title: Escin exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vivo and in vitro.
abstract: Escin, a natural mixture of triterpenoid saponins isolated from the seed of the horse chestnut (Aesculus hippocastanum), had been demonstrated to possess anti-edematous and anti-inflammatory effects. The present study was designed to investigate whether escin exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. The carrageenan-induced paw edema and pleuritis in bilaterally adrenalectomized rats were used to investigate the anti-inflammatory effects of escin and glucocorticoid alone or combined. The carrageenan-induced paw edema was inhibited only when escin and corticosterone (Cort) were administered together. Co-administration of escin with Cort significantly reduced the volume of exudates and the number of white blood cells of exudates in bilaterally adrenalectomized rats with pleuritis, but treatment with escin or Cort alone at a suboptimal concentration did not show any effect on the pleuritis rats. After the murine macrophagic RAW264.7 cells stimulated by lipopolysaccharide (LPS), they were treated with escin, Cort or escin and Cort. Then nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) of cell culture supernatants were analyzed. Escin or Cort markedly reduced the content of NO, TNF-α and IL-1β secreted by LPS-stimulated RAW264.7 macrophage cells. The combination of suboptimal concentrations of escin with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO, TNF-α and IL-1β in LPS-stimulated RAW264.7 macrophage cells. The findings suggest escin can synergize with glucocorticoids to enhance their anti-inflammatory effect.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Yantai University, Yantai 264005, PR China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Xin
authors.forename: Leiming
authors.initials: L
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.forename: Na
authors.initials: N
authors.lastname: Jiang
authors.forename: Huaying
authors.initials: H
authors.lastname: Fan
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: Fenghua
authors.initials: F
authors.lastname: Fu
mesh_terms: D031319:Aesculus / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004928:Escin / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010998:Pleurisy / Q000188:drug therapy; D011897:Random Allocation; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D004928:Escin