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Keywords = 27-hydroxymangiferolic acid

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18 pages, 4144 KiB  
Article
27-Hydroxymangiferolic Acid Extends Lifespan and Improves Neurodegeneration in Caenorhabditis elegans by Activating Nuclear Receptors
by Xiaoyan Gao, Jing Yu, Yin Li, Hang Shi, Lijun Zhang, Minglv Fang, Ying Liu, Cheng Huang and Shengjie Fan
Molecules 2025, 30(5), 1010; https://doi.org/10.3390/molecules30051010 - 21 Feb 2025
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Abstract
27-Hydroxymangiferolic acid (27-HMA) is a naturally occurring compound in mango fruits that exhibits diverse biological functions. Here, we show that 27-HMA activates the transcriptional activity of farnesoid X receptor (FXR), a nuclear receptor transcription factor, extending the lifespan and healthspan in Caenorhabditis elegans [...] Read more.
27-Hydroxymangiferolic acid (27-HMA) is a naturally occurring compound in mango fruits that exhibits diverse biological functions. Here, we show that 27-HMA activates the transcriptional activity of farnesoid X receptor (FXR), a nuclear receptor transcription factor, extending the lifespan and healthspan in Caenorhabditis elegans (C. elegans). Meanwhile, the longevity-promoting effect of 27-HMA was attenuated in the mutants of nhr-8 and daf-12, the FXR homologs, indicating that the longevity effects of 27-HMA in C. elegans may depend on nuclear hormone receptors (NHRs). Further analysis revealed potential associations between the longevity effects of 27-HMA and the insulin/insulin-like growth factor-1 signaling (IIS)/TORC1 pathway. Moreover, 27-HMA increased the toxin resistance of nematodes and activated the expression of detoxification genes, which rely on NHRs. Finally, 27-HMA improved the age-related neurodegeneration in Alzheimer’s disease (AD) and Parkinson’s disease (PD) C. elegans models. Taken together, our findings suggest that 27-HMA is a novel FXR agonist and may prolong lifespan and healthspan via activating NHRs. Full article
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