Therapeutic Effects of <i>Hemerocallis citrina</i> Baroni Extract on Animal Models of Neurodegenerative Diseases Through Serotonin and HLH-30/TFEB Dependent Mechanisms
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Hemerocallis citrina is an herbaceous perennial plant used in Asian cuisine and in Traditional Chinese Medicine. Here, we tested the therapeutic potential for a extracts (HCE30%, HCE50% and HCN) in vivo, using models of two human genetic neurodegenerative diseases – Machado-Joseph Disease/Spinocerebellar Ataxia type 3 and Frontotemporal Dementia with Parkinsonism associated to chromosome 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 signalling 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, also strengthen the use of these pathways as therapeutic targets for protein-related neurodegenerative disorders and confirm the utility of medicinal plants as a source of innovation, in the quest for new therapeutic agents.