期刊
MOLECULES
卷 17, 期 9, 页码 10052-10064出版社
MDPI
DOI: 10.3390/molecules170910052
关键词
INS-1; NF-kappa B; iNOS; formononetin; apoptosis
资金
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, Hanxiao)
- Natural Science Foundation of Jiangsu Province [BK2012752]
Several studies suggest that the inflammation plays a role in the pathogenesis of some glucose disorders in adults. Exposure of pancreatic beta-cells to cytokines, such as interleukin-1 beta (IL-1 beta), is thought to contribute to beta-cell apoptosis. One important event triggered by IL-1 beta is induction of nitric oxide synthase (iNOS), an enzyme that catalyzes intracellular generation of the cytotoxic free radical NO. Recent work have suggested that formononetin, as an O-methylated isoflavone found in a number of plants and herbs like Astragalus membranaceus, inhibited some pro-inflammatory cytokine production in macrophages. However, the roles of formononetin in pancreatic beta cells have not been fully established. The aim of the present study was to assess possible in vitro effects of formononetin on cell apoptosis induced by IL-1 beta in the rat insulinoma cell line, INS-1. Our results demonstrate that formononetin significantly prevents IL-1 beta-increased INS-1 cell death and blocks cytokine-induced apoptotic signaling (the reduction of Bax/Bcl-2 ratio and caspase-3 activity). Formononetin also inhibited the activation of nuclear factor-kappaB (NF-kappa B), which is a significant transcription factor for iNOS, so as to decease nitric oxide (NO) formation in a dose dependent manner in vitro. Our observations indicated that formononetin could protect against pancreatic beta-cell apoptosis caused by IL-1 beta and therefore could be used in the future as a new drug improving diabetes mellitus.
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