ginsenoside-ro and Inflammation

It is becoming increasingly accepted that macrophage activation play a crucial role in many diseases associated with chronic inflammation, such as metabolic disease, including atherosclerosis, obesity, and diabetes. Recent studies have indicated that the regulation of inflammation and energy metabolism are connected together through an antagonistic crosstalk between NF-κB and SIRT1 signaling pathways. In order to investigate anti-inflammatory drugs, we investigated whether SIRT1 is implicated in the lipopolysaccharide (LPS)-stimulated NF-κB signaling pathway in macrophage RAW264.7 cells when pretreated with chikusetsusaponin V (CsV). Griess assay and enzyme-linked immunosorbent assay were used to determine the effect of CsV on LPS-induced inflammatory cytokine secretion. Western blot was used to assess the effect of CsV on LPS-induced SIRT1 and Ac-NF-κB p65 expression. Results showed that CsV suppressed LPS-induced inflammatory cytokine NO, TNF-α, and IL-1β production in RAW264.7 cells. In addition, downregulation of SIRT1 and upregulation of Ac-NF-κB p65 induced by LPS were abolished by CsV in a dose-dependent manner in RAW264.7 cells. Meanwhile, inflammatory cytokines were regulated with CsV through SIRT1-Ac-NF-κB p65 signaling pathway. Therefore, our results demonstrate that CsV exerts an anti-inflammatory effect partly through SIRT1/NF-κB signaling pathways and SIRT1 may be a new target for anti-inflammation therapies.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Inflammation; Lipopolysaccharides; Mice; NF-kappa B; RAW 264.7 Cells; Receptor Cross-Talk; Saponins; Signal Transduction; Sirtuin 1

This study investigated effects of Ginsenoside Ro (Ro) on interleukin-1β (IL-1β)-induced apoptosis and inflammation in rat chondrocytes. The rat chondrocytes were co-treated with IL-1β (10 ng·kg(-1)) and Ro (50, 100 and 200 μmol·L(-1)) for 48 h. Chondrocytes viability was detected by the MTT assay and Annexin V-FITC/PI dual staining assay. Caspase 3 activity was measured by using caspase 3 colorimetric assay kit. Apoptosis related proteins Bax, Bad, Bcl-xL, PCNA, p53 and phospho-p53, along with inflammation related protein MMP 3, MMP 9 and COX-2, and the expression of phospho-NF-κB p65 were assayed by western blotting analyses. Ro could improve IL-1β-induced chondrocytes viability. Ro could suppress IL-1β-induced apoptosis by inhibiting levels of Bax and Bad, decreasing p53 phosphorylation and promoting the expression of Bcl-xL and PCNA. Ro inhibited caspase 3 activity. IL-1β-induced inflammation and matrix degration were also alleviated by Ro with down-regulating the expression of MMP 3, MMP 9 and COX-2. Moreover, Ro inhibited NF-κB p65 phosphorylation induced by IL-1β. In conclusion, these results suggested Ro exerted anti-apoptosis and anti-inflammation in IL-1β-induced rat chondrocytes, which might be related to NF-κB signal pathway. Therefore, we propose that Ro might be a potential novel drug for the treatment of osteoarthritis.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Apoptosis Regulatory Proteins; Caspase 3; Cell Survival; Chondrocytes; Cyclooxygenase 2; Down-Regulation; Drug Evaluation, Preclinical; Ginsenosides; Inflammation; Interleukin-1beta; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; NF-kappa B; Phosphorylation; Rats; Rats, Sprague-Dawley; Signal Transduction

Ginsenoside Ro, an oleanane-type saponin has been screened for activity in experimental models of inflammation. Ginsenoside Ro (10, 50, and 200 mg/kg, p.o.) inhibited an increase in vascular permeability in mice induced by acetic acid and reduced an acute paw edema in rats induced by compound 48/80 or carrageenin. Ginsenoside Ro did not suppress a developing adjuvant-induced edema in arthritic rats. However, ginsenoside Ro was found to be effective in hypercoagulable state, increase of connective tissue in the artery and calcium effluence from the bone in adjuvant-induced arthritic rats.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Edema; Ginsenosides; Inflammation; Kallikreins; Male; Panax; Plants, Medicinal; Rats; Rats, Inbred Strains; Saponins; Trypsin Inhibitors