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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 dietary supplementation attenuates pathological symptoms of DSS induced acute colitis.BALB/c mice were fed with MBF (20 mg/kg) for 10 days prior to exposure to 3% DSS in drinking water. Daily weights were measured (n = 6–8/group) and plotted as percentage of body weight change from initial weight (a). Pathological parameters including disease activity index (b), weight of spleen (c), spleen index (d) and colon length from experimental mouse groups (e,f) were measured as described in methods. Colorectal histology changes (f) were determined by immunohistochemical staining. Data are representative of two independent experiments (means ± SEM). *P < 0.05, **P < 0.01, ***P < 0.001 compared to DSS-only control.
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f6: MBF dietary supplementation attenuates pathological symptoms of DSS induced acute colitis.BALB/c mice were fed with MBF (20 mg/kg) for 10 days prior to exposure to 3% DSS in drinking water. Daily weights were measured (n = 6–8/group) and plotted as percentage of body weight change from initial weight (a). Pathological parameters including disease activity index (b), weight of spleen (c), spleen index (d) and colon length from experimental mouse groups (e,f) were measured as described in methods. Colorectal histology changes (f) were determined by immunohistochemical staining. Data are representative of two independent experiments (means ± SEM). *P < 0.05, **P < 0.01, ***P < 0.001 compared to DSS-only control.

Mentions: The therapeutic potential of MBF in suppressing acute colitis was investigated using the DSS induced mouse model. Compared to normal diet-fed mice, those fed with 3% DSS diet for 9 days appeared 10% loss in their initial body weight (Fig. 6a), 40% increase in spleen weight (Fig. 6c) and 35% shortening in colon length (Fig. 6d–f). However, these detrimental effects of DSS stimulation were significantly ameliorated by feeding mice with 5% or 10% MBF diet (Fig. 6a,c–f). Moreover, MBF diet significantly inhibited DSS induced disease activity index (Fig. 6b), a measurement of the production of bloody stools31. Likewise, results of histological analysis indicated that DSS induced severe injuries in colon crypts were significantly prevented by MBF dietary (Fig. 6g).


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 dietary supplementation attenuates pathological symptoms of DSS induced acute colitis.BALB/c mice were fed with MBF (20 mg/kg) for 10 days prior to exposure to 3% DSS in drinking water. Daily weights were measured (n = 6–8/group) and plotted as percentage of body weight change from initial weight (a). Pathological parameters including disease activity index (b), weight of spleen (c), spleen index (d) and colon length from experimental mouse groups (e,f) were measured as described in methods. Colorectal histology changes (f) were determined by immunohistochemical staining. Data are representative of two independent experiments (means ± SEM). *P < 0.05, **P < 0.01, ***P < 0.001 compared to DSS-only control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: MBF dietary supplementation attenuates pathological symptoms of DSS induced acute colitis.BALB/c mice were fed with MBF (20 mg/kg) for 10 days prior to exposure to 3% DSS in drinking water. Daily weights were measured (n = 6–8/group) and plotted as percentage of body weight change from initial weight (a). Pathological parameters including disease activity index (b), weight of spleen (c), spleen index (d) and colon length from experimental mouse groups (e,f) were measured as described in methods. Colorectal histology changes (f) were determined by immunohistochemical staining. Data are representative of two independent experiments (means ± SEM). *P < 0.05, **P < 0.01, ***P < 0.001 compared to DSS-only control.
Mentions: The therapeutic potential of MBF in suppressing acute colitis was investigated using the DSS induced mouse model. Compared to normal diet-fed mice, those fed with 3% DSS diet for 9 days appeared 10% loss in their initial body weight (Fig. 6a), 40% increase in spleen weight (Fig. 6c) and 35% shortening in colon length (Fig. 6d–f). However, these detrimental effects of DSS stimulation were significantly ameliorated by feeding mice with 5% or 10% MBF diet (Fig. 6a,c–f). Moreover, MBF diet significantly inhibited DSS induced disease activity index (Fig. 6b), a measurement of the production of bloody stools31. Likewise, results of histological analysis indicated that DSS induced severe injuries in colon crypts were significantly prevented by MBF dietary (Fig. 6g).

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