1. Gypenoside LXXV Alleviates Colitis by Reprograming Macrophage Polarization via the Glucocorticoid Receptor Pathway.
- Author
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Wu W, Qu X, Hu C, Zhu X, Wan M, Zhou Y, and Cheng H
- Subjects
- Animals, Humans, Male, Mice, Colitis drug therapy, Colitis metabolism, Colitis chemically induced, Mice, Inbred C57BL, NF-kappa B metabolism, NF-kappa B genetics, NF-kappa B immunology, Signal Transduction drug effects, Gynostemma chemistry, Macrophages drug effects, Macrophages metabolism, Plant Extracts pharmacology, Plant Extracts chemistry, Receptors, Glucocorticoid metabolism, Receptors, Glucocorticoid genetics
- Abstract
An imbalance in the macrophage phenotype is closely related to various inflammatory diseases. Here, we discovered that gypenoside LXXV (GP-75), a type of saponin from Gynostemma pentaphyllum , can reprogram M1-like macrophages into M2-like ones. On a mechanistic level, GP-75 inhibits NF-κB-COX2 signaling by targeting the glucocorticoid receptor (GR). Administration of GP-75, either orally or by intraperitoneal injection, significantly alleviates ulcerative colitis in mice, a pathogenesis associated with macrophage polarization. Clodronate liposomes, which deplete macrophages in mice, as well as GR antagonist RU486, abrogate the anticolitis effect of GP-75, thus confirming the pivotal role of macrophages in GP-75 function. We also showed that GP-75 has no toxicity in mice. Overall, this is the first report that demonstrates the effect of GP-75 on macrophage reprograming and as an agent against colitis. Because G. pentaphyllum is gaining popularity as a functional food, our findings offer new perspectives on the use of gypenosides as potential nutraceuticals for medical purposes.
- Published
- 2024
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