18α-glycyrrhetinic acid extracted from Glycyrrhiza radix inhibits proliferation and promotes apoptosis of the hepatic stellate cell line

Authors


  • Conflict of interest: None.

Correspondence to: Lun Gen LU, Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China. Email: lungenlu1965@yahoo.com

Abstract

Objective

To evaluate the effect of 18α-glycyrrhetinic acid (18α-GA) on the proliferation and apoptosis of hepatic stellate cells (HSCs) and its underlying mechanisms.

Methods

HSCs (both human and rat HSCs) were pretreated with or without selective peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist, GW9662, before 18a-GA treatment. Cell cycle and apoptosis of HSCs were analyzed by flow cytometry, and changes in cell cycle and apoptosis-related proteins were analyzed by Western blot. The effect of 18α-GA on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) DNA-binding activity was measured by ArrayStar transcription factor activity assay.

Results

18α-GA markedly reduced LX-2 cell numbers by 14.8% and 31.2% after 48 h and 72 h of treatment, respectively (P < 0.05). 18α-GA also significantly increased the percentage of LX-2 cells in phase G0/G1 and decreased it in phase S after treated for 48 h and 72 h compared with the control group. 18α-GA increased apoptosis to 6.8% at 48 h, compared with control (2.5%), and at 72 h the percentages of apoptotic cells in control and the treatment groups were 3.1% and 15.6%, respectively, in LX-2 cells (P < 0.01). Similar changes occurred in CCl4-cirrhotic fat-storing cells. Furthermore, 18α-GA induced expression of PPAR-γ and altered some cell cycle and apoptosis-related proteins. 18α-GA also inhibited NF-κB DNA-binding activity. All these effects were abolished by GW9662.

Conclusions

18α-GA inhibits the proliferation of activated HSCs and induces apoptosis in culture. It also increases PPAR-γ expression and decreases NF-κB DNA-binding activity, which may be involved in these effects.

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