Oridonin Attenuates Aβ1–42-Induced Neuroinflammation and Inhibits NF-κB Pathway

Abstract

Neuroinflammation induced by beta-amyloid (Aβ) plays a critical role in the pathogenesis of Alzheimer’s disease (AD), and inhibiting Aβ-induced neuroinflammation serves as a potential strategy for the treatment of AD. Oridonin (Ori), a compound of Rabdosia rubescens, has been shown to exert anti-inflammatory effects. In this study, we demonstrated that Ori inhibited glial activation and decreased the release of inflammatory cytokines in the hippocampus of Aβ1–42-induced AD mice. In addition, Ori inhibited the NF-κB pathway and Aβ1–42-induced apoptosis. Furthermore, Ori could attenuate memory deficits in Aβ1–42-induced AD mice. In conclusion, our study demonstrated that Ori inhibited the neuroinflammation and attenuated memory deficits induced by Aβ1–42, suggesting that Ori might be a promising candidate for AD treatment.

Paeoniflorin attenuates Aβ1-42-induced inflammation and chemotaxis of microglia in vitro and inhibits NF-κB- and VEGF/Flt-1 signaling pathways

“…Notably, a study from Zhong et al (2009) indicates that chronic intraperitoneal injection of PF significantly attenuates memory impairment and reduces neuronal apoptosis in Aβ 1-42 -treated rats in vivo (Zhong et al, 2009), implying PF may act beneficially in the treatment of AD. Over-activated NF-κB signaling leading to pathogenic inflammation has been reported to exacerbate the cytotoxic effects of Aβ oligomers in brain (Wang et al, 2014c). Interestingly, PF can abolish ischemia-induced abnormal activation NF-κB signaling in rat brain (Guo et al, 2012), but we lack of information of its effect on Aβ 1-42 -induced microglial NF-κB activation.…”

Targeting neuroinflammation in Alzheimer’s disease

“…The hope is to get satisfactory results from clinical studies with compounds that have been successful in vitro, ex vivo, and/or in vivo experiments, such as the administration of molecules like acetylpuerarin,138 edaravone,139 palmitoylethanolamide,38 N -[2-(4-hydroxyphenyl)ethyl]-2-(2,5-dimethoxyphenyl)-3-(3-methoxy-4-hydroxyphenyl) acrylamide (compound FLZ),140 oleuropeinaglycone,141 oridonin,142 protocatechuic acid,143 resveratrol,110 rutin,144 or immunotherapies145,146 and vaccinations 147…”

Discovery and development of natural product oridonin-inspired anticancer agents

“…Cheng et al demonstrated that oridonin induces L929 cell apoptosis by regulation of ROS-mediated signaling pathways, and simultaneously induces autophagy to block apoptosis by regulating p38/NF-κB signaling [39]. The anti-inflammatory and cytoprotective effects of oridonin have also been demonstrated using in vitro and in vivo models focused on the Nrf2 and NF-κB signaling pathways [40–42]. …”

“…Hence, additional attention should also be paid to explore other beneficial effects, including cytoprotection [40], anti-mycobacterial [126, 127], anti-fibrosis [128, 129] and anti-inflammatory effects [130], produced by oridonin and its derivatives. Interestingly, recent findings support that oridonin and its analogues may be considered a promising therapeutic option for Alzheimer’s disease (AD) and other neurodegenerative diseases [41, 42]. …”