Asthma is a chronic inflammatory pulmonary disease and respiratory syncytial virus (RSV) infection is a common cause of lower respiratory tract illness in infants and young children. α-Asarone presents many pharmacological effects and has been demonstrated to be useful in treating asthma. However, the functional mechanism of α-asarone in RSV-infected asthma has not been investigated. Long non-coding RNAs (lncRNAs) have been reported to play critical roles in many biological processes. Although many lncRNAs have been characterized, few were reported in asthma, especially in RSV-induced asthma. Currently, a novel post-transcriptional regulation has been proposed in which lncRNAs function as competing endogenous RNAs (ceRNAs) to competitively sponge miRNAs, thereby regulating the target genes. In the present study, we established an RSV-infected Sprague-Dawley rat model and demonstrated that lncRNA-PVT1 is involved in the mechanism of α-asarone in treating RSV-induced asthma, and lncRNA-PVT1 regulates the expression of E2F3 by functioning as a ceRNA which competitively sponges miR-203a.

Asthma is a common respiratory disease with inflammation in the lungs. Exosomes and microRNAs (miRNAs) play crucial role in inflammation, whereas the role of exosomal miRNA in asthma remains unknown. Here, we aimed to identify the key exosomal miRNAs and their underlying mechanisms involved in scorpio and centipede (SC) treatment in asthma. Eighteen mice were randomly divided into three groups: control group, asthma group, and SC treatment group. Effect of SC was assessed by hematoxylin-eosin staining and real-time PCR. Exosomes from asthma and SC treatment groups were analyzed by small RNA-seq. Results revealed SC significantly alleviated the pathogenesis of asthma and suppressed the release of inflammatory cytokines. A total of 328 exosomal miRNAs were differentially expressed between the exosomes from asthma and SC-treated mice, including 118 up- and 210 downregulated in SC-treated mice. The altered exosomal miRNAs were primarily involved in the function of transcription, apoptotic process, and cell adhesion; and pathway of calcium, Wnt, and MAPK signaling. Real-time PCR verified exosomal miR-147 was downregulated, while miR-98-5p and miR-10a-5p were upregulated in SC-treated mice compared to asthma mice. Moreover, the target genes of miR-147-3p, miR-98-5p, and miR-10a-5p were mainly enriched in Wnt and MAPK inflammatory signaling. miR-10a-5p promoted the proliferation of mouse lung epithelial cells and downregulated the expression of Nfat5 and Map2k6. These data suggest SC-induced exosomal miRNAs might mediate the inflammatory signaling and might be involved in the SC treatment in asthma. The exosomal miRNAs might be promising candidates for the treatment of asthma.

Asthma is one of the most common chronic inflammatory diseases. Although the scorpion and centipede (SC) significantly ameliorates asthma and changes exosomal miRNAs, the molecular mechanism is still obscure. Here, we show that SC improves inflammation in asthmatic mice and increases M2 macrophage-derived exosomes (M2Φ-Exos) by promoting M2 macrophage polarization. The M2Φ-Exos remarkably inhibits airway epithelial cell pyroptosis by reducing the expression of NLRP3, caspase-1, and LI-1β and mitochondrial swelling. Furthermore, miR-30b-5p is up-regulated in M2Φ-Exos compared with M1Φ-Exos. Overexpression of miR-30b-5p in M2Φ-Exos prevents airway epithelial cell pyroptosis, while down-regulation of miR-30b-5p promotes pyroptosis. We also uncover that pyroptosis is increased in asthmatic mice, while SC blocks pyroptosis. Moreover, miR-30b-5p overexpressed M2Φ-Exos further enhances the ameliorative effect of SC, which significantly down-regulates IRF7 expression. Our results collectively reveal that M2Φ-Exos induced by SC could carry miR-30b-5p to mitigate severe asthma by inhibiting airway epithelial cell pyroptosis. Most importantly, our findings may provide a potential clinical application of M2Φ-Exos for treating severe asthma.

KeChuanLiuWei‐Mixture (KCLW) is widely used as a Chinese medicine prescription to treat severe asthma. However, the underlying therapeutic mechanism of KCLW remains unclear. In this study, a network pharmacology method was used to identify the chemical constituents of KCLW by the TCMSP database and ultra‐performance liquid chromatography coupled with time‐of‐flight mass spectrometry. Differential expression identification, protein–protein interaction (PPI) network and functional enrichment analysis were used to screen key targets of KCLW for severe asthma. Our results confirmed that quercetin, luteolin, kaempferol, and wogonin are the most critical active ingredients in KCLW. Moreover, the 16 relevant severe asthma‐related targets of KCLW were obtained by overlapping the PPI networks of the KCLW putative targets and severe asthma‐related genes, among which the most important targets were IL‐6, NOS2, VEGFA, CXCL2, and PLAT. Functionally, the 16‐targets and their interacting differentially expressed genes were primarily related to biological functions and pathways related to immunity and inflammation, such as inflammatory response, T cell differentiation, Nrf2/HO‐1 signaling pathway, TGF‐β/Smad signaling pathway, and NF‐κB signaling pathway. KCLW inhibited inflammation in PDGF‐BB‐induced airway smooth muscle cells. In summary, this study demonstrates the active substance and potential therapeutic mechanism of KCLW in severe asthma, and offers a clinical direction for KCLW against severe asthma.