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Succinylated chitosan derivative has local protective effects on intestinal inflammation.

ABSTRACT: We have previously reported on the anti-inflammatory effects of a water-soluble chitosan derivative, zwitterionic chitosan (ZWC). In the present study, we hypothesized that orally-administered ZWC would provide local anti-inflammatory effects in the intestinal lumen. ZWC indeed showed anti-inflammatory effects in various in-vitro models including peritoneal macrophages, engineered THP1 monocytes, and Caco-2 cells. In Caco-2 cells, ZWC applied before the lipopolysaccharide (LPS) challenge was more effective than when it was applied after it in preventing LPS-induced cell damage. When administered to mice via drinking water as a prophylactic measure, ZWC protected the animals from 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis, helping them to recover the body weight, restore the gross and histological appearance of the colon, and generate FoxP3+ T cells. In contrast, orally-administered ZWC did not protect the animals from LPS-induced systemic inflammation. These results indicate that orally-administered ZWC reaches the colon with minimal absorption through the upper gastrointestinal tract and provides a local anti-inflammatory effect.

SUBMITTER: Hyun H

PROVIDER: S-EPMC5810976 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Succinylated chitosan derivative has local protective effects on intestinal inflammation.

Hyun Hyesun H Hashimoto-Hill Seika S Kim Myunghoo M Tsifansky Michael D MD Kim Chang H CH Yeo Yoon Y

ACS biomaterials science & engineering 20170605 8

We have previously reported on the anti-inflammatory effects of a water-soluble chitosan derivative, zwitterionic chitosan (ZWC). In the present study, we hypothesized that orally-administered ZWC would provide local anti-inflammatory effects in the intestinal lumen. ZWC indeed showed anti-inflammatory effects in various <i>in-vitro</i> models including peritoneal macrophages, engineered THP1 monocytes, and Caco-2 cells. In Caco-2 cells, ZWC applied before the lipopolysaccharide (LPS) challenge ...[more]

PMID: 29450257

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Project description:Intestinal inflammation frequently occurs alongside dysmotility, which is characterized by altered myosin light chain phosphorylation levels. Curcumin, an active component from the ginger family, is reported to confer anti‑inflammatory effects. However, the effects of curcumin on both diarrhea and constipation associated inflammation remains to be elucidated. The present study was designed to investigate the effects of curcumin on diarrhea and constipation and to determine the related mechanisms. Sprague‑Dawley rats were used to establish diarrhea and constipation models via intracolonic acetic acid (4%) instillation or cold water gavage for 2 weeks, respectively. Blood samples were collected to measure the serum levels of the cytokines TNF‑α and IL‑1β using ELISA kits. Western blotting was performed to measure NF‑κB, RhoA, Rho‑related kinase 2, phosphorylated MLC20, phosphorylated myosin phosphorylated target subunit 1, 130k Da‑MLC kinase (MLCK), c‑kit tyrosine kinase protein expression, and reverse transcription‑quantitative PCR was conducted to measure MLCK expression levels. The results indicated that curcumin reversed the elevations in the pro‑inflammatory cytokines IL‑1β and TNF‑α by inhibiting the NF‑κB pathway in rats with diarrhea and constipation. The results also indicated that myosin light chain (MLC) phosphorylation in intestinal smooth muscle was positively and negatively associated with the motility of inflammation‑related diarrhea and constipation in rats, respectively. Curcumin significantly reversed the increased MLC phosphorylation in the jejunum of the rats with diarrhea, significantly enhanced the reductions in inflammatory mediators, including TNF‑α and IL‑1β, of rats with constipation and significantly ameliorated the related hyper‑motility and hypo‑motility in rats with both diarrhea and constipation. In conclusion, the potential roles of the MLC kinase, c‑kit tyrosine and Rho A/Rho‑associated kinase 2 pathways, which are involved in curcumin‑induced amelioration of inflammation‑related diarrhea and constipation, were explored in the present study. Results from the present study suggested that curcumin has potential therapeutic value for treating intestinal inflammation and inflammation‑related motility disorders.

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Succinylated chitosan derivative has local protective effects on intestinal inflammation.

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Succinylated chitosan derivative has local protective effects on intestinal inflammation.

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