Ginsenoside Rg1, a Novel Glucocorticoid Receptor Agonist of Plant Origin, Maintains Glucocorticoid Efficacy with Reduced Side Effects

Abstract

Glucocorticoids (GCs) are widely used to treat inflammatory diseases. However, they cause debilitating side effects, which limit the use of these compounds. In the past decade, many researchers have attempted to find so-called dissociated GCs that have separate distinct transactivation and transrepression activities. Anti-inflammation of GCs is a result of glucocorticoid receptor (GR)-mediated transactivation and transrepression in some tissues, similar to their side effects; therefore, the goal to discover a compound that has anti-inflammatory properties, but lacks the negative side effects seen with GCs, has yet to be achieved. In the present study, we introduce a plant-derived compound, ginsenoside Rg1, which possesses GC and estrogen-like activities. In this study, we show that Rg1 downmodulates LPS-induced proinflammatory cytokine release and inhibits NF-κB nuclear translocation and DNA binding activity. The negative effects on NF-κB activation are due to a decrease in IκB phosphorylation and protein stabilization. Furthermore, the inhibitory effect of Rg1 on NF-κB is GR-dependent, as small interfering RNA knockdown of GR abrogated this function. Rg1 also displayed profound inhibitory effects on LPS-induced MAPK activation. Importantly, Rg1 did not impair proliferation or differentiation of mouse osteoblasts. Finally, we show that Rg1 can effectively inhibit acute and chronic inflammation in vivo, but it does not cause hyperglycemia or osteoporosis as seen with dexamethasone. These results suggest that ginsenoside Rg1 may serve as a novel anti-inflammatory agent and may exhibit a potential profile for therapeutic intervention in inflammatory diseases.

An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na+/Glucose Cotransporter 1 Gene Expression

“…Studies have also shown that the ligand-activated glucocorticoid receptor is essential for the negative regulation of EGFR signaling (Zhang et al, 2007;Lauriola et al, 2014). In fact, studies have indicated that Rg1 is a functional ligand of the glucocorticoid receptor (Lee et al, 1997;Du et al, 2011). These findings also suggest the notion that Rg1 might activate the glucocorticoid receptor, which may result in the inhibition of EGFR activation.…”

Critical role of aquaporin-3 in epidermal growth factor-induced migration of colorectal carcinoma cells and its clinical significance

“…Total protein was extracted as previously described (16). Briefly, the cells were lysed with RIPA lysis buffer (Beyotime, Haimen, Jiangsu, China) and then centrifuged at 12,000 x g for 15 min at 4˚C.…”

Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis

“…Ginseng, the root of Panax ginseng CA Meyer, has been a key component in traditional Chinese medicine for more than 1000 years [14] . The traditional beneficial effects of ginseng are replenishment of vital energy, longevity and mood elevation [15] .…”

“…The traditional beneficial effects of ginseng are replenishment of vital energy, longevity and mood elevation [15] . The molecular constituents responsible for the action of ginseng are ginsenosides, among which, Rg1 is the most abundant and active ingredient of P ginseng [14,16] . Several studies have shown that Rg1 or ginseng extract has a liver protective effect [16][17][18][19][20][21][22] .…”