کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2599889 1133234 2012 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Biotransformation of geniposide by human intestinal microflora on cytotoxicity against HepG2 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Biotransformation of geniposide by human intestinal microflora on cytotoxicity against HepG2 cells
چکیده انگلیسی

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.


► Intestinal microflora is able to metabolize geniposide (GS) to genipin (GP).
► Activated GS-induced toxicity was investigated.
► Activated GS inhibited Bcl-2 expression with an increase in Bax expression.
► Activated GS induces ROS generation and apoptosis through ROS/JNK signaling.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 209, Issue 3, 25 March 2012, Pages 246–254
نویسندگان
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