Major depressive disorder is a common severe psychiatric disorder with unknown etiology. Recent studies show that the loss and malfunction of oligodendrocytes are closely related to the neuropathological changes in depression, which can be reversed by antidepressant treatment. St. John’s wort is an effective and safe herbal treatment for depression in several clinical trials. However, the underlying mechanism of its therapeutic effects is unclear. In this study, we evaluated the effects of hyperforin, a major active component of this herb, on the proliferation, mitochondrial function and development of oligodendrocytes. We have demonstrated that hyperforin increases mitochondrial function and prevents mitochondrial toxin-induced cytotoxicity in oligodendrocyte lineage cells. Hyperforin promotes the maturation of oligodendrocytes but does not increase the proliferation of oligodendrocyte progenitor cell line and neural stem/progenitor cells. Our findings suggest that chronic hyperforin treatment may stimulate the development and function of oligodendrocytes. These results suggest a new mechanism of hyperforin in depression treatment. Future in vitro and in vivo studies are required to further characterize the mechanisms of hyperforin
