1. INTRODUCTION
Allergic diseases are associated with hypersensitivity to external
substances and are among the most common chronic diseases worldwide.
Common allergic diseases include bronchial asthma, allergic rhinitis,
allergic conjunctivitis, atopic dermatitis, and food allergies. Allergic
asthma is a complex chronic airway inflammatory disease that causes
sporadic breathing difficulties. It causes aberrant immune responses
with inhalation of allergens such as house dust mites, cockroaches,
animal allergens, pollens, and indoor mold. Allergic asthma has variable
and recurring symptoms, such as reversible airflow obstruction, airway
hyperresponsiveness (AHR), easily triggered bronchospasms, excessive T
cell-mediated immune responses, mucus hypersecretion, and airway
remodeling in the lung
(Fahy,
2015;
Ray
et al., 2016).
Recent studies have reported that allergic asthma is an aberrant
anaphylactic immune response that involves a variety of immune cells,
including eosinophils, T cells, B cells, mast cells, and airway
epithelial cells (Marshall et al., 2018). In particular, activated type
2 T helper (Th2) CD4+ cells release type 2 cytokines,
such as interleukin (IL)-4, IL-5, and IL-13, to stimulate the production
of immunoglobulin E (IgE). IgE plays an important role in inducing
asthmatic inflammation by promoting mast cell activation, goblet cell
hyperplasia, excessive mucus secretion, eosinophil infiltration, and AHR
(Fahy,
2015; Ray et al., 2016). Although the incidence of asthma has steadily
increased over the past few decades, current therapeutic approaches
still largely rely on anti-inflammatory corticosteroids and
bronchodilators (Papi et al., 2018). Despite advances in diagnosis and
treatment, asthma remains a serious global health problem, and many
patients do not have properly controlled disease (Quirt et al., 2018;
Zinellu et al., 2019). In fact, numerous immune cells and immune
cell-driven mediators contribute to the exacerbation and progression of
allergic asthma. Targeting these immune cells and mediators is a
potential modality for the treatment of asthma.
Sophoricoside is an isoflavone
glycoside isolated from Sophora japonica , a plant of the
Leguminosae family. Sophoricoside was initially isolated in 1996, when
its hormonal effect was reported
(Gabor,
1961). However, few biological and pharmacological activities of
sophoricoside have been reported. Its activities include IL-5 inhibitor
(Min et al., 1999; Jung et al., 2003), anti-inflammation and
immunosuppression (Kim et al., 2003; Kim et al., 2013; Lee et al.,
2013), estrogenic effect (El-Halawany et al., 2010), modulation of
lipogenesis and glucose consumption (Wu et al., 2013), hepatoprotection
(Li & Lu, 2018), and anti-osteoporosis (Abdallah et al., 2014).
Interestingly, sophoricoside inhibited the bioactivities of IL-3, IL-5,
and IL-6 in BAF/BO3, Y16, and MH60/BSF-2 cells, but not those of IL-1β,
tumor necrosis factor-alpha (TNF-α), and granulocyte-macrophage
colony-stimulating factor (GM-CSF) in A375.S2, WEHI-164, and TF-1 cells
(Yun et al., 2000). Sophoricoside also inhibited IL-6 and cyclooxygenase
(COX)-2 activities, but not the activities and expression of IL-1β,
TNF-α, and inducible nitric oxide synthase (iNOS) or the production of
reactive oxygen species (ROS) and nitric oxide (NO) in RAW264.7 cells
(Kim et al., 2003). Specifically, IL-3, IL-5, and IL-6 are Th2
cell-driven pro-inflammatory cytokines and are related to allergy and
asthma induced by antigen-mediated immune response (Lambrecht, Hammad,
& Fahy, 2019).
Based on this evidence, sophoricoside was isolated from the mature seeds
of S. japonica , and its anti-allergic and anti-asthmatic effects
were demonstrated using in vivo mouse models. Sophoricoside
ameliorated allergic asthma by preventing mast cell activation and
differentiation of CD4+ T cells in ovalbumin
(OVA)-induced mice.