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Anti-inflammatory activity of fruit fractions in vitro, mediated through toll-like receptor 4 and 2 in the context of inflammatory bowel disease.

ABSTRACT: Pattern recognition receptors such as Toll-Like Receptor 2 (TLR2) and 4 (TLR4) are important in detecting and responding to stress and bacterial stimuli. Defect or damage in the TLR2 and TLR4 pathways can lead to sustained inflammation, characteristic of inflammatory bowel disease (IBD). The goal of this study was to identify fruit fractions that can be tested further to develop them as complementary therapies for IBD. In order to do this, we identified fruit fractions that mediate their anti-inflammatory response through the TLR4 and TLR2 pathway. Human Embryonic Kidney (HEK)-hTLR4 and hTLR2 cells were stimulated with their respective ligands to induce inflammation. These cells were treated with one of the 12 fractionated fruits and the inflammatory effect measured. 10 of the fruits came up as anti-inflammatory in the hTLR4 assay and nine in the hTLR2 assays. Many of the fruit fractions mediated their anti-inflammatory actions either mainly in their hydrophobic fractions (such as elderberry) or hydrophilic fractions (such as red raspberry), or both. The strongest anti-inflammatory effects were seen for feijoa and blackberry. This study shows that fruits can have multiple fractions eliciting anti-inflammatory effects in a pathway specific manner. This suggests that the compounds found in fruits can act together to produce health benefits by way of reducing inflammation. Exploiting this property of fruits can help develop complimentary therapies for inflammatory diseases.

SUBMITTER: Nasef NA

PROVIDER: S-EPMC4245588 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Anti-inflammatory activity of fruit fractions in vitro, mediated through toll-like receptor 4 and 2 in the context of inflammatory bowel disease.

Nasef Noha Ahmed NA Mehta Sunali S Murray Pamela P Marlow Gareth G Ferguson Lynnette R LR

Nutrients 20141119 11

Pattern recognition receptors such as Toll-Like Receptor 2 (TLR2) and 4 (TLR4) are important in detecting and responding to stress and bacterial stimuli. Defect or damage in the TLR2 and TLR4 pathways can lead to sustained inflammation, characteristic of inflammatory bowel disease (IBD). The goal of this study was to identify fruit fractions that can be tested further to develop them as complementary therapies for IBD. In order to do this, we identified fruit fractions that mediate their anti-in ...[more]

PMID: 25415606

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Project description:BackgroundArdisia crispa (Thunb.) A.DC (Primulaceae), is a medicinal herb traditionally used by Asian people as remedies to cure inflammatory related diseases, including rheumatism. The plant roots possess various pharmacological activities including antipyretic, anti-inflammation and antitumor. Previous phytochemical studies of the plant roots have identified long chain alkyl-1,4-benzoquinones as major constituents, together with other phytochemicals. Hexane fraction of the plant roots (ACRH), was previously reported with anti-angiogenic and anti-arthritic properties, while its effect on their anti-arthritic in vitro, is yet unrevealed. Considering the significance of angiogenesis inhibition in developing new anti-arthritic agent, thus we investigated the anti-arthritic potential of Ardisia crispa roots by suppressing angiogenesis, in vitro.MethodsArdisia crispa roots hexane extract (ACRH) was prepared from the plant roots using absolute n-hexane. ACRH was fractionated into quinone-rich fraction (QRF) and further isolated to yield benzoquinonoid compound (BQ), respectively. In vitro experiments using VEGF-induced human umbilical vein endothelial cells (HUVECs) and IL-1β-induced human fibroblast-like synoviocytes for rheumatoid arthritis (HFLS-RA) were performed to evaluate the effects of these samples on VEGF-induced HUVECs proliferation and tube formation, and towards IL-1β-induced HFLS-RA proliferation, invasion, and apoptosis, respectively. Therapeutic concentrations (0.05, 0.5, and 5 μg/mL) tested in this study were predetermined based on the IC50 values obtained from the MTT assay.ResultsACRH, QRF, and BQ exerted concentration-independent antiproliferative effects on VEGF-induced HUVECs and IL-1β-induced HFLS-RA, with IC50 values at 1.09 ± 0.18, 3.85 ± 0.26, and 1.34 ± 0.16 μg/mL in HUVECs; and 3.60 ± 1.38, 4.47 ± 0.34, and 1.09 ± 0.09 μg/mL in HFLS-RA, respectively. Anti-angiogenic properties of these samples were verified via significant inhibition on VEGF-induced HUVECs tube formation, in a concentration-independent manner. The invasiveness of IL-1β-induced HFLS-RA was also significantly inhibited in a concentration-independent manner by all samples. ACRH and BQ, but not QRF, significantly enhanced the apoptosis of IL-1β-induced HFLS-RA elicited at their highest concentration (5 μg/mL) (P < 0.05).ConclusionsThese findings highlight the bioactive fractions and compound from Ardisia crispa roots as potential anti-arthritic agents by inhibiting both HUVECs and HFLS-RA's cellular functions in vitro, possibly mediated via their anti-angiogenic effects.

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Dataset Information

Anti-inflammatory activity of fruit fractions in vitro, mediated through toll-like receptor 4 and 2 in the context of inflammatory bowel disease.

Publications

Anti-inflammatory activity of fruit fractions in vitro, mediated through toll-like receptor 4 and 2 in the context of inflammatory bowel disease.

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