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Protection of Poria cocos-derived polysaccharide CMP33 against IBD in mice and its molecular mechanism

Abstract

In this study, the protective effects of a carboxymethyl polysaccharide CMP33 from Poria cocos against inflammatory bowel disease (IBD) were investigated using TNBS-induced colitis in mice. The results showed that CMP33 markedly ameliorated the colitis severity, including 2-fold decrease in the mortality rate, 50% decrease in disease activity index, 36%-44% decrease in macro- or microscopic histopathologic score, compared with TNBS administration. Moreover, CMP33 decreased the levels of pro-inflammatory cytokines and increased the levels of anti-inflammatory cytokines in colon tissue and serum of colitis mice. Using iTRAQ-coupled- nano-HPLC-MS/MS-based proteomics, the proteins profiles after TNBS, high-or low-dose CMP33 and drug Salazosulfapyridine (SASP) treatments were compared and many differentially expressed proteins were identified. Among them, 7 proteins (Hmgcs2, Fabp2, Hp, B4galnt2, B3gnt6, Sap and Ca1) were proposed to be the common targeting protein group (TPG) of CMP33 and drug SASP. Especially, some targeting proteins were CMP33-dose-specific: high-dose-specific TPG (Mtco3, Gal-6, Mptx, S100g and Hpx) and low-dose-specific TPG (Zg16, Hexb, Insl5, Cept1, Hspb6 and Ifi27l2b), suggesting the complex acting mechanism of CMP33. GC-TOF-MS-based metabolomics revealed that oleic acid and dihydrotestosterone could be the common targets of CMP33 and SASP. By integrative analysis of proteomics and metabolomics, key proteins-metabolites pathways (PMP) were identified, PMP for high-dose: 2-Hydroxybutyric acid – (GPT, GGH) – Glutathione – ALB –Testosterone –TTR–Dihydrotestosterone; PMP for low-dose: (PYY, FABP2, HMGCS2)–Oleic acid–TTR– Dihydrotestosterone. Totally, these results demonstrated the protective effect of CMP33 against IBD in mice through potential TPG and PMP.

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Publication details

The article was received on 11 Aug 2018, accepted on 08 Oct 2018 and first published on 08 Oct 2018


Article type: Paper
DOI: 10.1039/C8FO01604F
Citation: Food Funct., 2018, Accepted Manuscript
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    Protection of Poria cocos-derived polysaccharide CMP33 against IBD in mice and its molecular mechanism

    X. Liu, X. Yu, X. Xu, X. Zhang and X. Zhang, Food Funct., 2018, Accepted Manuscript , DOI: 10.1039/C8FO01604F

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