Astragaloside IV Mitigated Diabetic Nephropathy by Restructuring Intestinal Microflora and Ferroptosis

To investigate the underlying mechanism of Astragaloside IV (AS-IV) in ameliorating diabetic nephropathy (DN) by regulating intestinal microbiota ecology and intestinal mucosal barrier. Genetically db/db mice are used to establish DN mouse model to monitor the therapeutic effects of AS-IV and fecal...

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Published in:Molecular nutrition & food research Vol. 68; no. 6; p. e2300734
Main Authors: Lyu, Xin, Zhang, Ting‐ting, Ye, Zhen, Chen, Ce
Format: Journal Article
Language:English
Published: Germany Wiley Subscription Services, Inc 01.03.2024
Subjects:
Diabetes
Diabetes mellitus
Diabetic nephropathy
Digestive system
Dysbacteriosis
Ecological effects
Fecal microflora
Ferroptosis
Gastrointestinal tract
Gut microbiota
Intestinal microflora
Intestine
Microbiomes
Microbiota
Microorganisms
Mucosa
Nephropathy
Permeability
Renal function
Transplantation
intestinal microbiota
ferroptosis
Astragaloside IV
gut-renal axis
diabetic nephropathy
ISSN:1613-4125, 1613-4133, 1613-4133
Online Access:Get full text
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Summary:To investigate the underlying mechanism of Astragaloside IV (AS-IV) in ameliorating diabetic nephropathy (DN) by regulating intestinal microbiota ecology and intestinal mucosal barrier. Genetically db/db mice are used to establish DN mouse model to monitor the therapeutic effects of AS-IV and fecal microbiota transplantation (FMT) against DN. Supplementation with AS-IV dramatically attenuates several clinical indicators of DN in db/db mice. In addition, AS-IV markedly improves intestinal barrier function, modifies intestinal permeability, and reduces inflammation. Moreover, AS-IV treatment remarkably improves intestinal dysbiosis in db/db mice, characterized by an elevated abundance of Akkermansia, Ligilactobacillus, and Lactobacillus, indicating the fundamental role of the microbiome in DN progression. Furthermore, FMT derived from AS-IV-treated db/db mice is potentially efficient in antagonizing renal dysfunction, rebalancing gut microbiota, and improving intestinal permeability in recipient db/db mice. AS-IV-enriched Akkermansia muciniphila dramatically alleviates DN and intestinal mucosal barrier dysfunction in db/db mice. Intriguingly, AS-IV intervention dramatically diminishes ferroptosis in the kidney and colon tissues. CONCLUSION : Intestinal microbiome alterations and ferroptosis modulation by AS-IV may play instrumental roles in this mechanism, providing compelling evidence for the role of the gut-renal axis in DN.
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ISSN:1613-4125
1613-4133
1613-4133
DOI:10.1002/mnfr.202300734