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Rg1 improves LPS-induced Parkinsonian symptoms in mice via inhibition of NF-κB signaling and modulation of M1/M2 polarization.
- Source :
-
Acta pharmacologica Sinica [Acta Pharmacol Sin] 2020 Apr; Vol. 41 (4), pp. 523-534. Date of Electronic Publication: 2020 Mar 18. - Publication Year :
- 2020
-
Abstract
- Ginsenoside Rg1 is one of the most active ingredients in ginseng, which has been reported to protect dopaminergic neurons and improve behavioral defects in MPTP model, 6-OHDA model and rotenone model. However, it is unclear whether Rg1 exerted neuroprotection in LPS-induced sub-acute PD model. In this study, we investigated the neuroprotective effect of Rg1 in the sub-acute PD mouse model and explored the related mechanisms. Rg1 (10, 20, 40 mg·kg <superscript>-1</superscript> ·d <superscript>-1</superscript> ) was orally administered to mice for 18 days. A sub-acute PD model was established in the mice through LPS microinjection into the substantia nigra (SN) from D8 to D13. We found that Rg1 administration dose-dependently inhibited LPS-induced damage of dopaminergic neurons and activation of glial cells in the substantia nigra pars compacta (SNpc). The neuroprotective effects of Rg1 were associated with the reduction of pro-inflammatory cytokines and the improvement of anti-inflammatory cytokines and neurotrophin in the midbrain. Rg1 shifted the polarization of microglia towards the M2 phenotype from M1, evidenced by decreased M1 markers (inducible NO synthase, CD16, etc.) and increased M2 markers (arginase 1 (Arg1), CD206, etc) in the midbrain. Furthermore, Rg1 administration markedly inhibited nuclear translocation of NF-κB in midbrain microglia. In conclusion, Rg1 protects PD mice induced by continuous LPS injection by inhibiting the nuclear entry of NF-κB and regulating the polarization balance of microglia, shedding new light on a disease-modifying therapy of PD.
- Subjects :
- Administration, Oral
Animals
Araliaceae chemistry
Cytokines antagonists & inhibitors
Cytokines metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Ginsenosides administration & dosage
Ginsenosides isolation & purification
Lipopolysaccharides administration & dosage
Lipopolysaccharides antagonists & inhibitors
Lipopolysaccharides pharmacology
Male
Mice
Mice, Inbred C57BL
Microglia metabolism
NF-kappa B metabolism
Neuroprotective Agents administration & dosage
Neuroprotective Agents isolation & purification
Parkinsonian Disorders chemically induced
Phenotype
Signal Transduction drug effects
Ginsenosides pharmacology
Microglia drug effects
NF-kappa B antagonists & inhibitors
Neuroprotective Agents pharmacology
Parkinsonian Disorders drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1745-7254
- Volume :
- 41
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Acta pharmacologica Sinica
- Publication Type :
- Academic Journal
- Accession number :
- 32203085
- Full Text :
- https://doi.org/10.1038/s41401-020-0358-x