Paeoniflorin exerts neuroprotective effects by modulating the M1/M2 subset polarization of microglia/macrophages in the hippocampal CA1 region of vascular dementia rats via cannabinoid receptor 2

• DOI: 10.1186/s13020-018-0173-1
• Publication Date: 2018-04-04T00:18:54Z
• Authors: Xian-Qin Luo; Ao Li; Xue Yang; Xiao Xiao; Rong Hu; Tian-Wen Wang; Xiao-Yun Dou; Da-Jian Yang; Zhi Dong
• Keywords: Proinflammatory cytokine; Paeoniflorin

Cerebral hypoperfusion is a pivotal risk factor for vascular dementia (VD), which effective therapy remains inadequate. Persistent inflammatory responses and excessive chemotaxis of microglia/macrophages in the brain may accelerate progression VD. Endocannabinoids are involved neuronal protection against inflammation-induced injury. Cannabinoids acting at cannabinoid receptor 2 (CB2R) can decrease inflammation. Based on identification paeoniflorin (PF) as CB2R agonist, we investigated neuroprotective M1 to M2 polarization promoting effects PF permanent four-vessel occlusion rat model.One week after surgery, was intraperitoneally administered dose 40 mg/kg once day 28 successive days. The memory deficit were by Morris water maze test, hippocampal damage evaluated light microscope electron microscope. mRNA protein expression levels key molecules related M1/M2 assessed RT-qPCR Western blotting, respectively.Administration could significantly attenuate cerebral hypoperfusion-induced impairment learning reduce morphological ultrastructural changes CA1 region rats. Moreover, promoted an phenotype transition hippocampus In addition its inhibitory property proinflammatory mediator expression, such IL-1β, IL-6, TNF-α NO, dramatically up-regulated anti-inflammatory cytokines IL-10 TGF-β1. Importantly, antagonist AM630 abolished these beneficial produced learning, structure rats, well phenotype. Additionally, treatment inhibited mTOR/NF-κB pathway enhanced PI3K/Akt pathway. Effects signaling pathways effectively attenuated when rats co-treated with AM630, indicating that through activation.These findings demonstrated exerts effect shifts milieu toward resolution modulation microglia/macrophage via activation.