title: 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.
authors.affiliation: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Binbin
authors.initials: B
authors.lastname: Cheng
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhu
authors.forename: Changquan
authors.initials: C
authors.lastname: Ling
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000009:adverse effects* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011897:Random Allocation; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; C035054:ginsenoside Rg1