Polysaccharides from Panax ginseng promote intestinal epithelial cell migration through affecting the Ca2+ related regulators

J Ginseng Res. 2023 Jan;47(1):89-96. doi: 10.1016/j.jgr.2022.05.010. Epub 2022 May 27.

Abstract

Background and aim: Panax ginseng, a key herbal medicine of replenishing Qi and tonifying Spleen, is widely used in the treatment of gastrointestinal diseases in East Asia. In this study, we aim to investigate the potential effects and mechanisms of polysaccharides from P. ginseng (PGP) on intestinal mucosal restitution which is one of the crucial repair modalities during the recovery of mucosal injury controlled by the Ca2+ signaling.

Methods: Rat model of intestinal mucosal injury was induced by indomethacin. The fractional cell migration was carried out by immunohistochemistry staining with BrdU. The morphological observations on intestinal mucosal injury were also performed. Intestinal epithelial cell (IEC-6) migration in vitro was conducted by scratch method. Western-blot was adopted to determine the expressions of PLC-γ1, Rac1, TRPC1, RhoA and Cav-1. Immunoprecipitation was used to evaluate the levels of Rac1/PLC-γ1, RhoA/TRPC1 and Cav-1/TRPC1.

Results: The results showed that PGP effectively reduced the assessment of intestinal mucosal injury, reversed the inhibition of epithelial cell migration induced by Indomethacin, and increased the level of Ca2+ in intestinal mucosa in vivo. Moreover, PGP dramatically promoted IEC-6 cell migration, the expression of Ca2+ regulators (PLC-γ1, Rac1, TRPC1, Cav-1 and RhoA) as well as protein complexes (Rac1/PLC-γ1, Cav-1/TRPC1 and RhoA/TRPC1) in vitro.

Conclusion: PGP increases the Ca2+ content in intestinal mucosa partly through controlling the regulators of Ca2+ mobilization, subsequently promotes intestinal epithelial cell migration, and then prevents intestinal mucosal injury induced by indomethacin.

Keywords: BrdU, 5-bromo-2'-deoxyuridine; CCE, CapacitativeCa2+ entry; Ca2+; Cav-1, Caveolin-1; Cell migration; ER, Endoplasmic reticulum; HPGPC, High-performance gel permeation chromatography; IEC-6; IEC-6, Intestinal epithelial cell; IP3, Inositol (1,4,5)-tresphospate; Intestinal mucosal injury; PGP, Polysaccharides from Panax ginseng; PLC-γ1, Phospholipase C-γ1; Panax ginseng polysaccharides; Put, Putrescine; SOCs, Store-operated Ca2+channels; TCM, Traditional Chinese Medicine; TRPC1, Canonical transient receptor potential-1; [Ca2+]cyt, Cytosolic free Ca2+.