Natural Products & Plant Materials
Herbal Medicine Zhiqiao (Aurantii Fructus) Extract Eases Depression-Like Behavior in Mice by Suppressing Hippocampal Caspase-4
In an animal study, a water extract of Aurantii Fructus suppressed caspase-4 in the mouse hippocampus and increased neurogenesis and synaptic proteins.
An animal study published in the Journal of Ethnopharmacology reports that Aurantii Fructus, an herb that traditional Korean medicine classifies as one that relieves stagnation of qi, showed antidepressant-like effects in mouse models of depression. Researchers at the Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine) in China pointed to caspase-4, an inflammation-related enzyme in the hippocampus, as the key to the effect.
Confirmed in two stress models
The researchers first used ultra-performance liquid chromatography (UPLC) to quantify the main components of the Aurantii Fructus water extract, namely hesperidin, naringin, neohesperidin, nobiletin and tangeretin, and confirmed that batch-to-batch variation was under 5%. When mice subjected to chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) were given a single dose of the extract (2 g/kg), their preference for sugar water recovered within 24 hours, and their immobility time in the forced swim test fell to a level similar to that seen with ketamine.
The stress-induced rise in hippocampal caspase-4 returned to normal levels after the extract was given, and new neurons in the dentate gyrus and synaptic proteins (PSD95 and synaptophysin) increased. When caspase-4 was artificially overexpressed in the hippocampus, these effects disappeared, and the researchers interpreted suppression of this enzyme as central to the mechanism.
These are results from mice, and the dose of 2 g per kg of body weight is high. Whether the same effect occurs in human depression must be confirmed in clinical trials.
- Five main flavonoids in the Aurantii Fructus water extract quantified, with batch-to-batch variation under 5%
- Single dose improved depression-like behavior within 24 hours in CUMS and CRS mice
- Effect lost when hippocampal caspase-4 was overexpressed, suggesting it is the target of action
Limitations This is a mouse study using a high dose, and the results cannot be applied directly to people.
Original Research
- Wu L, et al. · Affiliated Hospital of Nanjing University of Chinese Medicine. Aurantii Fructus alleviates depression via modulating hippocampal caspase-4-linked neurogenesis and synaptic plasticity in mice. Journal of Ethnopharmacology. DOI: 10.1016/j.jep.2025.120406
Copyright in the original research belongs to its publisher and authors.