Neuroplasticity-related mechanisms underlying the antidepressant-like effects of traditional herbal medicines

Traditional herbal medicine can offer efficacious and safe alternative pharmacotherapies for depression. The ability of an herbal medicine to produce neuroadaptive processes, that enhance neuroplasticity and cellular resilience in response to chronic stress, may point to its antidepressant potential. We suggest that among many investigated herbal medicines, those that can enhance neuroplasticity may have stronger therapeutic potential. The current article presents a summary of traditional herbal medicines, which are thought to exert antidepressant-like effects in chronic stress models via neuroplasticity enhancement. Brain-derived neurotrophic factor (BDNF) is a biomarker for neuroplasticity-related mechanisms compromised in depression and recovered by conventional antidepressants, including synaptic plasticity, cell survival, neurogenesis and spine formation. We therefore presumed that if an herbal medicine up-regulates BDNF in the hippocampus and/or prefrontal cortex (PFC), its antidepressant-like effect is mediated, at least partially, via neuroplasticity-related mechanisms. Literature search was performed using the general terms depression, stress, neuroplasticity and herbal medicines. Screening of retrieved preclinical studies revealed 30 traditional herbal medicines: 8 single herbs, 15 bioactive constituents, and 7 herbal formulas. The antidepressant-like effects of these medicines were associated with reversal of chronic stress-induced impairment in neuroplasticity, most notably by BDNF up-regulation, activation of BDNF downstream signaling pathways and increase in neurogenesis in the hippocampus and/or PFC/frontal cortex. In light of the ability of these medicines to enhance neuroplasticity, we suggest that they may be suitable candidates for clinical investigation in depressed individuals. Once their efficacy, tolerability and safety will be substantiated, they may serve as natural alternatives to conventional antidepressants.