Aim

• The aim of the present review was to critically review and

evaluate the human literature for determining anti-

inflammatory effects of commonly consumed fruits and fruit

products (e.g., juice, wine), including apples, berries, grapes, red

wine, and oranges/orange juice.

Polyphenols

• Polyphenols are secondary metabolites of plants characterized

by the presence of large multiples of phenol structural units

• The number and characteristics of these phenol structures

underlie the unique physical, chemical, and biological

(metabolic, toxic, therapeutic, etc.) properties

• Pre-clinical data suggest that certain polyphenols have anti-

inflammatory properties

Polyphenols in Fruits

• Flavonoids are a major subclass of polyphenols and the most

commonly consumed fruit flavonoids in the diet are

anthocyanins, hesperetin, and quercetin

• The main fruit contributors to polyphenol intake were

strawberries, blueberries, raspberries, grapes, oranges and

orange juice, apples, and bananas

• Red wine is a rich source of polyphenols and contains phenolic

acids/derivatives, stilbenes, anthocyanins, flavonols, and

dihydroflavonols

Beneficial biological activity of polyphenols

• Antioxidant properties to prevent damage to cellular

biomolecules

• Inhibiting absorption of already oxidized products, such as lipid

hydroxyperoxides

• Potential prebiotic effect of polyphenols

• Increase the production of anti-inflammatory molecules

– IL-4, IL-10, IL-13, and adiponectin

• Action in cellular signaling in modifying pathways of

inflammation

Action in cellular signaling

• These actions include blocking or down regulating receptors or

transcription factors leading to pro-inflammatory gene

expression

– Eg:

• Interleukin (IL) receptors

• Toll-like Receptor (TLR)-4

• nuclear factor kappa B (NF-ҡB)

• activator protein (AP-1)

• c-Jun-Nterminal kinases (JNK)

Inflammation

• Inflammation is the normal protective response of the innate

immune system to tissue injury or detrimental external stimuli

such as pathogens, allergens, and other irritants

• In an inflammatory event, a cascade of biochemical events

propagates involving the local vascular system, the immune

system, and various cells within the injured tissue

• A main function of inflammation is to resolve infection and to

repair the damaged tissue

• However, obesity, energy dense- and nutrient poor-diets have been

shown to stimulate inflammation

Inflammatory responses

• Inflammatory responses are often characterized by the

production of pro-inflammatory molecules and cytokines that

provide signals between immune cells to coordinate with the

inflammatory response

– NF-kB, a major transcription factor that stimulates the encoding of a number of

