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

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 , Ki-Tae Ha .

Journal Name: Current Pharmaceutical Biotechnology

Volume 17 , Issue 13 , 2016

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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.

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

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Article Details

VOLUME: 17
ISSUE: 13
Year: 2016
Page: [1181 - 1188]
Pages: 8
DOI: 10.2174/1389201017666160920161238
Price: $58

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