Ginsenoside Rb3 Inhibits Pro-Inflammatory Cytokines via MAPK/AKT/NF-κB Pathways and Attenuates Rat Alveolar Bone Resorption in Response to Porphyromonas gingivalis LPS

Abstract

Conventional treatments for chronic periodontitis are less effective in controlling inflammation and often relapse. Therefore, it is necessary to explore an immunomodulatory medication as an adjuvant. Ginsenoside Rb3 (Rb3), one of the most abundant active components of ginseng, has been found to possess anti-inflammatory and immunomodulatory properties. Here, we detected the anti-inflammatory effect of Rb3 on Porphyromonas gingivalis LPS-stimulated human periodontal ligament cells and experimental periodontitis rats for the first time. We found that the expression of pro-inflammatory mediators, including IL-1β, IL-6 and IL-8, upregulated by lipopolysaccharide (LPS) stimulation was remarkably downregulated by Rb3 treatment in a dose-dependent manner at both transcriptional and translational levels. Network pharmacological analysis of Rb3 showed that the mitogen-activated protein kinase (MAPK) signaling pathway had the highest richness and that p38, JNK, and ERK molecules were potential targets of Rb3 in humans. Western blot analysis revealed that Rb3 significantly suppressed the phosphorylation of p38 MAPK and p65 NF-κB, as well as decreased the expression of total AKT. In experimental periodontitis rat models, reductions in alveolar bone resorption and osteoclast generation were observed in the Rb3 treatment group. Thus, we can conclude that Rb3 ameliorated Porphyromonas gingivalis LPS-induced inflammation by inhibiting the MAPK/AKT/NF-κB signaling pathways and attenuated alveolar bone resorption in experimental periodontitis rats.

Polarized Macrophages in Periodontitis: Characteristics, Function, and Molecular Signaling

“…Signaling pathways are interconnected and mediate a wide variety of responses between different cell types, which poses challenges to signaling pathway related immunotherapy. Sun et al (161) used ginsenoside 3 (Rb3) to treat lPS-induced experimental periodontitis rats and found that Rb3 inhibited MAPK/AKT/NF-kB signaling pathway, improved inflammation and reduced alveolar bone resorption in rats. Li et al (162) found that inhibition of NF-kB and JAK1/STAT1/3 signaling pathway is the main mechanism by which Mangiferin ameliorates experimental periodontitis in mice.…”

“…Sun et al. ( 161 ) used ginsenoside 3 (Rb3) to treat lPS-induced experimental periodontitis rats and found that Rb3 inhibited MAPK/AKT/NF-κB signaling pathway, improved inflammation and reduced alveolar bone resorption in rats. Li et al.…”

Whey fermented by Enterococcus faecalis M157 exhibits antiinflammatory and antibiofilm activities against oral pathogenic bacteria

“…These results indicate that M157-W suppresses P. gingivalis LPS-induced activation of MAPK and NF-κB, thereby attenuating the inflammatory responses in RAW 264.7 cells. The stimulation of cells with P. gingivalis LPS increased the production of proinflammatory cytokines, such as IL-1β and IL-6, through the upregulation of MAPK and NF-κB (Sun et al, 2020). NF-κB is crucially involved in inflammatory reactions; the inhibitors of NF-κB, including IκBα, are important in downregulating NF- κB activation (Wang et al, 2020).…”

The promising therapeutic potentials of ginsenosides mediated through p38 MAPK signaling inhibition

“… Decreased the expression of total Akt. [ 111 ] Ginsenoside Rc LPS-induced inflammation in RAW264.7 and HEK293 cells transfected with various inducers of inflammation . Blocked the production of cytokines derived from macrophages for tumor necrosis.…”

“…(2020) investigated that ginsenoside Rb3 potently suppressed LPS-induced cytokine production through MAPK/Akt/NF-κB signal and alleviated bone resorption. Ginsenoside Rb3 effectively decreased p38 MAPK and NF-κB phosphorylation and curbed IL-1β, IL-6, and IL-8 levels [ 111 ].…”