Chlorogenic acid inhibits LPS-induced microglial activation and improves survival of dopaminergic neurons

Pro-inflammatory factors released by activated microglia may contribute to the progression of neurodegenerative diseases. As a natural phenolic acid, chlorogenic acid (CGA) has been shown to have anti-inflammatory properties. However, it is unclear whether CGA has the ability to mediate microglial activation. The present study investigated the role of CGA in lipopolysaccharide (LPS)-stimulated microglia. Our data demonstrated that CGA significantly suppressed NO production and TNF-α release in LPS-stimulated primary microglia. In addition, CGA decreased LPS-stimulated phosphorylation and degradation of inhibitory kappa B-alpha (IκBα), and prevented translocation of nuclear factor-kappaB (NF-κB). Furthermore, CGA prevented neurotoxicity caused by microglial activation and ultimately improved survival of dopaminergic (DA) neuron. Finally, in vivo data showed that CGA pretreatment attenuated LPS-induced IL-1β and TNF-α release in substantia nigra (SN). Our results suggested that the pretreatment of CGA significantly inhibits the microglial activation, and CGA may be neuroprotective for pro-inflammatory factor-mediated neurodegenerative disorders.

► Chlorogenic acid (CGA) suppresses the production of NO and TNF-α in LPS-stimulated primary microglia.
► The anti-inflammatory effects of CGA on microglia could be related to the inhibition of NF-κB pathways.
► CGA prevents neurotoxicity caused by LPS stimulation in neuron-glia cultures.
► CGA reduces the expression of IL-1β and TNF-α in the LPS-injected SN in vivo.