Objectives: Kyungok-go (KOG) is a traditional multi-herbal medicine commonly used for enforcing weakened immunity for long time. Recently, there are several reports that KOG has anti-inflammatory and immuno-stimulatory activities in many experimental models. However, the protective effects of KOG on neuronal inflammation are still undiscovered. Thus, we investigated the neuro-protective activity of KOG on lipopolysaccharide (LPS)-stimulated mouse microglia cells. To find out KOG’s anti-neuroinflammatory effects on microglial cells, we examined the production of nitrite using griess assay, and mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and interleukin (IL)-1<i>β</i>, IL-6, tumor necrosis factor (TNF)-<i>α</i> using real time RT-PCR. In addition, to examine the regulating mechanisms of KOG, we investigated the protein expression of mitogen-activated protein kinases (MAPKs) and I<i>κ</i>-B<i>α</i> by western blot. KOG inhibited the elevation of nitrite, iNOS and COX-2 on LPS-stimulated BV2 cells. Also, KOG significantly inhibited the pro-inflammatory cytokines such as IL-1<i>β</i>, IL-6, and TNF-<i>α</i> on LPS-stimulated BV2 microglial cells. Moreover, KOG inhibited the activation of c-Jun N-terminal kinase (JNK), P38 and degradation of I<i>κ</i>-B<i>α</i> but not the activation of extracellular signal regulated kinase (ERK) on LPS-stimulated BV2 microglial cells. These results showed KOG has the anti-inflammatory effects through the inhibition on nitrite, iNOS, COX-2, IL-1<i>β</i>, IL-6, and TNF-<i>α</i> via the deactivation of JNK, p38 and nuclear factor (NF)-<i>κ</i>B on LPS-stimulated BV2 microglial cells. Thereby, KOG could offer the new and promising treatment for neurodegenerative disease related to neuroinflammation.

Objectives: Network pharmacology is a method of constructing and analyzing a drug-compound-target network to predict potential efficacy and mechanisms related to drug targets. In that large-scale analysis can be performed in a short time, it is considered a suitable tool to explore the function and role of herbal medicine. Thus, we investigated the potential functions and pathways of Chongmyunggongjin-dan (CMGJD) on Alzheimer’s disease (AD) via network pharmacology analysis.Methods: Using public databases and PubChem database, compounds of CMGJD and their target genes were collected. The putative target genes of CMGJD and known target genes of AD were compared and found the correlation. Then, the network was constructed using Cytoscape 3.9.1. and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms.Results: The result showed that total 104 compounds and 1157 related genes were gathered from CMGJD. The network consisted of 1157nodes and 10034 edges. 859 genes were interacted with AD gene set, suggesting that the effects of CMGJD are closely related to AD. Target genes of CMGJD are considerably associated with various pathways including ‘Positive regulation of chemokine production’, ‘Cellular response to toxic substance’, ‘Arachidonic acid metabolic process’, ‘PI3K-Akt signaling pathway’, ‘Metabolic pathways’, ‘IL-17 signaling pathway’ and ‘Neuroactive ligand-receptor interaction’.Conclusion: Through a network pharmacological method, CMGJD was predicted to have high relevance with AD by regulating inflammation. This study could be used as a basis for effects of CMGJD on AD.