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Abstract from Report IMM20104 on Echinacea Purpurea

Abstract

Report on the Immunotoxicity of Echinacea Purpurea in Female B6C3F1/N Mice (CAS No. 90028-20-9)

Report Date: November 2012

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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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.


Abstract

Echinacea purpurea grows in the wild in the middle and eastern United States and is cultivated in Europe. It has been used for hundreds of years as a medicine by American Indians and is purported to have a stimulatory effect on the immune system. ECH exposure has been shown to enhance the activation and phagocytic activity of neutrophils (Borsuk et al., 2011) and macrophages (Goel et al., 2002; Sullivan et al., 2008) and also to increase the production of various cytokines, including the pro-inflammatory cytokines IL-1, IL-6, and TNF-α (Burger et al., 1997; Sullivan et al., 2008; Kapai et al., 2011). Anti-viral and antibacterial effects have also been attributed to ECH (Sharma et al., 2010; Hudson 2012). Others have reported no observable immunoenhancing effects following ECH treatment (South and Exon, 2001). Recent evidence indicates that the part of the plant used (i.e., aerial or root) and the preparation method can influence the effects of ECH on the immune system, resulting in either pro-inflammatory/immunostimulatory or anti-inflammatory/immunosuppressive effects (Benson et al., 2010; Hudson 2012).

Previous range-finding studies following 28 days of treatment with ECH, conducted on behalf of the National Toxicology Program, demonstrated significant increases in the mixed leukocyte response and anti-CD3 mediated T cell proliferation, suggesting an enhancement of cell-mediated immune function. Based on these findings and its use pattern in humans, the NTP requested that additional studies be conducted to establish the potential for ECH to modulate host resistance. These studies were conducted in female B6C3F1/N mice. Animals were treated with vehicle, 300, 600 or 1000 mg/kg of ECH daily for 28 days via oral gavage. ECH was prepared weekly in 0.5% methylcellulose.

Toxicology Studies: ECH treatment did not affect combined body weights over the course of the study. Although sporadic increases in combined body weight gain were observed, these differences did not persist to the day of study termination. Organ weights were unaffected, with the exception of liver weights. In one study, absolute and relative liver weights were increased at the 600 mg/kg dose only, while in a second study, absolute liver weights were unaffected and relative liver weights were increased at the 1000 mg/kg dose only. Hematological parameters were unaffected overall, although increases in platelets at all dose levels and decreases in leukocytes at the 300 mg/kg dose were observed in one of two studies.

Immunology Studies: Spleen cell numbers were unaffected in one study, significantly decreased at the 1000 mg/kg dose in a second study, and significantly decreased at the 300 mg/kg and 1000 mg/kg doses in a third study. In the third study, absolute numbers of B cells, total T cells, T-helper (CD4+CD8-) cells, and double positive immature T cells were also decreased at the 1000 mg/kg dose. The percent values of the various phenotypes were unaffected, with the exception of an increase in the percentage of macrophages in animals treated with 300 mg/kg ECH. A repeat phenotyping study showed no effects on spleen cell numbers or on any of the absolute or percent values of the various phenotypes. The antibody-forming cell response to sheep erythrocytes was increased in one study at the 600 mg/kg dose only, but not in a second study, while serum anti-sRBC immunoglobulin M antibody levels were unaffected. No effects were observed on the MLR. However, a significant increase in anti-CD3 mediated T cell proliferation was observed at the 1000 mg/kg dose level, and studies evaluating cytotoxic T cell activity demonstrated statistically significant increases at all ECH dose levels (i.e., 300, 600, and 1000 mg/kg). Innate immunity, as evaluated by assessing natural killer cell activity, was unaffected.

Host Resistance Studies. Treatment with ECH did not affect host resistance to Listeria monocytogenes, B16F10 melanoma tumors, Streptococcus pneumoniae, or Influenza virus H3N2.

In conclusion, these results indicate that ECH treatment for 28 days in the female B6C3F1/N mouse did not significantly affect innate immunity (NK cell function) or the humoral immune response (AFC, sRBC ELISA). Significant enhancement of the cell-mediated immune response was observed following ECH treatment. Increased proliferation following anti-CD3 stimulation and increased CTL cytotoxic activity were observed, however, these effects did not translate into significant protection in any of the host resistance studies conducted.

References

Borsuk O.S., Masnaya N.V., Sherstoboev E.Y., Isaykina N.V., Kalinkina G.I., & Reihart D.V. (2011). Effects of drugs of plant origin on the development of the immune response. Bull Exp Biol Med. 151(2):194-6.

Goel V., Chang C., Slama J., Barton R., Bauer R., Gahler R., & Basu T. (2002). Echinacea stimulates macrophage function in the lung and spleen of normal rats. J Nutr Biochem. 13(8):487.

Sullivan A.M., Laba J.G., Moore J.A., & Lee T.D.G. (2008). Echinacea-induced macrophage activation. Immunopharmacol Immunotoxicol. 30:553-74.

Burger R.A., Torres A.R., Warren R.P., Caldwell V.D., & Hughes B.G. (1997). Echinacea-induced cytokine production by human macrophages. Int J Immunopharmacol. 19(7):371-9.

Kapai N.A., Anisimova N.Y., Kiselevskii M.V., Sitdikova S.M., & Slavetskaya M.B. (2011). Selective cytokine-inducing effects of low dose Echinacea. Bull Exp Biol Med. 150(6):711-3

Sharma S.M., Anderson M., Schoop S.R., & Hudson J.B. (2010). Bactericidal and anti-inflammatory properties of a standardized Echinacea extract (Echinaforce®): dual actions against respiratory bacteria. Phytomedicine. 17:563-8.

Hudson J.B. (2012). Applications of the phytomedicine Echinacea purpurea (purple coneflower) in infectios diseases. J Biomed Biotech. 2012:769896. PMID: 22131823.

South E.H. & Exon J.H. (2001). Multiple immune functions in rats fed Echinacea extracts. Immunopharmacol Immunotoxicol. 23(3):411-21.

Benson J.M., Pokorny A.J., Rhule A., Wener C.A., Kandhi V., Cech N.B., & Shepherd D.M. (2010). Echinacea purpurea extracts modulate murine dendritic cell fate and function. Food Chem Toxicol. 48(5): 1170-7.


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