Evidence mapPaperPMID 42232096Full record

ArticleDrug design, development and therapy2026

Astragaloside IV Alleviates Lupus Nephritis by Inhibiting Podocyte Ferroptosis via the PI3K/AKT/Nrf2 Pathway.

Zhongfu Tang, Lili Cheng, Ming Li, Chuanbing Huang

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Article in Drug design, development and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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4 authors.

Zhongfu Tang *Department of Rheumatology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, People's Republic of China.
Lili Cheng *Department of Rheumatology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, People's Republic of China.ORCID 0009-0008-0890-625X
Ming LiDepartment of Rheumatology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, People's Republic of China.ORCID 0000-0001-8882-6613
Chuanbing HuangDepartment of Rheumatology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, People's Republic of China.

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6 · The paper itself

Abstract

Purpose: Lupus nephritis (LN) is an immune complex-mediated glomerulonephritis caused by systemic lupus erythematosus (SLE) involving the kidneys. Astragaloside IV (AS-IV) is the main active ingredient of the traditional Chinese medicine Astragalus membranaceus, belonging to the cycloartane-type triterpenoid saponins, and has anti-inflammatory and antioxidant pharmacological effects. This study mainly explores the therapeutic potential and molecular mechanism of AS-IV for LN. Methods: Using MRL/lpr mice as an in vivo model, the effects of AS-IV on the histopathology and ultrastructure of renal tissues were evaluated by histopathological staining and transmission electron microscopy (TEM). Immunofluorescence and biochemical kits were used to assess the changes in renal damage indicators. Network pharmacology and molecular docking were employed to reveal the molecular targets of AS-IV in the intervention of lupus nephritis (LN). In vitro, a puromycin aminonucleoside (PAN)-induced ferroptosis model of MPC-5 cells was established to evaluate the effects of AS-IV on ferroptosis and the PI3K/AKT/Nrf2 pathway in MPC-5 cells, and further verification was carried out through rescue experiments. Results: AS-IV can improve the renal histopathology of MRL/lpr mice, reduce the glomerular score, perivascular wall score, foot process fusion rate, and electron-dense deposit density, and decrease the levels of 24hPRO, UTPCR, and UACR, showing a certain protective effect on the kidneys. Meanwhile, AS-IV can upregulate the damage-related proteins in MPC-5 cells, increase the levels of factors related to the PI3K/AKT/Nrf2 pathway, GPX4, SLC7A11, DHODH, FSP1, GSH, and SOD in MPC-5 cells, and reduce the levels of Fe Conclusion: AS-IV can inhibit podocyte ferroptosis by regulating the PI3K/AKT/Nrf2 axis, reduce the degree of kidney damage, and thus relieve LN. This also indicates that AS-IV has certain therapeutic potential in the treatment of LN.

Indexed as

FerroptosisLupus NephritisPodocytesSaponinsTriterpenesAnimalsCells, CulturedDisease Models, AnimalDose-Response Relationship, DrugFemaleMiceMice, Inbred MRL lprMolecular Docking SimulationMolecular StructureNF-E2-Related Factor 2Phosphatidylinositol 3-Kinasesastragaloside ANfe2l2 protein, mouseNF-E2-Related Factor 2Phosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSaponinsTriterpenesAstragaloside IVferroptosislupus nephritispodocytesrenal damage

Identifiers

PMID42232096
PMCPMC13225287

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.