An ultrasonic degraded polysaccharide extracted from Pueraria lobata ameliorate ischemic brain injury in mice by regulating the gut microbiota and LPS-TLR4 pathway
Ischemia brain injury is closely associated with the gut microbiota. Polysaccharides, as a typical prebiotic, have been extensively employed in stroke treatment. In our previous study, Pueraria lobata polysaccharide (PLP-3) with antioxidant activity was prepared via water extraction and alcohol prec...
Saved in:
Main Authors: | , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2025-01-01
|
Series: | Ultrasonics Sonochemistry |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1350417724004498 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
_version_ | 1841545968129933312 |
---|---|
author | Yulong Zhang Zuman Dou Shanshan Li Huaying Zhang Shanshui Zeng Xiangyu Zuo Yu Xiao Lingling Zhang Zhixin Li Qingfeng Zhu Wenyang Zhang Hui Niu Qingfei Duan Xiaoxia Chen Zhuang Li Hongwei Zhou Qian Wang |
author_facet | Yulong Zhang Zuman Dou Shanshan Li Huaying Zhang Shanshui Zeng Xiangyu Zuo Yu Xiao Lingling Zhang Zhixin Li Qingfeng Zhu Wenyang Zhang Hui Niu Qingfei Duan Xiaoxia Chen Zhuang Li Hongwei Zhou Qian Wang |
author_sort | Yulong Zhang |
collection | DOAJ |
description | Ischemia brain injury is closely associated with the gut microbiota. Polysaccharides, as a typical prebiotic, have been extensively employed in stroke treatment. In our previous study, Pueraria lobata polysaccharide (PLP-3) with antioxidant activity was prepared via water extraction and alcohol precipitation combined with ultrasonic degradation. In this study, the effects of PLP-3 on ischemia brain injury and its regulatory effects on the gut microbiota were further investigated. The results demonstrated that PLP-3 effectively reduced the infarct area, improves neurological function, and alleviates neuronal damage of cerebral ischemia injury. Mechanistically, PLP-3 significantly reduces serum LPS levels in MCAO mice, inhibiting TLR-4 activation in brain tissue and thereby reducing IL-1β and TNF-α levels. Meanwhile, PLP-3 significantly repaired the intestinal barrier injury by increasing the expression of tight junction proteins (ZO-1 and Occludin) and increasing the number of goblet cells. Additionally, the structure and composition of gut microbiota in MCAO mice after PLP-3 intervention, were also significantly changed, especially the enrichment of Lactobacillus and the reduction of Corynebacterium and Staphylococcus. At the same time, short chain fatty acid, metabolites of gut microbiota, were also significantly increased and significantly correlated with the abundance of Lactobacillus. Moreover, LC-MS untargeted metabolomics revealed that PLP-3 significantly improves the intestinal metabolic profile after cerebral ischemia injury, upregulating the amino acid biosynthesis pathway and enriching amino acids such as glutamine and arginine, as well as neuroprotective flavonoids such as fisetin and liquiritigenin. These results suggested that PLP-3 could protect mice from cerebral ischemia–reperfusion injury by regulating gut microbiota and repairing gut barrier, inhibiting brain LPS/TLR4/MyD88 inflammatory pathway, therefore we provide a theoretical basis for PLP-3 as a functional food to prevent ischemic brain injury. |
format | Article |
id | doaj-art-3c4d07ccd1da4514a1c8f987e264bbd3 |
institution | Kabale University |
issn | 1350-4177 |
language | English |
publishDate | 2025-01-01 |
publisher | Elsevier |
record_format | Article |
series | Ultrasonics Sonochemistry |
spelling | doaj-art-3c4d07ccd1da4514a1c8f987e264bbd32025-01-11T06:38:49ZengElsevierUltrasonics Sonochemistry1350-41772025-01-01112107200An ultrasonic degraded polysaccharide extracted from Pueraria lobata ameliorate ischemic brain injury in mice by regulating the gut microbiota and LPS-TLR4 pathwayYulong Zhang0Zuman Dou1Shanshan Li2Huaying Zhang3Shanshui Zeng4Xiangyu Zuo5Yu Xiao6Lingling Zhang7Zhixin Li8Qingfeng Zhu9Wenyang Zhang10Hui Niu11Qingfei Duan12Xiaoxia Chen13Zhuang Li14Hongwei Zhou15Qian Wang16Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaMicrobiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; Corresponding authors.Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaMicrobiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaMicrobiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaMicrobiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaMicrobiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaMicrobiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaMicrobiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaMicrobiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaCollege of Light Chemical Industry and Materials Engineering, Shunde Polytechnic, Foshan 528333, ChinaSchool of Food Science and Engineering, South China University of Technology, Guangzhou 510640, ChinaSchool of Food Science and Engineering, South China University of Technology, Guangzhou 510640, ChinaNutritional and Food Science Research Institute, Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan 030001, ChinaMicrobiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; Corresponding authors.Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; Corresponding authors.Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; Corresponding authors.Ischemia brain injury is closely associated with the gut microbiota. Polysaccharides, as a typical prebiotic, have been extensively employed in stroke treatment. In our previous study, Pueraria lobata polysaccharide (PLP-3) with antioxidant activity was prepared via water extraction and alcohol precipitation combined with ultrasonic degradation. In this study, the effects of PLP-3 on ischemia brain injury and its regulatory effects on the gut microbiota were further investigated. The results demonstrated that PLP-3 effectively reduced the infarct area, improves neurological function, and alleviates neuronal damage of cerebral ischemia injury. Mechanistically, PLP-3 significantly reduces serum LPS levels in MCAO mice, inhibiting TLR-4 activation in brain tissue and thereby reducing IL-1β and TNF-α levels. Meanwhile, PLP-3 significantly repaired the intestinal barrier injury by increasing the expression of tight junction proteins (ZO-1 and Occludin) and increasing the number of goblet cells. Additionally, the structure and composition of gut microbiota in MCAO mice after PLP-3 intervention, were also significantly changed, especially the enrichment of Lactobacillus and the reduction of Corynebacterium and Staphylococcus. At the same time, short chain fatty acid, metabolites of gut microbiota, were also significantly increased and significantly correlated with the abundance of Lactobacillus. Moreover, LC-MS untargeted metabolomics revealed that PLP-3 significantly improves the intestinal metabolic profile after cerebral ischemia injury, upregulating the amino acid biosynthesis pathway and enriching amino acids such as glutamine and arginine, as well as neuroprotective flavonoids such as fisetin and liquiritigenin. These results suggested that PLP-3 could protect mice from cerebral ischemia–reperfusion injury by regulating gut microbiota and repairing gut barrier, inhibiting brain LPS/TLR4/MyD88 inflammatory pathway, therefore we provide a theoretical basis for PLP-3 as a functional food to prevent ischemic brain injury.http://www.sciencedirect.com/science/article/pii/S1350417724004498Ultrasonic degradationPueraria lobata polysaccharideIschemic brain injuryGut microbiotaLPS/TLR4/MyD88 pathway |
spellingShingle | Yulong Zhang Zuman Dou Shanshan Li Huaying Zhang Shanshui Zeng Xiangyu Zuo Yu Xiao Lingling Zhang Zhixin Li Qingfeng Zhu Wenyang Zhang Hui Niu Qingfei Duan Xiaoxia Chen Zhuang Li Hongwei Zhou Qian Wang An ultrasonic degraded polysaccharide extracted from Pueraria lobata ameliorate ischemic brain injury in mice by regulating the gut microbiota and LPS-TLR4 pathway Ultrasonics Sonochemistry Ultrasonic degradation Pueraria lobata polysaccharide Ischemic brain injury Gut microbiota LPS/TLR4/MyD88 pathway |
title | An ultrasonic degraded polysaccharide extracted from Pueraria lobata ameliorate ischemic brain injury in mice by regulating the gut microbiota and LPS-TLR4 pathway |
title_full | An ultrasonic degraded polysaccharide extracted from Pueraria lobata ameliorate ischemic brain injury in mice by regulating the gut microbiota and LPS-TLR4 pathway |
title_fullStr | An ultrasonic degraded polysaccharide extracted from Pueraria lobata ameliorate ischemic brain injury in mice by regulating the gut microbiota and LPS-TLR4 pathway |
title_full_unstemmed | An ultrasonic degraded polysaccharide extracted from Pueraria lobata ameliorate ischemic brain injury in mice by regulating the gut microbiota and LPS-TLR4 pathway |
title_short | An ultrasonic degraded polysaccharide extracted from Pueraria lobata ameliorate ischemic brain injury in mice by regulating the gut microbiota and LPS-TLR4 pathway |
title_sort | ultrasonic degraded polysaccharide extracted from pueraria lobata ameliorate ischemic brain injury in mice by regulating the gut microbiota and lps tlr4 pathway |
topic | Ultrasonic degradation Pueraria lobata polysaccharide Ischemic brain injury Gut microbiota LPS/TLR4/MyD88 pathway |
url | http://www.sciencedirect.com/science/article/pii/S1350417724004498 |
work_keys_str_mv | AT yulongzhang anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT zumandou anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT shanshanli anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT huayingzhang anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT shanshuizeng anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT xiangyuzuo anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT yuxiao anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT linglingzhang anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT zhixinli anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT qingfengzhu anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT wenyangzhang anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT huiniu anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT qingfeiduan anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT xiaoxiachen anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT zhuangli anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT hongweizhou anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT qianwang anultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT yulongzhang ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT zumandou ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT shanshanli ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT huayingzhang ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT shanshuizeng ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT xiangyuzuo ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT yuxiao ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT linglingzhang ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT zhixinli ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT qingfengzhu ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT wenyangzhang ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT huiniu ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT qingfeiduan ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT xiaoxiachen ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT zhuangli ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT hongweizhou ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway AT qianwang ultrasonicdegradedpolysaccharideextractedfrompuerarialobataameliorateischemicbraininjuryinmicebyregulatingthegutmicrobiotaandlpstlr4pathway |