Morinda citrifolia and Its Active Principle Scopoletin Mitigate Protein Aggregation and Neuronal Apoptosis through Augmenting the DJ-1/Nrf2/ARE Signaling Pathway

Autor: Thangarajeswari Mohan, Divya Bhavani Ravi, Kalaiselvi Periandavan, Deepthy Jayakumar, Yogesh Kanna Sathyamoorthy, Kishore Kumar S Narasimhan, Saraswathi Uthamaraman, Prema Velusamy, Ashokkumar Srinivasan, Namakkal S. Rajasekaran
Rok vydání: 2019
Předmět:
Zdroj: Oxidative Medicine and Cellular Longevity
Oxidative Medicine and Cellular Longevity, Vol 2019 (2019)
ISSN: 1942-0994
1942-0900
DOI: 10.1155/2019/2761041
Popis: Given the role of oxidative stress in PD pathogenesis and off-target side effects of currently available drugs, several natural phytochemicals seem to be promising in the management of PD. Here, we tested the hypothesis that scopoletin, an active principle obtained from Morinda citrifolia (MC), efficiently quenches oxidative stress through DJ-1/Nrf2 signaling and ameliorates rotenone-induced PD. Despite reducing oxidative stress, the administration of MC extract (MCE) has lessened protein aggregation as evident from decreased levels of nitrotyrosine and α-synuclein. In vitro studies revealed that scopoletin lessened rotenone-induced apoptosis in SH-SY5Y cells through preventing oxidative injury. Particularly, scopoletin markedly upregulated DJ-1, which then promoted the nuclear translocation of Nrf2 and transactivation of antioxidant genes. Furthermore, we found that scopoletin prevents the nuclear exportation of Nrf2 by reducing the levels of Keap1 and thereby enhancing the neuronal defense system. Overall, our findings suggest that scopoletin acts through DJ-1-mediated Nrf2 signaling to protect the brain from rotenone-induced oxidative stress and PD. Thus, we postulate that scopoletin could be a potential drug to treat PD.
Databáze: OpenAIRE
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