ovalbumin and osthol

Asthma is a common chronic inflammatory airway disease. Recent studies have reported that interleukin (IL)‑33 is a potential link between the airway epithelium and Th2‑type inflammatory responses, which are closely related to the progression of asthma. The IL‑33 receptor, ST2, is highly expressed in group 2 innate lymphoid cells (ILC2s), Th2 cells, mast cells, eosinophils and natural killer (NK) cells. Cnidii Fructus is a Chinese herb with a long history of use in the treatment of asthma in China. Osthole is one of the major components of Cnidii Fructus. The present study examined the anti‑asthmatic effects of osthole in mice and aimed to elucidate the underlying mechanisms involving the IL‑33/ST2 pathway. BALB/c mice were sensitized and challenged with ovalbumin and then treated with an intraperitoneal injection of osthole (25 and 50 mg/kg). Subsequently, the airway hyper‑responsiveness (AHR) and inflammation of the lungs were evaluated. The amounts of IL‑4, IL‑5, IL‑13, interferon (IFN)‑γ and IL‑33 in the bronchoalveolar lavage fluid (BALF) were measured by Luminex assay and their mRNA levels in the lungs were measured by reverse transcription‑quantitative PCR. The histopathology of the lungs was performed with H&E, PAS and Masson's staining. The expression of ST2 in the lungs was evaluated by immunohistochemistry. The data demonstrated that osthole markedly reduced AHR and decreased the number of eosinophils and lymphocytes in BALF. It was also observed that osthole significantly inhibited the release of Th2‑type cytokines (IL‑4, IL‑5 and IL‑13) and upregulated the IFN‑γ level in BALF. Moreover, osthole significantly attenuated the IL‑33 and ST2 expression in the lungs of asthmatic mice. On the whole, osthole attenuated ovalbumin‑induced lung inflammation through the inhibition of IL‑33/ST2 signaling in an asthmatic mouse model. These results suggest that osthole is a promising target for the development of an asthma medication.

Topics: Animals; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Coumarins; Disease Models, Animal; Drugs, Chinese Herbal; Female; Gene Expression Regulation; Inflammation; Interferon-gamma; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukins; Lung; Lymphocyte Count; Mice; Mice, Inbred BALB C; Ovalbumin; Phytotherapy; Pulmonary Eosinophilia; Random Allocation; RNA, Messenger; Signal Transduction

Osthole, an active coumarin extracted from the dried fruits of Cnidium monnieri (L.) Cusson, is known to possess a variety of pharmacological activities. In the present study, we investigated and illuminated the mechanisms underlying the protective effects of osthole in an experimental model of allergic asthma. Our results show that osthole treatment significantly reduced the OVA-induced increase in serum IgE and inflammatory cytokines (IL-4, IL-5, IL-13) in bronchoalveolar lavage fluid (BALF), and decreased the recruitment of inflammatory cells in BALF and the lung. It also effectively attenuated goblet cell hyperplasia and mucus overproduction in lung tissue. In addition, western blot analysis demonstrated that osthole blocked NF-κB activation, which may be associated with a reduction in inflammatory cytokine production. These data suggest that osthole attenuated OVA-induced allergic asthma inflammation by inhibiting NF-κB activation. The present study identified the molecular mechanisms of action of osthole, which support the potential pharmaceutical application of osthole treatment for asthma and other airway inflammation disorders.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Bronchoalveolar Lavage Fluid; Coumarins; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Immunoglobulin E; Mice; NF-kappa B; Ovalbumin