Involvement of Multitargets in Paeoniflorin-Induced Preconditioning

Abstract

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-B pathway are associated with the mechanisms of PF preconditioning.Ischemic stroke is the second leading cause of death in China, leaving survivors burdened with severe disabilities. Deleterious infarctions of the middle cerebral artery (MCA) are at risk of developing massive edema because of the necrosis of cells located in the primary zone (Borlongan et al., 2005). The most effective drug, tissue plasminogen activator, the only Food and Drug Administration-approved thrombolytic drug used in ischemia, is widely employed in clinic. However, it has a very narrow therapeutic time window of 3 h, and only 1 to 3% of ischemic stroke patients have been benefited (Pulsinelli et al., 1997). Therefore, the current focus of stroke research requires investigation of novel neuroprotective agents and strategies, which could prolong the therapeutic window.Paeoniflorn (PF), the principal component of Paeoniae radix ("Shaoyao" in Chinese), has been widely investigated as antioxidant, cognitive enhancer, and endothelium-dependent vasodilator Ryu et al., 2001;Tabata et al., 2001). Recently, our laboratory found that PF could produce a dose-dependent decrease in both neurological impairment and infarct volume in acute transient cerebral ischemia through activating adenosine A 1 receptor in a manner different from its classic agonists (Liang et al., 2005;Liu et al., 2005b).Ischemic preconditioning (IPC) is an endogenous mechanism by which brief episodes of a sublethal insult induce a robust protection against the deleterious effects of subsequent, prolonged lethal ischemia. There are two kinds of protection: "classic IPC" and "delayed IPC." Various drugs ABBREVIATIONS: MCA, middle cerebral artery; PF, paeoniflorn; IPC, ischemic preconditioning; PPC, pharmacological preconditioning; DPCPX, 8-cyclopentyl-1,3-dipropylxanthine; TTC, 2,3,...

Natural compounds from traditional medicinal herbs in the treatment of cerebral ischemia/reperfusion injury

“…For instance, Paeoniflorin (PF), the principal component of Paeoniae radix (used in traditional Chinese medicine), displays a preconditioning neuroprotective effect against cerebral ischemia in mice. The related mechanism has been shown to involve multiple factors including the adenosine 1 receptor/regulator of G protein/K ATP signaling, the arachidonic acid cascade, the nitric oxide system, neuronal damage markers, molecules related to mitochondrial damage, mitogen-activated protein kinase, as well as the nuclear factor-κB pathway [73] . Pretreatment with another herb extract from Choto-san (Gouteng-san), a traditional Kampo medicine, also exhibits antidementia effects and neuroprotection against ischemia when administered at an appropriate dosage.…”

Dissection of the role of paeoniflorin in the traditional Chinese medicinal formula Si-Ni-San against contact dermatitis in mice

“…The main components of Si-Ni-San are Radix Bupleuri Chinensis (Chaihu), Radix Paeoniae Alba (Shaoyao), Fructus Citri Aurantii (Zhishi), and Radix Glycyrrhizae Uralensi (Gancao), with saikosaponin, paeoniflorin, naringin and glycyrrhizin as major active ingredients (Yamamoto et al,1975;Takagi and Harada,1969;Rouseff et al, 1987;Nikitina, 1966). Among these ingredients, paeoniflorin has been widely investigated as an antioxidant, cognitive enhancer, endotheliumdependent vasodilator, and neuroprotective agent (Goto et al, 1996;Ryu et al, 2001;Tabata et al, 2001;Chen et al, 2006). However, the actual contribution of paeoniflorin in Si-Ni-San against contact dermatitis, a typical T cell-mediated DTH response, remains unclear.…”

Total glucosides of peony attenuates experimental autoimmune encephalomyelitis in C57BL/6 mice

“…We found that TGP treatment prevented the reduction of BDNF in the lumbar spinal cord of EAE mice. The similar effect of TGP also occurred in rat middle cerebral artery occlusion and reperfusion model which shows the upregulated BDNF expression in the brain by PF preconditioning (Chen et al, 2006). CNPase is one of the most abundant proteins in CNS myelin and a possible auto-antigen in MS (Rosener et al, 1997).…”