Effects of Syo-seiryu-to and Its Constituent Crude Drugs on Phorbol Ester-Induced Up-Regulation of IL-33 and Histamine H1 Receptor mRNAs in Swiss 3T3 and HeLa Cells

Seiichi Nakano,Seiichiro Kamimura,Yuki Konishi,Takako Esu,Yoshiaki Kitamura,Hiroyuki Mizuguchi,Noriaki Takeda,Tatsuya Fujii,Sayaka Yamamoto,Shiho Naniwa,Hiroyuki Fukui,Tomoharu Wakugawa

doi:10.3390/allergies1030015

Seiichi Nakano, Seiichiro Kamimura + Show 10 more

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https://doi.org/10.3390/allergies1030015

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Abstract

Syo-seiryu-to (SST) is a traditional herbal medicine that has been used clinically to treat allergic rhinitis (AR) in Japan. SST improves acute symptoms, such as sneezing and rhinorrhea, as well as chronic symptoms, such as nasal obstruction, in patients with AR. However, its therapeutic mechanisms remain unknown. We examined the effects of SST and eight constituent crude drugs on phorbol 12-myristate-13-acetate (PMA)-induced gene up-regulation of IL-33 and histamine H1 receptor (H1R), which are responsible for the pathogenesis of AR. We found that SST and its crude drugs, except for Pinellia tuber, significantly and dose-dependently suppressed PMA-induced both IL-33 and H1R mRNA up-regulation in vitro. The half-maximal inhibitory concentration values of the seven crude drugs to inhibit PMA-induced IL-33 mRNA up-regulation were correlated with those related to H1R mRNA up-regulation, suggesting that they act on a common signal molecule. These results suggest that SST improves nasal congestion that is induced by IL-33-related eosinophil infiltration and inhibits sneezing and rhinorrhea that are induced by H1R-mediated histamine signaling in the nasal mucosa of AR patients through its inhibition of a common molecule in the gene expression pathways of IL-33 and H1R. The results could explain the advantages of traditional herbal medicine, in which mixing various crude drugs not only acts on a common target to enhance its pharmacological action, similar to the effect of a high concentration of a single crude extract but also has the benefit of reducing the side effects of each crude drug.

Highlights

We found that histamine increased the expression of H1 receptor (H1R) mRNA in HeLa cells [25,26] and that the gene expression levels of H1R in the nasal mucosa were correlated with the severity of nasal symptoms in allergic rhinitis (AR) patients [27,28]
Since SST is composed of eight crude drugs, we examined whether each constituent crude drug of SST suppresses phorbol 12-myristate-13-acetate (PMA)-induced IL-33 and H1R mRNA upregulation
We have shown that activation of the gene expression signaling pathways for H1R and IL-33 gene followed by the elevation of their mRNA levels are responsible for the pathogenesis of AR [27,28]

Summary

Introduction

SST improves acute symptoms, such as sneezing and rhinorrhea, as well as chronic symptoms, such as nasal obstruction, in patients with AR. We reported that SST suppressed nasal symptoms and gene expression of histamine H1 receptor (H1R), histidine decarboxylase (HDC), and Th2-cytokines including interleukin (IL)-4 and -5, in the nasal mucosa of AR model rats [10]. These pharmacological effects of SST reported are mainly for acute symptoms, and the underlying mechanisms for the chronic symptoms of SST remain to be elucidated

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