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.

1,3,6,7‐Tetrahydroxy‐8‐prenylxanthone ameliorates inflammatory responses resulting from the paracrine interaction of adipocytes and macrophages

“…MAPKs and NF‐κB signalling pathways are key regulators of inflammation (Qian et al, ). As expected, LPS treatment increased the phosphorylation of p38, JNK and ERK; remarkably, TPX blocked the phosphorylation of p38, JNK and ERK (Figure A).…”

“…Anti‐inflammatory therapies have been proved to improve insulin sensitivity in animals (Yuan et al, ; Lin et al, ). NO is a mediator and regulator of inflammatory responses, and is mainly produced in macrophages by iNOS (Qian et al, ). IL‐6 is a multifunctional cytokine produced by different cell types and is an important autocrine and paracrine regulator of adipose tissue metabolism (Mohamed‐Ali et al, ).…”

“…TPX significantly inhibited TNF‐α‐induced activation of the NF‐κB signalling pathway in adipocytes. MAPKs are a large family of seine/threonine kinases that mediate the inflammatory signalling upon extracellular stimulation, and include ERK, p38 and JNK (Qian et al, ). These cytoplasmic enzymes can phosphorylate and activate various transcription factors in the cytoplasm or nucleus (Hommes et al, ).…”

Genetic diversity among mulberry genotypes from seven countries

“…In the last decade, many studies showed that Morus has relatively significant effects on chronic diseases, like diabetes, and the nervous system (Yadav and Nade 2007;Yadav et al 2008;Nakamura et al 2009). Additionally, mulberry has both the anticancer and the anti-inflammatory properties, which act through different pathways (Kollar et al 2013;Eo et al 2014;Kwon et al 2015;Qian et al 2015). Some reports have demonstrated the leaf's role in ameliorating obesity-induced reactions, increasing bone density and antiplatelet activity (Ann et al 2015;Sungkamanee et al 2014;Kim et al 2014).…”

Protective Role of Dietary Berries in Cancer

“…Berry phenolics, despite extensive metabolism and structural changes, seem to maintain their protective effects in relation to colon carcinogenesis [48]. …”