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3,5,4'-Tri-O-acetylresveratrol Attenuates Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome via MAPK/SIRT1 Pathway.

Ma L, Zhao Y, Wang R, Chen T, Li W, Nan Y, Liu X, Jin F - Mediators Inflamm. (2015)

Bottom Line: The results showed that AC-Rsv significantly reduced the mortality of mice stimulated with LPS.What was more, AC-Rsv and Rsv treatment reduced the secretion of TNF-α, IL-6, and IL-1β in lungs and NR8383 cells, respectively.More importantly, in vivo results have also demonstrated that the protecting effects of Rsv on LPS-induced inflammation would be neutralized when SIRT1 was in-hibited by EX527.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.

ABSTRACT
The aim of the present research was to investigate the protecting effects of 3,5,4'-tri-O-acetylresveratrol (AC-Rsv) on LPS-induced acute respiratory distress syndrome (ARDS). Lung injuries have been evaluated by histological examination, wet-to-dry weight ratios, and cell count and protein content in bronchoalveolar lavage fluid. Inflammation was assessed by MPO activities and cytokine secretion in lungs and cells. The results showed that AC-Rsv significantly reduced the mortality of mice stimulated with LPS. Pretreatment of AC-Rsv attenuated LPS-induced histological changes, alleviated pulmonary edema, reduced blood vascular leakage, and inhibited the MPO activities in lungs. What was more, AC-Rsv and Rsv treatment reduced the secretion of TNF-α, IL-6, and IL-1β in lungs and NR8383 cells, respectively. Further exploration revealed that AC-Rsv and Rsv treatment relieved LPS-induced inhibition on SIRT1 expression and restrained the activation effects of LPS on MAPKs and NF-κB activation both in vitro and in vivo. More importantly, in vivo results have also demonstrated that the protecting effects of Rsv on LPS-induced inflammation would be neutralized when SIRT1 was in-hibited by EX527. Taken together, these results indicated that AC-Rsv protected lung tissue against LPS-induced ARDS by attenuating inflammation via p38 MAPK/SIRT1 pathway.

No MeSH data available.


Related in: MedlinePlus

Protecting effects of AC-Rsv on the LPS exposure induced lung injuries. (a–d) Morphological changes were evaluated 12 h after LPS exposure by H&E staining. LPS stimulation group (b) showed increasing lung edema, alveolar hemorrhage, neutrophil infiltration, and destroyed epithelial/endothelial cell structures compared with those of control (a), while significant improvement was observed in samples from the LPS + AC-Rsv group (c). AC-Rsv treatment alone barely affected the structure of lungs (d). (e) Wet-to-dry ratios of lung samples; data are expressed as mean ± S.D. n = 8. LPS injection significantly increased the W/D ratios of lung samples compared with that of control, ∗P < 0.05 versus control, while pretreatment of AC-Rsv dramatically decreased the W/D ratios of lung samples stimulated by LPS, ∗∗P < 0.05 versus ∗P. ((f) and (g)) Protein concentration (a) and cell count (b) in BALF. Data are expressed as mean ± S.D. n = 8. LPS exposure significantly increased cell and protein content in BALF compared with those of control, ∗P < 0.05 versus control; and pretreatment of AC-Rsv decreased the cell and protein content in BALF from lung stimulated by LPS, ∗∗P < 0.05 versus ∗P.
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fig3: Protecting effects of AC-Rsv on the LPS exposure induced lung injuries. (a–d) Morphological changes were evaluated 12 h after LPS exposure by H&E staining. LPS stimulation group (b) showed increasing lung edema, alveolar hemorrhage, neutrophil infiltration, and destroyed epithelial/endothelial cell structures compared with those of control (a), while significant improvement was observed in samples from the LPS + AC-Rsv group (c). AC-Rsv treatment alone barely affected the structure of lungs (d). (e) Wet-to-dry ratios of lung samples; data are expressed as mean ± S.D. n = 8. LPS injection significantly increased the W/D ratios of lung samples compared with that of control, ∗P < 0.05 versus control, while pretreatment of AC-Rsv dramatically decreased the W/D ratios of lung samples stimulated by LPS, ∗∗P < 0.05 versus ∗P. ((f) and (g)) Protein concentration (a) and cell count (b) in BALF. Data are expressed as mean ± S.D. n = 8. LPS exposure significantly increased cell and protein content in BALF compared with those of control, ∗P < 0.05 versus control; and pretreatment of AC-Rsv decreased the cell and protein content in BALF from lung stimulated by LPS, ∗∗P < 0.05 versus ∗P.

Mentions: Histopathological results showed that lung samples from control (Figure 3(a)) and AC-Rsv (Figure 3(d)) groups exhibited a normal structure with clear pulmonary alveoli, while LPS exposure led to infiltration of inflammatory cells, damage of alveoli, thickened alveolar wall, and formation of hyaline membranes (Figure 3(b)). However, LPS-induced changes in lung structure have been dramatically attenuated by AC-Rsv pretreatment (Figure 3(c)).


