The Screening Research of NF-?B Inhibitors from Moutan Cortex Based on Bioactivity-Integrated UPLC-Q/TOF-MS

Lu, Yujie; Liu, Wenjuan; Zhang, Man; Deng, Yanfang; Jiang, Min; Bai, Gang

The transcription factor NF-B acts a key role in the process of immune response and it can usually be activated when exposed to inflammatory cytokines such as TNF-, viral infection, ultraviolet irradiation, and other physiological and nonphysiological stimuli [10] [11] [12] . However, the activated NF-B signaling pathway participates not only in immune regulation and inflammation, but also in infection, cell cycle regulation, cell differentiation, and apoptosis [13] [14] [15] . If the activation cannot be eliminated in time, it may lead to serious pathological reactions, such as rheumatoid arthritis, systemic lupus erythematosus, septic shock, atherosclerosis, and cancer [16] [17] [18] . Consequently, inhibitors of NF-B activation are of primary significance in protecting cells from the potential damage of inflammation. Based on the efficient separation and analysis functions of UPLC-Q-TOF-MS and cell biological method, seven compounds with NF-B inhibitory activity were screened from MC. Among them, gallic acid could inhibit NF-B activation by prevention of RelA acetylation [19] . And paeoniflorin could significantly inhibit NF-B by reducing the expression of the phosphorylation of I B and p65 [20] . Additionally, paeonol could suppress NF-B signaling through blocking MAPK/p38 signaling pathway [21, 22] . Furthermore, oxypaeoniflorin could inhibit the elevation of the expression levels of NF-B although the mechanism remained unclear [23] . Additionally, NF-B inhibitory activity of galloylpaeoniflorin, benzoyloxypaeoniflorin, and mudanoside C has not been reported in previous studies. In the present study, those three compounds could inhibit the activation of NF-B induced by TNF-a and could be considered as novel NF-B inhibitors. In general, the efficacy of drugs depends mainly on their chemical structures [24] . According to our results, other monoterpenoids with paeoniflorin as the core structure may also have NF-B inhibitory activity, which can be used as a lead compound for the study of innovative drugs. Furthermore, the results demonstrated that the antiinflammatory activity of MC was related to the process of various components acting on multiple targets ( Figure 5) , which was consistent with the characteristics of TCMs with multiple components, multiple pathways, and multiple targets [25, 26] .