Honokiol induces apoptosis via cytochrome c release and caspase activation in activated rat hepatic stellate cells in vitro.
The therapeutic goal in liver fibrosis is the reversal of fibrosis and the selective clearance of activated hepatic stellate cells (HSCs) by inducing apoptosis. Over the past several years, we have screened for natural products that mediate apoptosis in activated HSCs. Among the candidate compounds, honokiol, isolated from Magnoliae cortex, was found to induce apoptotic death in activated rat HSCs, while there was no cell viability change in hepatocytes, at concentrations of 12.5-50 microM. Apoptosis was identified by DNA fragmentation, activation of caspase-3 and -9, and the proteolytic cleavage of poly(ADP-ribose) polymerase, down-regulation of bcl-2 and the release of mitochondrial cytochrome c into the cytoplasm.
Park
Eun-Jeon
EJ
Department of Pharmacy, Medicinal Resources Research Center, Wonkwang University, Iksan, Jeonbuk, Korea.
Zhao
Yu-Zhe
YZ
Kim
Young Ho
YH
Lee
Byung-Hoon
BH
Sohn
Dong Hwan
DH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D031566:Magnolia; D008297:Male; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D000498:Allyl Compounds; D010636:Phenols
D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D020169:Caspases; D045304:Cytochromes c; D004365:Drugs, Chinese Herbal; D017705:Lignans; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols