Nordihydroguaiaretic acid: a review of its numerous and varied biological activities

Nordihydroguaiaretic acid (NDGA) is a lignan found in large amounts in the ethnobotanically important plant, Larrea tridentata (Moc. & Sess.) Cov. (Zygophyllaceae). Research on this compound and its natural and synthetic derivatives has shown them to be potentially useful in the treatment of cancer, diabetes, viral and bacterial infections, and as regulators of fertility. The usefulness of these compounds is hindered by the lack of understanding of the mechanisms of action for each activity. While a great deal of observational and correlative data have been reported, there have been few comprehensive mechanistic or structure-function studies conducted on NDGA. Additionally, toxicological and pharmacokinetic data on NDGA is rather sparse and the metabolic breakdown products of this compound have not been reported. The present review is meant to summarize many of the biological activities reported for NDGA and its derivatives and to draw attention to areas which need to be further explored in the hopes of stimulating research on this potentially useful natural product.