A natural xanthone increases catalase activity but decreases NF-kappa B and lipid peroxidation in U-937 and HepG2 cell lines

Eur J Pharmacol. 2015 Oct 5;764:520-528. doi: 10.1016/j.ejphar.2015.07.046. Epub 2015 Jul 21.

Abstract

Mangiferin, a C-glycosyl xanthone, has shown anti-inflammatory, antioxidant, and anti-tumorigenic activities. In the present study, we investigated the molecular mechanism for the antioxidant property of mangiferin. Considering the role of nuclear transcription factor kappa B (NF-κB) in inflammation and tumorigenesis, we hypothesized that modulating its activity will be a viable therapeutic target in regulating the redox-sensitive ailments. Our results show that mangiferin blocks several inducers, such as tumor necrosis factor (TNF), lypopolysaccharide (LPS), phorbol-12-myristate-13-acetate (PMA) or hydrogen peroxide (H2O2) mediated NF-κB activation via inhibition of reactive oxygen species generation. In silico docking studies predicted strong binding energy of mangiferin to the active site of catalase (-9.13 kcal/mol), but not with other oxidases such as myeloperoxidase, glutathione peroxidase, or inducible nitric oxide synthase. Mangiferin increased activity of catalase by 44%, but had no effect on myeloperoxidase activity in vitro. Fluorescence spectroscopy further revealed the binding of mangiferin to catalase at the single site with binding constant and binding affinity of 3.1×10(-7) M(-1) and 1.046 respectively. Mangiferin also inhibits TNF-induced lipid peroxidation and thereby protects apoptosis. Hence, mangiferin with its ability to inhibit NF-κB and increase the catalase activity may prove to be a potent therapeutic.

Keywords: Antioxidant; Catalase; Mangiferin; NF-κB; Oxidative stress; TNF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Binding Sites
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / pathology
  • Catalase / chemistry
  • Catalase / metabolism*
  • Catalytic Domain
  • Dose-Response Relationship, Drug
  • Hep G2 Cells
  • Humans
  • I-kappa B Kinase / metabolism
  • Lipid Peroxidation / drug effects*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / pathology
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / enzymology
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Molecular Docking Simulation
  • NF-kappa B / metabolism*
  • Protein Binding
  • Protein Conformation
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Spectrometry, Fluorescence
  • Tumor Necrosis Factor-alpha / pharmacology
  • U937 Cells
  • Up-Regulation
  • Xanthones / chemistry
  • Xanthones / metabolism
  • Xanthones / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • NF-kappa B
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Xanthones
  • mangiferin
  • Catalase
  • I-kappa B Kinase