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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

Neutralizing effects of EX527 on the protecting effects of Rsv on LPS stimulated NR8383 cells. (a) Expression of SIRT1 was evaluated by western blot and normalized to the expression level of β-actin. LPS stimulation inhibited the expression of SIRT1 compared with that of control, ∗P < 0.05 versus control, while Rsv treatment significantly reversed the inhibiting effects, ∗∗P < 0.05 versus ∗P; on the contrary, EX527 and Rsv cotreatment counterbalanced the enhancing effects of Rsv on the expression of SIRT1, ∗∗∗P < 0.05 versus ∗∗P. (b–d) Contents of TNF-α, IL-6, and IL-1β were evaluated by ELISA. LPS stimulation increased the generation of TNF-α, IL-6, and IL-1β in NR8383 cells compared with that of control, ∗P < 0.05 versus control, while Rsv treatment significantly inhibited the formation of those cytokines in NR8383 cells when stimulated by LPS, ∗∗P < 0.05 versus ∗P; astonishingly, EX527 and Rsv cotreatment neutralized the inhibiting effects of Rsv on the generation of TNF-α, IL-6, and IL-1β. ∗∗∗P < 0.05 versus ∗∗P.
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fig8: Neutralizing effects of EX527 on the protecting effects of Rsv on LPS stimulated NR8383 cells. (a) Expression of SIRT1 was evaluated by western blot and normalized to the expression level of β-actin. LPS stimulation inhibited the expression of SIRT1 compared with that of control, ∗P < 0.05 versus control, while Rsv treatment significantly reversed the inhibiting effects, ∗∗P < 0.05 versus ∗P; on the contrary, EX527 and Rsv cotreatment counterbalanced the enhancing effects of Rsv on the expression of SIRT1, ∗∗∗P < 0.05 versus ∗∗P. (b–d) Contents of TNF-α, IL-6, and IL-1β were evaluated by ELISA. LPS stimulation increased the generation of TNF-α, IL-6, and IL-1β in NR8383 cells compared with that of control, ∗P < 0.05 versus control, while Rsv treatment significantly inhibited the formation of those cytokines in NR8383 cells when stimulated by LPS, ∗∗P < 0.05 versus ∗P; astonishingly, EX527 and Rsv cotreatment neutralized the inhibiting effects of Rsv on the generation of TNF-α, IL-6, and IL-1β. ∗∗∗P < 0.05 versus ∗∗P.

Mentions: NR8383 cells were exposed to normal culture, LPS, LPS + EX527 + Rsv, and LPS + Rsv for 12 h, and then the expression of SIRT1 and generation of cytokines were evaluated by western blot and ELISA method, respectively. The results (Figure 8(a)) showed that SIRT1 expression was dramatically suppressed by LPS compared with that of control, while Rsv treatment effectively reversed the decrease of SIRT1 expression. Astonishingly, cotreatment of EX527 and Rsv counterbalanced the elevating effects of Rsv on the expression of SIRT1.


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)

Neutralizing effects of EX527 on the protecting effects of Rsv on LPS stimulated NR8383 cells. (a) Expression of SIRT1 was evaluated by western blot and normalized to the expression level of β-actin. LPS stimulation inhibited the expression of SIRT1 compared with that of control, ∗P < 0.05 versus control, while Rsv treatment significantly reversed the inhibiting effects, ∗∗P < 0.05 versus ∗P; on the contrary, EX527 and Rsv cotreatment counterbalanced the enhancing effects of Rsv on the expression of SIRT1, ∗∗∗P < 0.05 versus ∗∗P. (b–d) Contents of TNF-α, IL-6, and IL-1β were evaluated by ELISA. LPS stimulation increased the generation of TNF-α, IL-6, and IL-1β in NR8383 cells compared with that of control, ∗P < 0.05 versus control, while Rsv treatment significantly inhibited the formation of those cytokines in NR8383 cells when stimulated by LPS, ∗∗P < 0.05 versus ∗P; astonishingly, EX527 and Rsv cotreatment neutralized the inhibiting effects of Rsv on the generation of TNF-α, IL-6, and IL-1β. ∗∗∗P < 0.05 versus ∗∗P.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663353&req=5

fig8: Neutralizing effects of EX527 on the protecting effects of Rsv on LPS stimulated NR8383 cells. (a) Expression of SIRT1 was evaluated by western blot and normalized to the expression level of β-actin. LPS stimulation inhibited the expression of SIRT1 compared with that of control, ∗P < 0.05 versus control, while Rsv treatment significantly reversed the inhibiting effects, ∗∗P < 0.05 versus ∗P; on the contrary, EX527 and Rsv cotreatment counterbalanced the enhancing effects of Rsv on the expression of SIRT1, ∗∗∗P < 0.05 versus ∗∗P. (b–d) Contents of TNF-α, IL-6, and IL-1β were evaluated by ELISA. LPS stimulation increased the generation of TNF-α, IL-6, and IL-1β in NR8383 cells compared with that of control, ∗P < 0.05 versus control, while Rsv treatment significantly inhibited the formation of those cytokines in NR8383 cells when stimulated by LPS, ∗∗P < 0.05 versus ∗P; astonishingly, EX527 and Rsv cotreatment neutralized the inhibiting effects of Rsv on the generation of TNF-α, IL-6, and IL-1β. ∗∗∗P < 0.05 versus ∗∗P.
Mentions: NR8383 cells were exposed to normal culture, LPS, LPS + EX527 + Rsv, and LPS + Rsv for 12 h, and then the expression of SIRT1 and generation of cytokines were evaluated by western blot and ELISA method, respectively. The results (Figure 8(a)) showed that SIRT1 expression was dramatically suppressed by LPS compared with that of control, while Rsv treatment effectively reversed the decrease of SIRT1 expression. Astonishingly, cotreatment of EX527 and Rsv counterbalanced the elevating effects of Rsv on the expression of SIRT1.

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