Ginsenoside Rh2 Downregulates LPS-Induced NF-κB Activation through Inhibition of TAK1 Phosphorylation in RAW 264.7 Murine Macrophage

Abstract EN

The present study was carried out to evaluate the inhibitory effects of ginsenoside Rh2 on nuclear-factor- (NF-) κB in lipopolysaccharide- (LPS-) activated RAW 264.7 murine macrophages.

RAW 264.7 cells were pretreated with indicated concentrations of ginsenoside Rh2 for 1 h prior to the incubation of LPS (1 μg/mL) for indicated time period.

Ginsenoside Rh2 reduced CD14 and Toll-like receptor 4 (TLR4) expressions 24 h after LPS stimulation.

Furthermore, ginsenoside Rh2 significantly inhibited TGF-beta-activated kinase 1 (TAK1) phosphorylation 30 min after LPS stimulation.

Ginsenoside Rh2 was further shown to inhibit NF-κB p65 translocation into the nucleus by suppressing IκB-α degradation.

Also, LPS increased mRNA expression of TNF-α and IL-1α time-dependently, while TQ reduced TNF-α within 3 h and IL-1α within 1 h.

And we firstly found that pretreatment of ginsenoside Rh2 successively inhibited hypoxia-inducible factor- (HIF-) 1α expression increased by LPS.

In conclusion, ginsenoside Rh2 may inhibit LPS-induced NF-κB activation and reduce HIF-1α accumulation, suggesting that ginsenoside Rh2 may be considered as a potential therapeutic candidate for chronic inflammatory diseases.