Aegeline and Atorvastatin Synergistically Attenuate oxLDL-Induced Inflammation and Intracellular Cholesterol Accumulation in THP-1 Macrophages

Authors

Rajkumar, A., Ramesh, C. M., Dhatchana moorthy Vedhanayaki, E. S., PERIANDAVAN, K.

Abstract

Abstract Background: Atherosclerosis is driven by macrophage foam cell formation resulting from excessive oxidized low-density lipoprotein (oxLDL) accumulation and chronic vascular inflammation. This study evaluated the therapeutic potential of Aegeline, Atorvastatin, and their combined in mitigating oxLDL-induced inflammatory responses, cholesterol accumulation, and oxLDL uptake in human THP-1 macrophages. Methods: THP-1 monocytes were differentiated into macrophages using a 72-hour differentiation protocol followed by a 48-hour resting period, confirmed via CD14 surface marker characterization. Macrophages were exposed to DiI-oxLDL and treated with Aegeline, Atorvastatin, or their combination. Key inflammatory cytokines and chemokines (CRP, TNF-, IL-6, and IL-8) were measured using ELISA. Cholesterol efflux capacity and cellular oxLDL uptake were quantitatively assessed using fluorescence retention assays and immunofluorescence imaging. Results: Differentiation of THP-1 monocytes to macrophages resulted in marked down-regulation of CD14 expression. DiI-oxLDL exposure triggered significant pro-inflammatory mediator secretion (p<0.001) and excessive intracellular cholesterol accumulation. Single-agent treatment with Aegeline or Atorvastatin significantly attenuated oxLDL-induced elevations of CRP, TNF-, IL-6, and IL-8. Atorvastatin alone strongly suppressed CRP expression back to physiological baseline levels (p=ns vs. control). Notably, the combination of Aegeline and Atorvastatin demonstrated enhanced, broad-spectrum anti-inflammatory efficacy, achieving superior suppression of TNF- (p=ns vs. control), IL-6, and IL-8 compared to monotherapies. Furthermore, both agents promoted cholesterol efflux and suppressed oxLDL uptake, with the combination treatment producing the lowest residual intracellular cholesterol levels (p<0.001). Conclusion: Aegeline and Atorvastatin effectively suppress oxLDL-induced macrophage inflammatory cascades and intracellular lipid overload. While Atorvastatin monotherapy exerts robust control over CRP and oxLDL loading, combining Aegeline with Atorvastatin provides synergistic efficacy, enhancing cholesterol efflux and restoring pro-inflammatory cytokine expression toward physiological levels.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 19 Aug 2026.

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