Rat brain microsomal Na, K-ATPase activity is inhibited significantly and rapidly by Ginsenoside Rb1. The IC50 of Ginsenoside Rb1 for Na,K-ATPase is 6.3±1.0 μM. The inhibition is enhanced with increasing the concentration of Ginsenoside Rb1 or decreasing that of Na and K. Kinetic analysis reveals that Ginsenoside is an uncompetitive inhibitor with respect to ATP.
Ginsenoside Rb1 significantly inhibits the activation of interleukin-1 receptor-associated kinase-1 (IRAK-1), IKK-β, NF-κB, and MAP kinases (ERK, JNK, and p-38); however, interaction between LPS and Toll-like receptor-4, IRAK-4 activation and IRAK-2 activation are unaffected. Ginsenoside Rb1 is an ingredient of a Chinese medicine Panax ginseng. Ginsenoside Rb1 is a major bioactive compound in the regulating pregnane X receptor (PXR)/NF-κB signaling. Ginsenoside Rb1 is the compound with potent anti-inflammatory activity in ginseng saponin extract (GSE). The concentration for Ginsenoside Rb1 (10 μM) is optimized from a preliminary study to ensure sufficient anti-inflammatory activity and without apparent cytotoxicity. Ginsenoside Rb1 significantly reduces TNF-α-induced upregulation of IL-1β and iNOS mRNA levels, and restores the mRNA levels of PXR and CYP3A4 in LS174T cells. TNF-α causes a significant reduction in PXR protein levels and increase in the ratio of phosphorylated to total NF-κB p65, both of which are significantly abrogated by Ginsenoside Rb1.