Planta Med 2007; 73(8): 777-781
DOI: 10.1055/s-2007-981547
Pharmacology
Letter
© Georg Thieme Verlag KG Stuttgart · New York

Butein Suppresses Bile Acid-Induced Hepatocyte Apoptosis through a JNK-Dependent but ERK-Independent Pathway

So-yeon Kim1 , Eun-Jeon Park1 , Yu-Zhe Zhao1 , Dong Hwan Sohn1
  • 1College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
Further Information

Publication History

Received: January 23, 2007 Revised: May 8, 2007

Accepted: May 15, 2007

Publication Date:
26 June 2007 (online)

Abstract

We investigated the protective effect of butein on glycochenodeoxycholic acid (GCDC)-induced apoptosis in primary cultured rat hepatocytes. Treatment with GCDC at a concentration of 100 μM for 4 h induced apoptosis, and treatment with butein at concentrations of 30 μM inhibited the GCDC-induced apoptosis as shown by the reduced cleavage of poly(ADP-ribose) polymerase, DNA fragmentation, and activation of caspases-3, -8, and -9. c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) play fundamental roles in cell survival, proliferation, and apoptosis. GCDC alone induced ERK and JNK phosphorylation. Butein alone induced ERK activation, and ERK activation was greater in hepatocytes treated with butein and GCDC than in hepatocytes exposed to GCDC alone. Butein treatment reduced JNK activation induced by GCDC. Addition of U0126, an inhibitor of ERK, did not alter the proapoptotic effect of GCDC or the antiapoptotic effect of butein. Addition of SP600125, a specific JNK inhibitor, protected hepatocytes against GCDC-induced apoptosis. These data suggest that butein has a protective effect against GCDC-induced hepatocyte apoptosis and that the protective effect of butein is JNK dependent but ERK independent.

Abbreviations

ERK:extracellular signal regulated kinase 1/2

GCDC:glycochenodeoxycholic acid

JNK:c-Jun N-terminal kinase

MAPKs:mitogen-activated protein kinases

PARP:poly(ADP-ribose) polymerase

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Dong Hwan Sohn

Department of Pharmacy

Wonkwang University

Iksan

Jeonbuk 570-749

Republic of Korea

Phone: +82-63-850-6822

Fax: +82-63-854-6038

Email: dhsohn@wonkwang.ac.kr