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image of Synergistic Enhancement of Anti-aging Effects on Human Umbilical Vein Endothelial Cells Treated With the Combination of Ferulic Acid and 
Rapamycin

Abstract

Introduction

Aging is a complex process involving cellular, genetic, metabolic, and mitochondrial changes. While significant progress has been made in understanding aging mechanisms and developing anti-aging drugs, single-drug treatments have limitations. This paper aims to investigate the synergistic effects of Ferulic acid (FA) and Rapamycin (Rapa) on anti-aging and to elucidate their underlying mechanisms, providing novel strategies for future anti-aging therapies.

Methods

The safe concentration ranges of FA and Rapa for Human umbilical vein endothelial cells (HUVECs) were determined Cell counting kit (CCK-8) and Senescence-associated β-Gal staining, with EC calculated by GraphPad Prism 8.0.2. Effects on cell cycle arrest and ROS in D-gal-induced aging HUVECs were assessed, with synergistic mechanisms explored by Western Blot and RT-qPCR for aging markers, inflammatory factors, and fibrosis genes.

Results

CCK-8 showed that 20-160 μM FA and 50-200 pM Rapa enhanced HUVECs proliferation, with EC of 37.78 μM for FA and 48.32 pM for Rapa. The optimal 1:2 combination ratio demonstrated reduced G0/G1 cells, decreased ROS, and lowered NF-κB p65, p53, , and expression. It also inhibited fibrosis-related gene transcription, downregulating aging markers and maintaining cellular homeostasis.

Discussion

These results align with previous studies highlighting FA’s antioxidant properties and Rapa’s role in mTOR inhibition, suggesting that their combination targets multiple aging pathways simultaneously. The dual approach—reducing oxidative damage while modulating inflammation and fibrosis—may offer superior efficacy compared to single-drug interventions.

Conclusion

In summary, this dual-target strategy presents a promising avenue for developing advanced anti-aging therapies, warranting further investigation in preclinical and clinical settings.

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2025-08-15
2025-10-30

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Synergistic Enhancement of Anti-aging Effects on Human Umbilical Vein Endothelial Cells Treated With the Combination of Ferulic Acid and 
Rapamycin
Bentham Science Publishers ; https://doi.org/10.2174/0118746098383170250728163902
/content/journals/cas/10.2174/0118746098383170250728163902
/content/journals/cas/10.2174/0118746098383170250728163902
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  • Article Type:     Research Article
Keywords: anti-aging mechanisms ; oxidative stress ; Enrichment analysis ; cell cycle ; drug combination ; anti-aging

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