[en] Parkinson's disease (PD), the second most prevalent neurodegenerative disorder afflicting human health, is primarily characterized by the degeneration of dopaminergic neurons in the midbrain, leading to movement disorders as the main clinical manifestation. Extensive research has demonstrated that the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and its accompanying neuroinflammation play a pivotal role in the progression of PD. ST-4, namely 15-oxosteviol, an analogue of the diterpene oridonin, exhibits potent and specific inhibition of NLRP3 in in vitro experiments. The anti-inflammatory effects of ST-4 were evaluated in mouse models of chronic and progressive disorders, in which it showed significant efficacy in ameliorating obesity, type 2 diabetes, and peritonitis. In this study, the potential interest of ST-4 for the treatment of neuroinflammatory diseases was further investigated in a PD mouse model. ST-4 effectively suppressed the activation of the NLRP3 inflammasome induced by lipopolysaccharide in neuronal cells. Additionally, treatment with ST-4 significantly improved various aspects of PD pathology, including behavioral impairments, loss of dopaminergic neurons, alterations in cerebral neurophysiology, and dysregulated gene expression associated with metabolic dysfunction, highlighting its therapeutic potential for the treatment of Parkinson's disease.
Disciplines :
Neurology Pharmacy, pharmacology & toxicology
Author, co-author :
Li, Wenqian; Institute for Medicinal Plants, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China ; Innovation Academy of International Traditional Chinese Medicinal Materials, Huazhong Agricultural University, Wuhan 430070, China
Zhang, Jiuliang ; College of Food Science & Technology, Huazhong Agricultural University, Wuhan 430070, China
Chen, Qiang; Institute for Medicinal Plants, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China ; Innovation Academy of International Traditional Chinese Medicinal Materials, Huazhong Agricultural University, Wuhan 430070, China
Luo, Biaobiao; College of pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, China
Zhou, Bo; Institute for Medicinal Plants, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China ; Innovation Academy of International Traditional Chinese Medicinal Materials, Huazhong Agricultural University, Wuhan 430070, China
Wang, Jun; Institute for Medicinal Plants, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China ; Innovation Academy of International Traditional Chinese Medicinal Materials, Huazhong Agricultural University, Wuhan 430070, China
Yang, Yang; Institute for Medicinal Plants, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China ; Innovation Academy of International Traditional Chinese Medicinal Materials, Huazhong Agricultural University, Wuhan 430070, China
Liu, Yi; College of Informatics, Huazhong Agricultural University, Wuhan 430070, China
Wen, Shuixiu; College of Informatics, Huazhong Agricultural University, Wuhan 430070, China
Kong, De-Xin; College of Informatics, Huazhong Agricultural University, Wuhan 430070, China
Chen, Jian; Hubei Cancer Hospital, Tongji Medical College, Colorectal cancer clinical research center of Hubei Province, Colorectal cancer clinical research center of Wuhan, Huazhong University of Science and Technology, Wuhan 430070, China
Wei, Shaozhong; Hubei Cancer Hospital, Tongji Medical College, Colorectal cancer clinical research center of Hubei Province, Colorectal cancer clinical research center of Wuhan, Huazhong University of Science and Technology, Wuhan 430070, China
Duez, Pierre ; Université de Mons - UMONS > Faculté de Médecine, Pharmacie et Sciences Biomédicales > Service de Chimie thérapeutique et Pharmacognosie
Sharipov, Avez; Scientific Laboratory of Innovative Pharmaceutical Compounds, Tashkent Pharmaceutical Institute, Oybek Street 45, Tashkent 100015, Uzbekistan
Li, Yan; Institute for Medicinal Plants, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China ; Innovation Academy of International Traditional Chinese Medicinal Materials, Huazhong Agricultural University, Wuhan 430070, China
Hu, Xuebo ; Institute for Medicinal Plants, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China ; Innovation Academy of International Traditional Chinese Medicinal Materials, Huazhong Agricultural University, Wuhan 430070, China
R550 - Institut des Sciences et Technologies de la Santé
Funders :
National Key Research and Development Program of China Shennongjia Academy of Forestry, Hubei, China Hubei Province Administration of Traditional Chinese Medicine Key Research and Development Program of Hubei Province for International Cooperation WBI-MOST project
Funding text :
This work was funded by the National Key R&D Program of China (No. 2021YFE0194000 to JZ) and the Hubei Province Administration of Traditional Chinese Medicine (No. ZY2023Z005 to SW). It is also supported by the Key R&D Program of Hubei Province for International Cooperation (No. 2022EHB047 to XH), the Shennongjia Academy of Forestry, Hubei, China (No. SAF202102 to XH), and the WBI-MOST project "CTCM-Cyt" (PD).
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