title: Andrographolide suppresses preadipocytes proliferation through glutathione antioxidant systems abrogation.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  In the present study, 3T3-L1 preadipocytes were employed to determine whether andrographolide could affect the proliferation of preadipocytes.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China. Electronic address: zjuchenwei@zju.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
mesh_terms: D041721:3T3-L1 Cells; D000111:Acetylcysteine / Q000494:pharmacology; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001865:Bongkrekic Acid / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D051379:Mice; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004224:Diterpenes; D017382:Reactive Oxygen Species; D001865:Bongkrekic Acid; D014268:Trifluoperazine; C030419:andrographolide; D005978:Glutathione; D000111:Acetylcysteine
keywords: Andrographolide; Glutathione peroxidase; Obesity; Preadipocytes; ROS