<p>Orengedokuto (OGT) is used to treat atopic dermatitis. We previously reported that OGT exerts anti-allergic effects by inhibiting effector T cell activation in a murine model of contact hypersensitivity (CHS). However, the active crude drugs and ingredients responsible for these effects remain unknown. Here, we evaluated the effects of hot water extracts of four crude drugs (Scutellaria radix, Coptidis rhizome, Phellodendri cortex and Gardenia fructus) constituted in OGT. The results showed that Phellodendri cortex is an active crude drug of OGT. As berberine-baicalin and berberine-wogonoside complexes precipitate in OGT decoction, we prepared the supernatant and precipitate fractions of OGT and then compared their anti-allergic effects on a 2,4,6-trinitrichlorobenzene-induced CHS mouse model. Interestingly, the precipitated fraction of OGT exhibited anti-allergic effects. Liquid chromatography-tandem mass spectrometry analysis of the serum concentration of berberine after oral administration of OGT or its fractions suggested that berberine is an active ingredient in OGT. Adoptive transfer experiments and ex vivo and in vitro studies demonstrated that berberine exerts anti-allergic effects via inhibiting effector T cell activation in a murine CHS model. In conclusion, Phellodendri cortex in OGT appears to be an active crude drug with anti-allergic action in a murine 2,4,6-trinitrichlorobenzene-induced CHS model, and berberine may be the active ingredient. The detailed molecular mechanism by which berberine inhibits T cell receptor stimulation and interferon-γ production in effector T cells remains unclear.</p> Graphical abstract <p></p>

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Berberine is a key active component underlying the anti-allergic actions of orengedokuto in a murine model of contact hypersensitivity

  • Mitsuhiko Nose,
  • Atsushi Tsuge,
  • Meika Mizuno,
  • Yuki Kodama,
  • Atsuki Watanabe,
  • Masato Kishi,
  • Fumiaki Ohashi,
  • Shinsuke Hisaka

摘要

Orengedokuto (OGT) is used to treat atopic dermatitis. We previously reported that OGT exerts anti-allergic effects by inhibiting effector T cell activation in a murine model of contact hypersensitivity (CHS). However, the active crude drugs and ingredients responsible for these effects remain unknown. Here, we evaluated the effects of hot water extracts of four crude drugs (Scutellaria radix, Coptidis rhizome, Phellodendri cortex and Gardenia fructus) constituted in OGT. The results showed that Phellodendri cortex is an active crude drug of OGT. As berberine-baicalin and berberine-wogonoside complexes precipitate in OGT decoction, we prepared the supernatant and precipitate fractions of OGT and then compared their anti-allergic effects on a 2,4,6-trinitrichlorobenzene-induced CHS mouse model. Interestingly, the precipitated fraction of OGT exhibited anti-allergic effects. Liquid chromatography-tandem mass spectrometry analysis of the serum concentration of berberine after oral administration of OGT or its fractions suggested that berberine is an active ingredient in OGT. Adoptive transfer experiments and ex vivo and in vitro studies demonstrated that berberine exerts anti-allergic effects via inhibiting effector T cell activation in a murine CHS model. In conclusion, Phellodendri cortex in OGT appears to be an active crude drug with anti-allergic action in a murine 2,4,6-trinitrichlorobenzene-induced CHS model, and berberine may be the active ingredient. The detailed molecular mechanism by which berberine inhibits T cell receptor stimulation and interferon-γ production in effector T cells remains unclear.

Graphical abstract