Suppression of MAPKs/NF-κB Activation Induces Intestinal Anti-Inflammatory Action of Ginsenoside Rf in HT-29 and RAW264.7 Cells

Abstract

This study investigated the intestinal anti-inflammatory action of ginsenoside Rf in inflammatory bowel disease (IBD). IBD is a chronic inflammatory disease that affects the intestinal tract. It is associated with elevated levels of various inflammatory mediators, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), nitric oxide (NO), and reactive oxygen species (ROS). Ginsenosides, the main active constituents of ginseng, have been reported to exert potent therapeutic effects against diverse diseases. However, ginsenoside Rf treatment for inflammation has not yet been examined. In this study, we evaluated the inhibitory effect of ginsenoside Rf on the inflammatory mediators downstream of p38/NF-kB activation on TNF-α-stimulated intestinal epithelial cells (HT-29) and mouse macrophage cells (RAW264.7). Our results showed that ginsenoside Rf significantly reduced the production of IL-1β, IL-6, TNF-α, NO, and ROS, which are most highly activated in IBD. In addition, ginsenoside Rf significantly suppressed TNF-α/LPS-induced NF-κB transcriptional activity. These results suggest that ginsenoside Rf contains a compound that has potent intestinal anti-inflammatory effects that could be used to treat diseases such as IBD.

Cellular stress response mechanisms as therapeutic targets of ginsenosides

“…Nuclear translocation, NF‐κB phosphorylation, and DNA binding are three important events in the final stage of NF‐κB pathway activation and have been shown to be inhibited by ginsenosides under various conditions. Nuclear translocation of NF‐κB p65 can be blocked by Rg1, 20( S )‐protopanaxatriol, Rh1, Rh2, Rb1, CK, Rg3, PF11, Rf, Rd, and Rb3 . The phosphorylation of NF‐κB p65 was found to be inhibited by Rg1, Rg3, and Ro .…”

“…Activated NF‐κB eventually binds to κB elements in the promoter region of target genes and initiates the transcriptional process of numerous genes . Recent investigations have demonstrated that the NF‐κB pathway is suppressed by a large number of ginsenosides, including Rg1, Rh2, Rb1, Compound K (CK), Rg3, Rb3, Rd, Pseudoginsenoside‐F11 (PF11), Re, Rh1, Rf, 20( S )‐protopanaxatriol, and Ro (Fig. ).…”

“…For example, Rh1 inhibited the activation of MAPKs in both human astroglioma U87MG and U373MG cells . LPS‐induced activation of MAPKs was suppressed by PF11 in N9 microglia, and by both Rg1 and Rf in RAW264.7 cells. Notably, three types of MAPKs may be differentially involved in inhibiting the NF‐κB pathway by ginsenosides, even in response to the same compound, under different stresses.…”

“…IBD is characterized by chronic and relapsing inflammation in all or part of the digestive tract . Rf can reduce the generation of several inflammatory mediators including IL‐1β, IL‐6, TNF‐α, NO, and reactive oxygen species (ROS), which are the most highly activated in IBD . Rg1, Rh1, and 20( S )‐protopanaxatriol, Rb1 and CK ameliorated the pathological changes of colitis and inhibited the production of proinflammatory cytokines.…”

“…Nuclear translocation of NF-B p65 can be blocked by Rg1, 50-52,54,55,57 20(S)-protopanaxatriol, 52 Rh1, 52 Rh2, 58,61 Rb1, 63,64 CK, 65,66 Rg3, 68 PF11, 77 Rf, 80 Rd, 75,74 and Rb3. 83 The phosphorylation of NF-B p65 was found to be inhibited by Rg1, [46][47][48][49]51 Rg3, 68,70,71 and Ro.…”