Phytochemicals in Grape - PowerPoint Presentation

Slide1

Phytochemicals in Grape

by Santosh, Yafei, MagnetSlide2

IntroductionThe world’s largest fruit crop, with approximately 65 million metric tons produced annually. (Mazza 1995)Total of 1610 phytochemical compound record (Pezzuto 2008)Slide3

IntroductionLuteinLycopeneCatechinResveratrolAnthocyaninZeaxanthinQuercetinMelatoninSlide4

ResveratrolSlide5

ResveratrolResveratrol is a naturally occurring polyphenolic phytoalexin A potent antioxidant (Cadenas and Barja, 1999)

P

otentially benefits

Cancer

Cardiovascular disease and other diseases

Both in vivo and in vitro

(

Bradamante

and others 2004,

Pezzuto

2008,

Afaq

and others 2003,

Sengottuvelan and others 2006, Jang and others 1997)Slide6

Cardiovascular diseaseSlide7

Cardiovascular diseaseThe cardioprotective effect of resveratrol in humans has yet to be demonstrated(Bradamante and others 2004)Slide8

Cardiovascular diseaseIn vitro and in vivo studies on animal model It may provide protection by a number of mechanisms Inhibition of (LDL) oxidation Inhibition of platelet aggregationSynthesis of proatherogenic

eicosanoids

Expression of

procoagulant

tissue factor

Inhibition of cell proliferation

Increased

vasorelaxation

and

upregulation

of NO synthase

(

Bradamante

and others 2004

)Slide9

Inhibition of (LDL) oxidation During LDL oxidation Polyunsaturated fatty acids are converted to fatty acid hydroperoxidesConjugated double bonds with a characteristic absorbance at 234 nm

(

Brito

and others 2002)Slide10

Inhibition of (LDL) oxidation The increase in the absorbance intensity is significantly reduced by the pre-incubator of LDL with resveratrol (2, 4 or 6 M) in a concentration dependent manner.

pointing out that resveratrol affords an efficient protection against the

ferrylmyoglobin

-mediated LDL oxidation.

(

Brito

and others 2002)Slide11

Potential ChemopreventionSlide12

ChemopreventionMediate positive responses with tumor transplant models for gastric cancers (Zhou and others 2005)Hepatoma (Wu and others 2004) Neuroblastoma (Chen and others 2004)Mammary (Garvin and others

2006)

Glioma

(Chen and others

2006)

Laryngeal

(Li and others 2005

)

However

, activity was not observed with 4T1 breast cancer

(

Bove

and others 2002) and leukemia (Gao and others 2002) Slide13

ChemopreventionChemopreventative activity Inhibits the cyclooxygenase activity of COX-1Induces quinone reductase activityReduces inflammatory

(Jang and others 1997)Slide14

Inflammation(Jang and others 1997)

Resveratrol significantly reduced pedal edema both in the acute phase (3 to 7 hours) and in the chronic phase (24 to 144 hours) in the carrageenan-induced model of inflammation in

rats.

Reveratrol

(



, 3mg per kilogram of body weight;



, 8 mg/kg

)

phenylbutazone

(

)

indomethacin () control group (



)Slide15

COX-1 and COX-2COX catalyzes the conversion of arachidonic acid Pro-inflammatory substances such as prostaglandinsStimulated tumor cell growthsuppress immune surveillance Activate

carcinogens

to forms

that damage genetic materialSlide16

COX-1 and COX-2

(Jang and others 1997)

Indomethacin (



) on COX-1 activity

Resveratrol on COX-1 (



) or COX-2 (



) activity

Resveratrol inhibit

the

cyclooxygenase activity

of COX-1

and this activity

correlates with antitumor promotion.

Although its inhibitory activity

was less

than

indomethacinSlide17

Skin cancerResveratrol also shows potentially prevention of short-term ultraviolet B radiation-mediated damages in hairless mice Reduces cutaneous edamaInhibit reactive oxygen species

I

nhibit

lipid peroxidation

(

Afaq

and others 2003)Slide18

UVB-mediated skin edema Bi-fold skin thickness and ear punch weight were evaluated 24 h after UVB irradiation To observe the protective effect of resveratrol on UVB-mediated skin edema(Afaq and others 2003)Slide19

UVB-mediated skin edema The exposure of the mice to UVB (180 mJ/cm2) resulted in a significant increase in bi-fold skin thickness and ear punch weight

Pretreatment of skin with resveratrol was found to result in a significant inhibition in the increases in bi-fold skin thickness and ear punch weight 24 h after UVB irradiation compared to the UVB-alone group

