alpha-Mangostin Inhibits the Activation of Myofibroblasts via Downregulation of Linc-ROR-Mediated TGFB1/Smad Signaling

Oral submucous fibrosis (OSF) is a premalignant disorder and persistent activation of myofibroblasts is implicated in this pathological progression. Increasing attention has been addressed towards non-coding RNA-regulated myofibroblasts activities and the effects of phytochemicals on non-coding RNA modulation are of great importance. In the present study, we examined the anti-fibrosis property of alpha-mangostin, a xanthone isolated from the pericarp of mangosteen. We found that alpha-mangostin exhibited inhibitory potency in myofibroblast activities and expression of fibrosis markers at the concentrations that caused neglectable damage to normal cells. Apart from the downregulation of TGF-beta 1/Smad2 signaling, we found that alpha-mangostin attenuated the expression of long non-coding RNA LincROR as well. Our results demonstrated that the effects of alpha-mangostin on myofibroblast activation were reverted when LincROR was overexpressed. Additionally, we showed the expression of LincROR in OSF specimens was elevated and silencing of LincROR successfully attenuated myofibroblast characteristics and TGF-beta 1/Smad2 activation. Taken together, these findings indicated that the anti-fibrosis effects of alpha-mangostin merit consideration and may be due to the attenuation of LincROR.