title: Neuroprotective Effects of Echinacoside on Regulating the Stress-Active p38MAPK and NF-κB p52 Signals in the Mice Model of Parkinson's Disease.
abstract: Herbal medicines have long been used to treat Parkinson's disease (PD). To systematically analyze the anti-parkinsonian activity of echinacoside (ECH) in a neurotoxic model of PD and provide a future basis for basic and clinical investigations, male C57BL/6 mice were randomized into blank control, PD model and ECH-administration groups. ECH significantly suppressed the dopaminergic neuron loss (P < 0.01) caused by MPTP and maintained dopamine content (P < 0.01) and dopamine metabolite content (P < 0.05) compared with that measured in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced damage. Additionally, ECH inhibited the activation of microglia and astrocytes in the substantia nigra, which suggested the involvement of neuroinflammation. The relevant cytokines were detected with a Proteome Profiler Array, which confirmed that ECH participated in the regulation of seven cytokines. Given that p38 mitogen-activated protein kinase (p38MAPK) and NF-kappaB (NF-κB) signals are considered to be closely related to neuroninflammation, the gene expression levels of p38MAPK and six NF-κB DNA-binding subunits were assessed. Western blotting analysis showed that both p38MAPK and the NF-κB p52 subunit were upregulated in the MPTP group and that ECH downregulated their expressions. Minocycline was administered as the positive control to inhibit neuroinflammation, and no differences were detected between the minocycline- and ECH-mediated inhibition of the p38MAPK and NF-κB p52 signals. In conclusion, echinacoside is a potential novel orally active compound for regulating neuroinflammation and related signals in Parkinson's disease and may provide a new prospect for clinical treatment.
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Jingsi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Zhennian
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Min
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Xiangting
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. dingfang_cai@sina.com.
authors.forename: Dingfang
authors.identifier: http://orcid.org/0000-0001-7647-2766
authors.initials: D
authors.lastname: Cai
mesh_terms: D000818:Animals; D006027:Glycosides / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052003:NF-kappa B p52 Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000517:prevention & control*; D011897:Random Allocation; D016896:Treatment Outcome; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D006027:Glycosides; D052003:NF-kappa B p52 Subunit; D018696:Neuroprotective Agents; D048051:p38 Mitogen-Activated Protein Kinases; C060297:echinacoside
keywords: Cytokines; Echinacoside; Microglia; Neuroinflammation; Neuroprotective