Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation
Siqi Tang,
Chunying Li,
Zongwu Suo,
Yi Xu,
Kaixin Wei,
Lei Zhao,
Hao Huang,
Xiangqian Liu,
Dongxu Liu,
Xiaojun Li
Affiliations
Siqi Tang
National Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, China
Chunying Li
College of Basic Medicine, Gannan Medical University, Ganzhou 341000, China
Zongwu Suo
National Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, China
Yi Xu
National Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, China
Kaixin Wei
National Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, China
Lei Zhao
College of Basic Medicine, Gannan Medical University, Ganzhou 341000, China
Hao Huang
National Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, China
Xiangqian Liu
School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China
Dongxu Liu
College of Basic Medicine, Gannan Medical University, Ganzhou 341000, China
Xiaojun Li
National Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, China
The traditional herb Eleutherococcus henryi Oliv. is commonly used to treat inflammatory conditions including rheumatism, arthritis, and hepatitis, as well as mental fatigue and amnesia, according to traditional Chinese medicine (TCM) theory. Savinin is a natural lignan obtained from the roots of E. henryi. The present study was undertaken to determine whether savinin can relieve LPS-induced neuroinflammation and if so, what the mechanism is. Groups of male C57BL/6 mice were administered savinin (5, 10, 20 mg/kg) and DEX (10 mg/kg) by gavage once daily for a continuous 7 days. On the 5th day of continuous pre-administration, LPS (2.5 mg/kg) was injected into the lateral ventricles of the mice for modeling 48 h. We found that treatment with savinin decreased the levels of neuroinflammatory cytokines and histopathological alterations dramatically. Consequently, it improved the LPS-induced neuroinflammatory response in mice. Furthermore, savinin inhibited the up-regulated expression of related proteins in the activated MAPK/NF-κB and NLRP3 inflammasome signaling pathways caused by LPS. Docking studies demonstrated the binding of savinin to three receptors (MAPK, NF-κB and NLRP3) using a well-fitting mode. These findings suggest that savinin may suppress neuroinflammation induced by LPS in vivo via modulating MAPK/NF-κB and NLRP3 signaling pathways.
