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The Role of Flavonoids as Modulators of Inflammation and on Cell Signaling Pathways

Abstract

Flavonoids are naturally occurring polyphenolic compounds widely distributed in the plant kingdom. These compounds have long been recognized to possess a broad spectrum of biological activities, such as antioxidant, anti-inflammatory, hepatoprotector, antibacterial, antiviral, antidiabetic, antiproliferative and anticarcinogenic. Although they are not regarded as nutrients, they are important constituents of the human diet. Flavonoids are present in leafy vegetables, apples, onions, broccoli, berries, citrus fruits, grapes and soybeans, also in tea, chocolate and red wine. Many studies have demonstrated that a high intake of flavonoids is associated with a reduced risk of cardiovascular disease, cancer and neurodegenerative disorders. In recent years, there has been an increasing progress in the elucidation of the mechanisms through which flavonoids exert their biological activities. In addition to the already known free radical scavenging effect, flavonoids exert beneficial effects through the interaction with nuclear transcription factor kappa-B, activator protein 1, Janus kinases and phosphatidylinositol-3 kinase signaling pathways. This chapter focuses on recent findings on the role of flavonoids as modulators of inflammation and on cell signaling pathways.

Keywords

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Abbreviations

4′-HW:

4′-hydroxywogonin

5B:

(E)-3-(3,4-dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl) prop-2-en-1-one

67LR:

67-kDa laminin receptor

AA:

Arachidonic acid

Afla:

Amentoflavone

Akt:

Protein kinase B

Alp:

Alpinetin

Amp:

Ampelopsin

AMPK:

Adenosine monophosphate-activated protein kinase

AP-1:

Activator protein-1

Api:

Apigenin

Ast:

Astragalin

BBB:

Blood-brain barrier

BMDM:

Bone marrow-derived macrophages

C3G:

Cyanidin-3-O-glucoside

CAMs:

Cell surface adhesion molecules

CAT:

Catalase

Cat:

Catechin

Chr:

Chrysin

CNS:

Central nervous system

COMT:

Catechol-O-methyltransferase

COX:

Cyclooxygenase

Dai:

Daidzein

DMH:

1,2-dimethyl hydrazine

DNA:

Deoxyribonucleic acid

EGCG:

Epigallocatechin-3-gallate

EGF:

Epidermal growth factor

eNOS:

Endothelial nitric oxide synthase

EpRE:

Electrophile-responsive element

ERK:

Extracellular signal-regulated kinases

Eup:

Eupatilin

Fis:

Fisetin

FlkA:

Flavokawain A

Gen:

Genisteína

GEN-27:

5-hydroxy-7-[2-hydroxy-3-(piperidin-1-yl) propoxy]-3-{4-[2-hydroxy-3-(piperidin-1-yl) propoxy] phenyl}-4H-chromen-4-one

GPx:

Glutathione peroxidase

HaCaT cells:

Human keratinocytes

hAs:

Human astrocytes

hBMEC:

Injured human brain microvascular endothelial cell

HCT116:

Human colon tumour

HGF:

Human gingival fibroblasts

HIF-1α:

Hypoxia-inducible factor 1-α

HMGB:

High-mobility group box

HMGB1:

High-mobility group box 1 protein

HO-1:

Heme oxygenase-1

hPBMCs:

Human peripheral blood mononuclear cells

HUVEC:

Human umbilical vein endothelial cell

Ibc:

Isobavachalcone

Ica:

Icariin

ICAM:

Intercellular adhesion molecule

ICT:

3,5,7-trihydroxy-4′-methoxy-8-(3-hydroxy-3-methylbutyl)-flavone

IFN:

Interferon

Ig:

Immunoglobulin

IKK:

IκB kinase

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

IRAK:

IL-1 receptor-associated kinase

IκB:

Inhibitor of kappa-B

JAK:

Janus kinase

JNK:

c-Jun N-terminal kinases

L2H17:

1-(3,4-Dihydroxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one

LicoC:

Licochalcone C

LOX:

Lypooxygenase

LPH:

Lactase phlorizin hydrolase

LPS:

Lipopolysaccharide

LT:

Leukotriene

Lut:

Luteolin

Mal:

Malvidin

Mal3OG:

Malvidin-3-O-glucoside

MALP-2:

Macrophage-activating lipopeptide 2-kDa

MAPK:

Mitogen-activated protein kinase

MCAO:

Middle cerebral artery occlusion

MCP:

Monocyte chemoattractant protein

MIP:

Macrophage inflammatory protein

mMEC:

Mouse mammary epithelial cell

MMP:

Matrix metalloproteinase

MPO:

Myeloperoxidase

mRNA:

Messenger ribonucleic acid

Nag:

Naringin

Nar:

Naringenin

NF-κB:

Nuclear factor kappa B

nNOS:

Neuronal NOS

NO:

Nitric oxide

NOS:

Nitric oxide synthase

Nrf2:

Nuclear factor-erythroid-related factor 2

NSAIDs:

Non-steroidal anti-inflammatory drugs

Ono:

Ononin

OroA:

Oroxylin A

OVA:

Ovalbumin

PAI-1:

Plasminogen activator inhibitor 1

PCB:

Polychlorinated biphenyl

PDGF:

Platelet-derived growth factor

Pel:

Pelargonidin

Peo:

Peonidin

PG:

Prostaglandin

Phl:

Phloretin

PI3K:

Phosphatidylinositol-3 kinase

Pin:

Pinocembrin

PKC:

Protein kinase C

poly[I:C]:

Polyriboinosinic polyribocytidylic acid

PPAR:

Peroxisome proliferator-activated receptor

Pru:

Prunetin

Pue:

Puerarin

Quer:

Quercetin

RAGE:

Receptor for advanced glycation end products

RANTES:

Regulated upon activation normal T-cell expressed and secreted

ROS:

Reactive oxygen species

Rut:

Rutin

SG:

Sophoraflavanone

SIRT:

Sirtuin

SOCS:

Suppressors of cytokine signaling

SOD:

Superoxide dismutase

STATs:

Signal transducer and activator of transcription

SULTs:

Sulfotransferases

TACR-1:

Tachykinin receptor 1

Tax:

Taxifolin

TBARS:

Thiobarbituric acid reactive substances

TGF:

Tumour growth factor

TLR:

Toll-like receptor

TNF-α:

Tumour necrosis factor-α

Tollip:

Toll-interacting protein

Tri:

Tricin

TX:

Thromboxane

UgoM:

Ugonin M

UGTs:

Uridine 5′-diphospho-glucuronosyltransferases

UV:

Ultraviolet

VCAM:

Vascular cell adhesion molecule

VEGF:

Vascular endothelial growth factor

Vel:

Velutin

Vix:

Vitexin

Won:

Wogonin

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Muschietti, L.V., Ulloa, J.L., Redko, F.D. (2018). The Role of Flavonoids as Modulators of Inflammation and on Cell Signaling Pathways. In: Cechinel Filho, V. (eds) Natural Products as Source of Molecules with Therapeutic Potential. Springer, Cham. https://doi.org/10.1007/978-3-030-00545-0_5

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