Abstract
BackgroundGuettarda speciosa is mainly found in tropical areas in Asia. Although G. speciosa is traditionally used to treat some of the inflammatory disorders, the experimental evidence supporting the anti-inflammatory effect of G. speciosa is limited. Here, we sought to obtain evidence that G. speciosa has anti-inflammatory activity using an acute lung injury (ALI) mouse model and to explore possible underlying mechanisms for the activity.MethodsThe methanol extract of G. speciosa Linn. (MGS) was fingerprinted by HPLC. Cytotoxicity was determined by MTT and flow cytometer. As for an ALI mouse model, C57BL/6 mice received an intratracheal (i.t.) injection of lipopolysaccharide (LPS). The effects of MGS on lung inflammation in the ALI mice were assessed by differential cell counting and FACS of inflammatory cells and hematoxylin and eosin staining of lung tissue. Proteins were analyzed by immunoprecipitation and immunoblotting, and gene expression was by real-time qPCR. Neutrophil elastase activity was measured by ELISA.ResultsMGS did not cause metabolic disarray or produce reactive oxygen species that could induce cytotoxicity. Similar to ALI patients, C57BL/6 mice that received an i.t. LPS developed a high level of neutrophils, increased pro-inflammatory cytokines, and inflicted tissue damage in the lung, which was suppressed by i.t. MGS administered at 2 h after LPS. Mechanistically, MGS activated Nrf2, which was related to MGS interrupting the ubiquitin-dependent degradation of Nrf2. MGS suppressed the nuclear localization of NF-κB induced by LPS, suggesting the inhibition of NF-κB activity. Furthermore, MGS inhibited the enzymatic activity of neutrophil elastase.ConclusionMGS could suppress lung inflammation in an ALI mouse model, the effect of which could be attributed to multiple mechanisms, including the activation of Nrf2 and the suppression of NF-κB and neutrophil elastase enzymatic activity by MGS.
Highlights
Guettarda speciosa is mainly found in tropical areas in Asia
MGS suppresses a pro-inflammatory factor NF-κB and neutrophil elastase activities Since MGS suppressed the expression of Tumor necrosis factor-α (TNF-α), IL-1β, and IL-6, we examined whether MGS suppresses NF-κB activity, a transcription factor that regulates the expression of those pro-inflammatory cytokines [16, 28]
With RAW 264.7 cells, we show that MGS activated an antiinflammatory factor nuclear erythroid 2-related factor 2 (Nrf2) and induced the expression of Nrf2-dependent genes such as heme oxygenase-1 (HO-1), glutamatecysteine ligase catalytic subunit (GCLC), and NAD(P)H:quinine oxidoreductase-1 (NQO1)
Summary
Guettarda speciosa is mainly found in tropical areas in Asia. G. speciosa is traditionally used to treat some of the inflammatory disorders, the experimental evidence supporting the anti-inflammatory effect of G. speciosa is limited. Guettarda speciosa is a perennial plant belonging to family Rubiaceae and found abundantly in tropical areas, such as the Okinawa Islands, Taiwan, tropical Asia, Australia, and the Polynesian Islands [1] People in these areas have used G. speciosa to treat inflammatory diseases, including fever, colds, sore throats, fever, dysentery, and headache [2], suggesting that G. speciosa contains possibly anti-inflammatory activity. TLR4 signaling activated by LPS on the bacteria ends up the activation of NF-κB [9], resulting in the expression of cytokines such as TNF-α, IL-1β, IL-6, and IL-8 [6] These cytokines promote inflammation by recruiting various inflammatory cells, notably neutrophils, to the lung [5]. For the study of anti-inflammatory activities of medicinal herbs, it would be necessary to use an inflammatory disease mouse model
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