Ginsenoside Rc attenuates DSS-induced ulcerative colitis, intestinal inflammatory, and barrier function by activating the farnesoid X receptor

Kaijia Tang; Danli Kong; Yuan Peng; Jingyi Guo; Yadi Zhong; Haibing Yu; Zhenhua Mai; Yanling Chen; Yingjian Chen; Tianqi Cui; Siwei Duan; Tianyao Li; Naihua Liu; Dong Zhang; Yuanlin Ding; Jiawen Huang

doi:10.3389/fphar.2022.1000444

Ginsenoside Rc attenuates DSS-induced ulcerative colitis, intestinal inflammatory, and barrier function by activating the farnesoid X receptor

Front Pharmacol. 2022 Oct 28:13:1000444. doi: 10.3389/fphar.2022.1000444. eCollection 2022.

Authors

Kaijia Tang¹, Danli Kong², Yuan Peng³, Jingyi Guo¹, Yadi Zhong¹, Haibing Yu², Zhenhua Mai⁴, Yanling Chen⁵, Yingjian Chen¹, Tianqi Cui¹, Siwei Duan¹, Tianyao Li¹, Naihua Liu¹, Dong Zhang⁶, Yuanlin Ding², Jiawen Huang¹

Affiliations

¹ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
² Department of Epidemiology and Medical Statistics, School of Public Health, Guangdong Medical University, Dongguan, China.
³ Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
⁴ Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
⁵ The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
⁶ The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.

Abstract

Objectives: Farnesoid X receptor (FXR) activation is involved in ameliorating inflammatory bowel disease (IBD), such as ulcerative colitis (UC), and inflammatory regulation may be involved in its mechanism. Ginsenoside Rc (Rc) is a major component of Panax ginseng, and it plays an excellent role in the anti-inflammatory processes. Our aim is to explore the alleviative effect of Rc on dextran sulfate sodium (DSS)-induced inflammation and deficiencies in barrier function based on FXR signaling. Materials and Methods: In vitro, we treated human intestinal epithelial cell lines (LS174T) with LPS to explore the anti-inflammatory effect of Rc supplementation. In vivo, a DSS-induced IBD mice model was established, and the changes in inflammatory and barrier function in colons after Rc treatment were measured using the disease activity index (DAI), hematoxylin and eosin (H&E) staining, immunofluorescence, ELISA, and qPCR. Molecular docking analysis, luciferase reporter gene assay, and qPCR were then used to analyze the binding targets of Rc. DSS-induced FXR-knockout (FXR^-/-) mice were used for further validation. Results: Rc significantly recovered the abnormal levels of inflammation indexes (TNF-α, IL-6, IL-1β, and NF-KB) induced by LPS in LS174T. DSS-induced C57BL/6 mice exhibited a significantly decreased body weight and elevated DAI, as well as a decrease in colon weight and length. Increased inflammatory markers (TNF-α, IL-6, IL-1β, ICAM1, NF-KB, F4/80, and CD11b displayed an increased expression) and damaged barrier function (Claudin-1, occludin, and ZO-1 displayed a decreased expression) were observed in DSS-induced C57BL/6 mice. Nevertheless, supplementation with Rc mitigated the increased inflammatory and damaged barrier function associated with DSS. Further evaluation revealed an activation of FXR signaling in Rc-treated LS174T, with FXR, BSEP, and SHP found to be upregulated. Furthermore, molecular docking indicated that there is a clear interaction between Rc and FXR, while Rc activated transcriptional expression of FXR in luciferase reporter gene assay. However, these reversal abilities of Rc were not observed in DSS-induced FXR^-/- mice. Conclusion: Our findings suggest that Rc may ameliorate inflammation and barrier function in the intestine, which in turn leads to the attenuation of DSS-induced UC, in which Rc may potentially activate FXR signaling to protect the intestines from DSS-induced injury.

Keywords: ginsenoside Rc; inflammation; inflammatory bowel disease; intestinal barriers; ulcerative colitis.