Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson's disease by activation of adenosine A1 receptor.
1. This study examined whether Paeoniflorin (PF), the major active components of Chinese herb Paeoniae alba Radix, has neuroprotective effect in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). 2. Subcutaneous administration of PF (2.5 and 5 mg kg(-1)) for 11 days could protect tyrosine hydroxylase (TH)-positive substantia nigra neurons and striatal nerve fibers from death and bradykinesia induced by four-dose injection of MPTP (20 mg kg(-1)) on day 8. 3. When given at 1 h after the last dose of MPTP, and then administered once a day for the following 3 days, PF (2.5 and 5 mg kg(-1)) also significantly attenuated the dopaminergic neurodegeneration in a dose-dependent manner. Post-treatment with PF (5 mg kg(-1)) significantly attenuated MPTP-induced proinflammatory gene upregulation and microglial and astrocytic activation. 4. Pretreatment with 0.3 mg kg(-1) 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor (A1AR) antagonist, 15 min before each dose of PF, reversed the neuroprotective and antineuroinflammatory effects of PF. 5. In conclusion, this study demonstrated that PF could reduce the MPTP-induced toxicity by inhibition of neuroinflammation by activation of the A1AR, and suggested that PF might be a valuable neuroprotective agent for the treatment of PD.
Department of Pharmacology II, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, China.
Hua-Qing
HQ
Liu
Wei-Yu
WY
Zhang
Xue-Ting
XT
Luo
Yang
Y
Ye
Xing-Zu
XZ
Zhu
D000818:Animals; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000473:pathology; D004298:Dopamine; D005960:Glucosides / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy*; D051379:Mice; D039821:Monoterpenes; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism*; D013378:Substantia Nigra / Q000473:pathology; D006027:Glycosides
D001565:Benzoates; D001952:Bridged-Ring Compounds; D004298:Dopamine; D005960:Glucosides; D039821:Monoterpenes; D018696:Neuroprotective Agents; D043682:Receptor, Adenosine A1; C015423:peoniflorin; D006027:Glycosides