作者
Yichi Zhang,Lu Yao,Xiaowen Zhang,Zhuo Yang,Yang Chen,Lingli Zheng,Yongzhe Zheng,Wei Yu,Nilufar Z. Mamadalieva,Bo Han,Pengfei Tu,R. F. Mukhamatkhanova,Ke‐Wu Zeng
摘要
Article Eupatorium Lindleyanum DC. Extract Protects against MPTP-induced Mouse of Parkinson’s Disease by Targeting Neuroinflammation Yichi Zhang 1, Lu Yao 1, Xiaowen Zhang 1, Zhuo Yang 1, Yang Chen 2, Lingli Zheng 1, Yongzhe Zheng 1, Wei Yu 2, Nilufar Z. Mamadalieva 3, Bo Han 2, Pengfei Tu 1, Rimma F. Mukhamatkhanova 3, and Kewu Zeng 1, * 1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China 2 School of Pharmacy/Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Shihezi University, Shihezi 832003, China 3 Institute of the Chemistry of Plant Substances AS RUz, Mirzo Ulugbek Str 77, Tashkent 100170, Uzbekistan * Correspondence: ZKW@bjmu.edu.cn Received: 10 May 2024; Revised: 14 May 2024; Accepted: 24 May 2024; Published: 6 June 2024 Abstract: Background: Neuroinflammation plays a vital role in the pathology of Parkinson’s disease (PD). Eupatorium lindleyanum DC. (EL) has previously reported to exert anti-inflammation activity. Methods: In the present study, we examined the effects of the EL extract (ELE) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and potential molecular mechanisms. The anti-neuroinflammation effect of ELE was also determined in lipopolysaccharide (LPS)-induced BV-2 cells in vitro. Moreover, the ELE-interacting target proteins were identified. And the bioinformatics analysis was performed based on the identified targets. Results: Our results showed that ELE significantly alleviated motor performance impairment and neuronal damage in MPTP-induced PD mice. In particular, ELE reversed MPTP-induced neuroinflammation via inhibiting microglial activation that was associated with progressive PD. Moreover, the anti-neuroinflammation effect of ELE was confirmed in LPS-induced BV-2 cells by detecting the release of pro-inflammatory factors such as nitric oxide (NO), interleukin-6 (Il-6), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, the ELE- interacting target proteins were identified by affinity purification-mass spectrometry-based proteomics strategy. Then, AMP-activated protein kinase (AMPK) signaling pathway was enriched by kyoto encyclopedia of genes and genomes (KEGG) analysis. We found that ELE markedly increased AMPK phosphorylation and inhibited nuclear factor-κB (NF-κB) signal in BV-2 cells. Conclusion: Collectively, these results indicate that ELE may exert significant neuroprotective effects against PD via targeting neuroinflammation.