Han Li, Qiong Han, Yan Liu, Jiaxin Duan, Beiping Su, Zhenlin Tang, Xinhe Huang
{"title":"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。","authors":"Han Li, Qiong Han, Yan Liu, Jiaxin Duan, Beiping Su, Zhenlin Tang, Xinhe Huang","doi":"10.2174/0118746098383170250728163902","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>In summary, this dual-target strategy presents a promising avenue for developing advanced anti-aging therapies, warranting further investigation in preclinical and clinical settings.</p>","PeriodicalId":11008,"journal":{"name":"Current aging science","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synergistic Enhancement of Anti-aging Effects on Human Umbilical Vein Endothelial Cells Treated With the Combination of Ferulic Acid and Rapamycin.\",\"authors\":\"Han Li, Qiong Han, Yan Liu, Jiaxin Duan, Beiping Su, Zhenlin Tang, Xinhe Huang\",\"doi\":\"10.2174/0118746098383170250728163902\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>In summary, this dual-target strategy presents a promising avenue for developing advanced anti-aging therapies, warranting further investigation in preclinical and clinical settings.</p>\",\"PeriodicalId\":11008,\"journal\":{\"name\":\"Current aging science\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-08-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current aging science\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/0118746098383170250728163902\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current aging science","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0118746098383170250728163902","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
Synergistic Enhancement of Anti-aging Effects on Human Umbilical Vein Endothelial Cells Treated With the Combination of Ferulic Acid and Rapamycin.
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.