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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

The anti-inflammatory activity of three compounds identified in MBF-DE.LPS (1 μg/ml) stimulated RAW 264.7 macrophage cells were treated with ethyl linolenate (EL), linoleic acid (LA) or Hydroxyl methylfurfural (HM) at concentrations indicated. Quercetin (Q) was used as the positive control. NO production (a), cell viability (b), iNOS expression (c) and p65 nuclear translocation (d) were determined as described in material and methods. Data represent means ± SEM; **P < 0.01, ***P < 0.001 compared to LPS control.
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f5: The anti-inflammatory activity of three compounds identified in MBF-DE.LPS (1 μg/ml) stimulated RAW 264.7 macrophage cells were treated with ethyl linolenate (EL), linoleic acid (LA) or Hydroxyl methylfurfural (HM) at concentrations indicated. Quercetin (Q) was used as the positive control. NO production (a), cell viability (b), iNOS expression (c) and p65 nuclear translocation (d) were determined as described in material and methods. Data represent means ± SEM; **P < 0.01, ***P < 0.001 compared to LPS control.

Mentions: To identify the potential functional component in MBF-DE, seven pooled fractions via silica-gel column chromatography with cyclohexane-ethyl acetate gradient were collected, and their impact on NO production and cell viability were measured in LPS stimulated RAW264.7 cells. Fraction 2 (F2), F5, F6, and F7 had shown more profound bioactivity in inhibiting NO production than other fractions, without altering cell viability (Supplementary Fig. 2). Therefore, F2, F5 and F6 were further purified by HPLC to obtain compound 1 (C1), C2 and C3. By combining the GC-MS and NMR analysis, the structure of C1, C2 and C3 were elucidated as linoleic acid (LA), ethyl linolenate (EL) and hydroxyl methylfurfural (HM) (Supplementary Fig. 3), respectively. Further experimental results indicated that EL and LA rather than HM exhibited significant anti-inflammatory activity by inhibiting NO production, expression of iNOS and nuclear translocation of NF-κB p65 in LPS stimulated macrophage cells, respectively (Fig. 5). These results showed that LA and EA could inhibit LPS induced inflammatory responses.


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)

The anti-inflammatory activity of three compounds identified in MBF-DE.LPS (1 μg/ml) stimulated RAW 264.7 macrophage cells were treated with ethyl linolenate (EL), linoleic acid (LA) or Hydroxyl methylfurfural (HM) at concentrations indicated. Quercetin (Q) was used as the positive control. NO production (a), cell viability (b), iNOS expression (c) and p65 nuclear translocation (d) were determined as described in material and methods. Data represent means ± SEM; **P < 0.01, ***P < 0.001 compared to LPS control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: The anti-inflammatory activity of three compounds identified in MBF-DE.LPS (1 μg/ml) stimulated RAW 264.7 macrophage cells were treated with ethyl linolenate (EL), linoleic acid (LA) or Hydroxyl methylfurfural (HM) at concentrations indicated. Quercetin (Q) was used as the positive control. NO production (a), cell viability (b), iNOS expression (c) and p65 nuclear translocation (d) were determined as described in material and methods. Data represent means ± SEM; **P < 0.01, ***P < 0.001 compared to LPS control.
Mentions: To identify the potential functional component in MBF-DE, seven pooled fractions via silica-gel column chromatography with cyclohexane-ethyl acetate gradient were collected, and their impact on NO production and cell viability were measured in LPS stimulated RAW264.7 cells. Fraction 2 (F2), F5, F6, and F7 had shown more profound bioactivity in inhibiting NO production than other fractions, without altering cell viability (Supplementary Fig. 2). Therefore, F2, F5 and F6 were further purified by HPLC to obtain compound 1 (C1), C2 and C3. By combining the GC-MS and NMR analysis, the structure of C1, C2 and C3 were elucidated as linoleic acid (LA), ethyl linolenate (EL) and hydroxyl methylfurfural (HM) (Supplementary Fig. 3), respectively. Further experimental results indicated that EL and LA rather than HM exhibited significant anti-inflammatory activity by inhibiting NO production, expression of iNOS and nuclear translocation of NF-κB p65 in LPS stimulated macrophage cells, respectively (Fig. 5). These results showed that LA and EA could inhibit LPS induced inflammatory responses.

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