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The aim of this study was to investigate the effect of electrical stimulation on activator protein-1 (AP-1) in recombinant liver cells. In order to elucidate the molecular effects of electrical stimulation on cells, AP-1 expression was detected by a luciferase assay. The parameters used were taken from clinical electroacupuncture (EA) therapy as follows: biphasic rectangular symmetrical pulses (frequency: 2, 10 and 100 Hz; pulse width: 50, 80, 130 and 250 μsec; intensity: 1, 2, 5 and 10 mA; time: 5, 10, 20 and 30 minutes). S (10% fetal bovine serum in medium), SF (serum free medium) and 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment represented the experimental, negative and positive groups, respectively. We found that electrical stimulation with 10 Hz, a pulse width of 130 μsec, and a duration of 30 minutes gave a significant increase in AP-1 activity. In contrast, the intensity of the stimulation had no significant effect on AP-1 activity. In conclusion, our data suggest that electrical stimulation with an appropriate frequency, duration and pulse width could cause an increase in AP-1 activity in cells.

Maydis Stigma (MS) is an herb traditionally used in many parts of the world. Previous studies have reported that MS plays a role in several biological activities, including antidiabetic and anticancer activities. However, the effects of a MS ethanolic extract (MSE) on the anti-inflammatory cellular mechanism remain unclear. Here, we investigated the anti-inflammatory properties of MSE and its molecular mechanism both in vitro and in vivo. The effects of MSE on the production of inflammatory mediators, cytokines, and related proteins and the identification of target genes were determined using LPS-stimulated macrophages. We also determined the analgesic and anti-inflammatory effects of MSE by examining acetic acid-induced writhing responses and xylene-induced ear edema in mice. Our results indicated that MSE markedly decreased iNOS and COX-2 levels without causing cytotoxicity and suppressed the secretion of NO in LPS-stimulated macrophages. MSE also inhibited the production of proinflammatory cytokines, such as TNF-$\alpha$, IL-6, and IL-1$\beta$, and induced the expression of HO-1. Moreover, MSE treatment significantly reduced the LPS-stimulated activation of MAPK, NF-$\kappa$B, and AP-1. Furthermore, MSE exerted an analgesic effect on the acetic acid-induced abdominal writhing response test and an anti-inflammatory effect on xylene-induced ear edema in ICR mice. Finally, we investigated the components of MSE using UPLC-ESI-MS and found that it contains the maysin as a marker component. Overall, these observations demonstrate that MSE has anti-inflammatory and antinociceptive effects both in vitro and in vivo, which may provide new scientific evidence for its use as a potential therapeutic agent for the treatment of inflammation.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) and Docking studies of novel quinazoline analogues, which are oral potential inhibitors towards the activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB), have been carried out. The 3D-QSAR study based on the comparative molecular field analysis (CoMFA) shows the established model having a significant statistical quality and excellent predictive ability, in which the correlation coefficient R is 0.972 and cross-validation coefficient q² is 0.619. The Docking results also show a considerable correlation (or trend) between the energy scores and the corresponding experimental values for these compounds at some sites. Meanwhile, it is very interesting to find the binding sites just fall on the joint regions between AP-1 (or NF-κB) and DNA. It may be the reason that the quinazoline analogues have inhibition function because their existence on these joint regions can effectively prevent free AP-1 and NF-κB from binding to DNA. Based on the established 3D-QSAR and Docking analyses, six new compounds of quinazoline analogues with higher inhibitory activities were theoretically designed and presented. The above results can offer some valuable theoretical references for the pharmaceutical molecular design as well as the action mechanism analysis.