n-Butyl-α-D-fructofuranoside Isolated from Ulmus davidiana Enhances Nrf2 Activity Through Activation of JNK

Title:n-Butyl-α-D-fructofuranoside Isolated from Ulmus davidiana Enhances Nrf2 Activity Through Activation of JNK

Volume: 17 Issue: 13

Author(s): Hee-Jin Choi, Hee-Jung Choi, Mi-Joo Park, Tae-Wook Chung, Myungsoo Joo, Cheorl-Ho Kim, Hyun-Wook Chang, Jong-Keun Son and Ki-Tae Ha

Affiliation:

Keywords: n-Butyl α-D-fructofuranoside, Ulmus davidiana, Nrf2, JNK, Macrophage, HO-1, NQO-1, Anti-inflammation.

Abstract: 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 analysis.

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 diseases.

Cite this article as:

Choi Hee-Jin, Choi Hee-Jung, Park Mi-Joo, Chung Tae-Wook, Joo Myungsoo, Kim Cheorl-Ho, Chang Hyun-Wook, Son Jong-Keun and Ha Ki-Tae, n-Butyl-α-D-fructofuranoside Isolated from Ulmus davidiana Enhances Nrf2 Activity Through Activation of JNK, Current Pharmaceutical Biotechnology 2016; 17 (13) . https://dx.doi.org/10.2174/1389201017666160920161238