Combined treatment with Rg1 and adipose-derived stem cells alleviates DSS-induced colitis in a mouse model

Abstract

Background Inflammatory bowel diseases, consisting of Crohn’s disease and ulcerative colitis constitute chronic inflammatory conditions that may compromise the whole gastrointestinal tract as well as the colonic mucosa. Currently, there are no curative interventions for IBD, and all available treatments have side effects that limit their use. Adipose-derived stem cell (ADSC) treatment is a prospective treatment option for IBD. Previous findings indicated that ginsenoside (Rg1) dampened inflammatory diseases like colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg ratio. The purpose of this work was to investigate whether Rg1 can increase the influence of ADSC in a mouse model of colitis triggered by dextran sulfate sodium (DSS). Methods ADSC was intravenously inoculated into mice with DSS-triggered colitis, while Rg1 was delivered via oral gavage. Colon inflammation was assessed via body weight, colon length along with H&E staining. Serum cytokine levels were measured using ELISA. Besides, flow cytometry was adopted to determine the percentage, as well as FMI of immune cells in the spleen. The effects of simultaneous Rg1 and ADSC treatment on TLR4-MyD88 signaling were assessed via immunofluorescence. Results Rg1 and ADSC effectively alleviated the impacts of colon inflammation, weight loss, and colon length reduction along with histological score. Treatment with Rg1 and ADSC reduced serum levels of the proinflammatory cytokines, IL-1β, TNF-α, IL-6, IL-4, and IL-17A and upregulated the level of immunosuppressive cytokine, IL-10. Compared with ADSC or Rg1 alone, combined treatment with Rg1 and ADSC significantly improved the structure of microbial community. Additionally, treatment with Rg1 plus ADSC selectively elevated the level of splenic regulatory T (Treg) cells and downregulated the proportion of T helper type 17 (Th17) cells, indicating restoration of intestinal homeostasis. Besides, we established that the combination of ADSC + Rg1 restored immunological balance more effectively than either ADSC or Rg1 alone, illustrating that Rg1's modulatory function on the gut microbiota may boost the impact of ADSCs in restoration of the immune balance. ADSC combined with Rg1 might downregulate the expression of TLR4 and MyD88, thereby suppressing TLR4-MyD8 signaling. The immunofluorescence results also suggested that co-therapy with Rg-1 and ADSC may optimize treatment strategies of IBD. Conclusions Here, we find that the combination of Rg1 and ADSC alleviates DSS-induced colitis in a mouse model more efficiently than ADSC alone, indicating that Rg1 enhances the effect of ADSC against colitis.

Genistein Alleviates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice by Regulating Th17/Treg Cell Balance: Implication for the G Protein-coupled Estrogen Receptor

“…Many phytochemicals have been proven to regulate Th17/Treg cell balance to alleviate UC. Such phytochemicals like curcumin, gingerol, and ginsenosides have been investigated, and as their side effects are limited, these compounds have promising prospects for their clinical application (Sheng et al, 2020;Xiao et al, 2022;Zhang et al, 2022). We found that genistein significantly alleviated DAI scores and pathological changes within the intestine and promoted increased integrity of the intestinal barrier.…”

Long‐term oral administration of burdock fructooligosaccharide alleviates DSS‐induced colitis in mice by mediating anti‐inflammatory effects and protection of intestinal barrier function

“…The shortening of colon length is another significant symptom of colitis, which exhibits a positive correlation with the severity of the disease. Moreover, restoration of colon length can be observed upon alleviation of inflammation 38,39 . At the end of the experiment, the colon lengths of the mice treated with different concentrations of BFO showed significant mitigation of the colon shortening induced by DSS, with the colons even restored to lengths similar to those of in the CK group.…”

“…Moreover, restoration of colon length can be observed upon alleviation of inflammation. 38,39 At the end of the experiment, the colon lengths of the mice treated with different concentrations of BFO showed significant mitigation of the colon shortening induced by DSS, with the colons even restored to lengths similar to those of in the CK group. The effects were more pronounced in the BFO-H group than in the other groups.…”