Cyclobenzaprine HCl ameliorates OVA-induced asthma through modulating the TLR4/MyD88/NF-κB and PI3K/AKT/mTOR signaling pathways.

Asthma is a heterogeneous respiratory system disease with chronic airway inflammation. Asthma patients exhibit respiratory symptoms including shortness of breath, coughing, chest tightness, and wheezing. The existing medications for controlling asthma lead to a significant reduction in the therapeutic effect due to their numerous adverse reactions and drug resistance. Therefore, there is an urgent need to develop new drugs with few side effects, good curative effect, and high cost-performance ratio. Cyclobenzaprine HCl (CBP) is a centrally acting skeletal muscle relaxant that has previously been used for the treatment of painful muscle spasms. Relevant research reports indicate that CBP has potential anti-inflammatory, analgesic, and antispasmodic effects, but there are no relevant reports on the treatment of asthma by CBP. To study the impact of CBP on asthma, we conducted a series of in vitro and in vivo experiments, including muscle tension measurement, patch clamp experiments, pulmonary function tests, pathological examination of lung tissues, and molecular experiments, etc. We found that CBP can relax the airway smooth muscle stimulated by high-concentration potassium ions (HK+) or acetylcholine (ACh) by regulating the channel currents of L-type voltage-dependent Ca2+ channel (L-VDCC) and nonselective cation channels (NSCC). Moreover, CBP reduced the accumulation of inflammatory cells in the lungs of asthma mice, such as eosinophils and lymphocytes. CBP effectively inhibited the expression of inflammatory factors. Additionally, CBP alleviated asthma airway inflammation by regulating TLR4/MyD88/NF-κB and PI3K/AKT/mTOR signaling pathways. Our data suggest that CBP is expected to become a potential new drug for relieving or treating asthma.