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eCAM Advance Access published online on October 27, 2009
eCAM, doi:10.1093/ecam/nep076
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© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Nordihydroguaiaretic Acid from Creosote Bush (Larrea tridentata) Mitigates 12-O-Tetradecanoylphorbol-13-Acetate-induced Inflammatory and Oxidative Stress Responses of Tumor Promotion Cascade in Mouse Skin

Shakilur Rahman1, Rizwan Ahmed Ansari1, Hasibur Rehman2, Suhel Parvez3 and Sheikh Raisuddin1

1Department of Medical Elementology and Toxicology, Hamdard University, New Delhi 110062, India, 2Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA and 3Department of Neurophysiology, Leibniz Institute for Neurobiology, Brenneckestrasse 6, Magdeburg D-39118, Germany

Nordihydroguaiaretic acid (NDGA) is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC) Coville (creosote bush). It has a long history of traditional medicinal use by the Native Americans and Mexicans. The modulatory effects of topically applied NDGA was studied on acute inflammatory and oxidative stress responses in mouse skin induced by stage I tumor promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA). Double TPA treatment adversely altered many of the marker responses of stage I skin tumor promotion cascade. Pretreatment of NDGA in TPA-treated mice mitigated cutaneous lipid peroxidation and inhibited production of hydrogen peroxide. NDGA treatment also restored reduced glutathione level and activities of antioxidant enzymes. Elevated activities of myeloperoxidase, xanthine oxidase and skin edema formation in TPA-treated mice were also lowered by NDGA indicating a restrained inflammatory response. Furthermore, results of histological study demonstrated inhibitory effect of NDGA on cellular inflammatory responses. This study provides a direct evidence of antioxidative and anti-inflammatory properties of NDGA against TPA-induced cutaneous inflammation and oxidative stress corroborating its chemopreventive potential against skin cancer.

Keywords: chemoprevention – creosote bush – inflammation – nordihydroguaiaretic acid – oxidative stress

For reprints and all correspondence: Sheikh Raisuddin, Associate Professor, Department of Medical Elementology and Toxicology, Hamdard University, New Delhi 110062, India. Tel: +91-11-26059688; Fax: +91-11-26059663; E-mail: sheikhraisuddin{at}yahoo.com

Received January 20, 2009; accepted June 2, 2009


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