Functional Components Onion and Their Relation of Cancer and Chronic Disease Prevention Bhimu Patil...

Functional Components Onion and Their Relation of Cancer and

Chronic Disease Prevention

Bhimu PatilPart-I

Phytochemicals• Naturally occurring biologically active components • Found in plant

Phytonutrient• Plant chemical with known nutrient properties• Consumed as part of a usual diet

Biologically active or Protect against DiseaseHealth Canada, 1998

Bioactive Compounds“Extranutritional” constituents that typically are naturally occurring in small quantities in plant products and lipid rich foods.

Kitts, 1994 Can J. Physiol Pharmacology 1994

Nutraceutical• Product isolated or purified from foods • Sold in medicinal forms - pill, powder, capsule

Functional Food• A conventional food• Consumed as part of a usual diet• Provide health benefit beyond basic nutrition

Biologically active or Protect against DiseaseHealth Canada, 1998

Fundamental Trends Driving Market

Aging Demographics

Emphasis on preventative measures to control health care costs

Increased interest, acceptance and utilization of “alternative” treatments

Expanding body of scientific evidence

Increasing Marketing and advertising activities

Claims of Food Harms vs Benefits in Media

IFIC, Food for Thought III, Feb, 2000

0

20

40

60

Benefits Harms

1995

1997

1999

Classification of Phytochemicals

Chemopreventive agents

• Micronutrients

–vitamins, beta carotene, molybdenum, calcium

• Phytochemicals

• Synthetics

–vitamin derivatives

–piroxicam

–tamoxifen

Phytochemicals

• Organosulfides

• Isothiocynates

• Indoles

• Dithiolthiones

• Polyphenols• Flavonoids• Tannins• Folic acid

Contd.

Phytochemicals

• Carotenoids

• Indole

• Saponins

• Coumarins• Dietary Fiber• Isoflavones• Protease

inhibitors


(Based on their mechanisms of action)

• Blocking agents

• Suppressing agents

Cancer Producing Compounds

Blocking Agents

Cells Attacked By Cancer Producing Compounds

Suppressing Agents

Cancer Wattenburg, 1993


• Blocking agents

– Flavonoids

– Indoles

– Isothiocynates

– Diallyl sulfides

– D-limonene

Chemopreventive agents• Suppressing agents

–D-limonene, Diallyl sulfides, vitamin D, vitamin A and retinoids, monoterpenes, carotenoids, polyphenols, protease inhibitors, selenium and calcium

Anticarcinogenic mechanisms

• Antioxidant effects

• Increased activity of enzymes that detoxify carcinogens

• Effect on cell differentiation

• Blocked formation of nitrosamines

• Altered estrogen metabolism

• Decreased cell proliferation

• Maintenance of normal DNA repair

• Angiogenesis

Can Phytochemicals

Prevent Cancer?

Initiation

Promotion

Phase I enzymes

Oxidative damageFree radicals

Quercetin, Lycopene, Lutein, Zeaxanthin and Beta carotene

Procarcinogens

CarcinogensElectrophiles

DNA Damage

Phase II enzymesGlutathione S-transferaseLimonoidsFlavonoids ?

Tumor

???

• What is Quercetin?

• How is it synthesized?

• What is its role in disease prevention?

What is Quercetin?

• Flavonoid

• Vacuoles of a plant cell

• Synthesized during bulb and leaf development

Background

• Flavonoids-non nutrient

• 1936-Szent-Gyorgyi, called flavonoids as vitamin P.

• 1950 disproved the theory

• Late seventies-mutagenecity of quercetin

• Recent research-anticarcinogenic

FLAVONOIDS

• Flavonols

• Flavonones

• Flavones

• Anthocyanidins-cyanidin

• Catechins-epigallocatechin

• Biflavans-proanthocynidin

O

OH

O R2

R1

HO

HO

Structure of flavonoids

X

7

6

5

3

2

4

8

6151

41

31

21

Flavonols: X=OH; Quercetin: R1=OH, R2=H; Kaempferol; R1=H, R2=H; Myrcetin: R1=OH, R2=OH.

