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Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice.

Qian Z, Wu Z, Huang L, Qiu H, Wang L, Li L, Yao L, Kang K, Qu J, Wu Y, Luo J, Liu JJ, Yang Y, Yang W, Gou D - Sci Rep (2015)

Bottom Line: In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6.In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage.In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group.

View Article: PubMed Central - PubMed

Affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.

ABSTRACT
Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2(-/-) mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials.

No MeSH data available.


Related in: MedlinePlus

MBF-DE blocks IκBα and MAPK pERK phosphorylation in LPS-induced RAW 264.7 macrophage cells.Cells were treated with MBF-DE (200 μg/ml) in absence or presence of LPS (1 μg/ml) for the indicated time. The protein level of phospho-IKKα/β, IKKα, IKKβ, phospho-IκBα, IκBα, phospho-p65, p65, phospho-p38 and phospho-JNK were detected by Western blotting analyses using their respective antibodies. β-actin or β-tubulin was used as internal loading control. Cell culture experiments were performed at least three times. Representative results of immunoblots (a,b) and their quantifications (c,d) to better view the difference between different treatment groups were shown. Data represent means ± SEM; **P < 0.01, ***P < 0.001 compared to LPS-induced control.
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f3: MBF-DE blocks IκBα and MAPK pERK phosphorylation in LPS-induced RAW 264.7 macrophage cells.Cells were treated with MBF-DE (200 μg/ml) in absence or presence of LPS (1 μg/ml) for the indicated time. The protein level of phospho-IKKα/β, IKKα, IKKβ, phospho-IκBα, IκBα, phospho-p65, p65, phospho-p38 and phospho-JNK were detected by Western blotting analyses using their respective antibodies. β-actin or β-tubulin was used as internal loading control. Cell culture experiments were performed at least three times. Representative results of immunoblots (a,b) and their quantifications (c,d) to better view the difference between different treatment groups were shown. Data represent means ± SEM; **P < 0.01, ***P < 0.001 compared to LPS-induced control.

Mentions: The above described finding prompted us to investigate whether MBF-DE treatment was involved in NF-κB and MAPK signaling pathways, which are known to regulate the transcription of proinflammatory genes282930. Compared to blank control, the phosphorylation status of IκBα/β, IκBα and p65 increased remarkably by LPS stimulation (Fig. 3a). However, the phosphorylation status of IκBα and p65 were significantly suppressed by the treatment with MBF-DE at 30 min of LPS stimulation (Fig. 3a,c). Concerning the MAPK pathway, a rapid decrease in phosphorylation of p38 but increase in extracellular signal-regulated kinase (ERK) was observed following LPS treatment (Fig. 3b,d). However, MBF-DE significantly blocked the change in phosphorylation status of pERK from 30 min of LPS stimulation, as compared with the same time point in the presence of LPS (Fig. 3b,d).


Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice.

Qian Z, Wu Z, Huang L, Qiu H, Wang L, Li L, Yao L, Kang K, Qu J, Wu Y, Luo J, Liu JJ, Yang Y, Yang W, Gou D - Sci Rep (2015)

MBF-DE blocks IκBα and MAPK pERK phosphorylation in LPS-induced RAW 264.7 macrophage cells.Cells were treated with MBF-DE (200 μg/ml) in absence or presence of LPS (1 μg/ml) for the indicated time. The protein level of phospho-IKKα/β, IKKα, IKKβ, phospho-IκBα, IκBα, phospho-p65, p65, phospho-p38 and phospho-JNK were detected by Western blotting analyses using their respective antibodies. β-actin or β-tubulin was used as internal loading control. Cell culture experiments were performed at least three times. Representative results of immunoblots (a,b) and their quantifications (c,d) to better view the difference between different treatment groups were shown. Data represent means ± SEM; **P < 0.01, ***P < 0.001 compared to LPS-induced control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663626&req=5

f3: MBF-DE blocks IκBα and MAPK pERK phosphorylation in LPS-induced RAW 264.7 macrophage cells.Cells were treated with MBF-DE (200 μg/ml) in absence or presence of LPS (1 μg/ml) for the indicated time. The protein level of phospho-IKKα/β, IKKα, IKKβ, phospho-IκBα, IκBα, phospho-p65, p65, phospho-p38 and phospho-JNK were detected by Western blotting analyses using their respective antibodies. β-actin or β-tubulin was used as internal loading control. Cell culture experiments were performed at least three times. Representative results of immunoblots (a,b) and their quantifications (c,d) to better view the difference between different treatment groups were shown. Data represent means ± SEM; **P < 0.01, ***P < 0.001 compared to LPS-induced control.
Mentions: The above described finding prompted us to investigate whether MBF-DE treatment was involved in NF-κB and MAPK signaling pathways, which are known to regulate the transcription of proinflammatory genes282930. Compared to blank control, the phosphorylation status of IκBα/β, IκBα and p65 increased remarkably by LPS stimulation (Fig. 3a). However, the phosphorylation status of IκBα and p65 were significantly suppressed by the treatment with MBF-DE at 30 min of LPS stimulation (Fig. 3a,c). Concerning the MAPK pathway, a rapid decrease in phosphorylation of p38 but increase in extracellular signal-regulated kinase (ERK) was observed following LPS treatment (Fig. 3b,d). However, MBF-DE significantly blocked the change in phosphorylation status of pERK from 30 min of LPS stimulation, as compared with the same time point in the presence of LPS (Fig. 3b,d).

Bottom Line: In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6.In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage.In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group.

View Article: PubMed Central - PubMed

Affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.

ABSTRACT
Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2(-/-) mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials.

No MeSH data available.


Related in: MedlinePlus