Abstract
Objective
To evaluate the combination of rhubarb, astragalus, red sage, ginger, and turmeric (mixture referred to as “NT”) together with gallic acid for evidence of reproductive toxicity in rats.
Methods
Fifty virgin female rats were cohabited with male rats. Day 0 of potential pregnancy was evidence of spermatozoa on vaginal smear. The presumably pregnant rats were randomized to five groups of 10 individuals and were fed by daily gavage on days 6–20 of presumed gestation with one of the following: deionized water placebo, 21.6 mg/kg per day, 215 mg/kg per day, 430 mg/kg per day, or 860 mg/kg per day of a mixture of NT (20%) and gallic acid (80%). Cesarean section was performed on day 21.
Results
All 50 rats had one or more live fetuses and survived until they were killed. Body weight was reduced in the 860 mg/kg per day group compared with placebo: mean (SD), 406.8 (23.0) vs. 430.1 (27.7) g, P<0.05. There were no dose-related adverse events or differences between groups in uterine size, food intake, corpora lutea, implantations, litter size, number of live fetuses, and gender distribution of fetuses or fetal resorptions. There were no dead fetuses, and all placentae appeared normal. All rats and tissues were normal at necropsy. Fetal weights did not differ between groups, and there were no fetal abnormalities.
Conclusion
The combination of NT and gallic acid gave no evidence of reproductive toxicity at 430 mg/kg per day or below, which is reassuring should this combination be used in the future as a dietary herbal supplement for the treatment of obesity.
Similar content being viewed by others
References
Wei K, Xu X. Herbal composition and method for controlling body weight and composition. United States Patent 6,541,046, April 1, 2003. Available at: www.freepatentsonline.com/6541046.html. Accessed: April 1, 2010.
York DA, Sonyja Thomas, Greenway FL, Liu Z, Rood JC. Effect of an herbal extract Number Ten (NT) on body weight in rats. Chin Med. 2006;2:10.
Greenway FL, Liu Z, Martin CK, Rood JC, Yu Y, Amen RJ. Safety and efficacy of NT, an herbal supplement, in treating human obesity. Int J Obes (Lond). 2006;30:1737–1741.
Glick Z. Modes of action of gallic acid in suppressing food intake of rats. J Nutr. 1981;111:1910–1916.
Niho N, Shibutani M, Tamura T, et al. Subchronic toxicity study of gallic acid by oral administration in F344 rats. Food Chem Toxicol. 2001;39:1063–1070.
Liu Z, Schwimer J, Liu D, Greenway FL, Anthony CT, Woltering EA. Black raspberry extract and fractions contain angiogenesis inhibitors. J Agric Food Chem. 2005;53:3909–3015.
Good Laboratory Practices (GLP) for Non-Clinical Laboratory Studies 21 CFR Part 58. Available at: www.fda.gov/ohrms/dockets/98fr/980335s1.PDF. Accessed: April 1, 2010.
National Research Council, Institute of Laboratory Animal Resources. Guide for the Care and Use of Laboratory Animals. Washington, DC: National Academy Press; 1996.
Rupnick MA, Panigrahy D, Zhang CY, et al. Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci U S A. 2002; 99:10730–10735.
Son MJ, Kim JS, Kim MH, et al. Combination treatment with temozolomide and thalidomide inhibits tumor growth and angiogenesis in an orthotopic glioma model. Int J Oncol. 2006;28:53–59.
Uhl K, Kennedy DL, Kweder SL. Risk management strategies in the Physicians’ Desk Reference product labels for pregnancy category X drugs. Drug Saf. 2002;25:885–892.
Parman T, Wiley MJ, Wells PG. Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity. Nat Med. 1999;5:582–285.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Booth, A., Amen, R.J., Scott, M. et al. Oral dose-ranging developmental toxicity study of an herbal supplement (NT) and gallic acid in rats. Adv Therapy 27, 250–255 (2010). https://doi.org/10.1007/s12325-010-0021-x
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12325-010-0021-x