genes responsible for production of molecules and cytokines which are involved

in inflammatory process

Inflammatory biomarkers

• Circulating concentrations of inflammatory molecules are used

in research as well as in clinical practice to evaluate

inflammation

• Inflammation can also be assessed by studying gene

expression of transcription factors, receptors, and protein

kinases in immune cells such as monocytes and macrophages

• levels of these markers help to identify mechanisms and

pathways that either stimulated or inhibited resulting in a

particular inflammatory outcome

Common inflammatory biomarkers

• Acute phase proteins

– ex: hs-CRP, Fibrinogen, Serum amyloid A

• Cytokines

– Ex: IL-6, IL-1b, TNF-a, MCP-1

• Adipokines

– Adiponectin, Leptin

• Adhesion molecules

– sVCAM-1, sICAM-1, sE-selectin

• Other

– NF-kB activation, Leukocyte count, Lp-PLA2

Inflammatory biomarkers and diseases Biomarker Associated Condition

hs-CRP CVD, DM

Fibrinogen Arterial thrombosis

Serum amyloid A Obesity, CVD risk

MCP-1 DM, CVD

Adiponectin Obese

sVCAM-1 Obesity, atherogenesis

sICAM-1 Atherogenesis, DM, obesity, hemodialysis

sE-selectin DM, obesity

PAI-1 MetS, asthma

Lp-PLA2 Obese with NAFLD

MMP-9 With HFHC intake

SOCS-3 With HFHC intake

TLR-2, -4 With HFHC intake

Postprandial inflammation

• Postprandial state is the slight variations that occur in

metabolic activities after consumption of meals

• Induced inflammatory conditions that associated with

consumption of energy dense- and nutrient poor-diets is called

postprandial inflammation

• Studies have shown that consumption of fruits rich in

polyphenolic bioactives with diet is effective to reduce

postprandial inflammation

Biomarker assays of postprandial state with

consumption of fruits Fruit Biomarkers

Biomarker Change in postprandial

period Strawberry IL-6 Decresed

hs-CRP Decresed

PAI-1 Decresed

IL-1b Decresed

Blueberry IL-10 Increased

Orange SOCS-3 Decresed

TLR-4 Decresed

TNF-a Decresed

IL-1b Decresed

NFkB binding Decresed

TLR-2 Decresed

TLR-4 Decresed

SOCS-3 Decresed

MMP-9 Decresed

Red wine NF-kB activation Decresed

t PAI-1 Increased

IL-6 Increased

White wine IL-6 Increased

Pomegranate sICAM-1 Decresed

sE-selectin Decresed

IL-6 Decresed

Fruit juice drink IL-17 Decresed

Effect of fruits in postprandial state

Fruit Effect in postprandial state

Strawberry Decrease in inflammatory and thrombolytic molecules

Blueberries Not effective in postprandial state

Oranges Minimization of inflammatory responses effective for certain meal compositions

Red wine Moderate wine intake is associated with beneficial effects

Grapes No short-term effect on circulating concentrations of inflammatory markers

Pomegranate Results only low-grade inflammation

Inflammation and chronic effects of fruit

polyphenols

• Inflammation is considered as a major contributor to chronic

disease pathologies

• Several studies have been carried out to investigate the effect

of fruit polyphenols towards inflammatory biomarker changes

that ultimately beneficial towards some chronic diseases

Chronic studies of fruit polyphenols

supplementation in humans Fruit Biomarker/s Biomarker change

Strawberry sVCAM-1 Decreased

Blueberry NK cells Increased

Cranberry sICAM-1, sVCAM-1, MMP-9 Decreased

Red wine

VLA-4e, monocyte adhesion, hs-CRP, fibrinogen, sVCAM-1, fibrinogen, hs-CRP, hs-CRP, IL-

6, sICAM-1, NF-kB activatione, MCP-1, sICAM-1, IL-6, MCP-1,

sVCAM-1

sVCAM-1, sE-selectin,

CD40L, monocyte adhesion

sICAM-1, IL-1a, VLA-4e,

LFA-1e, Mac-1e, MCP-1e

Decreased

Grape TNF-a, MCP-1, sE-selectin, IL-6, sICAM-1, Decreased

Raisin TNF-a, sICAM-1 Decreased

Red orange hs-CRP, IL-6, TNF-a Decreased

Apple

Plum CRP Decreased

Acai berry

Bilberry IL-6, hs-CRP, IL-15, MIG, TNF-a, sVCAM-1, adiponectin Increased

TNF-a Decreased

Sea buckthorn berry hs-CRP, TNF-a, Decreased

Pomegranate sICAM-1, sE-selectin, IL-6, TNF-a, fibrinogen Decreased

Effect of fruits in chronic diseases Fruit Action

Strawberry Alleviate inflammatory risk associated with CVD and diabetes

Blueberries Benificial in CVD associated inflamotory risk Cranberries

Anti inflammatory activity

Modulate CVD risk factors

Wine Anti inflammatory activity associated with type 2 diabetes and CVD

Grape Anti-inflammatory effects

Orange juice Effective for CVD associated inflamation

Apples limited anti-inflammatory effect (but effective with dried plum

supplementation)

Acai berry, bilberry, and sea buckthorn

berry Protective against CVD risk factors

Pomegranate fruit Effective for diabetes and CVD

Conclusion

• Fruit polyphenols has a significant effect on inflammatory

stress (both in postprandial inflammation and chronic disease

related inflammation)

• Consumption of fruits are more beneficial towards risk factors

associated with CVD, CHD, diabetes mellitus and metabolic

syndrome

• Further studies have to be conducted for acai berry, bilberry,

and sea buckthorn berry

Thank You! Presented By Rangika Munaweera