Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H₁ receptor and interleukin‐4 genes

Abstract

Kujin contains antiallergic compounds that inhibit upregulation of histamine H1 receptor (H1R) and interleukin (IL)-4 gene expression. However, the underlying mechanism remains unknown. We sought to identify a Kujin-derived antiallergic compound and investigate its mechanism of action. The H1R and IL-4 mRNA levels were determined by real-time quantitative RT-PCR. To investigate the effects of maackiain in vivo, toluene-2,4-diisocyanate (TDI)-sensitized rats were used as a nasal hypersensitivity animal model. We identified (−)-maackiain as the responsible component. Synthetic maackiain showed stereoselectivity for the suppression of IL-4 gene expression but not for H1R gene expression, suggesting distinct target proteins for transcriptional signaling. (−)-Maackiain inhibited of PKCδ translocation to the Golgi and phosphorylation of Tyr311 on PKCδ, which led to the suppression of H1R gene transcription. However, (−)-maackiain did not show any antioxidant activity or inhibition of PKCδ enzymatic activity per se. Pretreatment with maackiain alleviated nasal symptoms and suppressed TDI-induced upregulations of H1R and IL-4 gene expressions in TDI-sensitized rats. These data suggest that (−)-maackiain is a novel antiallergic compound that alleviates nasal symptoms in TDI-sensitized allergy model rats through the inhibition of H1R and IL-4 gene expression. The molecular mechanism underlying its suppressive effect for H1R gene expression is mediated by the inhibition of PKCδ activation.

Protein kinase C-δ signaling regulates glucagon secretion from pancreatic islets

“…We have demonstrated that PKCδ signaling is involved in PMAinduced upregulation of histamine H1 receptor (H1R) gene expression in HeLa cells and compounds, including quercetin and (-)-maackiain, suppressed H1R gene expression through the inhibition of PKCδ signaling (17)(18)(19). Thus, suppression of PKCδ signaling by these compounds could improve diabetic symptoms and help to further elucidate the mechanisms underlying these actions to better understand the role of PKCδ signaling in diabetes onset and progression.…”

Disruption of Heat Shock Protein 90 (Hsp90)-Protein Kinase Cδ (PKCδ) Interaction by (−)-Maackiain Suppresses Histamine H1 Receptor Gene Transcription in HeLa Cells

“…However, anti-allergic activity of (Ϫ)-maackiain had not yet been reported. We have shown that (Ϫ)-maackiain is the prominent component responsible for the anti-allergic activity of Kujin (14). Because (Ϫ)-maackiain did not show any antioxidant activity or inhibit PKC␦ enzymatic activity, it is likely that its anti-allergic activity proceeded through an unknown mechanism.…”

“…Rats-Previously, we have demonstrated that pretreatment with racemic maackiain and quercetin suppresses TDI-induced nasal symptoms and up-regulation of H1R and IL-4 gene expression in TDI-sensitized rats (8,14). In the present study, we investigated the effect of an additional Hsp90 inhibitor, celastrol, on TDI-induced nasal symptoms and up-regulation of H1R and IL-4 gene expression in the nasal mucosa of TDIsensitized rats.…”

“…In a previous study, we showed that Kujin extract inhibited up-regulation of H1R and IL-4 gene expression in TDI-sensitized rats (6). We have identified (Ϫ)-maackiain as an antiallergic component in Kujin (14). Treatment with synthetic maackiain alleviated nasal symptoms and suppressed up-regulation of H1R gene expression in TDI-sensitized rats.…”

Screening of Natural Product Libraries for the Extension of Cell Life-span through Immune System

“…304 kDa이다. Chiisanoside은 소장(small intestine)에서 지방 흡수를 방해하는 생물학적 기능이 있다 [13]. Corynoline의 알 려진 생물학적 기능은 세포간 결합을 방해하는 것이다 [7].…”