Network pharmacology and cell experiments suggest natural algal astaxanthin as an anti-atherosclerotic agent via the PPARγ/NF-κB pathway

Astaxanthin's anti-atherosclerotic targets/pathways identified via network pharmacology and cellular assays. • Astaxanthin alleviates endothelial injury via dual anti-inflammatory and antioxidant effects. • Astaxanthin acts through PPARγ/NF-κB axis, with GW9662 reversing its regulatory effect. Astaxanthin, a lipophilic carotenoid predominantly derived from microalgae such as Haematococcus pluvialis , exhibits potent anti-inflammatory and antioxidant properties. Despite previous reports of its anti-atherosclerotic effects, the underlying molecular mechanisms of astaxanthin remain unclear. This study aimed to elucidate the pharmacological mechanisms of astaxanthin in alleviating atherosclerosis progression via an integrated approach of network pharmacology, molecular docking, and in vitro experimental validation. Molecular docking revealed strong binding affinities between astaxanthin and core targets including TNF, IL-6, and PPARγ. In vitro experiments demonstrated that astaxanthin attenuated oxidative stress and suppressed the secretion of pro-inflammatory cytokines in oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs). Mechanistically, astaxanthin upregulated PPARγ expression and reduced the phosphorylation of p65 and IκBα, two key components of the NF-κB pathway. Co-treatment with the specific PPARγ antagonist GW9662 abrogated these protective effects, confirming a PPARγ-dependent regulatory mechanism. These findings indicate that astaxanthin exerts anti-atherosclerotic effects by modulating the PPARγ/NF-κB signaling axis, highlighting its potential as a functional food ingredient for cardiovascular protection.