3,5,4'-Tri-O-acetylresveratrol Attenuates Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome via MAPK/SIRT1 Pathway.

Ma L, Zhao Y, Wang R, Chen T, Li W, Nan Y, Liu X, Jin F - Mediators Inflamm. (2015)

Protecting effects of AC-Rsv on the LPS exposure induced lung injuries. (a–d) Morphological changes were evaluated 12 h after LPS exposure by H&E staining. LPS stimulation group (b) showed increasing lung edema, alveolar hemorrhage, neutrophil infiltration, and destroyed epithelial/endothelial cell structures compared with those of control (a), while significant improvement was observed in samples from the LPS + AC-Rsv group (c). AC-Rsv treatment alone barely affected the structure of lungs (d). (e) Wet-to-dry ratios of lung samples; data are expressed as mean ± S.D. n = 8. LPS injection significantly increased the W/D ratios of lung samples compared with that of control, ∗P < 0.05 versus control, while pretreatment of AC-Rsv dramatically decreased the W/D ratios of lung samples stimulated by LPS, ∗∗P < 0.05 versus ∗P. ((f) and (g)) Protein concentration (a) and cell count (b) in BALF. Data are expressed as mean ± S.D. n = 8. LPS exposure significantly increased cell and protein content in BALF compared with those of control, ∗P < 0.05 versus control; and pretreatment of AC-Rsv decreased the cell and protein content in BALF from lung stimulated by LPS, ∗∗P < 0.05 versus ∗P.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Protecting effects of AC-Rsv on the LPS exposure induced lung injuries. (a–d) Morphological changes were evaluated 12 h after LPS exposure by H&E staining. LPS stimulation group (b) showed increasing lung edema, alveolar hemorrhage, neutrophil infiltration, and destroyed epithelial/endothelial cell structures compared with those of control (a), while significant improvement was observed in samples from the LPS + AC-Rsv group (c). AC-Rsv treatment alone barely affected the structure of lungs (d). (e) Wet-to-dry ratios of lung samples; data are expressed as mean ± S.D. n = 8. LPS injection significantly increased the W/D ratios of lung samples compared with that of control, ∗P < 0.05 versus control, while pretreatment of AC-Rsv dramatically decreased the W/D ratios of lung samples stimulated by LPS, ∗∗P < 0.05 versus ∗P. ((f) and (g)) Protein concentration (a) and cell count (b) in BALF. Data are expressed as mean ± S.D. n = 8. LPS exposure significantly increased cell and protein content in BALF compared with those of control, ∗P < 0.05 versus control; and pretreatment of AC-Rsv decreased the cell and protein content in BALF from lung stimulated by LPS, ∗∗P < 0.05 versus ∗P.
Mentions: Histopathological results showed that lung samples from control (Figure 3(a)) and AC-Rsv (Figure 3(d)) groups exhibited a normal structure with clear pulmonary alveoli, while LPS exposure led to infiltration of inflammatory cells, damage of alveoli, thickened alveolar wall, and formation of hyaline membranes (Figure 3(b)). However, LPS-induced changes in lung structure have been dramatically attenuated by AC-Rsv pretreatment (Figure 3(c)).

Bottom Line: The results showed that AC-Rsv significantly reduced the mortality of mice stimulated with LPS.What was more, AC-Rsv and Rsv treatment reduced the secretion of TNF-α, IL-6, and IL-1β in lungs and NR8383 cells, respectively.More importantly, in vivo results have also demonstrated that the protecting effects of Rsv on LPS-induced inflammation would be neutralized when SIRT1 was in-hibited by EX527.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.

ABSTRACT
The aim of the present research was to investigate the protecting effects of 3,5,4'-tri-O-acetylresveratrol (AC-Rsv) on LPS-induced acute respiratory distress syndrome (ARDS). Lung injuries have been evaluated by histological examination, wet-to-dry weight ratios, and cell count and protein content in bronchoalveolar lavage fluid. Inflammation was assessed by MPO activities and cytokine secretion in lungs and cells. The results showed that AC-Rsv significantly reduced the mortality of mice stimulated with LPS. Pretreatment of AC-Rsv attenuated LPS-induced histological changes, alleviated pulmonary edema, reduced blood vascular leakage, and inhibited the MPO activities in lungs. What was more, AC-Rsv and Rsv treatment reduced the secretion of TNF-α, IL-6, and IL-1β in lungs and NR8383 cells, respectively. Further exploration revealed that AC-Rsv and Rsv treatment relieved LPS-induced inhibition on SIRT1 expression and restrained the activation effects of LPS on MAPKs and NF-κB activation both in vitro and in vivo. More importantly, in vivo results have also demonstrated that the protecting effects of Rsv on LPS-induced inflammation would be neutralized when SIRT1 was in-hibited by EX527. Taken together, these results indicated that AC-Rsv protected lung tissue against LPS-induced ARDS by attenuating inflammation via p38 MAPK/SIRT1 pathway.

No MeSH data available.


Related in: MedlinePlus