Paeoniflorin improves functional recovery through repressing neuroinflammation and facilitating neurogenesis in rat stroke model

Abstract

Background Microglia, neuron, and vascular cells constitute a dynamic functional neurovascular unit, which exerts the crucial role in functional recovery after ischemic stroke. Paeoniflorin, the principal active component of Paeoniae Radix, has been verified to exhibit neuroprotective roles in cerebralischemic injury. However, the mechanisms underlying the regulatory function of Paeoniflorin on neurovascular unit after cerebral ischemia are still unclear. Methods In this study, adult male rats were treated with Paeoniflorin following transient middle cerebral artery occlusion (tMCAO), and then the functional behavioral tests (Foot-fault test and modified improved neurological function score, mNSS), microglial activation, neurogenesis and vasculogenesis were assessed. Results The current study showed that Paeoniflorin treatment exhibited a sensorimotor functional recovery as suggested via the Foot-fault test and the enhancement of spatial learning as suggested by the mNSS in rat stroke model. Paeoniflorin treatment repressed microglial cell proliferation and thus resulted in a significant decrease in proinflammatory cytokines IL-1β, IL-6 and TNF-α. Compared with control, Paeoniflorin administration facilitated von Willebrand factor (an endothelia cell marker) and doublecortin (a neuroblasts marker) expression, indicating that Paeoniflorin contributed to neurogenesis and vasculogenesis in rat stroke model. Mechanistically, we verified that Paeoniflorin repressed JNK and NF-κB signaling activation. Conclusions These results demonstrate that Paeoniflorin represses neuroinflammation and facilitates neurogenesis in rat stroke model and might be a potential drug for the therapy of ischemic stroke.

Preclinical Evidence of Paeoniflorin Effectiveness for the Management of Cerebral Ischemia/Reperfusion Injury: A Systematic Review and Meta-Analysis

“…A total of 13 studies (Xiao, 2005;Wang, 2008;Tang et al, 2010;He, 2014;Mao et al, 2014;Rao, 2014;Zhang et al, 2015;Liu, 2016;Chu et al, 2017;Ko et al, 2018;Liao, 2018;Yu et al, 2018;Tang et al, 2021), including five English studies (Tang et al, 2010;Zhang et al, 2015;Chu et al, 2017;Ko et al, 2018;Tang et al, 2021) and eight Chinese studies (Xiao, 2005;Wang, 2008;He, 2014;Mao et al, 2014;Rao, 2014;Liu, 2016;Liao, 2018;Yu et al, 2018),were considered. The studies were published from 2005 to 2021.…”

Potential Mechanisms of White Peony against Primary Sjögren’s Syndrome Based on Network Pharmacology and Molecular Docking

“…Experimental evidence suggests that Pae can suppress the release of inflammatory cytokines, such as IL-6 and TNFα [60]. Furthermore, in rats with collagen-induced arthritis, Pae was proved to reduce phosphorylated Akt, resulting in decreased production of antibodies [35].…”

A Review of Traditional Chinese Medicine, Buyang Huanwu Decoction for the Treatment of Cerebral Small Vessel Disease

“…It is also effective in preventing prenatal stress-induced learning and memory impairment ( Wang X. et al, 2021 ). In a rat stroke model, paeoniflorin repressed neuroinflammation and facilitated neurogenesis ( Tang H. et al, 2021 ), protected against ischemic brain injury, inhibited apoptosis ( Liu et al, 2021 ), reduced cerebral oxidative stress, improved white matter integrity in hypoxic brain injury ( Yang et al, 2021 ), and attenuated early brain injury through reducing oxidative stress and neuronal apoptosis ( Wang T. et al, 2020 ). In a mouse model of Alzheimer’s disease (AD), paeoniflorin exerted neuroprotective effects via activation of adenosine A receptor ( Kong et al, 2020 ).…”