Multimodal Effects of (-)-Borneol on Gastrointestinal Motility and Postoperative Ileus in Mice

Gastrointestinal motility disorders, including irritable bowel syndrome and postoperative ileus, remain significant clinical challenges with limited effective therapies. (–)-Borneol, a naturally occurring monoterpene, possesses anti-inflammatory, antioxidant, and motility-modulating properties and has emerged as a potential therapeutic candidate. This study investigated the effects of (–)-Borneol on gastrointestinal motility under physiological and pathological conditions, as well as its underlying mechanisms through biochemical, computational, and pharmacokinetic approaches. Male and female Swiss mice were subjected to basal intestinal transit assays and pharmacologically induced delay models using atropine, verapamil, and ondansetron. Postoperative ileus was induced by intestinal manipulation. Biochemical analyses included the evaluation of myeloperoxidase activity, nitrate and nitrite levels, and reduced glutathione content. Computational molecular docking was performed on gastrointestinal targets, including serotonin type 3A receptors, serotonin type 4 receptors, muscarinic type 3 receptors, and L-type calcium channels of the Cav1.2 subtype, and the absorption, distribution, metabolism, excretion, and toxicity profile was predicted. Oral administration of (–)-Borneol at a dose of 100 milligrams per kilogram significantly enhanced basal intestinal transit and reversed motility delays induced by atropine, verapamil, and ondansetron. In the postoperative ileus model, (–)-Borneol restored gastrointestinal motility (65.0 ± 4.6% versus 28.8 ± 3.5% in the vehicle group; p < 0.05), reduced myeloperoxidase activity (0.44 ± 0.07 versus 0.83 ± 0.12 units per milligram), decreased nitrate and nitrite levels (2.31 ± 0.39 versus 7.45 ± 0.18 micromolar), and increased reduced glutathione content (19.1 ± 0.7 versus 8.5 ± 0.8 micrograms per gram). Molecular docking analyses suggested favorable interactions with serotonergic and muscarinic receptors and L-type calcium channels of the Cav1.2 subtype, while pharmacokinetic predictions indicated good intestinal absorption and low predicted toxicity. Collectively, these findings demonstrate that (–)-Borneol exerts prokinetic, antioxidant, and anti-inflammatory effects, supporting its potential as a novel herbal therapeutic for the management of gastrointestinal motility disorders, particularly postoperative ileus.