Heating and steaming processes have been applied to various natural medicines for either enhancing or altering their pharmacological activities, and the chemical compositions of the active components. While
ginsenoside Rb1, which is the major constituent of raw ginseng, has been studied extensively for its anti-inflammatory effect, the biological activity of
ginsenoside Rg5, a major constituent of steamed ginseng, remains to be explored. Here, we isolated Rg5 and examined anti-inflammatory effect in
lipopolysaccharide (LPS)-stimulated macrophages and on LPS-induced
lung inflammation. Rg5 inhibited the expression of proinflammatory
cytokines, IL-1β and TNF-α, as well as inflammatory
enzymes, COX-2 and iNOS in LPS-stimulated alveolar macrophages. Rg5 also reduced LPS-induced phosphorylation of
IL-1 receptor-associated
kinases (IRAK)-1 and IKK-β, as well as the degradation of IRAK-1 and IRAK-4. Rg5 inhibited the phosphorylation of NF-κB as well as the translocation of p65 into the nucleus. When macrophages were treated with Alexa Fluor 594-conjugated LPS in the presence of Rg5, the fluorescence intensity of LPS observed outside the cell membrane was lower than that in LPS-stimulated alveolar macrophages alone. Rg5, inhibited the levels of
protein and neutrophils in bronchoalveolar lavage fluid of LPS-stimulated mice, as well as pro-inflammatory
cytokines, TNF-α and IL-1β. Rg5 also inhibited iNOS and COX expressions, and NF-κB activation in LPS-stimulated
lung inflammation of mice. The inhibitory effect of Rg5 (10 mg/kg) was comparable to that of
dexamethasone (5 mg/kg). Based on these findings, Rg5 can ameliorate
lung inflammation possibly by inhibiting the binding of LPS to
toll-like receptor (TLR)-4 on macrophages.