Development of a new anti-atopic agent using the diarylheptanoid from the barks of Alnus japonica and its role in immunological activity

Recently, we have isolated several diarylheptanoid from the barks of Alnus japonica which were used in the oriental traditional medicine as remedy for fever, hemorrhage, diarrhea, alcoholism, various skin affections (chronic herpes, eczema and prurigo) and inflammation. Among those compounds, we found that oregonin and hirsutanonol have a high potency in anti-atopic properties. In order to develop a novel immunomodulator for application in treating atopic dermatitis, mouse splenocytes and immune cell lines were used with a standardized anti-CD3 and PMA/ionomycin stimulation system, and a mast cell line (RBL-2H3) was used for the degranulation of β-hexosaminidase. The compounds, glycoside (GO: oregonin) and aglycone (AGH: hirsutanonol) were identified from this screening. GO and AGH were not toxic under 250 and 100µg/mL, respectively. Moreover, GO (<50µg/mL) and AGH (>50µg/mL) were shown to inhibit anti-CD3 antibody-induced Th1 cytokine (IL-2) secretion in mouse splenocytes. In addition, AGH (100µg/mL) also effectively inhibited mRNA levels of Th2 cytokines, IL-4, IL-10, IL-13, which are closely related to the progression of an atopic dermatitis. Interestingly, AGH (100µg/mL) strongly suppressed the degranulation of β-hexosaminidase, a granul marker, from RBL-2H3 after IgE sensitization (p<0.001 vs. control). Taken together, GO and AGH inhibited a wide spectrum of cytokine production from Th1 and Th2, and suppressed β-hexosaminidase release in a dose-dependent manner. Therefore, we concluded that these compounds may be useful for treating atopic dermatitis if those results are confirmed by in vivo studies.

Acknowledgements: This work was supported by Seoul & BD program.

References: 1. Lee, M. W. et al. (2000) Biol. Pharm. Bull. 23: 517–518. 2. Kim, H.J. et al. (2005) Arch. Pharm. Res. 28: 177–179.