Therapeutic Effects of Hemerocallis citrina Baroni Extract on Animal Models of Neurodegenerative Diseases Through Serotonin and HLH-30/TFEB-Dependent Mechanisms

文献类型： 外文期刊

第一作者： Fernandes, Jorge H.

作者： Fernandes, Jorge H.;Costa, Marta Daniela;Vilasboas-Campos, Daniela;Ferreira-Lomba, Bruna;Pereira-Sousa, Joana;Teixeira-Castro, Andreia;Maciel, Patricia;Fernandes, Jorge H.;Costa, Marta Daniela;Vilasboas-Campos, Daniela;Ferreira-Lomba, Bruna;Pereira-Sousa, Joana;Teixeira-Castro, Andreia;Maciel, Patricia;Wang, Qiong;Wang, Fengzhong;Liu, Xinmin;Dias, Alberto C. P.

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关键词： medicinal plants; neurodegenerative diseases; Machado-Joseph disease/spinocerebellar ataxia type 3; Frontotemporal Dementia with Parkinsonism associated to chromosome 17

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES （ 影响因子：4.9； 五年影响因子：5.7 ）

ISSN： 1661-6596

年卷期： 2025 年 26 卷 9 期

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收录情况： SCI

摘要： Hemerocallis citrina is an herbaceous perennial plant used in Asian cuisine and Traditional Chinese Medicine. Here, we tested the therapeutic potential of extracts (HCE30%, HCE50%, and HCN) in vivo, using models of two human genetic neurodegenerative diseases-Machado-Joseph Disease/Spinocerebellar Ataxia type 3 (MJD/SCA3) and Frontotemporal Dementia with Parkinsonism associated to chromosome 17 (FTDP-17). Chronic treatment with HCE30% extract ameliorated the motor deficits typically observed in these models. Interestingly, we found that the effect on the motor phenotype of the MJD/SCA3 model was dependent on serotonergic signaling and on the action of the HLH-30/TFEB transcription factor, known to regulate the cellular response to amino acid starvation, the autophagy and mitophagy pathways, lysosome localization and biogenesis, exocytosis, and mitochondrial biogenesis. Altogether, our findings reinforce the idea that phytochemicals act through the modulation of serotonergic neurotransmission and introduce a novel layer to the HLH-30/TFEB regulatory network. Thus, it also strengthens the use of these pathways as therapeutic targets for protein-related neurodegenerative disorders and confirms the utility of medicinal plants as a source of innovation in the quest for new therapeutic agents.

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