Andrographolide suppresses preadipocytes proliferation through glutathione antioxidant systems abrogation

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• 作者：Wei Chen ; ^{zjuchenwei@zju.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Hongming Su ; Lina Feng ; Xiaodong Zheng
• 关键词：MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyltetrazolium ; BA ; bongkrekic acid ; TFP ; trifluoperazine ; MitoMP ; mitochondria membrane potential ; MPTP ; mitochondrial permeability transition pore ; ANT ; adenine nucleotide translocase ; NAC ; N-acetyl cysteine ; ROS ; reactive oxygen species ; Rh123 ; rhodamine 123 ; GSH ; reduced glutathione ; GPX ; glutathione peroxidase ; NAO ; nonyl acridine orange ; DAF ; DAF-FM diacetate
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 July 2016
• 年：2016
• 卷：156
• 期：Complete
• 页码：21-29
• 全文大小：955 K

文摘

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 μg/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.