Paeoniflorin is a major bioactive compound found in the root of Paeonia lactiflora, commonly used in traditional Chinese medicine. Over the past decade, several preclinical studies have investigated its potential antidepressant effects. Animal model research suggests that paeoniflorin may exert antidepressant-like effects by modulating neurotransmitter systems (such as serotonin and dopamine), reducing neuroinflammation, inhibiting oxidative stress, and protecting against neuronal apoptosis. For instance, studies in rodents subjected to chronic unpredictable mild stress have shown behavioral improvements following paeoniflorin administration, as well as biochemical changes consistent with reduced depression-like states.

Mechanistic studies have proposed that paeoniflorin influences signaling pathways such as BDNF/TrkB, CREB, and the HPA axis, which are often implicated in depression. However, these findings are largely limited to laboratory settings and animal models. Human clinical data are sparse; only a few small-scale or combined herbal formula studies include paeoniflorin as a component, making it difficult to attribute efficacy specifically to this compound.

In summary, while there is scientific interest and supportive preclinical evidence for paeoniflorin in depression, direct clinical validation in humans is lacking. Thus, the overall evidence supporting its use for depression is preliminary and rated as low (2/5), pending more robust human trials.