Flavones: X=H; Luteolin:R1=OH, R2=H; Apigenin: R1=H, R2=H

A

B

C

FLAVONOLS• Kaempferol

• Quercetin

• Myrcetin

O

OH

Kaempferol

O

OH

HO

HO

O

OH

Quercetin

O OH

OH

HO

HO

O

OH

Myricetin

O

OH

HO

HO

OH

OH

Biosynthesis of QuercetinPentose phosphate pathway Glycolysis

Shikimic acid pathway

Dihydroquercetin

Quercetin

Malonic acid pathway

Malonyl CoA 4 Coumaryl CoA

O

OH

O

HO

HO

OOH

OHOH

A

B

CA

B

Chalcone synthase

4 Coumaryl -Co A Malonyl-Co A

Chalcone isomerase

Naringenin Chalcone Flavonone (naringenin)

Case Control and Cohort Studies of All Types of Cancer (Contd.)

Steinmetz and Potter, 1996, JADA 96:1027-1039

Fruit No. of studiesInverse Positive

RawVegetables

33 2

Crucifers 38 8

Alliums 27 4

Legumes 14 16

GreenVegetables

61 13

Biological Effects of Quercetin

• In vitro– Mutagen– Genotoxic– DNA strand Scission

• In vivo– Anticarcinogenic

Contd.

Biological Effects of Quercetin

• Effects on Enzymes associated with cancer

• Miscellaneous effects

Quercetin Superoxide DNA Strand BreakageCu, Fe

In vitro

In vivo

In Salmonella

In mammalian Cells

Superoxide DismutaseCatalase

Glutothione Peroxidase

Defend against:SuperoxideHydrogen Peroxide

Free radicals

Incubation

Components of Quercetin

• Glucosides

–Quercetin 3, 4' diglucoside

–Quercetin 4' monoglucoside

–Present in vacuoles

• Free quercetin (Aglycone)

–Oil glands and waxy layers

Hydrolysis of flavonols

Quercetin Glycosides

HCL

H2 SO4

Enzymes

Quercetin (Aglycone)

Optimum Hydrolysis

Sample Conditions Quercetin(mg/kg dry wt)

Cranberry 1.2 M HCl/0.5 hr 1485Onion 1.2 M HCl/2 hr 5076Lettuce 2.0 M HCl/2 hr 319Celery 2.0 M HCl/4hr <10

Hydrolysis of flavonols

Quercetin Glycosides Glycosidase

Mouth

Gut

Stomach

Fecalase

Quercetin (Aglycone)

FLAVONOID CONTENT OF FRUITS AND VEGETABELS

Vegetable Quercetin Kaempferol

Onion 347 <2

Turniptops

7.3 48

Leek <1 30

Kale 110 211

Broccoli 30 72Hertog et al., (1992)

mg/kg fresh edible part

Vegetable Quercetin Kaempferol

Endive <1.3 46

Lettuce 14 <2

Frenchbeans

39 <12

Tomato 8 <2

Broad bean 20 <2Hertog et al., (1992)

mg/kg fresh edible part

FLAVONOID CONTENT OF BEVERAGES

Beverages Quercetin Myricetin

Red wine 4.1 7.5

Red Chainti1990

16 8.0

White wine <0.5 1.0

Grape juice 4.9 <0.5

Apple Juice 2.5 <0.5Hertog et al., (1992)

mg/L

Beverages Quercetin Myricetin

Tomato juice 13 <0.5

Lemon Juice 7.4 <0.5

Orange Juice 3.4 <0.5

Grapefruit Juice 4.9 <0.5

Beer (Heineken) <0.5 <0.5Hertog et al., (1992)

mg/L

Flavonol and flavone contents of common vegetables and fruits

Flavonol andflavone

Fruits andVegetables

High>50 mg/kg)

Broccoli, endive,kale, french beans,celery, onions,cranberries

Hollman et al (1996)

Flavonoland flavone

Fruits and Vegetables

Low<10 mg/kg

Cabbage, spinach,carrots, peas,mushrooms, peaches,strawberries, orangejuice, white wine, brewedcoffee

