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Abstract
The mechanisms of action of Kampo medicines as treatments for allergic rhinitis are unknown. In this study, we aimed to identify novel potential therapeutic agents for allergic rhinitis and to elucidate their underlying mechanisms. Different components of Kampo medicines (crude drugs) were screened for their ability to inhibit the secretion of thymic stromal lymphopoietin (TSLP), a cytokine secreted during allergen exposure. Synephrine (SYN) exhibited the strongest inhibitory effect. In an early-phase allergic reaction, histidine decarboxylase (HDC) and its receptor are activated, leading to the secretion of TSLP. Mucins are thought to be produced as a late-phase reaction. We examined the action of SYN in cultures of human nasal epithelial cells both during mono-stimulation and co-stimulation with activating agents. Based on its inhibition of the histamine H1 receptor and HDC mRNA expression, SYN was assumed to reduce the histamine production. Increased expression of the HDC protein was confirmed in tissues of patients with allergic rhinitis via western blotting. In addition, SYN inhibited TSLP at the mRNA and protein levels and inhibited mucin 5AC mRNA expression. Its inhibitory effects on both early- and late-phase allergic reactions indicate that SYN can serve as a novel therapeutic agent with potential leukotriene antagonist-like activity.
Public interest statement
We screened 55 Kampo drugs in an attempt to discover novel therapeutic agents for allergic rhinitis. The three major symptoms of allergic rhinitis are sneezing, rhinorrhea, and nasal congestion. The response mechanism is classified into an early-phase reaction, mainly involving IgE, mast cells, and basophils, and a late-phase reaction, mainly involving Th2 responses. The early-phase reaction is indicated to cause sneezing and rhinorrhea, and the late-phase reaction is indicated to cause eosinophil-associated nasal congestion, mucous secretion, and tissue remodeling. Histamine is important in the early-phase reaction, and leukotrienes are important in both early- and late-phase reactions. Our results demonstrate that the natural drug synephrine exerts its effects on the reaction pathways of both early- and late-phase reactions. This single drug showed efficacies similar to those of histamine H1 receptor antagonists and leukotriene antagonists and may become a novel therapeutic agent for amelioration of all three major symptoms of allergy.
Competing Interests
The authors declare no competing interest.
Acknowledgements
We would like to offer our sincere gratitude to the following individuals for their assistance in the implementation of the present study: Associate Professor Koichi Fukunaga at the Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, and Dr. Kenichiro Wakabayashi, Chief of the Department of Otorhinolaryngology at the Kitasato Institute Hospital, for their advice and cooperation in drafting the protocol of experiments with human nasal mucosa tissue; Dr. Kuninori Otsuka, Chief of the Department of Otorhinolaryngology, Saiseikai Yokohamashi Tobu Hospital, for his cooperation in harvesting tissue samples; and research assistant Tomoko Muraki for her assistance in cell culture experiments and other areas.
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Source: Author.
Correction
This article was originally published with errors, which have now been corrected in the online version. Please see Correction (https://doi.org/10.1080/23312025.2019.1620020)
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Notes on contributors
Katsuaki Dan
Katsuaki Dan, Ph.D. is in Keio University School of Medicine, he has been engaged in basic medical research on immunotherapy for cancer, starting with the development of diabetes drugs (Starsis) and antiviral drugs. Currently, the Research Organization is operating on the topic of anti-aging.
Sho Kanzaki
Sho Kanzaki M.D. and Ph.D. work as a Assistant Professor at Keio University's Department of Otorhinolaryngology, Head and Neck Surgery, Keio Univesity School of Medicine. He is otolaryngology specialist, he interested in clinical otology and research for allergy.
Kenji Watanabe
Kenji Watanabe is a Kampo medicine specialist with a M.D. and Ph.D. in internal medicine from Keio University School of Medicine. He works on clinical condition elucidation such as virus infection from the viewpoint of Kampo medicine.
Kaoru Ogawa
Kaoru Ogawa, M.D. and Ph.D. is Professor in Department of Otorhinolaryngology, Head and Neck Surgery, Keio Univesity School of Medicine. He is otolaryngology specialist, he manages otolaryngologic medical examination and clinical studies of Keio University Hospital.