(

Afaq

and others 2003)Slide20

Human Clinical trailAlthough animal studies data indicate promising activity of resveratrol human clinical trail and studies data are still limited (Walle and others 2004, Zamora-Ros and others 2006)Slide21

Plasma concentration

For oral dose, an

early

peak of total radioactivity

was reached

at about

1 h after the

dose and at

6 h after the

dose, there was second peak

For Intravenous, there

was a rapid fall of the plasma concentrations

of total radioactivity

Oral 25-mg (110

mol) () Intravenous

0.2-mg (0.8

mol

)

(



)

14C-resveratrol doses

in human subjectsSlide22

Recovery of total radioactivity in urine and feces

The

overall recoveries in urine and feces were 70.5

to 97.6

% after the oral

53.5

to 91.2% after the intravenous

doseSlide23

LC/MS of urinary excretion

Resveratrol

(RV)

Metabolites (M1–M5)

M1 was

a resveratrol

monoglucuronide

M2 was an isomeric resveratrol

monoglucuronide

M3 was a

dihydroresveratrol

monoglucuronide

.

M4 was a

resveratrol

monosulfate

M5 was

dihydroresveratrol

sulfateSlide24

Resveratrol and metabolite in plasmaResveratrol (RV)

Major

sulfate conjugates

M4/M5

10-min samples, unchanged

resveratrol with an estimated

concentration range

of 3.7 to 16.4

ng

/ml. Two subjects also demonstrated

a major

metabolite peak with an estimated concentration of 9 to 13.5

ng

/ml

30-min samples, the plasma from subjects 1 and 2 had no resveratrol, whereas in subject 3 there was a small amount

of resveratrol

left, but mostly the sulfate conjugate, M4/M5.

samples obtained

beyond 30 min, there was no unchanged resveratrol detected

in any

of the subjects. Slide25

AnthocyaninSlide26

AnthocyaninAnthocyanins are a group of abundant and widely consumed flavonoid constituentsAntioxidant activity

(Castaneda-

Ovando

and others 2009)

Disease prevention

Cardiovascular

illnesses

Diabetes

Visual dysfunction

Figure 1. General

anthocyanins

structureSlide27

Antioxidant activitiesReact with free radicalsInterrupt the propagation of new free radical speciesChelate metal ions such as Fe2+

Catalyze

lipid oxidation to alter their redox

potentials

Significantly

improve certain immune responses

(

Hertog

and others 1993)Slide28

Antioxidant activitiesFigure 2. Plots showing the correlation of total anthocyanin content of samples with (a) antiradical activity, (b) reducing power and (c) with hydroxyl free radical scavenging activitySlide29

Anthocyanins and cardiovascular diseaseIncreased consumption of anthocyanins lowers the risk of cardiovascular disease (CVD)May regulate different signaling pathways involved in the development of CVD

(

Demrow

and others 1995)Slide30

Anthocyanins and cardiovascular diseaseFigure 3. Representative tracing of the hemodynamic effect of intravenous grape juice(Demrow and others 1995)Slide31

Anthocyanins and anti-diabetic propertiesConsumption of fruits and vegetables decrease the incidence of type-2 diabetesProtect pancreatic β-cells from glucose induced oxidative stress(Al-

Awwadi

and others 2005)Slide32

Anthocyanins and anti-diabetic propertiesFigure 4. Insulin secreted by compounds 3 and 7-9 at 4 and 10 mM glucose concentrations(Jayaprakasam and others 2005)Slide33

Anthocyanins and anti-diabetic propertiesFigure 5. Percent inhibition of COX-1 and COX-2 enzymes by Vioxx, Celebrex, aspirin, naproxen, and ibuprofen(Zhang and others 2004)Slide34

Anthocyanins and vision improvementBritish Royal Air Force aviators ate bilberry jam to improve their night visionImpaired visual function is a techno-stress syndromecaused by concentrated work on video display terminals in today’s computerised

societySlide35

Anthocyanins and vision improvementTable 1. Contrast sensitivity before and after administration in placebo and anthocyanoside group(Lee and others 2005)Slide36

Melatonin in grapesStructure : Precursor : tryptophan.Slide37

Sources of melatonin Slide38

Metabolic PathywayFour enzymes from Try to MelMelatonin regulates your sleep and wake cycles.Light also affects the amount of melatonin production in your bodySlide39

Dynamic and cyclic nature of melatonin productionHuman blood levels range from 20 picograms per milliliter in the morning to 55 pg/mL at night (a picogram is one-trillionth of a gram). Natural production of melatonin by the human body declines with age.Melatonin are used to treat jet lag

 or

 Insomnia

(lack of sleep),

(SAD).