Medium<50 mg/kg

Lettuce, broad beans, redpepper, tomato, apples,grapes, cherries, tomatojuice, red wine, teabeverages

Flavone and Flavonol intake Quer

intake (mg/g)

Flavonol and flavone intake (mg/day)

Veg & fruits (%)

Red wine (%)

Tea (%)

Finland 6 6 100 0 0 USA 11 13 80 0 20 Siberia 10 12 98 2 0 Greece 21 16 97 3 0 Italy 13 27 54 46 0 Netherlands 30 33 36 0 64 Croatia 30 49 82 18 0 Japan 31 64 10 0 90

Hertog et al (1995)

Flavonoid intake

60%13%

10%

5%

4%8%

TeaOnionApplesEndiveKaleOthers

Diet and Quercetin

Daily Intake of Flavonoids

1 g (USA)

2.5 g (Other countries)

4-oxy flavonoids (170 mg)

Quercetin- 50 mg

Flavones

Flavonols

After ingesting 225 g fried onions

0

50

100

150

200

250

300

0 2 4 24 48

Time (hour)

Plasma Quercetin

(ng/ml)

McAnis et al., (1998)

After ingesting 225 g fried onions

1.5

1.55

1.6

1.65

1.7

1.75

1.8

0 2 4 24 48

Time (hour)

Antioxidant activity

mmol/ trolox equivalents)

McAnis et al., (1998)

0

1

2

3

4

5

Flavonoids

Trol

ox e

quiv

alen

t an

tioxi

dant

ac

tivity

Quercetin Rutin Catechin LuteolinApigenin Naringenin Hesperetin Kaempferol

Cathrine et al (1997)

Antioxidant Activity

Flavonols, Flavones and Coronary Heart Disease

Flavonol and flavone intake and coronary heart disease

0

0.2

0.4

0.6

0.8

1

1.2

0-19 19.1-29.9 >29.9

Flavonol and flavone intake (mg/day)

Re

lati

ve

Ris

k

Crude

Adjusted (age,dietand risk factors)

Hertog et al (1993)

Factors influencing quercetin content

• Cultivars- sweet vs. fall storage

• Production systems

• Developmental stages

• Scale age

• Postharvest gamma irradiation

Changes bioactive compound levels from plant to human?

Genetic selection /production practices

Food

matr

ix /

oth

er

meal

com

pon

en

ts

Processing/culinary practices

Ind

ivid

ual ch

ara

cteristics

Plant content

Bioavailable content

IngestionIngestion

AbsorptionAbsorption

Factors influencing micronutrient contents in plants

Carotenoids Vitamin C Phenoliccompounds

Variety *** *** ***

Light * ** **

Fertilization **(less N)

**(less N)

Maturity stage

*** * *

Amiot-Carlin MJ 2003 Quality of plant-derived products. Forum Nutr 56:318-321

Vitamins T° Light Oxidative agents

Acids Alkali

Carotenoids

K

B9

C

Very sensitive

sensitive

Factors degrading vitamins during processing





• Scale age


Sweet Onion Cultivars

050

100150200250300350

Cutlivars

To

tal Q

uer

ceti

n (

mg

/kg

)

Patil et al., 1995. J. Amer. Soc. Hort 120(6):909-913

Sweet Onion Genotypic Variation - Total Quercetin

0

50

100

150

200

250

Genotypes

Qu

erce

tin

(m

g/k

g f

resh

wt)


Sweet Onion Genotypic Variation- Free Quercetin

0

2

4

6

8

10

12

14

2035

6G

2035

2G

2035

5G

2035

4G

2027

5G

2027

7G

2027

0G

2036

6G

2035

7G

2027

2G

2030

3G

2029

1G

2027

4G

2028

8G

2027

6G

2028

0G

2029

0G

2030

1G

2025

3G

2033

0G

2026

3G

2031

6G

2033

8G

2025

1G

2030

5G

2025

9G

2024

9G

2025

7G

Genotypes

Fre

e Q

ue

rce

tin

(m

g/k

g f

res

h

wt)


