Safety and toxicological evaluation of demethylatedcurcuminoids; a novel standardized curcumin product

Turmeric is a well recognized and highly recommended herb in ayurvedic systems of medicine and it has also been used for culinary purposes for thousands of years. Bis-O-demethylatedcurcumin (BDMC) was found to be more efficacious than curcumin and the increased potentcy was attributed to a higher number of phenolic groups in BDMC. A novel demethylatedcurcuminoid composition (DC) comprising minimum 95% of total demethylatedcurcuminoids (67.8% bisdemethylcurcumin, 20.7% demethylmonodemethoxycurcumin, 5.86% bisdemethoxycurcumin, 2.58% demethylcurcumin) was prepared (PCT/IN05/00337, dated October 13, 2005) starting from Curcuma longa extract containing 95% total curcuminoids (C95). DC exhibited superior neuroprotective and anti-inflammatory efficacy compared to C95 in a GeneChip study. Based on these interesting findings, this study sought to determine the broad-spectrum safety of DC. Acute oral, acute dermal, primary skin and eye irritation, and dose-dependent 90 day sub-chronic toxicity studies were conducted. The acute oral LD50 of DC was found to be > 5000 mg/kg in female SD rats. No changes in body weight or adverse effects were observed following necropsy. Acute dermal LD50 of DC was found to be > 2000 mg/kg. Based on the data from primary skin irritation test conducted on New Zealand Albino rabbits, DC was classified as minimally irritating. Similarly, primary eye irritation test was conducted with DC on rabbits and based on the test outcome DC was classified as mildly irritating to the eye. A dose-dependent 90-day sub-chronic toxicity study demonstrated no significant changes in selected organ weights and as percentages of body and brain weights. DC supplementation did not cause changes in hepatic DNA fragmentation. Hematology, clinical chemistry, and histopathological evaluations did not show any adverse effects in any of the organs tested. These results demonstrate the broad spectrum safety of DC.