Based on Proteomics Reveals the Anti-inflammatory Mechanism of Phillygenin by Inhibition NF-κB Pathway

Abstract

Background: Inflammation is a common pathological phenomenon when homeostasis is seriously disturbed. Phillygenin (PHI) is a lignin component isolated from Forsythiae Fructus, which showed a good anti-inflammation effect. However, the mechanisms of PHI on anti-inflammation have not yet been systematically elucidated.Methods: In the study, the lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was established to investigate mechanisms of PHI on inflammation. The effect of PHI on LPS-induced IL-1β and PGE2 inflammatory factors was detected by ELISA, and the mRNA expression of IL-1β, IL-6 and TNF-α was detected by RT-qPCR. Proteomics studies the signaling pathways that may be affected by PHI. Molecular docking technology was used to study the possible targets of PHI on NF-kB pathway. Western blot was performed to detect progressive changes in protein expression.Results: The research showed that PHI significantly inhibited the robust increase of IL-1β and PGE2, and lowered the transcriptional level of inflammatory genes including IL-6, IL-1β and PGE2 in LPS-stimulated RAW264.7 cells. Proteomics results indicated that PHI was involved in the regulation of multiple signaling pathways. Molecular docking results indicated that PHI has an affinity for most proteins in NF-kB pathway. Western blot analysis showed that PHI inhibited LPS-induced NF-κB pathway activation. Conclusion: PHI inhibits the activation of NF-κB pathway, thereby inhibiting the expression of related inflammatory genes and the release of cytokines, thus showing remarkable anti-inflammatory effect.

Research Progress on the Mechanism of Traditional Chinese Medicine in the Treatment of Non-Alcoholic Fatty Liver Disease Based on Oxidative Stress

“…Lizhong Decoction capable of warming middle energizer and removing cold can be used for treating various diseases caused by deficiency of middle yang. Xiaoling Zhou et al [34] found that after treatment with Lizhong Decoction for NASH model rats, the liver lipid deposition, inflammatory cell infiltration degree, endoplasmic reticulum damage and mitochondrial damage were significantly improved, and the corresponding indicators serum liver function (ALT, AST),blood lipids (TG, TC),IKB inhibitory protein kinase α(IKK-α),nuclear transcription factor p65(NF-κBp65), IL-1β,IL-6,and TNF-α were all significantly decreased. The IKK/NF-κB signaling pathway is associated with ROS activation in Kupffer cells that further leads to the production of a large number of inflammatory factors [35][36].Therefore, this experiment concluded that Lizhong Decoction could reduce ROS production and relieve oxidative stress by reducing mitochondrial damage.…”