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.
Highlights
Mulberry (Morus alba L.), a genus of the Moraceae family, is widely cultivated in many regions of the world, predominantly in eastern, southern and southeastern Asia[1]
We investigated the anti-inflammatory activity of mulberry fruit (MBF) extracts in lipopolysaccharide (LPS) stimulated RAW264.7 macrophage cells, and the therapeutic efficacy of MBF diet in dextran sulfate sodium (DSS) exposed mice and MUC2−/− mice, which represent the acute colitis (AC) and colorectal cancer (CRC) models, respectively
We have demonstrated the in vitro and in vivo anti-inflammatory activity of MBF in RAW264.7 macrophages and DSS induced acute colitis mouse model, and its in vivo antitumor activity in MUC2−/− mice model of colon cancer
Summary
Mulberry (Morus alba L.), a genus of the Moraceae family, is widely cultivated in many regions of the world, predominantly in eastern, southern and southeastern Asia[1]. By combining treatment with mulberry leaf and fruit extracts, Lim et al found significant anti-obesity and anti-inflammatory activities in high-fat diet-induced obese mice[11]. These beneficial effects of MBF are putatively attributable to bioactive ingredients such as alkaloids, polyohenol, flavonoids anthocyanins and carotenoids[10,12,13,14]. We investigated the anti-inflammatory activity of MBF extracts in lipopolysaccharide (LPS) stimulated RAW264.7 macrophage cells, and the therapeutic efficacy of MBF diet in dextran sulfate sodium (DSS) exposed mice and MUC2−/− mice, which represent the acute colitis (AC) and colorectal cancer (CRC) models, respectively. Our results demonstrated that MBF extracts inhibited the expression of proinflammatory mediators by blocking both the NFκ B/p65 and pERK/MAPK signals in LPS-induced macrophage cells, and the MBF diet showed significant inhibitory effects on the development of DSS-induced AC and the progress of CRC in MUC2−/− mice
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