Integrating LC-MS and network pharmacology to uncover the mechanism of antidepressant effects of Illigera aromatica ethanol extract in rodent models.

Illigera aromatica, a traditional Chinese medicinal herb, has been historically utilized for treating depression. Although several phytochemical and pharmacological studies on Illigera aromatica have been reported, its antidepressant-like effects and the related mechanisms have not yet been systematically investigated.This study investigated the chemical profile, preliminary antidepressant-like activity, and short-term tolerability of the ethanol extract of Illigera aromatica (EEIA) in rodent models. LC-MS identified 21 constituents in EEIA, including 12 alkaloids. In normal mice, EEIA reduced immobility in the forced swimming and tail suspension tests; however, these findings should be interpreted as preliminary because locomotor control was not performed in the same mouse cohorts. In a reserpine-induced monoamine-depletion rat model, EEIA partially reversed behavioral and biochemical alterations, including ptosis, reduced locomotor activity, anhedonia, and decreased serum 5-HT and DA levels. Western blot analysis of hippocampal tissues suggested modulation of synaptic plasticity-related proteins, although these data should be regarded as pilot findings due to the small sample size. Acute oral toxicity evaluation showed that EEIA extract was tolerated at doses substantially higher than those used in the pharmacodynamic experiments. Overall, these results provide preliminary pharmacological evidence supporting further investigation of Illigera aromatica, while additional chronic stress models, chemical standardization, and subchronic toxicity studies are required.