An ethanolic extract of Arctium lappa L. leaves ameliorates experimental atherosclerosis by modulating lipid metabolism and inflammatory responses through PI3K/Akt and NF-κB singnaling pathways

Ethnopharmacological Relevance: Atherosclerosis (AS), an inflammatory condition induced by lipid accumulation in the arteries, is a major contributor to atherosclerotic cardiovascular diseases, including stroke. The leaf of Arctium lappa L. (ALL), a medicinal and edible herb in China, has been historically used to treat stroke, but the mechanisms behind its potential anti-AS effects are not fully understood.

Aim of the Study: To explore the AS-reducing effects and underlying mechanisms of an ethanolic extract of Arctium lappa L. leaves (ALLE).

Materials and Methods: ALLE was extracted using 70% ethanol, with quality control monitored by HPLC. AS was induced in rats using a high-fat diet (HFD) and vitamin D3, while oxidized low-density lipoprotein-induced RAW264.7 macrophage foam cells were used for in vitro studies. Simvastatin served as a positive control. Biochemical assays were used to measure lipid and inflammatory mediator levels. Histological assessments included H&E and Oil Red O staining. Cytotoxicity was evaluated using CCK-8 assays, and immunoblotting was employed to measure protein levels.

Results: ALLE treatment significantly reduced lipid accumulation and histopathological changes in the aortas and livers of AS rats. It improved serum lipid imbalances (TC, TG, LDL-C, HDL-C) and reduced inflammatory cytokines (TNF-α, IL-6, IL-1β, VCAM-1, ICAM-1, MMP-9). Mechanistically, ALLE inhibited PI3K, Akt, and NF-κB activation in both AS rat aortas and foam cells. The PI3K agonist 740Y-P reversed ALLE’s effects on lipid deposition, lipid production, and inflammatory markers, confirming the involvement of the PI3K/Akt and NF-κB pathways.

Conclusions: ALLE improves AS induced by HFD and vitamin D3 by modulating lipid metabolism and inflammatory responses. Its effects are mediated through the inhibition of the PI3K/Akt and NF-κB signaling pathways.PDGFR 740Y-P These findings support the traditional use of Arctium lappa L. in managing atherosclerotic diseases.