peoniflorin and Cognitive-Dysfunction

Alzheimer's disease (AD) is a neurodegenerative disease, associated with progressive cognitive impairment and memory loss. In the present study, we examined the protective effects of paeoniflorin against memory loss and cognitive decline in lipopolysaccharide (LPS)-induced mice. Treatment with paeoniflorin alleviated LPS-induced neurobehavioral dysfunction, as confirmed by behavioral tests, including the T-maze test, novel-object recognition test, and Morris water maze test. LPS stimulated the amyloidogenic pathway-related proteins (amyloid precursor protein, APP; β-site APP cleavage enzyme, BACE; presenilin1, PS1; presenilin2, PS2) expression in the brain. However, paeoniflorin decreased APP, BACE, PS1, and PS2 protein levels. Therefore, paeoniflorin reverses LPS-induced cognitive impairment via inhibition of the amyloidogenic pathway in mice, which suggests that paeoniflorin may be useful in the prevention of neuroinflammation related to AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Cognitive Dysfunction; Disease Models, Animal; Glucosides; Lipopolysaccharides; Maze Learning; Memory Disorders; Mice; Mice, Transgenic; Monoterpenes

Paeoniflorin (PF) has numerous benefits, including anti-inflammatory and anti-apoptosis effects. However, it is not clear if it has neuroprotective effects against cognitive impairment (CI) in Parkinson's disease (PD). Through network pharmacology, we identified probable targets as well as signal pathways through which PF might affect CI in PD. Then, we experimentally validated our findings. The core genes of the protein-protein interactions (PPI) network include MAPK8 (JNK), TP53, CASP3 (caspase-3), postsynaptic density protein-95 (PSD-95) and synaptophysin (SYN). Pathway enrichment analysis revealed that genes involved in apoptosis and mitogen-activated protein kinase (MAPK) signaling were significantly enriched. Because JNK is a key mediator of p53-induced apoptosis, we wondered if JNK/p53 pathway influences the effects of PF against apoptosis in mouse model of PD. Molecular docking analysis showed that PF had good affinity for JNK/p53. The results of the experiments indicated that PF ameliorated behavioral impairments and upregulated the expression of the dopamine (DA) neurons, suppressed cell apoptosis in substantia nigra pars compacta (SNpc) of PD. Additionally, PF improved 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury by inhibiting apoptosis in hippocampal neurons of the CA1 and CA3, and upregulating PSD-95 as well as SYN protein levels. Similar protective effects were observed upon JNK/p53 pathway inhibition using SP600125. Overall, PF improved CI in PD by inhibiting JNK/p53 pathway.

Topics: Animals; Cognitive Dysfunction; Dopaminergic Neurons; Glucosides; Mice; Molecular Docking Simulation; Monoterpenes; Parkinson Disease; Signal Transduction; Tumor Suppressor Protein p53

Paeoniflorin (PF) is a natural monoterpene glycoside in Paeonia lactiflora pall with anti-diabetic, antioxidant, anti-inflammatory, and neuro-protective properties. This study was designed to investigate the neuroprotective effects of PF against cognitive deficits induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in mice. STZ was injected twice intracerebroventrically (3 mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with PF (10 mg/kg per day, intraperitoneally) starting from the first dose of STZ for 21 days showed an improvement in ICV-STZ induced cognitive deficits as assessed by novel object recognition and Morris water maze (MWM) test. PF significantly attenuated STZ induced mitochondrial dysfunction manifested by dramatically elevated cytochrome c oxidase activity and ATP synthesis, and restoration of the mitochondrial membrane potential (MMP), and oxidative stress in hippocampus and in the cortex compared to control. Moreover, PF treatment also markedly increased synaptic density in the CA1 region of the hippocampus compared to control. Furthermore, PF ameliorated defective insulin signaling by up-regulating p-PI3K and p-Akt protein expression while downregulating p-IRS-1 protein expression. Taken together, the outcomes of the current study suggest the therapeutic potential of PF in the cognitive deficits induced by ICV-STZ.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibiotics, Antineoplastic; Brain; Cognitive Dysfunction; Disease Models, Animal; Electron Transport Complex IV; Glucosides; Injections, Intraventricular; Insulin; Male; Maze Learning; Membrane Potentials; Mice; Mice, Inbred C57BL; Mitochondria; Monoterpenes; Oxidative Stress; Recognition, Psychology; Signal Transduction; Streptozocin; Synapses

To explore the delayed neuroprotection induced by paeoniflorin (PF), the principal component of Paeoniae radix prescribed in Chinese medicine, and its underlying mechanisms in rats subjected to vascular dementia (VD).. A rat model of VD was induced by bilateral common carotid arteries occlusion (BCCAO). Low-dose or high-dose PF (20 or 40 mg/kg once per day) was administrated for 28 days after VD. The behavioral analysis of rat was measured by water morris. Regional cerebral blood volume (rCBV), regional cerebral blood flflow (rCBF) and mean transit time (MTT) were measured in the bilateral hippocampus by perfusion-weighted imaging (PWI). The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured by commercially available enzyme-linked immunosorbent assay kits. Protein levels were evaluated by western blot analysis. mRNA levels were evaluated by real time-polymerase chain reaction. Western blotting was used to estimate p65 translocation.. The behavioral analysis showed that PF could decrease the escape latency time (P<0.05), and increase the residence time of the original platform quadrant and the across platform frequency in water maze in VD rats (P<0.05). Likewise, PF remarkably promoted the rCBV (P<0.05), rCBF and decreased per minute MTT (P<0.05) in hippocampus of VD rats. Furthermore, PF decreased the release of IL-1β, IL-6 and TNF-α as well as inhibited the mRNA expression of IL-1β, IL-6 and TNF-α in the hippocampus of VD rats (P<0.05 or P<0.01). PF also could decrease the protein expressions of inducible nitric oxide synthase and cyclooxygenase-2 in the hippocampus of VD rats (P<0.05 or P<0.01). In addition, PF signifificantly inhibited the nuclear factor κB (NF-κB) pathway in the hippocampus of VD rats.. PF signifificantly attenuates cognitive impairment, improves hippocampus perfusion and inhibits inflflammatory response in VD rats. In addition, the anti-inflflammatory effects of PF might be due to inhibiting the NF-κB pathway. PF may be a potential clinical application in improving VD.

Topics: Animals; Cerebrovascular Circulation; Cognitive Dysfunction; Cyclooxygenase 2; Dementia, Vascular; Down-Regulation; Glucosides; Hippocampus; Inflammation Mediators; Male; Maze Learning; Memory Disorders; Monoterpenes; Nitric Oxide Synthase Type II; Rats, Sprague-Dawley; RNA, Messenger; Transcription Factor RelA