Antioxidant activities of aqueous leaf extracts of Toona sinensis on free radical-induced endothelial cell damage

J Ethnopharmacol. 2011 Sep 1;137(1):669-80. doi: 10.1016/j.jep.2011.06.017. Epub 2011 Jun 28.

Abstract

Ethnopharmacological relevance: In Taiwan, Toona sinensis (Toona sinensis) is well known as a traditional Chinese medicine, while the underlying pharmacological mechanisms of this drug are still a matter of debate.

Materials and methods: The purpose of this study was to evaluate the protective effects of non-cytotoxic concentrations of aqueous leaf extracts of Toona sinensis (TS extracts; 50-100 μg/mL) and gallic acid (5 μg/mL), a major component of these extracts, against AAPH-induced oxidative cell damage in human umbilical vein endothelial cells (ECs).

Results: Exposure of ECs to AAPH (15 mM) decreased cell viability from 100% to 43%. However, ECs were pre-incubated with TS extracts prior to AAPH induction resulted in increased resistance to oxidative stress and cell viability in a dose-dependent manner. An increase in ECs-derived PGI(2) and IL-1 β in response to AAPH exposure was positively correlated with cytotoxicity and negatively with TS extracts concentrations. In addition, gallic acid also suppressed PGI(2) and IL-1 β production in AAPH-induced ECs. Notably, TS extracts/gallic acid treatment significantly inhibited ROS generation, MDA formation, SOD/catalase activity, and Bax/Bcl-2 dysregulation in AAPH-stimulated ECs. Pretreatment of ECs with TS extracts/gallic acid also suppressed AAPH-induced cell surface expression and secretion of VCAM-1, ICAM-1 and E-selectin, which was associated with abridged adhesion of U937 leukocytes to ECs. Moreover, TS extracts/gallic acid treatment significantly inhibited the AAPH-mediated up regulation of PAI-1 and down regulation of t-PA in ECs, which may decrease fibrinolytic activity.

Conclusions: Therefore, Toona sinensis may possess antioxidant properties that protect endothelial cells from oxidative stress. Our results also support the traditional use of Toona sinensis in the treatment of free radical-related diseases and atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines / toxicity
  • Antioxidants / chemistry
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Catalase / metabolism
  • Cell Survival / drug effects
  • Coculture Techniques
  • Cytoprotection
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • E-Selectin / metabolism
  • Epoprostenol / metabolism
  • Free Radicals / metabolism*
  • Gallic Acid / chemistry
  • Gallic Acid / isolation & purification
  • Gallic Acid / pharmacology*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-1beta / metabolism
  • Malondialdehyde / metabolism
  • Meliaceae* / chemistry
  • Oxidants / toxicity
  • Oxidative Stress / drug effects*
  • Plant Leaves
  • Plants, Medicinal
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Solvents / chemistry*
  • Superoxide Dismutase / metabolism
  • Tissue Plasminogen Activator / metabolism
  • U937 Cells
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Water / chemistry*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Amidines
  • Antioxidants
  • BAX protein, human
  • Drugs, Chinese Herbal
  • E-Selectin
  • Free Radicals
  • Interleukin-1beta
  • Oxidants
  • Plasminogen Activator Inhibitor 1
  • Proto-Oncogene Proteins c-bcl-2
  • SELE protein, human
  • SERPINE1 protein, human
  • Solvents
  • Vascular Cell Adhesion Molecule-1
  • bcl-2-Associated X Protein
  • Water
  • Intercellular Adhesion Molecule-1
  • Malondialdehyde
  • Gallic Acid
  • 2,2'-azobis(2-amidinopropane)
  • Epoprostenol
  • Catalase
  • Superoxide Dismutase
  • Tissue Plasminogen Activator