Abstract
Neuroinflammation can cause multiple neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). Recent studies have shown that the artemisinin derivative dihydroartemisinin (DHA) can be used as an immunomodulatory, anti-inflammatory and anti-tumor agent. The anti-neuroinflammatory effects of DHA were evaluated in our study, and the underlying mechanisms were explored using the Morris water maze test (MWMT), Open-field test (OFT) and Closed-field test (CFT), Elevated plus maze test (EPMT), Nissl Staining, Immunofluorescence analysis, RT-PCR, and Western Blot. Our results show that DHA significantly inhibits LPS-induced inflammation and attenuates LPS-induced behavioral and memory disorders. 1. Behavioral test results: 1) in the water maze test, the mice in the LPS group showed increased escape latency and length of the movement path on the third day; they also had a decreased number of crossings of the target quadrant after the platform was removed on the 5th day and remained in the target quadrant for less time; 2) in the open- and closed-field experiment, the number of activities and activities in the open-field were significantly reduced; 3) in the elevated cross maze experiment, LPS-treated mice exhibited a significant reduction in the number of times and the time to enter the open arm; the above behavior was reversed after DHA treatment. 2. Nissl staining results: compared with the Control group, the LPS group showed significant damage, and the number of damaged cells in the hippocampal CA1, CA2, CA3 and DG regions was increased; DHA treatment reduced cell damage. 3. RT-PCR results: compared with the Control group, the LPS group showed increased expression of IL-1β and IL-6 but decreased expression after DHA treatment. 4. GFAP fluorescent staining: compared with the control group, the corresponding reactivity of positive cells in the LPS-induced group was increased in the CA1-CA3 and DG regions of the hippocampus; compared with the LPS-induced mice, cells in the LPS + DHA group showed significantly reduced reactivity (GFAP). 5. Western blot results: compared with the Control group, the LPS group showed increased expression of P-PI3K/PI3K, P-AKT/AKT, IL-6 and TNFα and a decreased expression of P-PI3K/PI3K, IL-6, TNF and P-AKT/AKT after DHA treatment. Our findings provide direct evidence for the potential use of DHA in the treatment of neuroinflammatory diseases.
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Acknowledgments
This work was supported by the Jiangsu Students’ Platform for Innovation and Entrepreneurship Training Program (201810313040Y), the National Demonstration Center for Experimental Basic Medical Science Education (Xuzhou Medical University).
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YTG, SYJ and YLW contributed to the conception and design of the study. SJZ, NAK and XFM analyzed the data. CYF and BC drafted the manuscript and figures
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The C57 / BL6 mice used in the laboratory were purchased from the Experimental Animal Center of Xuzhou Medical University and used after being approved by medical ethics.
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All animal procedures were approved by the Ethics Committee of the Catholic University of Korea and were performed in accordance with the National Institutes of Health’s Guide for the Care and Use of Laboratory Animals (NIH Publication No. 80–23). None of the authors performed any human experiments as part of this research.
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Gao, Y., Cui, M., Zhong, S. et al. Dihydroartemisinin ameliorates LPS-induced neuroinflammation by inhibiting the PI3K/AKT pathway. Metab Brain Dis 35, 661–672 (2020). https://doi.org/10.1007/s11011-020-00533-2
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DOI: https://doi.org/10.1007/s11011-020-00533-2