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Formononetin Attenuates IL-1β-Induced Apoptosis and NF-κB Activation in INS-1 Cells
Key Laboratory of Human Functional Genomics of Jiangsu Province, Clinical Diabetes Centre of Jiangsu Province, Nanjing Medical University, Nanjing 210029, Jiangsu, China
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Southeast University, No.87 Dingjiaqiao Road, Nanjing 210009, Jiangsu, China
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 10 July 2012; in revised form: 18 July 2012 / Accepted: 3 August 2012 / Published: 24 August 2012
Abstract: Several studies suggest that the inflammation plays a role in the pathogenesis of some glucose disorders in adults. Exposure of pancreatic β-cells to cytokines, such as interleukin-1β (IL-1β), is thought to contribute to β-cell apoptosis. One important event triggered by IL-1β 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-1β in the rat insulinoma cell line, INS-1. Our results demonstrate that formononetin significantly prevents IL-1β-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-κB), 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 β-cell apoptosis caused by IL-1β and therefore could be used in the future as a new drug improving diabetes mellitus.
Keywords: INS-1; NF-κB; iNOS; formononetin; apoptosis
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Wang, Y.; Zhu, Y.; Gao, L.; Yin, H.; Xie, Z.; Wang, D.; Zhu, Z.; Han, X. Formononetin Attenuates IL-1β-Induced Apoptosis and NF-κB Activation in INS-1 Cells. Molecules 2012, 17, 10052-10064.
Wang Y, Zhu Y, Gao L, Yin H, Xie Z, Wang D, Zhu Z, Han X. Formononetin Attenuates IL-1β-Induced Apoptosis and NF-κB Activation in INS-1 Cells. Molecules. 2012; 17(9):10052-10064.
Wang, Yao; Zhu, Yunxia; Gao, Lu; Yin, Han; Xie, Zuoling; Wang, Dong; Zhu, Zhengqiu; Han, Xiao. 2012. "Formononetin Attenuates IL-1β-Induced Apoptosis and NF-κB Activation in INS-1 Cells." Molecules 17, no. 9: 10052-10064.