Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 01 06 1 13 Wen Zhou Department of Respiratory Asthma, Xi'an Qidi Children's Hospital, Xi’an, Shaanxi, China Jinping Gao Department of Integrated Traditional Chinese and Western Medicine, Xi'an Qidi Children's Hospital, Xi’an, Shaanxi, China 2025 03 30 2025 06 12 Bronchial asthma (BA) has a complex pathogenesis involving immune imbalance and airway remodeling (AR). Cannabinoid receptor 2 (CB2) plays a role in inflammation regulation, so this study explored the therapeutic potential of a CB2 inverse agonist on BA rats’ AR and Th1/Th2 imbalance, and its mechanism via Toll-like receptor 4/nuclear factor kappa B(TLR4/NF-κB) pathway. Twenty-seven male SD rats (180-220 g) were divided into control (CG), model (MG), and intervention (IG) groups (n=9 each). MG/IG were BA-modeled by ovalbumin (OVA) sensitization (days 1/8: 100 μg OVA +1 mg aluminum hydroxide gel, i.p.) and 1% OVA aerosol challenge (day 15, 3×/week, 8 weeks). IG received CB2 inverse agonist (5 mg/kg, i.p., 3×/week, 4 weeks); CG/MG got saline. TH1/TH2 cytokines, subsets, AR parameters, and lung TLR4/NF-κB-related molecules were detected. Compared with CG, MG had TH1/TH2 imbalance, higher AR indices, upregulated TLR4/NF-κB, shorter asthma latency, and longer attack duration. vs. MG, IG reversed TH1/TH2 imbalance, reduced TLR4/NF-κB-related protein/mRNA (except elevated NFKBIA). CB2 inverse agonist has BA prevention/treatment potential by regulating Th1/Th2 balance, inhibiting AR, and acting on the TLR4/NF-κB pathway. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4400 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4400/2280