Ginsenoside Rg5 ameliorates lung inflammation in mice by inhibiting the binding of LPS to toll-like receptor-4 on macrophages

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• 作者：Tae-Wan Kim^a ; Eun-Ha Joh^b ; Baek Kim^c ; ^{Baek_Kim@urmc.rochester.edu} ; Dong-Hyun Kim^b ; ^{dhkim@khu.ac.kr}
• 关键词：ALI ; acute lung injury ; ANOVA ; analysis of variance ; BALF ; bronchoalveolar lavage fluid ; COX-2 ; cyclooxygenase-2 ; ERK ; extracellular signal-regulated kinase ; IL ; interleukin ; iNOS ; inducible nitric oxide synthase ; IRAK ; interleukin-1 receptor-associated k
• 刊名：International Immunopharmacology
• 出版年：2012
• 出版时间：January 2012
• 年：2012
• 卷：12
• 期：1
• 页码：110-116
• 全文大小：959 K

文摘

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-1¦Â and TNF-¦Á, 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-¦Â, as well as the degradation of IRAK-1 and IRAK-4. Rg5 inhibited the phosphorylation of NF-¦ÊB 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-¦Á and IL-1¦Â. Rg5 also inhibited iNOS and COX expressions, and NF-¦ÊB 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.