Toll-like Receptors as a Target of Food-derived Anti-inflammatory Compounds

Shibata, Takahiro; Nakashima, Fumie; Honda, Kazumasa; Lu, Yu‐Jhang; Kondo, Toshiyuki; Ushida, Yusuke; Aizawa, Katsuo; Suganuma, Hiroyuki; Oe, Sho; Tanaka, Hiroshi; Takahashi, Takashi; Uchida, Koji

doi:10.1074/jbc.m114.585901

Cited by 49 publications

(41 citation statements)

References 49 publications

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“…PRR activation by DF has been mainly described for TLR2 and 4 9,10 . Lemon pectin with DM of 74% activated TLR2 and 4, but TLR4 was activated to a lesser extent than TLR2 12 .…”

Section: Discussionmentioning

confidence: 99%

Pectin Interaction with Immune Receptors is Modulated by Ripening Process in Papayas

Prado

Beukema

Jermendi

et al. 2020

Sci Rep

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Dietary fibers have been shown to exert immune effects via interaction with pattern recognition receptors (pRR) such as toll-like receptors (tLR) and nucleotide-binding oligomerization domain (noD)like receptors. Pectin is a dietary fiber that interacts with PRR depending on its chemical structure. Papaya pectin retains different chemical structures at different ripening stages. How this influence PRR signaling is unknown. The aim of this work was to determine how ripening influences pectin structures and their ability to interact with TLR2, 3, 4, 5 and 9, and NOD1 and 2. It was evaluated the interaction of the water-soluble fractions rich in pectin extracted from unripe to ripe papayas. The pectin extracted from ripe papayas activated all the TLR and, to a lesser extent, the NOD receptors. The pectin extracted from unripe papayas also activated TLR2, 4 and 5 but inhibited the activation of TLR3 and 9. The differences in pectin structures are the higher methyl esterification and smaller galacturonan chains of pectin from ripe papayas. Our finding might lead to selection of ripening stages for tailored modulation of pRR to support or attenuate immunity. Dietary fibers (DF) commonly represent a wide variety of polysaccharides originating from fruits, vegetables, whole grains and legumes with several health benefits. Such benefits include slow gastric empty 1 and improve physical bowel function 2. Besides the physical benefits, DF can also interact directly with intestinal cells and/or the immune cells from the mucosa 3-5. It is not just the direct effects of DF on cells may trigger immune modulations 6 but also the DF fermentation in the gut 7,8. The direct interaction of DF with the intestinal cells may occur through pattern recognition receptors (PRR) 9. The PRR are germline-encoded sensors expressed in intestinal epithelial cells and gut immune cells. PRR are the key receptors responsible for the recognition of exogenous molecules by the host 5,9. Toll-like receptors (TLR) are a family of PRR that play a central role in the activation of innate immunity 10 and have been shown to be involved in DF-induced immune signaling as described below. The immune response mediated by TLR activation requires the recruitment of myeloid differentiation primary response protein 88 (MyD88) adaptor and the translocation of NF-κB to the nucleus 10. Only TLR3 NF-κB activation is not dependent on MyD88 protein which is mediated by TIR domain-containing adapter inducing IFN-β (TRIF), though 11. The interactions between wide variety of DF and TLR have been extensively studied. DF have a complex and heterogeneous structure and some DF activate TLR to different extents 12 while other DF (such as pectin) seem to block TLR signaling and attenuate intestinal inflammation 6. Nucleotide-binding oligomerization domains (NOD) have also been shown to be influenced by DF, such as β2 → 1-fructans. NOD are proteins responsible for the recognition of intracellular bacteria 10. Through this signaling via PRR, DF have been shown to mediate several ho...

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“…PRR activation by DF has been mainly described for TLR2 and 4 9,10 . Lemon pectin with DM of 74% activated TLR2 and 4, but TLR4 was activated to a lesser extent than TLR2 12 .…”

Section: Discussionmentioning

confidence: 99%

Pectin Interaction with Immune Receptors is Modulated by Ripening Process in Papayas

Prado

Beukema

Jermendi

et al. 2020

Sci Rep

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“…Among 40 natural compounds docked to IRAK-4, apigenin, bilobetin, curcumin, ginkgetin, quercetin, berberine, and pseudopterosin showed higher affinity compared to the native ligand. Quercetin was reported to show IRAK-4 inhibitory activity [40]. Affinity of quercetin to the binding site was supported by hydrogen bond between 4-hydroxy of B-ring with Lys213B and Glu233B residues, while the aromatic rings contributed by forming hydrophobic interaction with Val200B, Tyr262B, and Leu318B.…”

Section: Interaction To Interleukin-1 Receptor-associated Kinase-4 (Imentioning

confidence: 99%

Molecular Docking Analysis: Interaction Studies of Natural Compounds to Anti-inflammatory Targets

Herowati¹,

Widodo²

2017

Quantitative Structure-Activity Relationship

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A variety of compounds from medicinal plants have been reported to possess antiinflammatory properties. Selected natural compounds that exhibit anti-inflammatory properties were subjected to docking simulation using AutoDock Vina to investigate their interaction modes to the potential macromolecular targets. The docking was performed using different molecular targets, i.e., cyclooxygenase-2, phospholipase A2, NF-κB inhibitor, and interleukin-1 receptor. It revealed that flavonoids have the highest affinity to the macromolecular targets (the lowest binding energy values) and the highest consistency of interaction model. Some terpenoids were identified to have potential inhibitor of phospholipase A2.

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“…Moreover, an anti-inflammatory effect mediated via attenuation of tumor necrosis factor α (TNF-α), NFκB and mitogen-activated protein kinases (MAPK), as well as depletion of IL-6, IL-1β, IL-8 or monocyte chemoattractant protein-1 (MCP-1) gene expression has also been attributed to this polyphenol [143]. …”

Section: Single Nutrients and Bioactive Compoundsmentioning

confidence: 99%

Dietary Strategies Implicated in the Prevention and Treatment of Metabolic Syndrome

Iglesia

Loria-Kohen

Zulet

et al. 2016

IJMS

138

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Metabolic syndrome (MetS) is established as the combination of central obesity and different metabolic disturbances, such as insulin resistance, hypertension and dyslipidemia. This cluster of factors affects approximately 10%–50% of adults worldwide and the prevalence has been increasing in epidemic proportions over the last years. Thus, dietary strategies to treat this heterogenic disease are under continuous study. In this sense, diets based on negative-energy-balance, the Mediterranean dietary pattern, n-3 fatty acids, total antioxidant capacity and meal frequency have been suggested as effective approaches to treat MetS. Furthermore, the type and percentage of carbohydrates, the glycemic index or glycemic load, and dietary fiber content are some of the most relevant aspects related to insulin resistance and impaired glucose tolerance, which are important co-morbidities of MetS. Finally, new studies focused on the molecular action of specific nutritional bioactive compounds with positive effects on the MetS are currently an objective of scientific research worldwide. The present review summarizes some of the most relevant dietary approaches and bioactive compounds employed in the treatment of the MetS to date.

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Toll-like Receptors as a Target of Food-derived Anti-inflammatory Compounds

Cited by 49 publications

References 49 publications

Pectin Interaction with Immune Receptors is Modulated by Ripening Process in Papayas

Pectin Interaction with Immune Receptors is Modulated by Ripening Process in Papayas

Molecular Docking Analysis: Interaction Studies of Natural Compounds to Anti-inflammatory Targets

Dietary Strategies Implicated in the Prevention and Treatment of Metabolic Syndrome

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