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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Ultrasonics Sonochemistry
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Online Access:http://www.sciencedirect.com/science/article/pii/S1350417724004498
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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.
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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
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