Immunomodulative and anti-atopic properties of flavonoids from the roots of Rhododendron mucronulatum
Rhododendron mucronulatum (RM) is used for the treatment of rheumatitis, neuralgia and as antiphlogistic in Korean and Japanese traditional medicine. In this study, we examined the immunomodulating effect useful for treating atopic dermatitis of taxifolin and taxifolin 3-O-β-D-glucopyranoside which were isolated from the roots of RM. We screened the effect of glycoside (GT) and aglycone (AGT) in mouse splenocytes and immune cell lines with a standardized anti-CD3 and PMA/ionomycin stimulation system, and a rat basophilic leukemia (RBL-2H3) cell line for the degranulation test. Levels of gene expression in mouse splenocytes were determined by semi-quantitative RT-PCR, and serum interleukin IL-2 (IL-2) level in mice was quantified by ELISA. AGT (200µg/mL) significantly inhibited the induction of IL-2 by splenic lymphocytes when stimulated with anti-CD3, whereas GT was not effective even at higher dose. We also found that AGT(<200µg/mL) strongly inhibited mRNA levels of Th2 cytokines, IL-4, IL-10, IL-13, which are closely related to the progression of atopic dermatitis. Interestingly, AGT (<200µg/mL) effectively suppressed the degranulation of β-hexosaminidase, a granul marker, from RBL-2H3 after IgE sensitization. In summary, AGT effectively inhibits a wide spectrum of cytokine production from Th1 and Th2, and suppressed β-hexosaminidase release in a dose-dependent manner, whereas GT was not significantly effective. Therefore, flavonoids isolated from the roots of RM should be considered in their aglycone form in order to develop an anti-atopic agent. In conclusion, AGT may be useful for treating atopic dermatitis and possibly for skin allergies after more in-depth clinical results.
Acknowledgements: This work was supported by Seoul & BD program.
References: 1. Agrawal, P. K. et al. (1989) Carbon-13 NMR of flavonoids, Elsevier, New York. 316–317
2. An, B. J. et al. (2005) Korean Soc. Appl. Biol. Chem. 48: 280–284.