The methanol extract of Guettarda speciosa Linn. Ameliorates acute lung injury in mice

Abstract

Background: Guettarda 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. Methods: The 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.Results: MGS 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 proinflammatory 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.Conclusion: MGS 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.

Alismol Purified from the Tuber of Alisma orientale Relieves Acute Lung Injury in Mice via Nrf2 Activation

“…injection of PBS or LPS (2 mg/kg m.b.w. ), which was sufficient to induce neutrophilic lung inflammation [22]. Two hours after LPS instillation, mice received two different amounts of an i.t.…”

“…Taken together, these results suggest that alismol can suppress neutrophilic lung inflammation elicited in the ALI mouse model. Since neutrophilic infiltration to the lung is correlated with the level of pro-inflammatory cytokines [22], we examined whether alismol decreases the production of inflammatory cytokines that promote inflammation, including TNF-α, IL-1β, and IL-6. From ALI mouse lungs, we collected and analyzed bronchoalveolar lavage fluid (BALF) for detecting excreted cytokines.…”

Phytochemistry and Pharmacology of Guettarda speciosa L.

“…In vivo excision wound model using Wistar albino female rats [12] Leaf Anti-ulcer Ethanol In vivo ethanol and pyloric ligation (PL) induced gastric ulcer model using Wistar albino rats [21] Leaf Antioxidant Aqueous In vitro nitric oxide (NO) radical scavenging assay [22] Stem and leaves Anti-inflammatory Methanol In vivo acute Lung Injury (ALI) mouse model using male C57BL/6 mice [23] Unspecified plant part Anti-inflammatory Methanol In vitro LPS-induced murine macrophages RAW 264.7 cell model [11] The 95% ethanolic inner bark extract exhibited an increase in neurotransmitter (noradrenaline, dopamine, serotonin, and gamma-amino butyric acid) levels after induction of seizure via MES and PTZ model on Wistar albino rats [14]. The methanolic extract of the inner bark of the plant exhibited hepatoprotective activity against CCl4induced hepatotoxicity [20].…”

“…However, only the aqueous leaf extract showed antioxidant activity in in vitro nitric oxide scavenging assay [22]. The stem and leaf methanolic extracts exhibited antiinflammatory activity in in vivo studies [23]. Concentrations of 50 µg/mL and 100 µg/ mL of the methanolic extract of G. speciosa did not cause metabolic disarray or any significant reactive oxygen species (ROS) on RAW 264.7 cells [23].…”