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

Q3 Medicine
Han Li, Qiong Han, Yan Liu, Jiaxin Duan, Beiping Su, Zhenlin Tang, Xinhe Huang
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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 via Cell counting kit (CCK-8) and Senescence-associated β- Gal staining, with EC50 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 EC50 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, IL-1β, and TNF-α 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.

阿魏酸与雷帕霉素联用对人脐静脉内皮细胞抗衰老作用的协同增强。
衰老是一个复杂的过程,涉及细胞、遗传、代谢和线粒体的变化。虽然在了解衰老机制和开发抗衰老药物方面取得了重大进展,但单药治疗仍有局限性。本文旨在探讨阿魏酸(FA)和雷帕霉素(Rapamycin)在抗衰老中的协同作用,并阐明其潜在机制,为未来抗衰老治疗提供新的策略。方法:采用细胞计数试剂盒(CCK-8)和衰老相关β- Gal染色法测定人脐静脉内皮细胞(HUVECs) FA和Rapa的安全浓度范围,采用GraphPad Prism 8.0.2计算EC50。我们评估了d -gal诱导的衰老HUVECs对细胞周期阻滞和ROS的影响,并通过Western Blot和RT-qPCR探索了衰老标志物、炎症因子和纤维化基因的协同机制。结果:CCK-8显示,20-160 μM FA和50-200 pM Rapa对HUVECs增殖有促进作用,FA和pM的EC50分别为37.78 μM和48.32 μM。最佳1:2组合比例显示G0/G1细胞减少,ROS减少,NF-κB p65, p53, IL-1β和TNF-α表达降低。它还能抑制纤维化相关基因的转录,下调衰老标志物,维持细胞稳态。讨论:这些结果与先前的研究一致,强调FA的抗氧化特性和Rapa在mTOR抑制中的作用,表明它们的组合同时针对多种衰老途径。与单一药物干预相比,双重方法-减少氧化损伤,同时调节炎症和纤维化-可能提供更好的疗效。结论:总之,这种双靶点策略为开发先进的抗衰老疗法提供了一条有希望的途径,值得在临床前和临床环境中进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current aging science
Current aging science Medicine-Geriatrics and Gerontology
CiteScore
3.90
自引率
0.00%
发文量
40
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