| Biotransformation of geniposide by human intestinal microflora on cytotoxicity against HepG2 cells. | |
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MedLine Citation:
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PMID: 22245672 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Intestinal microflora (IM) is able to produce toxic and carcinogenic metabolites and induce more potent cytotoxicity against cells than non-metabolites. This study was performed to investigate the cytotoxic responses of geniposide (GS) and its metabolite and to determine the role of metabolism by IM in GS-induced cytotoxicity. Genipin (GP), a GS metabolite, increased cytotoxic effects in cells, but GS did not. Following GS incubation with IM for metabolic activation, increased cytotoxicity was detected compared to GS. Western blot analysis revealed that the activated GS inhibited Bcl-2 expression with a subsequent increase in Bax expression. Likewise, GS activation by IM stimulated caspase-3 and the production of reactive oxygen species (ROS). In addition, activated GS-induced apoptosis was confirmed by apoptosis and ROS assays; N-acetyl-l-cysteine (NAC) suppressed ROS production and apoptotic cell death. Activated GS induced sustained JNK phosphorylation. Moreover, activated GS-induced cell death was reversed by SP600125. Taken together, these findings suggest that human IM is able to metabolize GS into GP, and the related biological activities induce apoptosis through ROS/JNK signaling. |
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Authors:
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Tilak Khanal; Hyung Gyun Kim; Jae Ho Choi; Minh Truong Do; Min Jeong Kong; Mi Jeong Kang; Kyeumhan Noh; Hee Kyung Yeo; Young Tae Ahn; Wonku Kang; Dong Hyun Kim; Tae Cheon Jeong; Hye Gwang Jeong |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-9 |
Journal Detail:
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Title: Toxicology letters Volume: - ISSN: 1879-3169 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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