• Xin Gong, Zhijian Tan, Henghui Xu, Xu Jiang, and Lei Chen.
• Department of Neurosurgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P. R. China.
• Am. J. Chin. Med. 2024 Jan 1; 52 (7): 213121592131-2159.

AbstractThis study is to explore the effects of paeoniflorin (PF) on oxidative stress (OS) and inflammation in Parkinson's disease (PD) via the HSF1-NRF1 axis. SH-SY5Y cells were pretreated with PF and induced with α-synuclein preformed fibrils (PFF), followed by gain- and loss-of-function assays. Afterward, detection was conducted on cell viability, mitochondrial membrane potential ([Formula: see text]m), and reactive oxygen species (ROS), cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) levels. The binding of HSF1 to NRF1 promoter was evaluated. HSF1 and NRF1 expression was examined. Lastly, PD mouse models were established, followed by observation of the behavioral features of mice. Apoptosis; cleaved-Caspase 3, cleaved-Caspase 8, repulsive guidance molecule A (RGMa), GAP-43, and brain-derived neurotrophic factor (BDNF) expression; and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT), tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, and IL-10 levels were determined in mice and cells. HSF1 and NRF1 were downregulated, and HSF1 promoted NRF1 transcription and PF dose-dependently augmented HSF1 and NRF1 expression. PF dose-dependently reduced RGMa expression, ROS, MDA, TNF-α, IL-2, and IL-6 levels; mitigated apoptosis; and lowered cleaved-Caspase 3, cleaved-Caspase 8, COX-2, and iNOS expression while improving cell viability; increasing [Formula: see text]m, GAP-43, and BDNF expression; and raising SOD, GSH-Px, CAT, and IL-10 levels in PFF-induced SH-SY5Y cells. These effects were neutralized by HSF1 knockdown. In conclusion, PF dose-dependently activated the HSF1-NRF1 axis and alleviated OS and inflammation in PFF-treated mice, thereby impeding PD progression in mice.

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