Biomol Ther.  2016 Nov;24(6):581-588. 10.4062/biomolther.2016.141.

Lonchocarpine Increases Nrf2/ARE-Mediated Antioxidant Enzyme Expression by Modulating AMPK and MAPK Signaling in Brain Astrocytes

Affiliations
  • 1Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University, School of Medicine, Seoul 07985, Republic of Korea. hskimp@ewha.ac.kr
  • 2Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.

Abstract

Lonchocarpine is a phenylpropanoid compound isolated from Abrus precatorius that has anti-bacterial, anti-inflammatory, antiproliferative, and antiepileptic activities. In the present study, we investigated the antioxidant effects of lonchocarpine in brain glial cells and analyzed its molecular mechanisms. We found that lonchocarpine suppressed reactive oxygen species (ROS) production and cell death in hydrogen peroxide-treated primary astrocytes. In addition, lonchocarpine increased the expression of antioxidant enzymes, such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), and manganese superoxide dismutase (MnSOD), which are all under the control of Nrf2/antioxidant response element (ARE) signaling. Further, mechanistic studies showed that lonchocarpine increases the nuclear translocation and DNA binding of Nrf2 to ARE as well as ARE-mediated transcriptional activities. Moreover, lonchocarpine increased the phosphorylation of AMP-activated protein kinase (AMPK) and three types of mitogen-activated protein kinases (MAPKs). By treating astrocytes with each signaling pathway-specific inhibitor, AMPK, c-jun N-terminal protein kinase (JNK), and p38 MAPK were identified to be involved in lonchocarpine-induced HO-1 expression and ARE-mediated transcriptional activities. Therefore, lonchocarpine may be a potential therapeutic agent for neurodegenerative diseases that are associated with oxidative stress.

Keyword

Lonchocarpine; Astrocytes; Antioxidant enzymes; AMPK; MAPK; Nrf2/ARE signaling

MeSH Terms

Abrus
AMP-Activated Protein Kinases*
Antioxidants
Astrocytes*
Brain*
Cell Death
DNA
Heme Oxygenase-1
Hydrogen
Mitogen-Activated Protein Kinases
Neurodegenerative Diseases
Neuroglia
Oxidative Stress
p38 Mitogen-Activated Protein Kinases
Phosphorylation
Protein Kinases
Reactive Oxygen Species
Response Elements
Superoxide Dismutase
AMP-Activated Protein Kinases
Antioxidants
DNA
Heme Oxygenase-1
Hydrogen
Mitogen-Activated Protein Kinases
Protein Kinases
Reactive Oxygen Species
Superoxide Dismutase
p38 Mitogen-Activated Protein Kinases
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