[2Ep] Bone metabolism, Mineral metabolism, Antioxidation

[2Ep-07] Sesaminol prevents Parkinson's disease by activating the Nrf2-ARE signaling pathway

*Akiko Kojima-Yuasa^1,2, Haruka Kaji², Ayano Omura³, Kunio Kiyomoto³, Isao Matsui-Yuasa^1,2 (1. Osaka Metropolitan University, 2. Osaka City University, 3. Kiyomoto Co., Ltd.)

Keywords:Sesaminol, Parkinson's disease, Nrf2-ARE signaling pathway

Objective: Parkinson's disease (PD) is a neurodegenerative disorder caused by the degeneration and loss of dopaminergic neurons in the substantia nigra. Sesaminol, a sesame lignan, possesses strong antioxidant properties. This study investigated the preventive effects of sesaminol on PD and its mechanisms using in vitro and in vivo PD models. Methods: An in vitro PD model was created by adding 6-hydroxydopamine (6-OHDA) to human neuroblastoma cells (SH-SY5Y). Sesaminol was added two hours prior to 6-OHDA treatment. An in vivo PD model was established by orally administering the neurotoxin rotenone to C57BL6/J mice for 29 days. The mice were fed a sesaminol-containing diet starting one week before rotenone administration. Results: Cell viability of SH-SY5Y cells significantly decreased by 6-OHDA was restored to control levels by sesaminol. Intracellular reactive oxygen species production was increased by 6-OHDA but significantly suppressed by sesaminol. Nuclear translocation of Nrf2, which was not observed in the control, was induced by sesaminol. The activity of NQO1, an antioxidant enzyme, was significantly enhanced by sesaminol. The motor function of mice significantly declined due to rotenone administration, but returned to control levels with sesaminol intake. Similar results were observed for gastrointestinal motility. α-Synuclein expression in the substantia nigra was increased in the rotenone group but decreased in the sesaminol diet group. Additionally, while the rotenone group exhibited shortening and damage of the colonic mucosa, these abnormalities were scarcely observed in the sesaminol diet group. Conclusion: Sesaminol have preventive effects on PD through the activation of the Nrf2-ARE signaling pathway.