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Rosmarinic acid attenuates inflammatory responses through inhibiting HMGB1/TLR4/NF-κB signaling pathway in a mouse model of Parkinson's disease
- Source :
- Life Sciences. 223:158-165
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Inflammation contributes to the pathological processes in patients and animal models of PD. Rosmarinic acid (RA) has been demonstrated to protect neurons in PD models. The present study aimed to evaluate the anti-inflammatory effect of RA on PD and reveal possible pharmacological mechanisms. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) was injected to mice to establish PD model in vivo. BV-2 cells were exposed to 1-methyl-4-phenylpyridinium (MPP+) and α-synuclein to establish PD model in vitro. Results showed that treatment with RA dose-dependently improved motor function of PD mice, increased the number of tyrosine hydroxylase-positive cells, reduced production of pro-inflammatory cytokines, and inhibited microglia activation in ventral midbrain. In cell study, RA also decreased MPP+ or α-synuclein-induced secretion of pro-inflammatory cytokines. Furthermore, RA treatment downregulated the expression levels of HMGB1, TLR4 and Myd88 and inhibited NF-κB nuclear expression both in PD animal and cell models. These findings indicated that RA could attenuate inflammatory responses through suppressing HMGB1/TLR4/NF-κB signaling pathway, which may contribute to its anti-PD activity.
- Subjects :
- Male
0301 basic medicine
Cell
Anti-Inflammatory Agents
Inflammation
Motor Activity
Pharmacology
HMGB1
Depsides
030226 pharmacology & pharmacy
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Parkinsonian Disorders
In vivo
medicine
Animals
HMGB1 Protein
General Pharmacology, Toxicology and Pharmaceutics
Behavior, Animal
biology
Microglia
MPTP
NF-kappa B
General Medicine
Mice, Inbred C57BL
Toll-Like Receptor 4
030104 developmental biology
medicine.anatomical_structure
chemistry
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Cinnamates
biology.protein
TLR4
Cytokines
medicine.symptom
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 00243205
- Volume :
- 223
- Database :
- OpenAIRE
- Journal :
- Life Sciences
- Accession number :
- edsair.doi.dedup.....73f36d54285fd0ae6383404c4d020b4a