Journal
AGING-US
Volume 14, Issue 14, Pages 5855-5877Publisher
IMPACT JOURNALS LLC
Keywords
sepsis-associated acute kidney injury; Astragalus membranaceus; Astragaloside IV; network pharmacology; PI3K
Categories
Funding
- National Natural Science Foundation of China [81973551]
- Scientific and Technologic Innovation Action of Shanghai Municipal Science and Technology Commission [18401932700]
- Health Commission of Shanghai Municipality [ZY(2021-2023)-0203-04]
- Chinese Major Scientific and Technological Special Project for Major New Drug Creation [2018X09201008-002-071]
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Astragalus membranaceus and its active monomer Astragaloside IV (AS-IV) can attenuate sepsis-induced kidney tubular injury by activating the PI3K/AKT pathway.
Background: Acute kidney injury (AKI) is the most common target organ damage in sepsis. Sepsis-associated AKI (SA-AKI) may be characterized by damage to the renal tubular epithelium. In this study, the pharmacological mechanisms of Astragalus membranaceus and its active monomer Astragaloside IV (AS-IV) were predicted based on a network pharmacology approach and validated both in vitro and in vivo using the SA-AKI model. Method: We constructed an in vivo sepsis model using a mouse cecum ligation puncture (CLP) and HK-2 cells were treated with lipopolysaccharide (LPS) to mimic Gram (-) induced sepsis to assess the renal-protective efficacy of Astragalus membranaceus and AS-IV. Results: The findings demonstrated that Astragalus membranaceus and AS-IV attenuate renal tubular injury in mice with polymicrobial sepsis, including vacuolization, loss of brush border, mitochondrial ultrastructural changes, and increased staining of kidney injury molecule-1 (KIM-1). AS-IV protected human proximal tubular epithelial (HK-2) cells against LPS induced cell viability loss. Both Astragalus membranaceus and AS-IV activated the PI3K/AKT pathway both in vitro and in vivo, as shown by Western blot and immunohistochemistry analysis. Conclusion: The findings demonstrate that Astragalus membranaceus and AS-IV protect against sepsis-induced kidney tubular injury by activating the PI3K/AKT pathway.
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