Novel ginsenoside monomer RT4 promotes colitis repair in mice by regulating miR‐144‐3p/SLC7A11 signaling pathway

Abstract

BackgroundGinsenoside RT4 (RT4) is a new biologically active compound extracted from ginseng that possesses numerous medicinal and pharmacological properties. However, its potential therapeutic effect of ginsenoside RT4 on ulcerative colitis remains unknown.Methods and resultsIn this study, we investigated the anti‐inflammatory effects of ginsenoside RT4 and its underlying molecular mechanism in the treatment of ulcerative colitis mice induced with dextran sulfate sodium (DSS). Our results demonstrate that ginsenoside RT4 effectively reduced weight, shortening of colonic tract length, colonic bowel damage, and disease activity index (DAI) scores in DSS‐induced colitis mice. Additionally, ginsenoside RT4 regulates miR‐144‐3p expression in DSS‐induced colitis mice, and we further confirmed that the solute carrier family 7 member 11 (SLC7A11) was the target gene of miR‐144‐3p by database analysis. Finally, ginsenoside RT4 inhibits the activation of the miR‐144‐3p/SLC7A11 signaling pathway, which alleviates colitis. Ginsenoside RT4 significantly decreased the expression of pro‐inflammatory cytokines TNF‐α and IL‐1β and increased the anti‐inflammatory cytokine IL‐10.ConclusionsThese findings suggest that ginsenoside RT4 may have therapeutic potential for treating ulcerative colitis by downregulating levels of miR‐144‐3p/SLC7A11 signaling pathway, which are expected to be useful in treating clinical ulcerative colitis.

Study on the Anti-Ulcerative Colitis Effect of Pseudo-Ginsenoside RT4 Based on Gut Microbiota, Pharmacokinetics, and Tissue Distribution

“…The highly specific distribution of intestinal inflammation sites, as well as mucosal healing, are particularly important treatment strategies. RT4 (a natural product) showed positive anti-inflammatory effects in LPS-induced RAW 264.7 cells and in DSSinduced UC mice (intraperitoneal injected with RT4) [20]. However, oral administration is more suitable for treating ulcerative colitis.…”

“…It has been reported that RT4 shows both a hepatocytoprotective effect [17] and an anti-inflammatory effect [18,19]. It is worth mentioning that intraperitoneal injections of RT4 have the potential to alleviate disease symptoms, increase colon length and weight, and improve the pathological state of colonic tissues in UC mice [20]. It has further been revealed that RT4 could downregulate the levels of pro-inflammatory cytokines (IL-1β, TNF-α) and up-regulate the level of anti-inflammatory cytokines (IL-10) in the colonic tissue of UC mice.…”

“…It has further been revealed that RT4 could downregulate the levels of pro-inflammatory cytokines (IL-1β, TNF-α) and up-regulate the level of anti-inflammatory cytokines (IL-10) in the colonic tissue of UC mice. It has also been discovered that RT4 has the same effect on inflammatory factors in the RAW 264.7 cell inflammation model constructed with lipopolysaccharides (LPS) [20]. However, compared to intra-peritoneal injections, oral administration is more convenient and shows a better patient compliance with the drug regimen.…”