Garcinone D, a natural xanthone promotes C17.2 neural stem cell proliferation: Possible involvement of STAT3/Cyclin D1 pathway and Nrf2/HO-1 pathway

• Garcinone D promotes the C17.2 neural stem cell proliferation.
• Garcinone D increases the protein levels of phosphorylated STAT3 and Cyclin D1.
• Garcinone D enhances the protein levels of Nrf2 and HO-1.
• Nrf2 inhibitor partially reverses garcinone D-induced C17.2 cell proliferation.

Garcinia mangostana L. (Mangosteen) has been used to treat various pathological conditions, including inflammation and urinary tract infections. Here, we observed that garcinone D, a natural xanthone from mangosteen, promoted the proliferation of C17.2 neural progenitor cells and also resulted in a larger percentage of cells in S phase compared with the control group. Moreover, garcinone D increased the protein levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and Cyclin D1 in concentration- and time- dependent manners. Garcinone D also increased the protein levels of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in concentration- and time- dependent manners, and inhibiting Nrf2 activation by brusatol could partly reverse garcinone D-induced C17.2 cell proliferation. Taken together, it is the first time to show that garcinone D promotes the proliferation of C17.2 neural stem cells, which may involve the STAT3/Cyclin D1 pathway and Nrf2/HO-1 pathway. It would provide new inspiration to develop garcinone D as a lead compound to promote the proliferation of endogenous neural stem cells (NSCs).