduces pathology in AD transgenic mice associated with elevated cerebral blood flow (CBF). Here, we show that XST partially rescues deficits in lymphatic structures, improves clearance of amyloid-β (Aβ) from the brain, and reduces the inflammatory responses in the serum and brains of transgenic AD mice. In addition, we showed that this improvement in the lymphatic system occurs independently of elevated CBF, suggesting independent modulation and limited interaction between blood circulation and lymphatic systems. Moreover, XST treatment leads to a significant increase in GLT-1 level and a significantly lower level of MMP-9 and restores AQP4 polarity in APP/PS1 mice. These results provide the basis for further exploration of XST to enhance or restore LV functions, which may be beneficial to treat neurodegenerative diseases or promote healthy aging.https://www.frontiersin.org/articles/10.3389/fphar.2021.605814/fullAlzheimer’s diseaselymphatic vesselsXSTceftriaxoneAPP/PS1 mice
spellingShingle Rui Zheng
Yang-mei Huang
Qiang Zhou
Xueshuantong Improves Functions of Lymphatic Ducts and Modulates Inflammatory Responses in Alzheimer’s Disease Mice
Frontiers in Pharmacology
Alzheimer’s disease
lymphatic vessels
XST
ceftriaxone
APP/PS1 mice
title Xueshuantong Improves Functions of Lymphatic Ducts and Modulates Inflammatory Responses in Alzheimer’s Disease Mice
title_full Xueshuantong Improves Functions of Lymphatic Ducts and Modulates Inflammatory Responses in Alzheimer’s Disease Mice
title_fullStr Xueshuantong Improves Functions of Lymphatic Ducts and Modulates Inflammatory Responses in Alzheimer’s Disease Mice
title_full_unstemmed Xueshuantong Improves Functions of Lymphatic Ducts and Modulates Inflammatory Responses in Alzheimer’s Disease Mice
title_short Xueshuantong Improves Functions of Lymphatic Ducts and Modulates Inflammatory Responses in Alzheimer’s Disease Mice
title_sort xueshuantong improves functions of lymphatic ducts and modulates inflammatory responses in alzheimer s disease mice
topic Alzheimer’s disease
lymphatic vessels
XST
ceftriaxone
APP/PS1 mice
url https://www.frontiersin.org/articles/10.3389/fphar.2021.605814/full
work_keys_str_mv AT ruizheng xueshuantongimprovesfunctionsoflymphaticductsandmodulatesinflammatoryresponsesinalzheimersdiseasemice
AT yangmeihuang xueshuantongimprovesfunctionsoflymphaticductsandmodulatesinflammatoryresponsesinalzheimersdiseasemice
AT qiangzhou xueshuantongimprovesfunctionsoflymphaticductsandmodulatesinflammatoryresponsesinalzheimersdiseasemice