A role of paeoniflorin in mediating microbiota-gut-brain axis

Major depressive disorder (MDD), which is characterized by persistently low mood, diminished interest and suicidal ideation, has been one of the most prevalent and debilitating mental illnesses in China. Although its mechanism has not been fully understood, evidence has suggested a potential mechanism by which the gut microbiota could play a role via the microbiota-gut-brain axis. A recent study published in General Psychiatry investigated how paeoniflorin, a compound from traditional Chinese medicine, affects depression-like behaviors through this axis.

Based on a rat model of chronic unpredictable mild stress, researchers treated the animals with either paeoniflorin or fluoxetine. A series of behavioural tests, hippocampal cytokine analysis, microbiome profiling, metabolomics, histological staining, and hippocampal electrophysiology were performed.

Notably, paeoniflorin treatment significantly reduced depression-like behaviours in stressed rats, as shown by improved body weight gain, increased sucrose preference, greater locomotor activity, reduced immobility, and enhanced exploration in behavioural tests. Additionally, gut microbiota analysis revealed that the treatment corrected imbalances in key metabolites associated with brain function. Following that, the positive effects were transferred to other rats through the shared gut microbiota-metabolite axis, reducing neuroinflammation and restoring synaptic function.

“Paeoniflorin was shown to alleviate depression-like behaviour in rats by regulating intestinal flora imbalance and correcting metabolite disorders,” the authors mentioned, “This aligns with the therapeutic merits of traditional Chinese medicine, which is characterised by its multi-target and multi-pathway approach.”

Overall, this work provides new insight into how traditional Chinese medicine compounds may regulate the microbiota-gut-brain axis to improve depression and supports further validation through microbiota transplantation and mechanistic studies. Although these results are promising, further research is needed to confirm if the same effects occur in humans due to differences in gut microbiota.