Polysaccharides derived from Ganoderma lucidum fungus mycelia ameliorate indomethacin-induced small intestinal injury via induction of GM-CSF from macrophages

Abstract

Non-steroidal anti-inflammatory drugs often cause ulcers in the human small intestine, but few effective agents exist to treat such injury. Ganoderma lucidum Karst, also known as "Reishi" or "Lingzhi", is a mushroom. We previously reported that a water-soluble extract from G. lucidum fungus mycelia (MAK) has anti-inflammatory effects in murine colitis induced by trinitrobenzene sulfonic acid, and induction of granulocyte macrophage colony-stimulating factor (GM-CSF) by MAK may provide anti-inflammatory effects. However, its effects on indomethacin-induced small intestinal injuries are unknown. The present study investigated the preventative effects of MAK via immunological function and the polysaccharides from MAK on indomethacin-induced ileitis in mice. Peritoneal macrophages (PMs) were stimulated in vitro with MAK and adoptively transferred to C57BL/6 mice intraperitoneally, which were then given indomethacin. Intestinal inflammation was evaluated after 24h. We performed in vivo antibody blockade to investigate the preventive role of GM-CSF, which derived from PMs stimulated with MAK. We then used PMs stimulated with MAK pre-treated by pectinase in an adoptive transfer assay to determine the preventive role of polysaccharides. Indomethacin-induced small intestinal injury was inhibited by adoptive transfer of PMs stimulated in vitro with MAK. In this transfer model, pre-treatment with anti-GM-CSF antibody but not with control antibody reversed the improvement of small intestinal inflammation by indomethacin. Pectinase pretreatment impaired the anti-inflammatory effect of MAK. PMs stimulated by MAK appear to contribute to the anti-inflammatory response through GM-CSF in small intestinal injury induced by indomethacin. The polysaccharides may be the components that elicit the anti-inflammatory effect.

Protective effect of Gloeostereum�incarnatum on ulcerative colitis via modulation of Nrf2/NF‑κB signaling in C57BL/6 mice

“…Recently, edible mushrooms have attracted researchers' attention due to their diverse pharmacological effects and minimal adverse effects. For example, Ganoderma lucidum alleviates intestinal damage induced by indomethacin in mice ( 43 ) and Hericium erinaceus improves testicular damage via its antioxidative effects and regulation of the GPR41/43 receptor in UC rats and Caco-2 cells ( 44 ). Based on the immunomodulatory and anti-inflammatory effects of GI reported previously ( 7 ), the present study successfully confirmed its protective effect against UC in C57BL/6 mice.…”

Animal Models of Undernutrition and Enteropathy as Tools for Assessment of Nutritional Intervention

“…Indomethacin (10 mg/kg) subcutaneous injection in mice increased intestinal permeability and induced ulcers 24 h post administration [135]. These consequences have also been observed 24 h after oral indomethacin administration [137,138] in mice (10 mg/kg) and rats (15 mg/kg). Gut permeability increased over the first hours after a single indomethacin gavage in rats (20 mg/kg) and returned to normal four days post treatment [139].…”

Suppression of Th17 Cell Response in the Alleviation of Dextran Sulfate Sodium-Induced Colitis by Ganoderma lucidum Polysaccharides

“…Our results proved the beneficial effects of GLP on the symptoms of colitis, which were depicted when assessing the survival rate, body weight loss, colon length, histopathological scores, and DAI score ( Figure 1 ). Recent results showed that polysaccharides derived from G. lucidum fungus mycelia ameliorate indomethacin-induced small intestinal injury by induction of granulocyte macrophage colony-stimulating factor (GM-CSF) from macrophages [ 45 ]. However, the result of our study showed that GLP had no effects on the populations of macrophage and the neutrophils in colonic LP in mice with DSS-induced acute colitis ( Figure 2 ).…”