Triptolide suppresses human synoviocyte MH7A cells mobility and maintains redox balance by inhibiting autophagy.

Affiliation

Department of Rheumatology, Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan Province, China. Electronic address: [Email]

Abstract

Triptolide (TPL), the main active ingredient in Tripterygium glycosides, has been reported to exert anti-inflammation and anti-tumor effects. The present study was designed to investigate the effects of TPL on rheumatoid arthritis (RA) and explore the underlying mechanisms. By using human synoviocyte MH7A cells, TPL was proven to significantly impede migration and invasion of MH7A cells, and also inhibited MMP-2 and MMP-9 expression. Moreover, TPL was found to increase SOD, CAT, GSH-Px activities while decrease MDA activity, indicating that TPL maintained redox balance in MH7A cells. TPL could down-regulate the number of LC3+ puncta, Beclin1 expression and LC3 II/I ratio in a concentration-dependent manner, indicating that TPL inhibited autophagy in MH7A cells. Activation of autophagy was found to counteract the effects of TPL on MH7A cells while inhibition of autophagy had the opposite effects. Our data demonstrated that TPL suppressed cell mobility and maintained redox balance through inhibiting autophagy in MH7A cells. Finally, our data revealed that TPL increased p-AKT/AKT ratio significantly and inhibition of PI3K/AKT signaling pathway activated autophagy in MH7A cells, suggesting that TPL suppressed autophagy through activating AKT signaling pathway in MH7A cells. Taken together, our present study revealed that TPL inhibited cell mobility and maintained redox balance in human synoviocyte MH7A cells through autophagy inhibition. Our findings suggested the potential clinical application of TPL on RA treatment.

Keywords

Autophagy,MH7A,Redox balance,Triptolide,