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Issue 9, 2018
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Silibinin decreases hepatic glucose production through the activation of gut–brain–liver axis in diabetic rats

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Abstract

Silibinin, a flavonolignan derived from milk thistle (Silybum marianum), has been revealed to have a beneficial effect on improving diabetes-impaired glycemic control. However, the underlying mechanism is still unclear. In the present study, to evaluate whether the gut–brain–liver axis, an important neural pathway for the control of hepatic glucose production, is involved in silibinin-regulated glucose homeostasis, the expression of glucagon-like peptide-1 receptor (GLP1R) in the duodenum, activation of neurons in the nucleus of the solitary tract (NTS), as well as glycogen accumulation and expression of gluconeogenic enzymes in the livers of diabetic SHRSP·Z-Leprfa/IzmDmcr (SP·ZF) rats with 4-week oral administration of silibinin (100 and 300 mg kg−1 day−1) were evaluated. Common hepatic branch vagotomy was further conducted in high-fat diet/streptozotocin (HFD/STZ)-induced diabetic SD rats to confirm the role of the gut–brain–liver axis in silibinin-improved glycemic control. The results revealed a significant inhibition of fasting blood glucose after SP·ZF rats were administrated with silibinin for 4 weeks. The expression of GLP1R in the duodenum and the activation of neurons in the NTS increased, while hepatic glucose production decreased on silibinin administration. However, the hypoglycemic effect of silibinin was reversed by common hepatic branch vagotomy in diabetic SD rats. Our study suggested that silibinin may be useful as a potential functional food ingredient against diabetes by triggering the gut–brain–liver axis.

Graphical abstract: Silibinin decreases hepatic glucose production through the activation of gut–brain–liver axis in diabetic rats

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Publication details

The article was received on 25 Mar 2018, accepted on 12 Aug 2018 and first published on 17 Aug 2018


Article type: Paper
DOI: 10.1039/C8FO00565F
Food Funct., 2018,9, 4926-4935

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    Silibinin decreases hepatic glucose production through the activation of gut–brain–liver axis in diabetic rats

    F. Xu, J. Yang, H. Negishi, Y. Sun, D. Li, X. Zhang, T. Hayashi, M. Gao, K. Ikeda and T. Ikejima, Food Funct., 2018, 9, 4926
    DOI: 10.1039/C8FO00565F

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