Total ginsenosides promote the IEC-6 cell proliferation via affecting the regulatory mechanism mediated by polyamines

Yiping Zhu; Anrong Wang; Ruliu Li; Huibin Zhu; Ling Hu; Weiwen Chen

doi:10.1016/j.jsps.2021.09.007

Total ginsenosides promote the IEC-6 cell proliferation via affecting the regulatory mechanism mediated by polyamines

Saudi Pharm J. 2021 Oct;29(10):1223-1232. doi: 10.1016/j.jsps.2021.09.007. Epub 2021 Sep 20.

Authors

Yiping Zhu¹, Anrong Wang¹, Ruliu Li¹, Huibin Zhu¹, Ling Hu¹, Weiwen Chen¹

Affiliation

¹ Pi-wei Institute, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, 12 Jichang road, Guangzhou 510405, PR China.

Abstract

Epithelial cell proliferation has been demonstrated to be a critical modality for mucosal repair after gastrointestinal mucosal injury. This research aimed to investigate the effect of total ginsenosides upon the proliferation of intestinal epithelial cells (IEC-6), and elucidate its potential mechanisms through polyamine-regulated pathway including the expression of proliferation-related proteins. Total ginsenosides (PGE3) were extracted from Panax ginseng, a Chinese herbal medicine, whose chromatogram was obtained by high performance liquid chromatographic method with evaporative light scattering detection (HPLC-ELSD). The cell proliferation, cell cycle distribution and the level of c-Myc, RhoA, Cdk2 proteins were detected to determine the effects of PGE3 at 25, 50 and100 mg/l doses on IEC-6. Furthermore, rats model of intestinal mucosal injury were induced by the subcutaneous injection of indomethacin, and the effect of Panax ginseng aqueous extracts (PGE1) on intestinal mucosal injury was observed. PGE3 could promote IEC-6 cell proliferation, reduce the proportion of G0/G1 phase cells and elevate the proportion of G2/M + S phase cells, and revert the proliferation and cell cycle arrest induced by DFMO (DL-a-difluoromethylornithine, an inhibitor of polyamines synthesis). PGE3 exposure enhanced the level of c-Myc, RhoA and Cdk2 proteins, and reversed the inhibition of these proteins expression induced by DFMO. The results of gross and pathological scores showed administration of PGE1 significantly alleviated intestinal mucosal injury of rats. Our findings indicate that total ginsenosides promoted the IEC-6 proliferation presumably via its regulation on cell cycle and the expression of proliferation-related proteins regulated by polyamines, and provided a novel perspective for exploring the repair effect of Panax ginseng upon gastrointestinal mucosal injury.

Keywords: Cdk2, cyclin-dependent protein kinase 2; Cell cycle; Cell proliferation; DFMO, DL-α-difluoromethylornithine; IEC-6, intestinal epithelial cells; Intestinal epithelial cells; PGE, Panax ginseng extracts; PGE1, Panax ginseng aqueous extracts; PGE3, total ginsenosides; Protein expression; RQSS, reinforcing Qi strengthening spleen; RhoA, Ras homolog family member A; Total ginsenosides.