Journal
LIFE SCIENCES
Volume 156, Issue -, Pages 21-29Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2016.05.030
Keywords
Andrographolide; Preadipocytes; Obesity; ROS; Glutathione peroxidase
Funding
- National Key Technology R&D Program of China [2012BAD33B08]
- Research Foundation of the Education Department of Zhejiang Province [Y201328143]
- Qianjiang Scholars Program of Zhejiang Province [2013R10044]
- Foundation of Fuli Institute of Food Science, Zhejiang University [FULI2013]
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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.
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