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Methyl Protodioscin from the Roots of Asparagus cochinchinensis Attenuates Airway Inflammation by Inhibiting Cytokine Production.

Lee JH, Lim HJ, Lee CW, Son KH, Son JK, Lee SK, Kim HP - Evid Based Complement Alternat Med (2015)

Bottom Line: This downregulating effect of proinflammatory cytokine production was found to be mediated, at least in part, via inhibition of c-Jun N-terminal kinase (JNK) and c-Jun activation pathway.When examined on an in vivo model of airway inflammation in mice, lipopolysaccharide- (LPS-) induced acute lung injury, ACE, and MP significantly inhibited cell infiltration in the bronchoalveolar lavage fluid by the oral treatment at doses of 100-400 mg/kg and 30-60 mg/kg, respectively.All of these findings provide scientific evidence supporting the role of A. cochinchinensis as a herbal remedy in treating airway inflammation and also suggest a therapeutic value of MP on airway inflammatory disorders.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.

ABSTRACT
The present study was designed to find pharmacologically active compound against airway inflammation from the roots of Asparagus cochinchinensis. The 70% ethanol extract of the roots of A. cochinchinensis (ACE) was found to inhibit IL-6 production from IL-1β-treated lung epithelial cells (A549) and the major constituent, methyl protodioscin (MP), also strongly inhibited the production of IL-6, IL-8, and tumor necrosis factor- (TNF-) α from A549 cells at 10-100 μM. This downregulating effect of proinflammatory cytokine production was found to be mediated, at least in part, via inhibition of c-Jun N-terminal kinase (JNK) and c-Jun activation pathway. When examined on an in vivo model of airway inflammation in mice, lipopolysaccharide- (LPS-) induced acute lung injury, ACE, and MP significantly inhibited cell infiltration in the bronchoalveolar lavage fluid by the oral treatment at doses of 100-400 mg/kg and 30-60 mg/kg, respectively. MP also inhibited the production of proinflammatory cytokines such as IL-6, TNF-α, and IL-1β in lung tissue. All of these findings provide scientific evidence supporting the role of A. cochinchinensis as a herbal remedy in treating airway inflammation and also suggest a therapeutic value of MP on airway inflammatory disorders.

No MeSH data available.


Related in: MedlinePlus

Cellular mechanisms of inhibition of IL-6 production by Asparagus radix (ACE) and methyl protodioscin (MP) in A549 cells. (a) Time course study of MAPK activation. (b) Effects of ACE and MP on MAPK activation. (c) Effects of ACE and MP on the activation of transcription factors. (d) Effects of SP600125 (JNK inhibitor) on IL-6 production and signal transduction molecules. The IL-6 concentration of the IL-1β-treated group was 1.0 ± 0.15 ng/mL while the baseline level was 0.0 ± 0.0 ng/mL. No cytotoxic action of SP600125 was observed at the concentrations examined by MTT assay. All blots are the results of Western blotting analysis. One representative result from three separate experiments in blotting studies was represented here. +P < 0.1, ∗P < 0.05, and ∗∗P < 0.01, significantly different from the IL-1β-treated group (n = 3).
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fig3: Cellular mechanisms of inhibition of IL-6 production by Asparagus radix (ACE) and methyl protodioscin (MP) in A549 cells. (a) Time course study of MAPK activation. (b) Effects of ACE and MP on MAPK activation. (c) Effects of ACE and MP on the activation of transcription factors. (d) Effects of SP600125 (JNK inhibitor) on IL-6 production and signal transduction molecules. The IL-6 concentration of the IL-1β-treated group was 1.0 ± 0.15 ng/mL while the baseline level was 0.0 ± 0.0 ng/mL. No cytotoxic action of SP600125 was observed at the concentrations examined by MTT assay. All blots are the results of Western blotting analysis. One representative result from three separate experiments in blotting studies was represented here. +P < 0.1, ∗P < 0.05, and ∗∗P < 0.01, significantly different from the IL-1β-treated group (n = 3).

Mentions: In order to elucidate the cellular inhibitory mechanisms of IL-6 production, the effects on MAPK activation and transcription factors were examined. For finding the effects on MAPK activation, the time course study was carried out and the activation time of 15 min was found to be appropriate (Figure 3(a)). Under this condition, ACE and MP clearly inhibited the activation of c-Jun N-terminal kinase (JNK) at 100–300 μg/mL and 50–100 μM, respectively, while the activation of p38 MAPK and extracellular signal-regulated kinase (ERK) was not significantly affected (Figure 3(b)). When the effects on transcription factors (NF-κB and AP-1) were examined, ACE and MP were revealed to strongly interrupt the activation of c-Jun whereas they did not significantly inhibit the activation of NF-κB and c-Fos (Figure 3(c)). These results indicate that ACE and MP may inhibit IL-6 production at least in part by blocking JNK/c-Jun activation pathway. In order to verify these results, the effects of JNK inhibitor were examined. As expected, SP600125 was found to inhibit IL-6 production in A549 cells and the same compound did inhibit c-Jun activation (Figure 3(d)). All these findings suggest that ACE and MP inhibit proinflammatory cytokine generation in lung epithelial cells and the cellular mechanism of these compounds is blocking JNK/c-Jun signaling pathway.


