Range-Finding Report on the Immunotoxicity of Gugulipid 2.5% Granules (Gum Guggul Extract) in Female B6C3F1 Mice
Report Date: February 2011
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
Gugulipid, also known as gum guggul extract, was nominated to the National Toxicology Program for toxicological characterization based on its expanding use as a dietary supplement and a lack of available information to adequately assess safe use in humans (Nohr et al., 2009). One of the traditional uses of GGL, by the people of India, has been as an anti-inflammatory remedy (Niranjan et al., 2010). However, a review of the literature failed to reveal data related to the immunotoxicity of GGL. Based on the interaction of GGL with various receptors in the body, e.g., farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, and receptors for androgen, estrogen, progesterone, glucocorticoid and mineralocorticoid (Urizar et al., 2002; Cui et al., 2003; Brobst et al., 2004; Burris et al., 2005), there are concerns regarding potential immunotoxic effects of GGL (Gelfand et al., 2005; Salavert et al., 2007).
The NTP requested that a dose range-finding study be performed to establish the potential effects of GGL on the immune system. These studies were conducted in female B6C3F1 mice. Five GGL dose levels (31.25, 62.5, 125, 250, and 500 mg/kg) for 28 days were utilized. The in-life phase of these studies was carried out between 21, November 2006 and 26, July 2007. GGL was prepared weekly as a suspension in the vehicle corn oil.
Administration of GGL did not adversely affect body weight, body weight gain, or the major organs of the immune system, the thymus and the spleen. Overall, splenic differentials (both absolute and percent values) were unaffected. Treatment with GGL had no effect on the responses of the plaque assay, sheep red blood cell enzyme-linked immunosorbent assay, or keyhole limpet hemocyanin ELISA , all indicators of effects on humoral immunity. Furthermore, no effects were observed in assays used to evaluate cell-mediated immunity, which included the mixed leukocyte response, cytotoxic T-lymphocyte activity and anti-CD3-mediated proliferation. In addition, innate immunity was not affected by treatment with GGL in female B6C3F1 mice, as evidenced by a lack of effect on natural killer cell activity and the functional activity of the mononuclear phagocytic system.
In conclusion, GGL, when administered at doses from 31.25 to 500 mg/kg, as conducted in this study, produced no adverse functional immunotoxic effects in female B6C3F1 mice. The no observable effect level for GGL in this study was 500 mg/kg, the highest dose evaluated.
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