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生物类黄酮柚皮苷的体内抗衰老作用:以出芽酵母酿酒酵母作为模式生物的研究见解

In vivo anti-aging effects of naringin, a bioflavonoid: insights from the budding yeast Saccharomyces cerevisiae as a model organism.

作者信息

Alugoju Phaniendra, Suwanchaikasem Pipob, Senabunyarith Apinan, Prasad Ankush, Tencomnao Tewin

机构信息

Natural Products for Neuroprotection and Anti-Ageing Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand.

Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.

出版信息

Biogerontology. 2025 Aug 5;26(4):155. doi: 10.1007/s10522-025-10295-y.

DOI:10.1007/s10522-025-10295-y
PMID:40764880
Abstract

Naringin is an antioxidant flavonoid rich in diverse plant species, including citrus plants. While the antioxidant activity of naringin is well documented, there has been limited research on its anti-aging potential. The aim of this study is to investigate the in vivo anti-aging effects of naringin in the budding yeast Saccharomyces cerevisiae as a model. Our findings showed that naringin substantially increased cell viability during the chronological lifespan of wild-type yeast by mitigating oxidative and apoptotic stress markers. However, naringin did not affect the viability of yeast null mutants lacking antioxidant enzymes (sod2Δ, cta1Δ, ctt1Δ, gpx1Δ, gpx2Δ, gsh1Δ; except sod1Δ and tsa1Δ), but slightly increased the viability of only pep4Δ and fis1Δ mutants, not mca1Δ. Gene expression results indicate that naringin altered the expression of genes associated with the TORC1 signaling pathway and other anti-aging genes such as SIR2 and ATG1. The study's findings also demonstrate that naringin could not increase cell viability of yeast null mutants lacking signaling pathway genes (tor1Δ, rim15Δ ras2Δ, and atg1Δ), except sch9Δ mutant during CLS. Metabolomic studies suggest that naringin treatment affects the levels of diverse class of metabolites such as amino acids, nucleotides and related compounds, vitamins, carbohydrates, and lipids in stationary phase yeast. Altogether, these findings suggest that naringin might exerts its anti-aging effects via modulating the nutrient sensing TORC1 signaling pathway, paving the way for future research to explore other aging associated gene targets.

摘要

柚皮苷是一种抗氧化类黄酮,广泛存在于包括柑橘类植物在内的多种植物中。虽然柚皮苷的抗氧化活性已有充分记载,但其抗衰老潜力的研究却很有限。本研究旨在以出芽酵母酿酒酵母为模型,研究柚皮苷在体内的抗衰老作用。我们的研究结果表明,柚皮苷通过减轻氧化应激和凋亡应激标志物,显著提高了野生型酵母在时序寿命期间的细胞活力。然而,柚皮苷对缺乏抗氧化酶的酵母缺失突变体(sod2Δ、cta1Δ、ctt1Δ、gpx1Δ、gpx2Δ、gsh1Δ;除sod1Δ和tsa1Δ外)的活力没有影响,但仅略微提高了pep4Δ和fis1Δ突变体的活力,对mca1Δ突变体则没有影响。基因表达结果表明,柚皮苷改变了与TORC1信号通路以及其他抗衰老基因(如SIR2和ATG1)相关的基因表达。研究结果还表明,柚皮苷在CLS期间不能提高缺乏信号通路基因(tor1Δ、rim15Δ、ras2Δ和atg1Δ)的酵母缺失突变体的细胞活力,但对sch9Δ突变体除外。代谢组学研究表明,柚皮苷处理会影响静止期酵母中多种代谢物的水平,如氨基酸、核苷酸及相关化合物、维生素、碳水化合物和脂质。总之,这些发现表明柚皮苷可能通过调节营养感应TORC1信号通路发挥其抗衰老作用,为未来探索其他衰老相关基因靶点的研究铺平了道路。

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本文引用的文献

1
Exploring the anti-aging potential of natural products and plant extracts in budding yeast : A review.探索天然产物和植物提取物在芽殖酵母中的抗衰老潜力:综述
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Effect of levan polysaccharide on chronological aging in the yeast Saccharomyces cerevisiae.低聚果糖对酿酒酵母老化的影响。
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Mutations of ribosomal protein genes induce overexpression of catalase in Saccharomyces cerevisiae.
核糖体蛋白基因的突变诱导酿酒酵母中过氧化氢酶的过表达。
FEMS Yeast Res. 2024 Jan 9;24. doi: 10.1093/femsyr/foae005.
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Comparative Analysis of Gut Microbiota from Rats Induced by Se Deficiency and T-2 Toxin.硒缺乏和 T-2 毒素诱导大鼠肠道微生物群的比较分析。
Nutrients. 2023 Dec 7;15(24):5027. doi: 10.3390/nu15245027.
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The Yeast Protein Kinase Sch9 Functions as a Central Nutrient-Responsive Hub That Calibrates Metabolic and Stress-Related Responses.酵母蛋白激酶Sch9作为一个核心营养响应枢纽,可校准代谢和应激相关反应。
J Fungi (Basel). 2023 Jul 26;9(8):787. doi: 10.3390/jof9080787.
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Water extract from delays the aging of via improving antioxidant activity.来自……的水提取物通过提高抗氧化活性延缓……的衰老。 (注:原文中部分内容缺失,导致翻译不够完整准确)
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7
Naringin Prevents Cognitive Dysfunction in Aging Rats by Inhibiting Toll-Like Receptor 4 (TLR4)/NF-B Pathway and Endoplasmic Reticulum Stress.柚皮苷通过抑制Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路和内质网应激预防衰老大鼠的认知功能障碍
Evid Based Complement Alternat Med. 2023 Feb 21;2023:2919811. doi: 10.1155/2023/2919811. eCollection 2023.
8
The nutrient-responsive CDK Pho85 primes the Sch9 kinase for its activation by TORC1.营养感应型 CDK Pho85 为 Sch9 激酶被 TORC1 激活做准备。
PLoS Genet. 2023 Feb 15;19(2):e1010641. doi: 10.1371/journal.pgen.1010641. eCollection 2023 Feb.
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Gentirigeoside B from Franch Prolongs Yeast Lifespan via Inhibition of TORC1/Sch9/Rim15/Msn Signaling Pathway and Modification of Oxidative Stress and Autophagy.来自滇紫堇的绅替瑞甙B通过抑制TORC1/Sch9/Rim15/Msn信号通路以及调节氧化应激和自噬来延长酵母寿命。
Antioxidants (Basel). 2022 Nov 30;11(12):2373. doi: 10.3390/antiox11122373.