Methyl Protodioscin from the Roots of Asparagus cochinchinensis Attenuates Airway Inflammation by Inhibiting Cytokine Production.

Lee JH, Lim HJ, Lee CW, Son KH, Son JK, Lee SK, Kim HP - Evid Based Complement Alternat Med (2015)

Cellular mechanisms of inhibition of IL-6 production by Asparagus radix (ACE) and methyl protodioscin (MP) in A549 cells. (a) Time course study of MAPK activation. (b) Effects of ACE and MP on MAPK activation. (c) Effects of ACE and MP on the activation of transcription factors. (d) Effects of SP600125 (JNK inhibitor) on IL-6 production and signal transduction molecules. The IL-6 concentration of the IL-1β-treated group was 1.0 ± 0.15 ng/mL while the baseline level was 0.0 ± 0.0 ng/mL. No cytotoxic action of SP600125 was observed at the concentrations examined by MTT assay. All blots are the results of Western blotting analysis. One representative result from three separate experiments in blotting studies was represented here. +P < 0.1, ∗P < 0.05, and ∗∗P < 0.01, significantly different from the IL-1β-treated group (n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4562339&req=5

fig3: Cellular mechanisms of inhibition of IL-6 production by Asparagus radix (ACE) and methyl protodioscin (MP) in A549 cells. (a) Time course study of MAPK activation. (b) Effects of ACE and MP on MAPK activation. (c) Effects of ACE and MP on the activation of transcription factors. (d) Effects of SP600125 (JNK inhibitor) on IL-6 production and signal transduction molecules. The IL-6 concentration of the IL-1β-treated group was 1.0 ± 0.15 ng/mL while the baseline level was 0.0 ± 0.0 ng/mL. No cytotoxic action of SP600125 was observed at the concentrations examined by MTT assay. All blots are the results of Western blotting analysis. One representative result from three separate experiments in blotting studies was represented here. +P < 0.1, ∗P < 0.05, and ∗∗P < 0.01, significantly different from the IL-1β-treated group (n = 3).
Mentions: In order to elucidate the cellular inhibitory mechanisms of IL-6 production, the effects on MAPK activation and transcription factors were examined. For finding the effects on MAPK activation, the time course study was carried out and the activation time of 15 min was found to be appropriate (Figure 3(a)). Under this condition, ACE and MP clearly inhibited the activation of c-Jun N-terminal kinase (JNK) at 100–300 μg/mL and 50–100 μM, respectively, while the activation of p38 MAPK and extracellular signal-regulated kinase (ERK) was not significantly affected (Figure 3(b)). When the effects on transcription factors (NF-κB and AP-1) were examined, ACE and MP were revealed to strongly interrupt the activation of c-Jun whereas they did not significantly inhibit the activation of NF-κB and c-Fos (Figure 3(c)). These results indicate that ACE and MP may inhibit IL-6 production at least in part by blocking JNK/c-Jun activation pathway. In order to verify these results, the effects of JNK inhibitor were examined. As expected, SP600125 was found to inhibit IL-6 production in A549 cells and the same compound did inhibit c-Jun activation (Figure 3(d)). All these findings suggest that ACE and MP inhibit proinflammatory cytokine generation in lung epithelial cells and the cellular mechanism of these compounds is blocking JNK/c-Jun signaling pathway.

Bottom Line: This downregulating effect of proinflammatory cytokine production was found to be mediated, at least in part, via inhibition of c-Jun N-terminal kinase (JNK) and c-Jun activation pathway.When examined on an in vivo model of airway inflammation in mice, lipopolysaccharide- (LPS-) induced acute lung injury, ACE, and MP significantly inhibited cell infiltration in the bronchoalveolar lavage fluid by the oral treatment at doses of 100-400 mg/kg and 30-60 mg/kg, respectively.All of these findings provide scientific evidence supporting the role of A. cochinchinensis as a herbal remedy in treating airway inflammation and also suggest a therapeutic value of MP on airway inflammatory disorders.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.

ABSTRACT
The present study was designed to find pharmacologically active compound against airway inflammation from the roots of Asparagus cochinchinensis. The 70% ethanol extract of the roots of A. cochinchinensis (ACE) was found to inhibit IL-6 production from IL-1β-treated lung epithelial cells (A549) and the major constituent, methyl protodioscin (MP), also strongly inhibited the production of IL-6, IL-8, and tumor necrosis factor- (TNF-) α from A549 cells at 10-100 μM. This downregulating effect of proinflammatory cytokine production was found to be mediated, at least in part, via inhibition of c-Jun N-terminal kinase (JNK) and c-Jun activation pathway. When examined on an in vivo model of airway inflammation in mice, lipopolysaccharide- (LPS-) induced acute lung injury, ACE, and MP significantly inhibited cell infiltration in the bronchoalveolar lavage fluid by the oral treatment at doses of 100-400 mg/kg and 30-60 mg/kg, respectively. MP also inhibited the production of proinflammatory cytokines such as IL-6, TNF-α, and IL-1β in lung tissue. All of these findings provide scientific evidence supporting the role of A. cochinchinensis as a herbal remedy in treating airway inflammation and also suggest a therapeutic value of MP on airway inflammatory disorders.

No MeSH data available.


Related in: MedlinePlus