Abstract

Hydroxysafflor yellow A (HSYA) is an effective ingredient of the Chinese herb Carthamus tinctorius L. In this study, we aimed to evaluate the effects of HSYA on ovalbumin (OVA)-induced asthma in guinea pigs, and to elucidate the underlying mechanisms. We established a guinea pig asthma model by intraperitoneal injection and atomized administration OVA. Guinea pigs were injected intraperitoneally with HSYA (50, 75, 112.5 mg/kg) once daily from days 2 to 22 before OVA administration. We examined biomarkers including lung function, pulmonary histopathology, immunoglobulin E (IgE), Th1/Th2 relative inflammatory mediators, and related pathways. Pathological changes in lung tissues were detected by hematoxylin and eosin and periodic acid-Schiff staining. Phosphorylation levels of JNK mitogen-activated protein kinase (MAPK), p38 MAPK, ERK MAPK, and inhibitor of nuclear factor κBα (IκBα) were detected by western blot. plasma levels of total IgE, platelet-activating factor (PAF), and interleukin (IL)-3 were detected by enzyme-linked immunosorbent assay (ELISA). Expression levels of tumor necrosis factor (TNF)-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-13, and interferon (IFN)-γ were detected by ELISA and real-time quantitative polymerase chain reaction. HSYA significantly reduced airway resistance, improved dynamic lung compliance, and attenuated the pathologic changes. HSYA also inhibited the phosphorylation of JNK MAPK, p38 MAPK, ERK MAPK, and IκBα, and inhibited the OVA-induced elevations of IgE, PAF, IL-1β, IL-6, IL-4, IL-5, and IL-13 and the decreases in TNF-α, IFN-γ, IL-2, and IL-3. These findings suggest that HSYA has a protective effect on OVA-induced asthma through inhibiting the Th1/Th2 cell imbalance and inhibiting activation of the MAPK signaling pathway.

Highlights

  • Bronchial asthma is a chronic inflammatory airway disease characterized by airway inflammation, airway hyperresponsiveness (AHR), and airflow obstruction (Khorasanizadeh et al, 2017)

  • This study focused on the effects of Hydroxysafflor yellow A (HSYA) on the Th1/Th2 balance and mitogen-activated protein kinase (MAPK) pathways in a guinea pig model of asthma

  • We showed that HSYA could effectively reduce the increase of eosinophil and mucus secretion in lung tissue of asthmatic guinea pigs, and inhibit the synthesis of specific immunoglobulin E (IgE)

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Summary

Introduction

Bronchial asthma is a chronic inflammatory airway disease characterized by airway inflammation, airway hyperresponsiveness (AHR), and airflow obstruction (Khorasanizadeh et al, 2017). An excessive Th2 immune response has been observed in the pathogenesis of allergic asthma, with the overproduction of Th2-type cytokines, such as interleukin (IL)-4, IL-5, IL-6, and IL-13 (Zhou et al, 2015). Glucocorticoids can effectively treat asthma by modulating the Th1 and Th2 responses (Hu et al, 2018), but their long-term use is associated with debilitating systemic side effects and potential exacerbation of Th2 immune responses (Stock et al, 2005). Overall, these observations provide strong evidence to suggest that regulating the imbalance in Th1/Th2 responses is an effective way to prevent the development and progression of asthma

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