Mechanistic Advances in Hypoglycemic Effects of Natural Polysaccharides: Multi-Target Regulation of Glycometabolism and Gut Microbiota Crosstalk

Natural polysaccharides (NPs), as a class of bioactive macromolecules with multitarget synergistic regulatory potential, exhibit significant advantages in diabetes intervention. This review systematically summarizes the core hypoglycemic mechanisms of NPs, covering structure–activity relationships,...

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Main Authors: Liquan Zhou, Jiani Li, Chen Ding, Yimiao Zhou, Zuowei Xiao
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/30/9/1980
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author Liquan Zhou
Jiani Li
Chen Ding
Yimiao Zhou
Zuowei Xiao
author_facet Liquan Zhou
Jiani Li
Chen Ding
Yimiao Zhou
Zuowei Xiao
author_sort Liquan Zhou
collection DOAJ
description Natural polysaccharides (NPs), as a class of bioactive macromolecules with multitarget synergistic regulatory potential, exhibit significant advantages in diabetes intervention. This review systematically summarizes the core hypoglycemic mechanisms of NPs, covering structure–activity relationships, integration of the gut microbiota–metabolism–immunity axis, and regulation of key signaling pathways. Studies demonstrate that the molecular weight, branch complexity, and chemical modifications of NPs mediate their hypoglycemic activity by influencing bioavailability and target specificity. NPs improve glucose metabolism through multiple pathways: activating insulin signaling, improving insulin resistance (IR), enhancing glycogen synthesis, inhibiting gluconeogenesis, and regulating gut microbiota homeostasis. Additionally, NPs protect pancreatic β-cell function via the nuclear factor E2-related factor 2 (Nrf2)/Antioxidant Response Element (ARE) antioxidant pathway and Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) anti-inflammatory pathway. Clinical application of NPs still requires overcoming challenges such as resolving complex structure–activity relationships and dynamically integrating cross-organ signaling. Future research should focus on integrating multi-omics technologies (e.g., metagenomics, metabolomics) and organoid models to decipher the cross-organ synergistic action networks of NPs, and promote their translation from basic research to clinical applications.
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spelling doaj-art-9b3ebd25751240afa5303a40e62f28a82025-08-20T02:30:47ZengMDPI AGMolecules1420-30492025-04-01309198010.3390/molecules30091980Mechanistic Advances in Hypoglycemic Effects of Natural Polysaccharides: Multi-Target Regulation of Glycometabolism and Gut Microbiota CrosstalkLiquan Zhou0Jiani Li1Chen Ding2Yimiao Zhou3Zuowei Xiao4Homologous Innovation Laboratory of Medicine and Food, Hunan University of Chinese Medicine, Changsha 410208, ChinaHomologous Innovation Laboratory of Medicine and Food, Hunan University of Chinese Medicine, Changsha 410208, ChinaHomologous Innovation Laboratory of Medicine and Food, Hunan University of Chinese Medicine, Changsha 410208, ChinaHomologous Innovation Laboratory of Medicine and Food, Hunan University of Chinese Medicine, Changsha 410208, ChinaHomologous Innovation Laboratory of Medicine and Food, Hunan University of Chinese Medicine, Changsha 410208, ChinaNatural polysaccharides (NPs), as a class of bioactive macromolecules with multitarget synergistic regulatory potential, exhibit significant advantages in diabetes intervention. This review systematically summarizes the core hypoglycemic mechanisms of NPs, covering structure–activity relationships, integration of the gut microbiota–metabolism–immunity axis, and regulation of key signaling pathways. Studies demonstrate that the molecular weight, branch complexity, and chemical modifications of NPs mediate their hypoglycemic activity by influencing bioavailability and target specificity. NPs improve glucose metabolism through multiple pathways: activating insulin signaling, improving insulin resistance (IR), enhancing glycogen synthesis, inhibiting gluconeogenesis, and regulating gut microbiota homeostasis. Additionally, NPs protect pancreatic β-cell function via the nuclear factor E2-related factor 2 (Nrf2)/Antioxidant Response Element (ARE) antioxidant pathway and Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) anti-inflammatory pathway. Clinical application of NPs still requires overcoming challenges such as resolving complex structure–activity relationships and dynamically integrating cross-organ signaling. Future research should focus on integrating multi-omics technologies (e.g., metagenomics, metabolomics) and organoid models to decipher the cross-organ synergistic action networks of NPs, and promote their translation from basic research to clinical applications.https://www.mdpi.com/1420-3049/30/9/1980natural polysaccharideshypoglycemiamechanism of actiongut microbiotasignaling pathway
spellingShingle Liquan Zhou
Jiani Li
Chen Ding
Yimiao Zhou
Zuowei Xiao
Mechanistic Advances in Hypoglycemic Effects of Natural Polysaccharides: Multi-Target Regulation of Glycometabolism and Gut Microbiota Crosstalk
Molecules
natural polysaccharides
hypoglycemia
mechanism of action
gut microbiota
signaling pathway
title Mechanistic Advances in Hypoglycemic Effects of Natural Polysaccharides: Multi-Target Regulation of Glycometabolism and Gut Microbiota Crosstalk
title_full Mechanistic Advances in Hypoglycemic Effects of Natural Polysaccharides: Multi-Target Regulation of Glycometabolism and Gut Microbiota Crosstalk
title_fullStr Mechanistic Advances in Hypoglycemic Effects of Natural Polysaccharides: Multi-Target Regulation of Glycometabolism and Gut Microbiota Crosstalk
title_full_unstemmed Mechanistic Advances in Hypoglycemic Effects of Natural Polysaccharides: Multi-Target Regulation of Glycometabolism and Gut Microbiota Crosstalk
title_short Mechanistic Advances in Hypoglycemic Effects of Natural Polysaccharides: Multi-Target Regulation of Glycometabolism and Gut Microbiota Crosstalk
title_sort mechanistic advances in hypoglycemic effects of natural polysaccharides multi target regulation of glycometabolism and gut microbiota crosstalk
topic natural polysaccharides
hypoglycemia
mechanism of action
gut microbiota
signaling pathway
url https://www.mdpi.com/1420-3049/30/9/1980
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