18α-glycyrrhetinic acid extracted from Glycyrrhiza radix inhibits proliferation and promotes apoptosis of the hepatic stellate cell line.
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.
Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Lei
L
Zong
Ying
Y
Qu
Ming Yi
MY
Xu
Yu Wei
YW
Dong
Lun Gen
LG
Lu
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000032:analysis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D016328:NF-kappa B; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; C119129:18alpha-glycyrrhetinic acid; D004247:DNA; D006034:Glycyrrhetinic Acid