Antiasthmatic Compounds Targeting β<sub>2</sub>-Adrenergic Receptor from <i>Perilla frutescens</i> Improved Lung Inflammation by Inhibiting the NF-κB Signaling Pathway.
Wang J, Gao Q, Wan S, Hao J, Lian X, Ma J, Zhang X, Zheng Z, Li Q.
Asthma is a highly prevalent and heterogeneous chronic respiratory disease and is often treated with inhaled corticosteroids or in combination with a β<sub>2</sub>-adrenergic receptor (β<sub>2</sub>-AR) agonist. However, around 5% of asthma remains uncontrolled, and more effective antiasthmatic drugs with known mechanisms are in high demand. Herein, we immobilized β<sub>2</sub>-AR on the polystyrene amino microsphere surface in a one-step fashion. The successful immobilization of β<sub>2</sub>-AR was verified by scanning electron microscopy and chromatographic analysis. We screened rosmarinic acid (RA) as the bioactive compound targeting β<sub>2</sub>-AR in <i>Perilla frutescens</i> (L.) Britton by mass spectroscopy. The binding constant between RA and β<sub>2</sub>-AR was determined to be 2.95 × 10<sup>4</sup> M<sup>-1</sup> by adsorption energy distribution and frontal analysis. The antiasthmatic effect and mechanism of RA were examined on a murine model of allergic asthma induced by ovalbumin (OVA) and aluminum hydroxide. The results showed that RA significantly reduced lung inflammatory cell numbers, the production of Th2 cytokines, and the secretion of total IgE, OVA-specific IgE, and eotaxin. The decreased inflammatory cell infiltration and mucus hypersecretion were associated with the inhibition of the NF-κB signaling pathway. Moreover, the mRNA expression levels of AMCase, CCL11, CCR3, Ym2, and E-selectin in the lung tissues were effectively reduced. It is the first time that RA was proven to target β<sub>2</sub>-AR and be effective in counteracting allergic airway inflammation via the NF-κB signaling pathway. Therefore, the immobilized β<sub>2</sub>-AR preserves the potential in screening antiasthmatic compounds from herbal medicine, and RA can be developed as an effective agent for the treatment of allergic asthma.