Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (1): 194-199.doi: 10.4103/1673-5374.343892

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DL-3-n-butylphthalide alleviates motor disturbance by suppressing ferroptosis in a rat model of Parkinson’s disease

Chun-Bo Hu1, 2, #, Hui Jiang2, #, Yin Yang1, Guo-Hua Wang2, Qiu-Hong Ji1, Zhong-Zheng Jia3, Li-Hua Shen1, *, Qian-Qian Luo2, *   

  1. 1Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China; 2Department of Physiology and Hypoxic Biomedicine, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China; 3Department of Medical Imaging, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
  • Online:2023-01-15 Published:2022-06-17
  • Contact: Li-Hua Shen, MD, PhD, lihuashennt@126.com; Qian-Qian Luo, PhD, qianqianluo@ntu.edu.cn.
  • Supported by:
    This work was funded by the National Natural Science Foundation of China, No. 81873924 (to QQL), No. 82171190 (to GHW); Nantong Science and Technology Project of China, No. MS22021010 (to LHS); and High-level Innovation and Entrepreneurship Talents Introduction Program of Jiangsu Province of China (to QQL).

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Abstract: DL-3-n-butylphthalide (NBP)—a compound isolated from Apium graveolens seeds—is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke. NBP has shown recent potential as a treatment for Parkinson’s disease. However, the underlying mechanism of action of NBP remains poorly understood. In this study, we established a rat model of Parkinson’s disease by intraperitoneal injection of rotenone for 28 successive days, followed by intragastric injection of NBP for 14–28 days. We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson’s disease, inhibited loss of dopaminergic neurons and aggregation of α-synuclein, and reduced iron deposition in the substantia nigra and iron content in serum. These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor, ferritin light chain, and transferrin 1. NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson’s disease. Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition, oxidative stress, and ferroptosis in the substantia nigra.

Key words: cystine/glutamate antiporter solute carrier family 7 member 11, DL-3-n-butylphthalide, ferritin light chain, ferroportin 1, ferroptosis, glutathione peroxidase 4, oxidative stress, iron, rotenone, transferrin receptor