Background/Objectives: Lauric acid (LA), a medium-chain fatty acid, is a promising drug for asthma treatment. This study evaluated the toxicity of repeated doses and the effect of LA on pulmonary ventilation and tracheal reactivity in asthmatic Wistar rats and identified possible molecular targets of LA action in silico. Methods: The rats were divided into control (CG) and LA-treated groups at 100 mg/kg (AL100G) for toxicity analysis. Pulmonary ventilation and tracheal reactivity were assessed in the control (CG), asthmatic (AG), asthmatic treated with LA at 25, 50, or 100 mg/kg (AAL25G, AAL50G, and AAL100G), and dexamethasone-treated groups (ADEXAG). Results: The results showed that LA at a dose of 100 mg/kg did not cause death or toxicity. A pulmonary ventilation analysis indicated that AG had reduced minute volume, which was prevented in AAL25G. LA at all doses prevented carbachol-induced tracheal hyper-responsiveness and reduced the relaxing effect of aminophylline, as observed in AG. An in silico analysis revealed that LA had a good affinity for nine proteins (β₂-adrenergic receptor, Ca_V, BK_Ca, K_ATP, adenylyl cyclase, PKG, eNOS, iNOS, and COX-2). Conclusions: LA at 100 mg/kg has low toxicity, prevents hyper-responsiveness in an asthma model in rats, and acts as a multitarget compound with a good affinity for proteins related to airway hyper-responsiveness.

Lauric acid, or dodecanoic acid, a medium-chain fatty acid, prevents alterations in pulmonary ventilation and tracheal hyperresponsiveness in Wistar rats with allergic asthma induced by ovalbumin (OVA). Therefore, the aim was to evaluate the mechanism of action of lauric acid (LA) in its preventive effect on changes caused by asthma. Rats were randomly divided into a control group (CG), an asthmatic group (AG), and an asthmatic lauric acid 25-mg/kg group (ALA25G). Rats in the AG and ALA25G groups were sensitized and challenged with OVA. For the experimental protocols, the trachea and lungs were isolated after euthanasia. A reduction in the contractile reactivity to CCh was observed in the asthmatic group in the presence of indomethacin, zileuton, L-NAME, apocynin, and tempol, inhibitors of COX, 5-LOX, NOS, NADPH oxidase, and a mimetic of superoxide dismutase (SOD), respectively. In the ALA25G, the contractile reactivity was reduced in the presence of indomethacin, L-NAME, and apocynin. Furthermore, an increase in lipid peroxidation (MDA) and nitrite levels and a reduction of reduced glutathione (GSH) levels and SOD activity were observed in the pulmonary homogenate of the AG. Treatment with lauric acid at a dose of 25 mg/kg prevented all of these alterations, except for the reduction in GSH levels. In conclusion, LA reduces tracheal hyperresponsiveness in Wistar rats with allergic asthma by negatively modulating both the COX and NO pathways and oxidative stress imbalance.