Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation

Abstract

BackgroundNeuroinflammation is an important factor causing numerous neurodegenerative pathologies. Inflammation can lead to abnormal neuronal structure and function and even death, followed by cognitive dysfunction. There is growing evidence that chlorogenic acid has anti-inflammatory effects and immunomodulatory activity.PurposeThe aim of this study was to elucidate the potential targets and molecular mechanisms of chlorogenic acid in the treatment of neuroinflammation.MethodsWe used the lipopolysaccharide-induced neuroinflammation mouse model and the lipopolysaccharide-stimulated BV-2 cells in vitro model. Behavioral scores and experiments were used to assess cognitive dysfunction in mice. HE staining and immunohistochemistry were used to assess neuronal damage in the mouse brain. Immunofluorescence detected microglia polarization in mouse brain. Western blot and flow cytometry detected the polarization of BV-2 cells. The migration of BV-2 cells was detected by wound healing assay and transwell assay. Potential targets for chlorogenic acid to exert protective effects were predicted by network pharmacology. These targets were then validated using molecular docking and experiments.ResultsThe results of in vivo experiments showed that chlorogenic acid had an obvious ameliorating effect on neuroinflammation-induced cognitive dysfunction. We found that chlorogenic acid was able to inhibit BV-2 cells M1 polarization and promote BV-2 cells M2 polarization in vitro while also inhibiting the abnormal migration of BV-2 cells. Based on the network pharmacology results, we identified the TNF signaling pathway as a key signaling pathway in which chlorogenic acid exerts anti-neuroinflammatory effects. Among them, Akt1, TNF, MMP9, PTGS2, MAPK1, MAPK14, and RELA are the core targets for chlorogenic acid to function.ConclusionChlorogenic acid can inhibit microglial polarization toward the M1 phenotype and improve neuroinflammation-induced cognitive dysfunction in mice by modulating these key targets in the TNF signaling pathway.

Folic Acid Rescues Dopaminergic Neurons in MPTP-Induced Mice by Inhibiting the NLRP3 Inflammasome and Ameliorating Mitochondrial Impairment

“…Mitochondrial dysfunction is a critical initiator of dopaminergic neuronal degeneration and is intimately linked with PD. , This dysfunction often results from the inhibitory effects of abnormal α-synuclein and toxins like MPTP on mitochondrial complex I of the electron transport chain . MPTP, being lipophilic, crosses the blood–brain barrier and is converted to toxic MPP + in glial cells, impeding complex I, disrupting electron flow, reducing ATP production, and generating ROS, thereby creating a feedback loop that escalates oxidative stress. Importantly, mitochondrial dysfunction also plays a significant role in activating the NLRP3 inflammasome .…”

Effects of Dendropanax morbiferus Leaf Extract on Sleep Parameters in Invertebrate and Vertebrate Models

“…Fernández et al analyzed the effect of rutin on sleep time and sedative action through thiopental-induced sleep test and behavioral analysis and reported on the possibility of use as a sleep-promoting material [42]. Previous studies have shown that subacute ingestion of chlorogenic acids decreased sleep latency in clinical trials [43], and in vitro and in vivo studies have reported that it prevents cognitive decline and nerve damage through tumor necrosis factor (TNF) and nuclear factor erythroid 2 related factor 2 (Nrf2)-nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) signaling pathways [44,45].…”

Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials

“…The potential contributive mechanism was Nrf2/PPAR activation [235]. CGA attenuates the polarization of macrophages and alleviates cognitive impairments in an LPS-induced neuroinflammation mouse model by targeting the TNFα signaling pathway [236]. CGA improves memory dysfunction and attenuates frontal cortex inflammation in diabetic rats [237].…”

“…Mouse model of anxiety [234]; sleep-deprived mice activation [235]; LPS-induced neuroinflammation mouse model [236]; diabetic rats [237]; corticosterone-induced depression-like mice [238] Activation of Nrf2/PPAR [235]; inhibition of the TNFα signaling pathway [236] CGA Healthy subjects with mild cognitive impairment [269][270][271]; healthy subjects observed [272,273] n.a. CGA; CGA-enriched coffee berry extracts Neuropathic pain (Section 6.6)…”