Andrographolide suppresses preadipocytes proliferation through glutathione antioxidant systems abrogation

Aims: Oxidative stress is considered to play a profound role in lipid storage and whole-body energy homeostasis. Inhibition of preadipocytes proliferation by natural products is one of the strategies to prevent obesity. Andrographolide, a small molecule, has been reported to possess versatile bioactivities. However, molecular mechanism underlying the potential effect of andrographolide on preadipocytes proliferation remains obscure. Main methods: In the present study, 3T3-L1 preadipocytes were employed to determine whether andrographolide could affect the proliferation of preadipocytes. Key findings: Our results demonstrated andrographolide suppressed 3T3-L1 preadipocytes proliferation. The casual relationship analysis indicated that andrographolide (10 and 20 mu g/ml) appeared to exert the proliferation inhibitory effect through suppression of glutathione peroxidase 1 (GPX1) activity and depleting GSH by promoting its efflux in 3T3-L1 preadipocytes, which subsequently resulted in 2.06-2.41 fold increase in ROS accumulation. Excessive ROS eruption could account for oxidative damage to mitochondrial membranes as well as ultimately inhibition of cell proliferation. Significance: Taken together, our study reveals that suppression of GPX1 and GSH depletion by andrographolide seems to play a critical role in the inhibition of 3T3-L1 preadipocytes proliferation, which might have implication for obesity prevention and treatment. (C) 2016 Elsevier Inc. All rights reserved.