title: Stevioside protects LPS-induced acute lung injury in mice.
abstract: Stevioside, a diterpene glycoside component of Stevia rebaudiana, has been known to exhibit anti-inflammatory properties. To evaluate the effect and the possible mechanism of stevioside in lipopolysaccharide (LPS)-induced acute lung injury, male BALB/c mice were pretreated with stevioside or dexamethasone 1 h before intranasal instillation of LPS. Seven hours later, tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid (BALF) were measured by using enzyme-linked immunosorbent assay. The number of total cells, neutrophils, and macrophages in the BALF were also determined. The right lung was excised for histological examination and analysis of myeloperoxidase activity and nitrate/nitrite content. Cyclooxygenase 2 (COX-2), inducible NO synthase (iNOS), nuclear factor-kappa B (NF-κB), inhibitory kappa B protein were detected by western blot. The results showed that stevioside markedly attenuated the LPS-induced histological alterations in the lung. Stevioside inhibited the production of pro-inflammatory cytokines and the expression of COX-2 and iNOS induced by LPS. In addition, not only was the wet-to-dry weight ratio of lung tissue significantly decreased, the number of total cells, neutrophils, and macrophages in the BALF were also significantly reduced after treatment with stevioside. Moreover, western blotting showed that stevioside inhibited the phosphorylation of IκB-α and NF-κB caused by LPS. Taken together, our results suggest that anti-inflammatory effect of stevioside against the LPS-induced acute lung injury may be due to its ability of inhibition of the NF-κB signaling pathway. Stevioside may be a promising potential therapeutic reagent for acute lung injury treatment.
authors.affiliation: Department of Rheumatology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang Province, 150086, People's Republic of China.
authors.forename: Nie
authors.initials: N
authors.lastname: Yingkun
authors.forename: Wang
authors.initials: W
authors.lastname: Zhenyu
authors.forename: Lin
authors.initials: L
authors.lastname: Jing
authors.forename: Lu
authors.initials: L
authors.lastname: Xiuyun
authors.forename: Yu
authors.initials: Y
authors.lastname: Huimin
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D051546:Cyclooxygenase 2 / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D045786:Diterpenes, Kaurane / Q000627:therapeutic use*; D005960:Glucosides / Q000627:therapeutic use*; D051550:I-kappa B Kinase / Q000032:analysis / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D009566:Nitrates / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D009573:Nitrites / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D045786:Diterpenes, Kaurane; D005960:Glucosides; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; C012043:stevioside; D003907:Dexamethasone; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase