203
Views
50
CrossRef citations to date
0
Altmetric
Original Research

Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways

, , , , , , & show all
Pages 5215-5228 | Published online: 12 Jul 2019

Figures & data

Figure 1 Graphical representation polymeric oil-core nanocapsules loaded with trans-resveratrol.

Figure 1 Graphical representation polymeric oil-core nanocapsules loaded with trans-resveratrol.

Figure 2 Effect of treatment with RSV or RSV-LNCs on bronchoalveolar accumulation of leukocytes at different time points. A/J mice were orally pretreated with RSV or RSV-LNCs (5 mg/kg) 1 h, 4 h, 6 h, 12 h or 24 h before challenge with LPS. BALF leukocytes were assessed 24 h after LPS provocation.

Notes: Data are expressed as the mean ± SEM (n=5–7). +++P<0.001 compared with the saline group; *P<0.05 and *** P<0.001 compared to the LPS group.

Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; LPS, lipopolysaccharide.

Figure 2 Effect of treatment with RSV or RSV-LNCs on bronchoalveolar accumulation of leukocytes at different time points. A/J mice were orally pretreated with RSV or RSV-LNCs (5 mg/kg) 1 h, 4 h, 6 h, 12 h or 24 h before challenge with LPS. BALF leukocytes were assessed 24 h after LPS provocation.Notes: Data are expressed as the mean ± SEM (n=5–7). +++P<0.001 compared with the saline group; *P<0.05 and *** P<0.001 compared to the LPS group.Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; LPS, lipopolysaccharide.

Figure 3 Effect of treatment with RSV or RSV-LNCs on total (A) and differential (B) BALF leukocytes and lung MPO activity (C). A/J mice orally pretreated with RSV, RSV-LNCs (2.5–10 mg/kg), ULNCs or Dexamethasone (Dexa, 5 mg/kg) 4 h before challenge with LPS. Analyses were performed 24 h after LPS stimulation.

Notes: Data are expressed as the mean ± SEM (n=5–7). ++P<0.01 and +++P<0.001 compared with the saline group; ***P<0.001 compared to the LPS group.

Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; Dexa, dexamethasone; MPO, myeloperoxidase; LPS, lipopolysaccharide.

Figure 3 Effect of treatment with RSV or RSV-LNCs on total (A) and differential (B) BALF leukocytes and lung MPO activity (C). A/J mice orally pretreated with RSV, RSV-LNCs (2.5–10 mg/kg), ULNCs or Dexamethasone (Dexa, 5 mg/kg) 4 h before challenge with LPS. Analyses were performed 24 h after LPS stimulation.Notes: Data are expressed as the mean ± SEM (n=5–7). ++P<0.01 and +++P<0.001 compared with the saline group; ***P<0.001 compared to the LPS group.Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; Dexa, dexamethasone; MPO, myeloperoxidase; LPS, lipopolysaccharide.

Figure 4 Effect of treatment with RSV or RSV-LNCs on lung pathological changes. A/J mice were orally pretreated with RSV, RSV-LNCs (2.5–10 mg/kg),ULNCs or Dexa (5 mg/kg) 4 h before challenge with LPS. Analyses were performed 24 h after LPS stimulation. (A-J) Representative images of LPS-induced pathological changes and (K) analysis of lung damage by semiquantitative score system.

Notes: Data are expressed as the mean ± SEM (n=5–7). +++P<0.001 compared with the saline group and ***P<0.001 compared to the LPS group.

Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; Dexa, dexamethasone; LPS, lipopolysaccharide.

Figure 4 Effect of treatment with RSV or RSV-LNCs on lung pathological changes. A/J mice were orally pretreated with RSV, RSV-LNCs (2.5–10 mg/kg),ULNCs or Dexa (5 mg/kg) 4 h before challenge with LPS. Analyses were performed 24 h after LPS stimulation. (A-J) Representative images of LPS-induced pathological changes and (K) analysis of lung damage by semiquantitative score system.Notes: Data are expressed as the mean ± SEM (n=5–7). +++P<0.001 compared with the saline group and ***P<0.001 compared to the LPS group.Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; Dexa, dexamethasone; LPS, lipopolysaccharide.

Figure 5 Effect of treatment with RSV or RSV-LNCs on lung tissue production of IL-6 (A), KC (B), MIP-1α (C), MIP-2 (D), MCP-1 (E) and RANTES (F). A/J mice orally pretreated with RSV, RSV-LNCs (2.5–10 mg/kg), ULNCs or Dexa (5mg/kg) 4 h before challenge with LPS. Analyses were performed 24 h after LPS stimulation.

Notes: Data are expressed as the mean ± SEM (n=5–7). +++P<0.001 compared with the saline group; **P<0.01 and ***P<0.001 compared to the LPS group.

Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; Dexa, dexamethasone; LPS, lipopolysaccharide.

Figure 5 Effect of treatment with RSV or RSV-LNCs on lung tissue production of IL-6 (A), KC (B), MIP-1α (C), MIP-2 (D), MCP-1 (E) and RANTES (F). A/J mice orally pretreated with RSV, RSV-LNCs (2.5–10 mg/kg), ULNCs or Dexa (5mg/kg) 4 h before challenge with LPS. Analyses were performed 24 h after LPS stimulation.Notes: Data are expressed as the mean ± SEM (n=5–7). +++P<0.001 compared with the saline group; **P<0.01 and ***P<0.001 compared to the LPS group.Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; Dexa, dexamethasone; LPS, lipopolysaccharide.

Figure 6 Effect of treatment with RSV or RSV-LNCs on airway hyperresponsiveness. A/J mice orally pretreated with RSV, RSV-LNCs (5 mg/kg) or ULNCs 4 h before challenge with LPS. Analyses were performed 24 h after LPS stimulation.

Notes: Data are expressed as the mean ± SEM (n=5–7). ++P<0.01 and +++P<0.001 compared with the saline group and *** P<0.001 compared to the LPS group.

Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; LPS, lipopolysaccharide.

Figure 6 Effect of treatment with RSV or RSV-LNCs on airway hyperresponsiveness. A/J mice orally pretreated with RSV, RSV-LNCs (5 mg/kg) or ULNCs 4 h before challenge with LPS. Analyses were performed 24 h after LPS stimulation.Notes: Data are expressed as the mean ± SEM (n=5–7). ++P<0.01 and +++P<0.001 compared with the saline group and *** P<0.001 compared to the LPS group.Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; LPS, lipopolysaccharide.

Figure 7 Effect of treatment with RSV or RSV-LNCs on lung MDA levels (A) and SOD activity (B). A/J mice orally pretreated with RSV or RSV-LNCs (5 mg/kg) 4 h before challenge with LPS. Analyses were performed 24 h after LPS stimulation.

Notes: Data are expressed as the mean ± SEM (n=5–7). +P<0.05 compared with the saline group and * P<0.05 compared to the LPS group.

Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; MDA, malondialdehyde; SOD, superoxide dismutase; LPS, lipopolysaccharide.

Figure 7 Effect of treatment with RSV or RSV-LNCs on lung MDA levels (A) and SOD activity (B). A/J mice orally pretreated with RSV or RSV-LNCs (5 mg/kg) 4 h before challenge with LPS. Analyses were performed 24 h after LPS stimulation.Notes: Data are expressed as the mean ± SEM (n=5–7). +P<0.05 compared with the saline group and * P<0.05 compared to the LPS group.Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; MDA, malondialdehyde; SOD, superoxide dismutase; LPS, lipopolysaccharide.

Figure 8 Western blot analysis of AKT (A) and ERK (B) phosphorylation in A/J mice orally pretreated with RSV or RSV-LNCs (5 mg/kg) 4 h before challenge with LPS. (C) and (D) demonstrate the densitometric values obtained for the phosphorylated and total protein of AKT and ERK, respectively. Treatments were normalized to their respective controls that were not exposed to LPS (control bar; 100%). Analyses were performed 24 h after LPS stimulation. Data are expressed as a ratio of the normalized percentages of phosphorylated and total protein.

Notes: Bars represent the mean ± SEM (n=5–7). +P<0.05 and ++P<0.01 compared with the saline group, *P<0.05 compared to the LPS group.

Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; LPS, lipopolysaccharide.

Figure 8 Western blot analysis of AKT (A) and ERK (B) phosphorylation in A/J mice orally pretreated with RSV or RSV-LNCs (5 mg/kg) 4 h before challenge with LPS. (C) and (D) demonstrate the densitometric values obtained for the phosphorylated and total protein of AKT and ERK, respectively. Treatments were normalized to their respective controls that were not exposed to LPS (control bar; 100%). Analyses were performed 24 h after LPS stimulation. Data are expressed as a ratio of the normalized percentages of phosphorylated and total protein.Notes: Bars represent the mean ± SEM (n=5–7). +P<0.05 and ++P<0.01 compared with the saline group, *P<0.05 compared to the LPS group.Abbreviations: RSV, resveratrol; RSV-LNCs, resveratrol-loaded lipid-core nanocapsules; LPS, lipopolysaccharide.