Ginseng Volatile Oil Alleviates Loperamide‐Induced Constipation in Mice by Regulating the Microbiota/Metabolism/Neural Network

ABSTRACT Constipation is a common digestive dysfunction, and treatment options without side effects are limited. Ginseng volatile oil (GVO) has various biological activities, including antioxidant and neuroprotective effects. However, its potential to relieve constipation remains unclear. In this study, male BALB/c mice ( n = 10 per group) were randomly divided into the control, loperamide (Lop; 10 mg/kg), Lop + mosapride (Mos, 2 mg/kg), and Lop + GVO‐L/M/H (6.75, 13.5, and 27 mg/kg) groups. The mechanism by which GVO alleviates constipation was analyzed using a Lop‐induced constipation mouse model. GVO increased the rate of gastric emptying and small bowel propulsion, decreased serum 5‐hydroxytryptamine (5‐HT) and vasoactive intestinal peptide levels, and upregulated substance P and motilin levels ( p < 0.05). GVO decreased Firmicutes and increased Bacteroidota levels and increased butyric and valeric acid levels ( p < 0.05), thereby restoring Lop‐induced gut microbial dysbiosis. GVO also enhanced intestinal motility by modulating 5‐hydroxytryptaminergic synaptic activity and promoting 5‐HT3 and 5‐HT4 receptor expression. GVO treatment upregulated claudin and occludin expression, which may exert antioxidant and enteroprotective effects by activating the Nrf2 / HO‐1 pathway. Thus, GVO offers a safe, side‐effect‐free constipation remedy by modulating gut flora, neurotransmitters, and oxidative stress, providing a promising natural therapeutic strategy for functional gastrointestinal disorders.