1. Introduction
Allergic rhinitis (AR) is an allergic inflammation of the nasal airways and is characterized by sneezing, rhinorrhea, itching, and nasal congestion. These clinical conditions are widely known to be induced by inflammatory mediators, including histamine, leukotrienes, and inflammatory cytokines, which are secreted by eosinophils (Pawankar, Mori, Ozu, & Kimura, 2011). AR is one of the world’s most common chronic illnesses among children and young adults, and its prevalence is estimated to range from approximately 10–50% (Bellanti & Wallerstedt, 2000). Anti-allergic and anti-histamine agents are commonly used in the treatment of allergic rhinitis; however, their effects are transient as they are only able to suppress the symptoms of the inflammatory response (Adamia, Jorjoliani, Khachapuridze, Katamadze, & Chkuaseli, 2015). Therefore, it is important to develop novel therapeutic strategies that are effective for the treatment of AR (Mowen & Glimcher, 2004). A T-box protein expressed in T cells (T‐bet) is a transcription factor specifically expressed in Type 1 helper T (Th1) cells. GATA-3, on the other hand, has been shown to be an important factor in mediating allergic airway inflammation in vivo (Zhang et al., 1999). Effective therapeutic strategies would aim to either downregulate Th2 or Th17 cytokines or to downregulate the transcription factors that inhibit their production. Retinoic acid-related orphan nuclear receptor (ROR) γt is a splice variant of ROR, which has been identified as an essential transcription factor during Th17 cellular differentiation (Chen et al., 2011). Patients with AR show an inflammatory Immunoglobulin E (IgE)-mediated response characterized by the Th2 immunological pattern together with mast cells, goblet cells, and eosinophil activation, as well as the release of inflammatory mediators, such as interleukin (IL)-4 and IL-5, against allergen exposure (Durham et al., 1992). Th1/Th2 cells are associated with a series of immune and inflammatory diseases, such as bacterial and viral infectious diseases (Meagher, Wines, & Cooper, 2002; Walker, Virchow, Bruijnzeel, & Blaser, 1991). To date, the discovery of Th17 cells has introduced complexity into the existing Th1/Th2 balance paradigm and expanded our understanding of the pathogenesis of AR (S. B. Wang et al., 2014). Th17 cells are newly emerged immune/inflammatory cell subsets, which are now widely believed to be critical for the regulation of various chronic immune diseases (Halwani, Al-Muhsen, & Hamid, 2013). Th17 cells enhance eosinophilic airway inflammation, which is mediated by Th2 cells (Wakashin et al., 2008). Nuclear factor-kappa B (NF-κB) is a multicellular transcrip­tion factor, and it plays an important role in inflammatory and immune responses by regulating the gene expression of immune and inflammation-related cytokines and inflammatory mediators, which is a vital role in the initiation and perpetuation of allergic inflammation (Kumar, Takada, Boriek, & Aggarwal, 2004; Wan & Lenardo, 2010). The transcription factor T-bet drives Th1 differentiation, while the transcription factor GATA-3 drives Th2 differentiation. Natural products are regarded as abundant sources of novel drug candidates, and their pharmacological usefulness has been proven through decades of research (Newman & Cragg, 2016). In addition, drugs derived from natural products are known to induce fewer side effects than many synthetic drugs (Mathur & Hoskins, 2017). Saikosaponin D (SSD, chemical structure shown in Fig. 1A), one of the triterpenoid saponins derived from Bupleurum falcatum L, is a commonly prescribed agent against inflammatory diseases in China, Japan, and other Asian countries (Lu et al., 2012; Wong et al., 2013). Several studies have shown that SSD has anti-inflammatory, immunomodulatory, antiviral, and anticancer activities (H. W. Wang, Liu, Zhong, & Fang, 2015). Other researchers have found that SSD exhibited an anti-proliferative effect on the activated T lymphocyte via suppression of the NF-κB, NF-AT, and AP-1 signaling pathways (Sun, Cai, Zhou, & Xu, 2009; Wong et al., 2013). However, the mechanism underlying the anti-allergic effect of SSD on allergic rhinitis remains unclear. In the current study, we explore the protective effects and therapeutic efficacy of SSD on an ovalbumin (OVA)-induced AR mice model, which potentially involves the regulation of the Th1/Th2 and Th17 cellular responses.