Ginsenoside Rg1 ameliorated experimental colitis by regulating the balance of M1/M2 macrophage polarization and the homeostasis of intestinal flora

Abstract

Aberrant M1/M2 macrophage polarization and dysbiosis are involved in the pathogenesis of ulcerative colitis (UC). Ginsenoside Rg1 exhibits optimal immunomodulatory and anti-inflammatory effects in treating UC of humans and animals, but the action mechanism through the regulation of M1/M2 macrophage polarization and intestinal flora composition remain unclear. Here, experimental colitis was induced in BALB/c mice using dextran sulfate sodium, and Rock1 inhibitor Y27632 was used to explore the action mechanism of ginsenoside Rg1. Following treatment with ginsenoside Rg1 (200 mg/kg/day) and Y27632 (10 mg/kg/day) for 14 consecutive days, the rate of change in mouse body weight, mouse final weight, colonic weight, colonic length, colonic weight index and pathological damage scores of colitis mice were effectively improved, accompanied by less ulcer formation and inflammatory cell infiltration, lower levels of interleukin (IL)-6, IL-33, chemokine (C-C motif) ligand 2 (CCL-2), tumor necrosis factor alpha (TNF-α), and higher IL-4 and IL-10. Importantly, ginsenoside Rg1 and Y27632 significantly down-regulated CD11b⁺F4/80⁺, CD11b⁺F4/80⁺Tim-1⁺ and CD11b⁺F4/80⁺TLR4⁺ macrophages, and CD11b⁺F4/80⁺iNOS⁺ M1 macrophages, and significantly up-regulated CD11b⁺F4/80⁺CD206⁺ and CD11b⁺F4/80⁺CD163⁺ M2 macrophages in colitis mice; concomitantly, ginsenoside Rg1 improved the diversity of colonic microbiota and regulated Lachnospiraceae, Staphylococcus, Bacteroide and Ruminococcaceae_UCG_014 at genus level in colitis mice, but the flora regulated by Y27632 was not identical to it. Moreover, ginsenoside Rg1 and Y27632 down-regulated the protein levels of Rock1, RhoA and Nogo-B in colitis mice. These results suggested that ginsenoside Rg1 and Y27632 ameliorated colitis by regulating M1/M2 macrophage polarization and microbiota composition, associated with inhibition of the Nogo-B/RhoA signaling pathway.

Keywords: Colitis; Ginsenoside Rg1; Intestinal flora; M1/M2 macrophage polarization; Nogo-B/RhoA signalling pathway.