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n-Butanol extract from Folium isatidis inhibits lipopolysaccharide-induced inflammatory cytokine production in macrophages and protects mice against lipopolysaccharide-induced endotoxic shock.

Jiang L, Lu Y, Jin J, Dong L, Xu F, Chen S, Wang Z, Liang G, Shan X - Drug Des Devel Ther (2015)

Bottom Line: Studies have shown beneficial pharmacological effects for Folium isatidis.The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components.Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.

ABSTRACT
Sepsis, which is caused by severe infection, is an important cause of mortality, but effective clinical treatment against sepsis is extremely limited. As the main component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) plays a major role in inflammatory responses. Studies have shown beneficial pharmacological effects for Folium isatidis. The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components. Our study showed that pretreatment with n-butanol extract from Folium isatidis not only significantly inhibited LPS-induced tumor necrosis factor-α and interleukin-6 production but also markedly and dose dependently enhanced the recruitment of MyD88, the phosphorylation of extracellular signal-regulated kinase, and the degradation of IκB-α. Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock. Eight main active compounds were identified, including organic acids, glycoside, indolinones, and flavonoids. These findings provide a perspective on the respiratory protection offered by n-butanol extract from Folium isatidis in LPS-induced sepsis and outline a novel therapeutic strategy for the treatment of sepsis.

No MeSH data available.


Related in: MedlinePlus

The n-butanol extract from Folium isatidis inhibited LPS-induced MyD88 recruitment, IκB-α degradation, and ERK phosphorylation.Notes: Following pretreatment with vehicle control (DMSO) or a different concentration of the n-butanol extract for 2 hours, MPMs were incubated with LPS (0.5 µg/mL) for 30 minutes. The protein levels of MyD88 (A) and IκB-α (B) were examined using western blotting and were normalized to GAPDH. The protein levels of p-ERK, p-p38, and p-JNK (C) were examined using western blotting and were normalized to ERK, p38, and JNK. Statistical significance compared with the LPS group is indicated, *P<0.05, **P<0.01.Abbreviations: ERK, extracellular signal-regulated kinase; JNK, c-jun N-terminal kinase; LPS, lipopolysaccharide; MPM, mouse peritoneal macrophage.
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f3-dddt-9-5601: The n-butanol extract from Folium isatidis inhibited LPS-induced MyD88 recruitment, IκB-α degradation, and ERK phosphorylation.Notes: Following pretreatment with vehicle control (DMSO) or a different concentration of the n-butanol extract for 2 hours, MPMs were incubated with LPS (0.5 µg/mL) for 30 minutes. The protein levels of MyD88 (A) and IκB-α (B) were examined using western blotting and were normalized to GAPDH. The protein levels of p-ERK, p-p38, and p-JNK (C) were examined using western blotting and were normalized to ERK, p38, and JNK. Statistical significance compared with the LPS group is indicated, *P<0.05, **P<0.01.Abbreviations: ERK, extracellular signal-regulated kinase; JNK, c-jun N-terminal kinase; LPS, lipopolysaccharide; MPM, mouse peritoneal macrophage.

Mentions: LPS is known to activate the toll-like receptor-4 (TLR-4)/MyD88 signaling pathway; thus, the effect of the n-butanol extract from Folium isatidis on LPS-induced MyD88 recruitment was evaluated. The results (Figure 3A) showed that pretreatment with the extract significantly reduced LPS-induced MyD88 recruitment. NF-κB has been shown to be a pivotal factor for the activation of pro-inflammatory molecules, and the degradation of IκB-α constitutes the first step in NF-κB activation. To investigate whether the effect of the n-butanol extract from Folium isatidis is attributable to suppression of this pathway, we evaluated the total IκB-α in total cell protein extracts. As illustrated in Figure 3B, LPS exposure for 1 hour resulted in a rapid loss of IκB-α in MPMs. Conversely, increased IκB-α was observed in cells pretreated with the n-butanol extract from Folium isatidis.


n-Butanol extract from Folium isatidis inhibits lipopolysaccharide-induced inflammatory cytokine production in macrophages and protects mice against lipopolysaccharide-induced endotoxic shock.

