Glycyrrhetinic Acid Maintains Intestinal Homeostasis via HuR.

Gang Chen,Bei Bei,Zhe Jiang,Jian-Yong Si,Ning Li,De-Gang Qing,Juan Zhang,Yuan Feng,Xuezheng Li

doi:10.3389/fphar.2019.00535

Abstract

Glycyrrhetinic acid (GA) is one of the main components of the traditional Chinese medicine of licorice, which can coordinate and promote the effects of other medicines in the traditional prescription. We found that GA could promote the proliferation, decrease the apoptotic rate, and attenuate DFMO-elicited growth arrest and delay in restitution after wounding in IEC-6 cells via HuR. GA failed to promote proliferation and to suppress apoptosis after silencing HuR by siRNA in IEC-6 cells. Furthermore, with the model of small intestinal organoids developed from intestinal crypt stem cells, we found that GA could increase HuR and its downstream ki67 levels to promote intestinal organoid development. In the in vivo assay, GA was shown to maintain the integrity of the intestinal epithelium under the circumstance of 48 h-fasting in rats via raising HuR and its downstream genes such as EGF, EGFR, and MEK. These results suggested that via HuR modulation, GA could promote intestinal epithelium homeostasis, and therefore contribute to the absorption of constituents from other medicines co-existing in the traditional prescription with licorice in the small intestine. Our results provide a new perspective for understanding the effect of licorice on enhancing the therapeutic effect of traditional prescriptions according to the traditional Chinese medicine theory.

Highlights

Glycyrrhetinic acid is one of the main components of licorice (Glycyrrhiza uralensis Fisch and Glycyrrhiza inflata Batal)
With the model of small intestinal organoids developed from intestinal crypt stem cells, we found that Glycyrrhetinic acid (GA) could increase Hu-antigen R (HuR) and its downstream ki67 levels to promote intestinal organoid development
In the in vivo assay, GA was shown to maintain the integrity of the intestinal epithelium under the circumstance of 48 h-fasting in rats via raising HuR and its downstream genes such as epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), and MAPK and ERK kinase (MEK). These results suggested that via HuR modulation, GA could promote intestinal epithelium homeostasis, and contribute to the absorption of constituents from other medicines co-existing in the traditional prescription with licorice in the small intestine

Summary

Introduction

Glycyrrhetinic acid is one of the main components of licorice (Glycyrrhiza uralensis Fisch and Glycyrrhiza inflata Batal). According to traditional Chinese drug theory, licorice has a “coordinating effect” by modulating the effects of other medicines coexisting with it in the same prescription, and thereby. Glycyrrhetinic Acid Maintains Intestinal Homeostasis improves the therapeutic effect of the prescription, and this special feature of it becomes the main reason of its utilization rate. One theory is that licorice might be able to enhance the absorption of molecules from other traditional medicines. As almost all the traditional medicines are used by the way of decoction, it is believed that in the traditional prescription, licorice might be able to maintain and/or restore the intestine homeostasis so as to assure the effective absorption of molecules from other ingredients

Methods

Results

Conclusion