Chaihu-shugan san inhibits inflammatory response to improve insulin signaling in liver and prefrontal cortex of CUMS rats with glucose intolerance
Jia KK, Pan SM, Ding H, Liu JH, Zheng YJ, Wang SJ, Pan Y, Kong LD · Biomedicine & Pharmacotherapy · 2018 July
DOI 10.1016/j.biopha.2018.04.171
Objective
To investigate whether Chaihu-shugan san improves glucose tolerance through its antidepressant activity in a rat model of depression and to explore the underlying mechanisms involving the liver-brain inflammation axis.
Conclusions
Chaihu-shugan san ameliorated depressive-like behaviors and improved glucose tolerance in chronic unpredictable mild stress rats by inhibiting the liver-brain inflammation axis through suppression of the toll-like receptor 4, myeloid differentiation protein 88, nuclear factor-kappa B pathway and NLRP3 inflammasome activation, improvement of insulin signaling, and up-regulation of microRNA-155.
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Insights
Chaihu-shugan san, a traditional Chinese medicine formula, has been found to improve depression and glucose tolerance by inhibiting inflammation in the liver-brain axis.
The researchers used male Wistar rats in which a model of depression was induced by chronic unpredictable mild stress (CUMS) over the course of 6 weeks. The rats were then administered Chaihu-shugan san water extract via gavage for the succeeding 6 weeks. The researchers assessed depressive-like behaviors through a sucrose consumption test and the glucose tolerance of the rats using an oral glucose tolerance test. Serum alanine aminotransferase (ALT) and interleukin-1 beta (IL-1β) levels were measured using commercial kits. Key proteins in inflammatory signaling cascades and insulin signaling in the liver and prefrontal cortex of the rats were also evaluated using Western blot. Immunohistochemical staining and Western blot were used to note nuclear entry of a certain protein in the liver and prefrontal cortex of the rats.
In the ensuing discussions of the results, it was observed that Chaihu-shugan san increased sucrose consumption and reduced serum glucose levels in the CUMS rats, indicating its effectiveness in improving both depression and glucose tolerance. Treatment with Chaihu-shugan san also resulted in reduced serum levels of ALT and IL-1β. The drug demonstrated an ability to inhibit hepatic and prefrontal cortical inflammatory responses by suppressing certain inflammatory pathways and also improved insulin signaling in the rats. Notably, the treatment was observed to increase expression of a specific microRNA in the liver and prefrontal cortex of the rats.
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