European journal of pharmacologyJul 17, 2026

Astragaloside IV may reduce artery plaque by controlling cell cleanup and stress through the Nrf2/PINK1/Parkin pathway

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 18, 2026

Abstract

AS-IV reduced aortic plaque burden and alleviated endothelial injury in ApoE^-/- mice.

AS-IV is associated with improved mitochondrial function and reduced oxidative stress in human umbilical vein endothelial cells.
Enhanced mitophagy was observed following AS-IV treatment.
AS-IV promoted the translocation of Nrf2 to the nucleus and increased the activity of the PINK1/Parkin pathway.
Silencing Nrf2 or PINK1, or inhibiting Nrf2, diminished the protective effects of AS-IV and decreased mitophagy.
Molecular simulations suggest a potential binding of AS-IV within the Keap1 pocket, supporting its mechanism of action.

Simplified

Astragaloside IV (AS-IV) exhibits cardiovascular protective effects, but its role in mitochondrial quality control during atherosclerosis remains unclear. This study evaluated whether AS-IV attenuates atherosclerosis by regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)-PTEN-induced putative kinase 1 (PINK1)/Parkin pathway. High-fat diet-fed apolipoprotein E-deficient (ApoE^-/-) mice and oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs) were used as in vivo and in vitro models. AS-IV reduced aortic plaque burden and alleviated endothelial injury in ApoE^-/- mice. In HUVECs, AS-IV decreased oxidative stress and improved mitochondrial function, accompanied by enhanced mitophagy. Mechanistically, AS-IV promoted Nrf2 nuclear translocation and upregulated the PINK1/Parkin axis. Silencing Nrf2 or PINK1, or pharmacological inhibition of Nrf2 with ML385, abolished the cytoprotective effects of AS-IV and suppressed mitophagy. Molecular docking and molecular dynamics simulations provided supportive structural context for a plausible AS-IV pose within the Kelch-like ECH-associated protein 1 (Keap1) pocket in the simulated system. Mechanistically, AS-IV appears to mitigate atherosclerotic progression by promoting Nrf2-driven, PINK1/Parkin-dependent mitophagy.

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Funding

Competing interests

No financial or personal ties reported.

PubMed

Astragaloside IV may reduce artery plaque by controlling cell cleanup and stress through the Nrf2/PINK1/Parkin pathway

Abstract

Full Text

Funding

Competing interests

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