Identification of pyrogallol from Awa-tea as an anti-allergic compound that suppresses nasal symptoms and IL-9 gene expression.

Abstract

As the expression level of allergic disease sensitive genes are correlated with the severity of allergic symptoms, suppression of these gene expressions could be promising therapeutics. We demonstrated that protein kinase Cδ / heat shock protein 90-mediated H1R gene expression signaling and nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression signaling are responsible for the pathogenesis of pollinosis. Treatment with Awa-tea combined with wild grape hot water extract suppressed these signaling and alleviated nasal symptoms in toluene-2,4-diisocyanate (TDI)-sensitized rats. However, the underlying mechanism of its anti-allergic activity is not elucidated yet. Here, we sought to identify an anti-allergic compound from Awa-tea and pyrogallol was identified as an active compound. Pyrogallol strongly suppressed ionomycin-induced up-regulation of IL-9 gene expression in RBL-2H3 cells. Treatment with pyrogallol in combination with epinastine alleviated nasal symptoms and suppressed up-regulation of IL-9 gene expression in TDI-sensitized rats. Pyrogallol itself did not inhibit calcineurin phosphatase activity. However, pyrogallol suppressed ionomycin-induced dephosphorylation and nuclear translocation of NFAT. These data suggest pyrogallol is an anti-allergic compound in Awa-tea and it suppressed NFAT-mediated IL-9 gene expression through the inhibition of dephosphorylation of NFAT. This might be the underlying mechanism of the therapeutic effects of combined therapy of pyrogallol with antihistamine. J. Med. Invest. 67 : 289-297, August, 2020.

• Authors: Tomohiro Nakano, Mitsuhiro Ikeda, Tomoharu Wakugawa, Yoshiki Kashiwada, Osamu Kaminuma, Noriko Kitamura, Masam Yabumoto, Hiromichi Fujino, Yoshiaki Kitamura, Hiroyuki Fukui, Noriaki Takeda, Hiroyuki Mizuguchi
• Journal: The journal of medical investigation : JMI (J Med Invest) Vol. 67 Issue 3.4 Pg. 289-297 ( 2020) ISSN: 1349-6867 [Electronic] Japan
• PMID: 33148904 (Publication Type: Journal Article)

Chemical References

• Anti-Allergic Agents
• Interleukin-9
• NFATC Transcription Factors
• Tea
• Pyrogallol
• Toluene 2,4-Diisocyanate

Topics

• Animals
• Anti-Allergic Agents (isolation & purification, pharmacology)
• Cells, Cultured
• Fermentation
• Gene Expression Regulation (drug effects)
• Interleukin-9 (genetics)
• Male
• NFATC Transcription Factors (physiology)
• Pyrogallol (isolation & purification, pharmacology, therapeutic use)
• Rats
• Rats, Inbred BN
• Rhinitis, Allergic, Seasonal (drug therapy)
• Tea (chemistry)
• Toluene 2,4-Diisocyanate (pharmacology)