ABSTRACT
BACKGROUND: Esculentoside A (EsA) is a saponin isolated from the Chinese herb Phytolacca esculenta. In our study, we sought to investigate the protective effects of EsA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. MATERIALS AND METHODS: To determine the effects of EsA on the reduction of histopathologic changes in mice with ALI, inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung wet-to-dry weight ratio were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. Next, cytokine production induced by LPS in BALF was measured by enzyme-linked immunosorbent assay. To further study the mechanism of EsA protective effects on ALI, IκBa, p38, and extracellular signal receptor-activated kinase pathways were investigated in lung tissue of mice with ALI. RESULTS: In the present investigation, EsA showed marked effects by reducing inflammatory infiltration, thickening of the alveolar wall, and pulmonary congestion. Levels of tumor necrosis factor α and interleukin 6 elevated by LPS were significantly decreased in BALF in EsA-pretreated ALI model. Furthermore, EsA significantly suppressed phosphorylation of IκBa, p38, and extracellular signal receptor-activated kinase. CONCLUSIONS: Taken together, our results suggest that EsA suppressed inflammatory responses in LPS-induced ALI through inhibition of the nuclear factor kappa B and mitogen activated protein kinase signaling pathways. EsA may be a promising potential preventive agent for ALI treatment.
Subject(s)
Acute Lung Injury/immunology , Acute Lung Injury/prevention & control , Drugs, Chinese Herbal/pharmacology , Oleanolic Acid/analogs & derivatives , Saponins/pharmacology , Acute Lung Injury/chemically induced , Animals , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Disease Models, Animal , Drugs, Chinese Herbal/chemistry , I-kappa B Proteins/immunology , Lipopolysaccharides/pharmacology , Lung/drug effects , Lung/immunology , Lung/metabolism , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/immunology , Male , Mice , Mice, Inbred BALB C , NF-KappaB Inhibitor alpha , Oleanolic Acid/chemistry , Oleanolic Acid/pharmacology , Pulmonary Edema/chemically induced , Pulmonary Edema/immunology , Pulmonary Edema/prevention & control , Saponins/chemistryABSTRACT
Phillyrin (Phil) is one of the main chemical constituents of Forsythia suspensa (Thunb.), which has shown to be an important traditional Chinese medicine. We tested the hypothesis that Phil modulates pulmonary inflammation in an ALI model induced by LPS. Male BALB/c mice were pretreated with or without Phil before respiratory administration with LPS, and pretreated with dexamethasone as a control. Cytokine release (TNF-α, IL-1ß, and IL-6) and amounts of inflammatory cell in bronchoalveolar lavage fluid (BALF) were detected by ELISA and cell counting separately. Pathologic changes, including neutrophil infiltration, interstitial edema, hemorrhage, hyaline membrane formation, necrosis, and congestion during acute lung injury in mice were evaluated via pathological section with HE staining. To further investigate the mechanism of Phil anti-inflammatory effects, activation of MAPK and NF-κB pathways was tested by western blot assay. Phil pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by Phil pretreatment. In addition, Phil decreased the production of the proinflammatory cytokines including (TNF-α, IL-1ß, and IL-6) and the concentration of myeloperoxidase (MPO) in lung tissues. Phil pretreatment also significantly suppressed LPS-induced activation of MAPK and NF-κB pathways in lung tissues. Taken together, the results suggest that Phil may have a protective effect on LPS-induced ALI, and it potentially contributes to the suppression of the activation of MAPK and NF-κB pathways. Phil may be a new preventive agent of ALI in the clinical setting.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Forsythia/chemistry , Glucosides/therapeutic use , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Phytotherapy , Pneumonia/drug therapy , Animals , Anti-Inflammatory Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Glucosides/pharmacology , Hemorrhage/prevention & control , Interleukin-6/metabolism , Lipopolysaccharides , Lung/drug effects , Lung/metabolism , Lung/pathology , Male , Mice , Mice, Inbred BALB C , Neutrophil Infiltration/drug effects , Peroxidase/metabolism , Pneumonia/chemically induced , Pneumonia/metabolism , Pneumonia/pathology , Pulmonary Edema/chemically induced , Tumor Necrosis Factor-alpha/metabolismABSTRACT
In an attempt to search for bioactive natural products, two new prenylflavonols, 2''-hydroxy-3''-en-anhydroicaritin (1) and 2''-hydroxy-beta-anhydroicaritin (2), were isolated from the Chinese medicinal herb Epimedium brevicornum. Their structures were determined by 1D and 2D NMR spectroscopic analysis. The effects of compounds 1 and 2 on cytokine production in vitro were investigated. Compound 1 could significantly downregulate tumor necrosis factor-alpha (TNF-alpha) production and increase interleukin-10 (IL-10) production. These results suggested that compound 1 may have anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated mouse macrophages. In addition, the biogenetic relationships among compounds 1 and 2 are discussed.
