Nerolidol attenuates airway inflammation and airway remodeling and alters gut microbes in ovalbumin‐induced asthmatic mice.

Asthma is a common respiratory disease associated with airway inflammation. Nerolidol is an acyclic sesquiterpenoid with anti‐inflammatory properties. BALB/C mice were sensitized with ovalbumin (OVA) to induce asthma symptoms and given different doses of Nerolidol. We found that Nerolidol reduced OVA‐induced inflammatory cell infiltration, the number of goblet cells and collagen deposition in lung tissue. Nerolidol reduced the OVA‐specific IgE levels in serum and alveolar lavage fluid in an asthma model. Immunohistochemical staining of α‐SMA (the marker of airway smooth muscle) showed that Nerolidol caused bronchial basement membrane thinning in asthmatic mice. The hyperplasia of airway smooth muscle cells (ASMCs) is an important feature of airway remodeling in asthma. ASMCs were treated with 10 ng/mL TGF‐β to simulate the pathological environment of asthma in vitro and then treated with different doses of Nerolidol. Nerolidol inhibited the activity of TGF‐β/Smad signaling pathway both in the lung tissue of OVA‐induced mouse and TGF‐β‐stimulated ASMCs. 16s rRNA sequencing was performed on feces of normal mice, the changes of intestinal flora in OVA‐induced asthmatic mice and Nerolidol‐treated asthmatic mice were studied. The results showed that Nerolidol reversed the reduced gut microbial alpha diversity in asthmatic mice. Nerolidol changed the relative abundance of gut bacteria at different taxonomic levels. At the phylum level, the dominant bacteria were Bacteroidota, Firmicutes, and Proteobacteria. At the genus level, the dominant bacteria were Lactobacillus, Muribaculaceae, Bacteroides, and Lachnospiraceae. We conclude that Nerolidol attenuates OVA‐induced airway inflammation and alters gut microbes in mice with asthma via TGF‐β/Smad signaling. Significance statement: This research has demonstrated a mitigating effect of Nerolidol on the progress of asthma. TGF‐β/Smad signaling pathway is the critical target of Nerolidol. Intestinal flora disorders induced by asthma are also regulated by Nerolidol. [ABSTRACT FROM AUTHOR]