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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 inhibited intestinal inflammation and tumorigenesis in Muc2−/− mice.(a) several inflammation in small intestine. Small intestine showed large and continuous epithelium lesions, ulceration (large arrows) and intensive infiltrations of numerous inflammatory cells (small arrows) throughout the villus, mucosa, submucosa and even muscle layer of the intestinal wall; (b), MBF treated mouse small intestine showed virtually normal appearing mucosa and villus (large arrow) except for some inflammatory cell infiltration (small arrow); (c), Large intestine showed mucosa damage (large arrow) and tumor (dotted area) with inflammatory cells (small arrows) infiltration in the mucosa and tumor area; (d), MBF treated mouse large intestine showed virtually normal appearing mucosa (large arrow) except for few inflammatory cell infiltration (small arrow) in large intestine.
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f7: MBF dietary supplementation inhibited intestinal inflammation and tumorigenesis in Muc2−/− mice.(a) several inflammation in small intestine. Small intestine showed large and continuous epithelium lesions, ulceration (large arrows) and intensive infiltrations of numerous inflammatory cells (small arrows) throughout the villus, mucosa, submucosa and even muscle layer of the intestinal wall; (b), MBF treated mouse small intestine showed virtually normal appearing mucosa and villus (large arrow) except for some inflammatory cell infiltration (small arrow); (c), Large intestine showed mucosa damage (large arrow) and tumor (dotted area) with inflammatory cells (small arrows) infiltration in the mucosa and tumor area; (d), MBF treated mouse large intestine showed virtually normal appearing mucosa (large arrow) except for few inflammatory cell infiltration (small arrow) in large intestine.

Mentions: According to our previous reports3233, the MUC2−/− mouse spontaneously developed chronic intestinal inflammation at early age and progressed to intestinal tumors after 3 months. As shown in Table 1 and Fig. 7, 100% of the MUC2−/− mice fed with normal diet developed intestinal tumors, but 5% or 10% dietary MBF significantly inhibited intestinal tumor formation, deceased tumor incidence to 20% and 30%, respectively. Consistent with the inhibition of tumor incidence, tumor numbers decreased from 2.3 ± 1.0 per mouse in normal diet groups to 0.2 ± 0.1 and 0.3 ± 0.1 tumors per mouse in 5% or 10% dietary MBF groups, respectively. Moreover, the dietary MBF also prevented intestinal inflammation. As shown in Fig. 7, the MUC2−/− mice on normal rodent diet developed severe intestinal inflammation. The small intestine showed large and continuous epithelium damage, ulceration and intensive infiltrations of numerous inflammatory cells throughout the villus, mucosa, submucosa and even muscle layer of the intestinal wall (Fig. 7a). However, these lesions could be prevented by MBF supplementation, in which, the MBF-treated mouse small intestine showed virtually normal appearing mucosa and villus except for some inflammatory cell infiltration (Fig. 7b). Moreover, the large intestine of the normal dietary mice showed the development of tumor and inflammation, demonstrating the damage of mucosa and lymphocyte infiltration in the mucosa (Fig. 7c). In contrast, MBF treated mouse large intestine showed virtually normal appearing mucosa except for few inflammatory cell infiltration (Fig. 7d), similar as seen in the small intestine. Compared to 50% of normal diet-fed mice, only 10% and 20% of the mice fed with 5% or 10% dietary MBF developed intestinal inflammation.


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 inhibited intestinal inflammation and tumorigenesis in Muc2−/− mice.(a) several inflammation in small intestine. Small intestine showed large and continuous epithelium lesions, ulceration (large arrows) and intensive infiltrations of numerous inflammatory cells (small arrows) throughout the villus, mucosa, submucosa and even muscle layer of the intestinal wall; (b), MBF treated mouse small intestine showed virtually normal appearing mucosa and villus (large arrow) except for some inflammatory cell infiltration (small arrow); (c), Large intestine showed mucosa damage (large arrow) and tumor (dotted area) with inflammatory cells (small arrows) infiltration in the mucosa and tumor area; (d), MBF treated mouse large intestine showed virtually normal appearing mucosa (large arrow) except for few inflammatory cell infiltration (small arrow) in large intestine.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: MBF dietary supplementation inhibited intestinal inflammation and tumorigenesis in Muc2−/− mice.(a) several inflammation in small intestine. Small intestine showed large and continuous epithelium lesions, ulceration (large arrows) and intensive infiltrations of numerous inflammatory cells (small arrows) throughout the villus, mucosa, submucosa and even muscle layer of the intestinal wall; (b), MBF treated mouse small intestine showed virtually normal appearing mucosa and villus (large arrow) except for some inflammatory cell infiltration (small arrow); (c), Large intestine showed mucosa damage (large arrow) and tumor (dotted area) with inflammatory cells (small arrows) infiltration in the mucosa and tumor area; (d), MBF treated mouse large intestine showed virtually normal appearing mucosa (large arrow) except for few inflammatory cell infiltration (small arrow) in large intestine.
Mentions: According to our previous reports3233, the MUC2−/− mouse spontaneously developed chronic intestinal inflammation at early age and progressed to intestinal tumors after 3 months. As shown in Table 1 and Fig. 7, 100% of the MUC2−/− mice fed with normal diet developed intestinal tumors, but 5% or 10% dietary MBF significantly inhibited intestinal tumor formation, deceased tumor incidence to 20% and 30%, respectively. Consistent with the inhibition of tumor incidence, tumor numbers decreased from 2.3 ± 1.0 per mouse in normal diet groups to 0.2 ± 0.1 and 0.3 ± 0.1 tumors per mouse in 5% or 10% dietary MBF groups, respectively. Moreover, the dietary MBF also prevented intestinal inflammation. As shown in Fig. 7, the MUC2−/− mice on normal rodent diet developed severe intestinal inflammation. The small intestine showed large and continuous epithelium damage, ulceration and intensive infiltrations of numerous inflammatory cells throughout the villus, mucosa, submucosa and even muscle layer of the intestinal wall (Fig. 7a). However, these lesions could be prevented by MBF supplementation, in which, the MBF-treated mouse small intestine showed virtually normal appearing mucosa and villus except for some inflammatory cell infiltration (Fig. 7b). Moreover, the large intestine of the normal dietary mice showed the development of tumor and inflammation, demonstrating the damage of mucosa and lymphocyte infiltration in the mucosa (Fig. 7c). In contrast, MBF treated mouse large intestine showed virtually normal appearing mucosa except for few inflammatory cell infiltration (Fig. 7d), similar as seen in the small intestine. Compared to 50% of normal diet-fed mice, only 10% and 20% of the mice fed with 5% or 10% dietary MBF developed intestinal inflammation.

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