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3-(3-pyridylmethylidene)-2-indolinone reduces the severity of colonic injury in a murine model of experimental colitis.

Wang KP, Zhang C, Zhang SG, Liu ED, Dong L, Kong XZ, Cao P, Hu CP, Zhao K, Zhan YQ, Dong XM, Ge CH, Yu M, Chen H, Wang L, Yang XM, Li CY - Oxid Med Cell Longev (2015)

Bottom Line: However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes.Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals.The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.

ABSTRACT
Nrf2 is the key transcription factor regulating the antioxidant response which is crucial for cytoprotection against extracellular stresses. Numerous in vivo studies indicate that Nrf2 plays a protective role in anti-inflammatory response. 3-(3-Pyridylmethylidene)-2-indolinone (PMID) is a synthesized derivative of 2-indolinone compounds. Our previous study suggested that PMID induces the activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated cell death. However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes. In the present study we determined if PMID treatment protects mice from dextran sodium sulphate- (DSS-) induced colitis. The result suggests that treatment with PMID prior to colitis induction significantly reduced body weight loss, shortened colon length, and decreased disease activity index compared to control mice. Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals. The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation. The expression levels of Nrf2-dependent genes such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However, PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice. These data indicate that PMID pretreatment in mice confers protection against DSS-induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in anti-inflammatory response.

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Related in: MedlinePlus

PMID pretreatment attenuated the levels of proinflammatory markers in serum of DSS-induced ICR mice. Following treatment with the indicated doses of PMID per os for 7 days, colitis was induced by DSS (3%) via drinking water for 7 days. Then the serum was collected and the protein levels of TNFα, IL-6, IFN-γ, and MCP-1 were analyzed using CBA just as “Section 2” described. Results represented mean ± SD. n = 10/group. The statistical difference between the samples was demonstrated as *P ≤ 0.05 or **P ≤ 0.01.
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fig2: PMID pretreatment attenuated the levels of proinflammatory markers in serum of DSS-induced ICR mice. Following treatment with the indicated doses of PMID per os for 7 days, colitis was induced by DSS (3%) via drinking water for 7 days. Then the serum was collected and the protein levels of TNFα, IL-6, IFN-γ, and MCP-1 were analyzed using CBA just as “Section 2” described. Results represented mean ± SD. n = 10/group. The statistical difference between the samples was demonstrated as *P ≤ 0.05 or **P ≤ 0.01.

Mentions: The levels of various proinflammatory biomarkers, IL-6, TNFα, MCP-1, and IFN-γ, in serum of DSS-induced ICR mice were analyzed using ELISA. As shown in Figure 2, DSS treatment led to increased serum levels of IL-6, TNFα, MCP-1, and IFN-γ, and PMID pretreatment significantly lessens the levels of these biomarkers.


3-(3-pyridylmethylidene)-2-indolinone reduces the severity of colonic injury in a murine model of experimental colitis.

Wang KP, Zhang C, Zhang SG, Liu ED, Dong L, Kong XZ, Cao P, Hu CP, Zhao K, Zhan YQ, Dong XM, Ge CH, Yu M, Chen H, Wang L, Yang XM, Li CY - Oxid Med Cell Longev (2015)

PMID pretreatment attenuated the levels of proinflammatory markers in serum of DSS-induced ICR mice. Following treatment with the indicated doses of PMID per os for 7 days, colitis was induced by DSS (3%) via drinking water for 7 days. Then the serum was collected and the protein levels of TNFα, IL-6, IFN-γ, and MCP-1 were analyzed using CBA just as “Section 2” described. Results represented mean ± SD. n = 10/group. The statistical difference between the samples was demonstrated as *P ≤ 0.05 or **P ≤ 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4385690&req=5

fig2: PMID pretreatment attenuated the levels of proinflammatory markers in serum of DSS-induced ICR mice. Following treatment with the indicated doses of PMID per os for 7 days, colitis was induced by DSS (3%) via drinking water for 7 days. Then the serum was collected and the protein levels of TNFα, IL-6, IFN-γ, and MCP-1 were analyzed using CBA just as “Section 2” described. Results represented mean ± SD. n = 10/group. The statistical difference between the samples was demonstrated as *P ≤ 0.05 or **P ≤ 0.01.
Mentions: The levels of various proinflammatory biomarkers, IL-6, TNFα, MCP-1, and IFN-γ, in serum of DSS-induced ICR mice were analyzed using ELISA. As shown in Figure 2, DSS treatment led to increased serum levels of IL-6, TNFα, MCP-1, and IFN-γ, and PMID pretreatment significantly lessens the levels of these biomarkers.

Bottom Line: However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes.Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals.The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.

ABSTRACT
Nrf2 is the key transcription factor regulating the antioxidant response which is crucial for cytoprotection against extracellular stresses. Numerous in vivo studies indicate that Nrf2 plays a protective role in anti-inflammatory response. 3-(3-Pyridylmethylidene)-2-indolinone (PMID) is a synthesized derivative of 2-indolinone compounds. Our previous study suggested that PMID induces the activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated cell death. However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes. In the present study we determined if PMID treatment protects mice from dextran sodium sulphate- (DSS-) induced colitis. The result suggests that treatment with PMID prior to colitis induction significantly reduced body weight loss, shortened colon length, and decreased disease activity index compared to control mice. Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals. The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation. The expression levels of Nrf2-dependent genes such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However, PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice. These data indicate that PMID pretreatment in mice confers protection against DSS-induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in anti-inflammatory response.

Show MeSH
Related in: MedlinePlus