title: Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice.
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.
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.|Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Zhengjiang
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Huang
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Yao
authors.affiliation: School of Basic Medical Sciences, Shenzhen University, Shenzhen, Guangdong, 518000, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Kang
authors.affiliation: Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Junle
authors.initials: J
authors.lastname: Qu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University,Yangling, 712100, Shaanxi, China.
authors.forename: Yonghou
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University,Yangling, 712100, Shaanxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052 Australia.
authors.forename: Johnson J
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: School of Basic Medical Sciences, Shenzhen University, Shenzhen, Guangdong, 518000, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining, Shandong, 272067, China.
authors.forename: Wancai
authors.initials: W
authors.lastname: Yang
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Deming
authors.initials: D
authors.lastname: Gou
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D003092:Colitis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D019587:Dietary Supplements; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005638:Fruit / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D019787:Linoleic Acid / Q000737:chemistry; D008042:Linolenic Acids / Q000737:chemistry; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D031625:Morus / Q000737:chemistry*; D055262:Mucin-2 / Q000172:deficiency; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D021381:Protein Transport; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008042:Linolenic Acids; D008070:Lipopolysaccharides; D055262:Mucin-2; D016328:NF-kappa B; D010936:Plant Extracts; D009569:Nitric Oxide; D016264:Dextran Sulfate; D019787:Linoleic Acid; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; C039896:ethyl linolenate