Jiang L, Lu Y, Jin J, Dong L, Xu F, Chen S, Wang Z, Liang G, Shan X - Drug Des Devel Ther (2015)

The n-butanol extract from Folium isatidis inhibited LPS-induced MyD88 recruitment, IκB-α degradation, and ERK phosphorylation.Notes: Following pretreatment with vehicle control (DMSO) or a different concentration of the n-butanol extract for 2 hours, MPMs were incubated with LPS (0.5 µg/mL) for 30 minutes. The protein levels of MyD88 (A) and IκB-α (B) were examined using western blotting and were normalized to GAPDH. The protein levels of p-ERK, p-p38, and p-JNK (C) were examined using western blotting and were normalized to ERK, p38, and JNK. Statistical significance compared with the LPS group is indicated, *P<0.05, **P<0.01.Abbreviations: ERK, extracellular signal-regulated kinase; JNK, c-jun N-terminal kinase; LPS, lipopolysaccharide; MPM, mouse peritoneal macrophage.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4608600&req=5

f3-dddt-9-5601: The n-butanol extract from Folium isatidis inhibited LPS-induced MyD88 recruitment, IκB-α degradation, and ERK phosphorylation.Notes: Following pretreatment with vehicle control (DMSO) or a different concentration of the n-butanol extract for 2 hours, MPMs were incubated with LPS (0.5 µg/mL) for 30 minutes. The protein levels of MyD88 (A) and IκB-α (B) were examined using western blotting and were normalized to GAPDH. The protein levels of p-ERK, p-p38, and p-JNK (C) were examined using western blotting and were normalized to ERK, p38, and JNK. Statistical significance compared with the LPS group is indicated, *P<0.05, **P<0.01.Abbreviations: ERK, extracellular signal-regulated kinase; JNK, c-jun N-terminal kinase; LPS, lipopolysaccharide; MPM, mouse peritoneal macrophage.
Mentions: LPS is known to activate the toll-like receptor-4 (TLR-4)/MyD88 signaling pathway; thus, the effect of the n-butanol extract from Folium isatidis on LPS-induced MyD88 recruitment was evaluated. The results (Figure 3A) showed that pretreatment with the extract significantly reduced LPS-induced MyD88 recruitment. NF-κB has been shown to be a pivotal factor for the activation of pro-inflammatory molecules, and the degradation of IκB-α constitutes the first step in NF-κB activation. To investigate whether the effect of the n-butanol extract from Folium isatidis is attributable to suppression of this pathway, we evaluated the total IκB-α in total cell protein extracts. As illustrated in Figure 3B, LPS exposure for 1 hour resulted in a rapid loss of IκB-α in MPMs. Conversely, increased IκB-α was observed in cells pretreated with the n-butanol extract from Folium isatidis.

Bottom Line: Studies have shown beneficial pharmacological effects for Folium isatidis.The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components.Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.

ABSTRACT
Sepsis, which is caused by severe infection, is an important cause of mortality, but effective clinical treatment against sepsis is extremely limited. As the main component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) plays a major role in inflammatory responses. Studies have shown beneficial pharmacological effects for Folium isatidis. The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components. Our study showed that pretreatment with n-butanol extract from Folium isatidis not only significantly inhibited LPS-induced tumor necrosis factor-α and interleukin-6 production but also markedly and dose dependently enhanced the recruitment of MyD88, the phosphorylation of extracellular signal-regulated kinase, and the degradation of IκB-α. Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock. Eight main active compounds were identified, including organic acids, glycoside, indolinones, and flavonoids. These findings provide a perspective on the respiratory protection offered by n-butanol extract from Folium isatidis in LPS-induced sepsis and outline a novel therapeutic strategy for the treatment of sepsis.

No MeSH data available.


Related in: MedlinePlus