Background: The root bark of Ulmus davidiana Nakai (Ulmaceae), a traditional Korean medicinal
plant, is used for treating inflammatory diseases.
Objective: We investigated the Nrf2-activating effect of U. davidiana and identified a novel Nrf2 activator
from its constituent compounds.
Methods: Cytotoxicity was measured by MTT assay, and the Nrf2 activity was examined by luciferasereporter
assay and western blot analysis. The expression of Nrf2-dependent antioxidant genes was estimated
by RT-PCR. The signal pathway related to Nrf2 activation was analyzed by treating specific signaling
inhibitors. Anti-inflammatory effects were determined using an NO assay and western blot
Results: Ulmus davidiana and its constituent compounds, including catechin-3-O-α-L-rhamnopyranoside,
α-nigerose, n-butyl α-D-fructofuranoside (NBF), and procyanidin B3, enhanced the transcriptional activity
of Nrf2. Of these compounds, only NBF possessed a distinctive structure and exhibited ROS-independent
Nrf2 activation. In addition, NBF significantly increased the nuclear translocation of Nrf2 and the expression
of Nrf2-dependent detoxifying enzymes, including HO-1 and NQO-1, in dose-dependent manner. The
Nrf2 activation induced by NBF was mediated by the phosphorylation of JNK. Consequently, pretreatment
with NBF inhibited the LPS-induced expression of pro-inflammatory genes.
Conclusion: To the best of our knowledge, this is the first study to report on the Nrf2-activating effect
of U. davidiana and NBF. Given the importance of Nrf2 as a negative regulator in various inflammatory
diseases, NBF could be considered as a novel candidate for the prevention and treatment of inflammatory