Gypenoside LXXV\nAlleviates Colitis by Reprograming\nMacrophage Polarization via the Glucocorticoid Receptor Pathway

An imbalance in the macrophage phenotype is closely related\nto\nvarious inflammatory diseases. Here, we discovered that gypenoside\nLXXV (GP-75), a type of saponin from Gynostemma pentaphyllum, can reprogram M1-like macrophages into M2-like ones. On a mechanistic\nlevel, GP-75 inhibits NF-κB-COX2 signaling by targeting the\nglucocorticoid receptor (GR). Administration of GP-75, either orally\nor by intraperitoneal injection, significantly alleviates ulcerative\ncolitis in mice, a pathogenesis associated with macrophage polarization.\nClodronate liposomes, which deplete macrophages in mice, as well as\nGR antagonist RU486, abrogate the anticolitis effect of GP-75, thus\nconfirming the pivotal role of macrophages in GP-75 function. We also\nshowed that GP-75 has no toxicity in mice. Overall, this is the first\nreport that demonstrates the effect of GP-75 on macrophage reprograming\nand as an agent against colitis. Because G. pentaphyllum is gaining popularity as a functional food, our findings offer new\nperspectives on the use of gypenosides as potential nutraceuticals\nfor medical purposes.