Involvement of multitargets in paeoniflorin-induced preconditioning.
Paeoniflorin (PF) is the principal component of Paeoniae radix prescribed in traditional Chinese medicine. The delayed neuroprotection induced by PF preconditioning and its underlying mechanisms were investigated in rat middle cerebral artery occlusion (MCAO) and reperfusion model. At a dosage of 20 or 40 mg/kg, PF preconditioning 48 h before MCAO followed by 24-h reperfusion significantly reduced the mortality and infarct volume and reversed the neurological deficits caused by ischemia. Likewise, the ameliorative effects on mortality, infarct size, and neurological impairment induced by MCAO emerged as well when PF was administered 24 h, 48 h, or 5 days before MCAO at the dose of 20 mg/kg. Furthermore, comparative proteomics analysis was adopted to identify the differentially expressed proteins induced by PF preconditioning itself. The relative levels of 42 proteins were altered after PF preconditioning, among which 20 were elevated and 22 reduced. In summary, A(1) receptor-regulator of G protein signaling-K(ATP) signaling, arachidonic acid cascade, nitric oxide system, markers of neuronal damage, mitochondrial damage-related molecules, and the mitogen-activated protein kinase and nuclear factor-kappaB pathway are associated with the mechanisms of PF preconditioning.
Chen
Dong-Mei
DM
Department of Pharmacology, 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.
Xiao
Liang
L
Cai
Xin
X
Zeng
Rong
R
Zhu
Xing-Zu
XZ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D019194:Ischemic Preconditioning; D020935:MAP Kinase Signaling System; D008297:Male; D008969:Molecular Sequence Data; D039821:Monoterpenes; D016328:NF-kappa B / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D020710:RGS Proteins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000502:physiology; D006027:Glycosides
D000255:Adenosine Triphosphate; D016718:Arachidonic Acid; D001565:Benzoates; D019208:Brain-Derived Neurotrophic Factor; D001952:Bridged-Ring Compounds; D005960:Glucosides; D018840:HSP70 Heat-Shock Proteins; D039821:Monoterpenes; D016328:NF-kappa B; D009270:Naloxone; D018696:Neuroprotective Agents; D015221:Potassium Channels; D020710:RGS Proteins; D043682:Receptor, Adenosine A1; C015423:peoniflorin; D006027:Glycosides