Harmine stimulates proliferation of human neural progenitors
PeerJ – December 06, 2016
Source: OpenAlex
Summary
Harmine, a key component of Ayahuasca, significantly boosts the proliferation of human neural progenitor cells (hNPCs) by 71.5% after just four days of treatment. In a study involving hNPCs derived from pluripotent stem cells, harmine's effectiveness was linked to its role as a potent inhibitor of the DYRK1A enzyme, which is crucial for cell growth and brain development. Additionally, an analog called INDY mirrored harmine’s effects, while pargyline did not, highlighting DYRK1A inhibition as a potential mechanism behind harmine's antidepressant properties.
Abstract
Harmine is the β -carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo .