Sophora Flavescens Suppresses Lung Eosinophilia By Inhibiting Both Eosinophil Hematopoiesis and Migration

Hirofumi Tsuzuki, Yojiro Arinobu, Kohta Miyawaki, Ayako Takaki, Shun-ichiro Ota, Naoko Ueki, Yuri Ota, Siamak Jabbarzadeh Tabrizi, Mitsuteru Akahoshi, Hiroaki Niiro, Hiroshi Tsukamoto, Takahiko Horiuchi, Shoichiro Ohta, Kenji Izuhara, MD, PhD, Hiroyuki Fukui, Koichi Akashi; Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka City, Japan, Clinical Education Center, Kyushu University Hospital, Fukuoka City, Japan, Department of Rheumatology, Internal medicine and connective tissue disorders, Shimonoseki City Hospital, Shimonoseki City, Japan, Division of Nephrology and Rheumatology, Fukuoka University Hospital, Fukuoka City, Japan, Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu City, Japan, Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga City, Japan, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Japan. RATIONALE: A dried root of Sophora flavescens (S. flavescens) is a traditional Chinese herbal medicine used for the treatment of allergic diseases. Previous studies have demonstrated that S. flavescens possesses antiinflammatory activities and suppresses allergic inflammation such as allergic rhinitis. However, the mechanism of anti-asthmatic effect of S. flavescens is not yet clarified. METHODS: To clarify the effect of S. flavescens on asthma, we analyzed OVA-induced asthma mice treated with S. flavescens extract. We also conducted flow cytometry, cell count assay and gene expression analysis to evaluate the effect of S. flavescens on eosinophil hematopoiesis. To reveal the effect of S. flavescens on eosinophil chemotaxis, we performed transwell migration assay. RESULTS: Lung eosinophilic inflammation inOVA-induced asthmamice was suppressed by the treatment of S. flavescens. In addition, S. flavescens inhibited allergen-induced increment of eosinophil progenitors (EoPs) in the bonemarrow. In vitro, S. flavescens suppressed IL-5-induced expansion of EoPs and eosinophil lineage specification directly. Moreover, IL-5 expression was suppressed in CD4 T cells isolated from asthmatic mice treatedwith Sophora flavescens. In terms of eosinophil migration, S. flavescens suppressed eosinophil chemotaxis for eotaxin-1, one of themajor chemokines for eosinophil migration. CONCLUSIONS: S. flavescens suppressed eosinophil accumulation in the lung of asthmatic mice by inhibiting both eosinophil hematopoiesis and migration. S. flavescens might be valuable for the treatment of eosinophil-related diseases such as asthma.