Immunotoxicity of a standardized citrus polymethoxylated flavone extract.
Polymethoxylated flavones (PMFs) from citrus inhibit production of TNF-alpha and other pro-inflammatory cytokines. As TNF-alpha also modulates NK cell activity, the current studies were conducted to assess the potential for a standardized citrus PMF mixture to suppress humoral and innate immune functions. PMFs were isolated from orange peel oil using a procedure that obtained a consistent mixture of PMFs both in identity and proportion. The mixture consisted of nobiletin (30.7%), 3,3',4',5,6,7,8-heptamethoxyflavone (27.9%), trimethylscutellarein (14.5%), tangeretin (10.4%), sinensetin (5.8%), 5-demethyl-nobiletin (2.0%), hexa-O-methylquercetagetin (1.3%), 5-demethyl-tetramethylscutellarein (0.6%), and other flavonoids (2.7%). To assess the effect of the PMF mixture on humoral immune responses, female B(6)C(3)F(1) mice (n=8) were exposed to the PMF by gavage at 5, 50, 150 and 500 mg/kg/day for 28 days. On day 25, mice were sensitized to sRBC by tail vein injection and AFC response determined 4 days later. Humoral immunity was insensitive to suppression following exposure to all concentrations of the PMF mixture. Suppression of NK cell activity was observed only following 500 mg/kg/day for 28 days. Body weights were not affected by exposure to any concentration of the PMF mixture in sRBC immunized or non-immunized mice. However, in sRBC-immunized mice, higher concentrations of PMF were associated with a statistically insignificant increase in spleen weight (P>0.05). No change in spleen weight was observed in non-immunized mice. As anticipated, based on previously published in vitro observations, long-term, high-dose exposure to a standardized mixture of citrus PMFs caused a mild suppression of NK cell activity; however, humoral immunity was not sensitive to suppression at the same exposure levels.
Delaney
B
B
Cargill Nutraceuticals, PO Box 9300, MS110, Minneapolis, MN 55440-9300, USA. bryan_delaney@cargill.com
Phillips
K
K
Buswell
D
D
Mowry
B
B
Nickels
D
D
Cox
D
D
Wang
H B
HB
Manthey
J
J
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002860:Chromium Radioisotopes; D002957:Citrus / Q000737:chemistry*; D005260:Female; D005419:Flavonoids / Q000633:toxicity; D006462:Hemolytic Plaque Technique; D000922:Immunotoxins / Q000633:toxicity*; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000633:toxicity; D010938:Plant Oils / Q000633:toxicity; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D002860:Chromium Radioisotopes; D005419:Flavonoids; D000922:Immunotoxins; D010936:Plant Extracts; D010938:Plant Oils