Melatonin supplement how safe are they? Overdose? Contamination? OTC or requires prescription?Slide40

Melatonin’s functions in plantsPhoto-periodic reactions in higher plants. Night signalsAntioxidant activity ( protection of germen to oxidative stress).Redox cycling doesn’t occur in melatonin(suicidal antioxidant);stable end productGrowth stimulating factorSlide41

Melatonin concentration in plants??Slide42

GRAPESMelatonin in grapes:It is available in wide concentrations ranging from pg to ug/g tissue ( cultivars, ripeness, harvest time , light intensity).Skins and seeds contain more melatonin than pulp/juice. Red grapes contain higher melatonin than white one.In wine , fermentation also generates melatoinin synthesized by yeasts.When plants defense activator, Benzothiadiazole

(BTH) is used to treat grape vine, increase in concentration of melatonin has been observed.  Melatonin is found considerably higher in some cultivars, such as

Nebbiolo

, and which can be raised further by BTH treatment. 

Melatonin isomers also exists in grapes.Slide43

Melatonin concentration in the eight grape cultivars examined and in the two plasma samples used as controlSample

Melatonin

a

(

pg ml

−1

)

Melatonin

b

 (

ng

g

−1

)

Plasma control 1

10.6 ± 3.2

ND

Plasma control 2

134.7 ± 10.3

ND

Barbera

25.5 ± 2.5

0.633

Croatina

304.6 ± 23.4

0.870

Cabernet Sauvignon

183.6 ± 18.8

0.422

Cabernet Franc

2.4 ± 0.6

0.005

Marzemino

14.9 ± 4.1

0.031

Nebbiolo

428.3 ± 32.1

0.965

Sangiovese

255.5 ± 16.3

0.332

Merlot

114.2 ± 7.2

0.264

Merlot, BTH-treated

301.5 ± 22.5

0.726

a

Melatonin concentration in plasma and grape skin extracts as determined by ELISA (means ± SE from three extraction experiments).

b

Melatonin content in

ng

, referred to 1 g of grape skin and calculated from the means in the other column of data.

Iriti

et al.(2006)Slide44

HEALTH SIGNIFICANCEIs melatonin a Panacea ??Slide45

References supporting antioxidant activities of melatoninGalano, A., Tan, D. X., & Reiter, R. J. (2011). Melatonin as a natural ally against oxidative stress: a physicochemical examination. Journal of pineal research, 51(1), 1-16.Rodriguez, C., Mayo, J. C., Sainz, R. M., Antolin, I., Herrera, F.,

Martín

, V., & Reiter, R. J. (2004). Regulation of

antioxidant enzymes

: a significant role for melatonin. 

Journal of pineal research

, 

36

(1), 1-9.

Tan, D. X., Manchester, L. C.,

Terron

, M. P., Flores, L. J., & Reiter, R. J. (2007).

One molecule, many derivatives

: A never‐ending interaction of melatonin with reactive oxygen and nitrogen species?. Journal of pineal research, 42(1), 28-42.Reiter, R. J., Tan, D. X., Osuna

, C., & Gitto, E. (2000). Actions of melatonin in the reduction of oxidative stress. Journal of Biomedical Science, 

7

(6), 444-458.Slide46

Antioxidant activity : mechanismsFigure . Hypothetical pathways involved in melatonin regulation of antioxidant enzyme gene expression and activity.Slide47

Some of the proposed mechanisms by which melatonin interferes with the growth of estrogen-mediated mammary cancer cell growth. Slide48

References supporting to treat sleep disorders in Alzheimer’s disease patients.Cardinali, D. P., Brusco, L. I., Liberczuk, C., & Furio, A. M. (2002). The use of melatonin in Alzheimer's disease. Neuro endocrinology letters, 23, 20-23.Slide49

Sewerynek, E. (2002). Melatonin and the cardiovascular system. Neuro endocrinology letters, 23, 79.Melatonin may reduce blood pressure via the following mechanisms: 1) by a direct effect on the hypothalamus; 2) as an antioxidant which lowers blood pressure; 3) by decreasing the level of

catecholamines

, or

4) by relaxing the smooth muscle in the aorta wall.Slide50

Melatonin and immune systemCarrillo-Vico, A., Guerrero, J. M., Lardone, P. J., & Reiter, R. J. (2005). A review of the multiple actions of melatonin on the immune system. Endocrine,27(2), 189-200.Skwarlo-Sonta, K. (2002). Melatonin in immunity: comparative aspects. 

Neuro

endocrinology letters

, 

23

, 61.

Szczepanik

, M. (2007).

Melatonin and its influence on immune system

. 

Journal of physiology and pharmacology

, 

58

(6), 115-124.Slide51

Hypothetical scheme of melatonin regulation of cytokine production.