RESUMEN
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.
Asunto(s)
Antiinflamatorios/uso terapéutico , Forsythia/química , Glucósidos/uso terapéutico , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Fitoterapia , Neumonía/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Glucósidos/farmacología , Hemorragia/prevención & control , Interleucina-6/metabolismo , Lipopolisacáridos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Infiltración Neutrófila/efectos de los fármacos , Peroxidasa/metabolismo , Neumonía/inducido químicamente , Neumonía/metabolismo , Neumonía/patología , Edema Pulmonar/inducido químicamente , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
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.
Asunto(s)
Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/prevención & control , Medicamentos Herbarios Chinos/farmacología , Ácido Oleanólico/análogos & derivados , Saponinas/farmacología , Lesión Pulmonar Aguda/inducido químicamente , Animales , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Proteínas I-kappa B/inmunología , Lipopolisacáridos/farmacología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Inhibidor NF-kappaB alfa , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Edema Pulmonar/inducido químicamente , Edema Pulmonar/inmunología , Edema Pulmonar/prevención & control , Saponinas/químicaRESUMEN
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.