bongkrekic-acid and andrographolide

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.. In the present study, 3T3-L1 preadipocytes were employed to determine whether andrographolide could affect the proliferation of preadipocytes.. Our results demonstrated andrographolide suppressed 3T3-L1 preadipocytes proliferation. The casual relationship analysis indicated that andrographolide (10 and 20μg/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.. 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.

Topics: 3T3-L1 Cells; Acetylcysteine; Adipocytes; Animals; Antioxidants; Apoptosis; Bongkrekic Acid; Cell Proliferation; Diterpenes; Glutathione; Mice; Mitochondrial Membranes; Reactive Oxygen Species; Trifluoperazine