Formononetin Exerts Neuroprotection in Parkinson’s Disease via the Activation of the Nrf2 Signaling Pathway
Parkinson’s disease (PD) is a prevalent neurodegenerative disease for which no effective treatment currently exists. In this study, we identified formononetin (FMN), a neuroprotective component found in herbal medicines such as <i>Astragalus membranaceus</i> and <i>Glycyrrhiza ural...
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2024-11-01
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| author | Xiaotong Wang Nianxin Kang Ying Liu Guojie Xu |
| author_facet | Xiaotong Wang Nianxin Kang Ying Liu Guojie Xu |
| author_sort | Xiaotong Wang |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a prevalent neurodegenerative disease for which no effective treatment currently exists. In this study, we identified formononetin (FMN), a neuroprotective component found in herbal medicines such as <i>Astragalus membranaceus</i> and <i>Glycyrrhiza uralensis</i>, as a potential agent targeting multiple pathways involved in PD. To investigate the anti-PD effects of FMN, we employed <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) PD models, specifically the transgenic strain NL5901 and the MPP(+)-induced strain BZ555, to investigate the effects of FMN on the key pathological features of PD, including dyskinesia, dopamine neuron damage, and reactive oxygen species (ROS) accumulation. The MPP(+)-induced SH-SY5Y cell PD model was utilized to evaluate the effects of FMN on cell viability, ROS accumulation, and mitochondrial dysfunction. The signaling pathway induced by FMN was analyzed using transcriptomic techniques and subsequently validated in vitro. Our results indicate that FMN significantly reduced ROS accumulation and improved both dopaminergic neuron vitality and dyskinesia in the <i>C. elegans</i> PD models. In the cell PD model, FMN significantly reduced ROS accumulation and enhanced mitochondrial membrane potential (MMP) and cell viability. A transcriptomic analysis suggested that the effects of FMN are associated with Nrf2 activation. Furthermore, ML385, a specific Nrf2 inhibitor, blocked the beneficial effects of FMN in vitro, indicating that FMN ameliorates dyskinesia and protects dopaminergic neurons through Nrf2 signaling pathway activation. In addition, the effects of FMN on ameliorating dyskinesia and protecting dopamine neurons were comparable to those of the Nrf2 agonist of sulforaphane (SFN) in vivo. The results of this study confirm that FMN exerts significant anti-PD effects primarily through the Nrf2 signaling pathway. These findings provide crucial insights for the development of anti-PD therapies. |
| format | Article |
| id | doaj-art-955943c40bf547989f2c5989fe2b3d85 |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-955943c40bf547989f2c5989fe2b3d852025-08-20T01:53:57ZengMDPI AGMolecules1420-30492024-11-012922536410.3390/molecules29225364Formononetin Exerts Neuroprotection in Parkinson’s Disease via the Activation of the Nrf2 Signaling PathwayXiaotong Wang0Nianxin Kang1Ying Liu2Guojie Xu3School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, ChinaParkinson’s disease (PD) is a prevalent neurodegenerative disease for which no effective treatment currently exists. In this study, we identified formononetin (FMN), a neuroprotective component found in herbal medicines such as <i>Astragalus membranaceus</i> and <i>Glycyrrhiza uralensis</i>, as a potential agent targeting multiple pathways involved in PD. To investigate the anti-PD effects of FMN, we employed <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) PD models, specifically the transgenic strain NL5901 and the MPP(+)-induced strain BZ555, to investigate the effects of FMN on the key pathological features of PD, including dyskinesia, dopamine neuron damage, and reactive oxygen species (ROS) accumulation. The MPP(+)-induced SH-SY5Y cell PD model was utilized to evaluate the effects of FMN on cell viability, ROS accumulation, and mitochondrial dysfunction. The signaling pathway induced by FMN was analyzed using transcriptomic techniques and subsequently validated in vitro. Our results indicate that FMN significantly reduced ROS accumulation and improved both dopaminergic neuron vitality and dyskinesia in the <i>C. elegans</i> PD models. In the cell PD model, FMN significantly reduced ROS accumulation and enhanced mitochondrial membrane potential (MMP) and cell viability. A transcriptomic analysis suggested that the effects of FMN are associated with Nrf2 activation. Furthermore, ML385, a specific Nrf2 inhibitor, blocked the beneficial effects of FMN in vitro, indicating that FMN ameliorates dyskinesia and protects dopaminergic neurons through Nrf2 signaling pathway activation. In addition, the effects of FMN on ameliorating dyskinesia and protecting dopamine neurons were comparable to those of the Nrf2 agonist of sulforaphane (SFN) in vivo. The results of this study confirm that FMN exerts significant anti-PD effects primarily through the Nrf2 signaling pathway. These findings provide crucial insights for the development of anti-PD therapies.https://www.mdpi.com/1420-3049/29/22/5364Parkinson’s diseaseformononetinNrf2mitochondrion |
| spellingShingle | Xiaotong Wang Nianxin Kang Ying Liu Guojie Xu Formononetin Exerts Neuroprotection in Parkinson’s Disease via the Activation of the Nrf2 Signaling Pathway Molecules Parkinson’s disease formononetin Nrf2 mitochondrion |
| title | Formononetin Exerts Neuroprotection in Parkinson’s Disease via the Activation of the Nrf2 Signaling Pathway |
| title_full | Formononetin Exerts Neuroprotection in Parkinson’s Disease via the Activation of the Nrf2 Signaling Pathway |
| title_fullStr | Formononetin Exerts Neuroprotection in Parkinson’s Disease via the Activation of the Nrf2 Signaling Pathway |
| title_full_unstemmed | Formononetin Exerts Neuroprotection in Parkinson’s Disease via the Activation of the Nrf2 Signaling Pathway |
| title_short | Formononetin Exerts Neuroprotection in Parkinson’s Disease via the Activation of the Nrf2 Signaling Pathway |
| title_sort | formononetin exerts neuroprotection in parkinson s disease via the activation of the nrf2 signaling pathway |
| topic | Parkinson’s disease formononetin Nrf2 mitochondrion |
| url | https://www.mdpi.com/1420-3049/29/22/5364 |
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