Comparison of quercetin

Authors mg/kg fresh wt

Hertog et al., 1993 544

Hermann et al., 1976 104-1060

Bilyk et al., 1986 15-62

Patil et al., 1995 54-202 ( sweet onion)500 (fall onions)

Price et al., 1997 89-1778

Variation of Quercetin: BiotechnologyTomato

Cultivar Conc. (ppm)

Roma 11

Cherry 15

Allsa Craig (Hp/Hp) 12

Allsa Craig (hp/hp) 220

Dr. James Giovannoni’s lab





• Scale age


Differences in location

• Griffin & Brand

–Soil: sandy loam

–400 m from Rio Grande River

• Starr County

–Soil: slightly heavier

–Two miles east of Rio Grande River, south of Rio Grande City

Growing location effect on quercetin

0

50

100

150

200

1607

B*

1613

B*

1627

B*

1631

B

1656

B

TG1015

Y*

Cultivars

Qu

erc

eti

n (

mg

/kg

fre

sh

w

t)

Griffin and Brand, McAllen, TX Starr County, TX

Patil et al., 1995. New Phytology 130(3):349-355





• Scale age


Quercetin content during

'TG1015Y' bulb development

0

20

40

60

80

100

9 March (0) 23 March(14)

1 April (24) 14 April(37)

21 April(44)

Date (Days after bulb development)

Qu

erc

eti

n (

mg

/kg

fre

sh

w

t)

Sandy loam clay

Patil and Pike 1995. J. Hort Sci. 70(4):643-640

Very earlylifting

Earlylifting

Latelifting

Very latelifting

Erect leaves

Fallen leaves

1 x Q 2 x Q

Common practiceCourtsey from Dr. Mogren

Lifting time – fresh onions

0% 50% 80% 100%0

20

40

60

80

100

120

140

160

180

200Q

ue

rce

tin g

luco

sid

e c

on

ten

t (m

g k

g-1 fw

)

Onions with fallen leaves at lifting

a

b

c

d

Mogren et al., 2006

When?

100%

0%50%

Lifting timein practise

Mogren et al., 2006





• Scale age


Different onion scales

Outer scales

Middle scales

Inner scales

Courtsey from Dr. Mogren

Distribution among edible parts

050

100150200250300350400

Kadavan Red Bone TG1015Y TG502 Contessa

Different scales

Qu

erc

eti

n c

on

ten

t (m

g/k

g

fre

sh

wt)

1-2 rings 5-6 rings 7-10 rings


Distribution among edible parts

0

100

200

300

400

500

600

700

Fresh Weight (mg/kg) Dry Weight (g/kg)

Different scales

Qu

erc

eti

n c

on

ten

t (m

g/k

g

fre

sh

wt)

1-2 rings 3-4 rings 5-6 rings 7-10 rings


Field curing

Sun exposure ≈ 10 days

Before: 1 x Q

After: 1.5 x QMogren et al., 2006





• Scale age


Effect of gamma irradiation

0

5

10

15

0.0 kGy 0.8 kGy 1.2 kGy

Treatments

Fre

e q

uer

cet

in

con

ten

t (m

g/k

g

fres

h w

t)

Patil et al., 1999. Subtropical Plant Science 51:15-21

Effect of gamma irradiation

0

50

100

150

200

250

0.0 kGy 0.8 kGy 1.2 kGy

Treatments

To

tal q

uer

ceti

n

con

ten

t (m

g/k

g f

resh

w

t)

Patil et al., 1999. Subtropical Plant Science 51:15-21

Effect of Processing

0

100

200

300

400

None Fried Boiled Microwaved

Cooking

Qu

erce

tin

(u

g/g

)

Crozier et al., 1997

Summary-Quercetin

• Sweet and fall storage onions differ significantly

• Within a group there are significant cultivar differences

• Influenced more by genotype than by environment

• Concentration gradient: outer scales greatest

Toxicity of Quercetin• Average human consumption-50 mg/day

• for 60 kg man would be less than 1 mg/kg.

• Plasma concentration of 12 uM quercetin was achieved by 100 mg without any side effects (Gugler et al., 1975)

• 1g/day/adult (Barnes, 1990) without any side effects

Functional Components Onion and Their Relation of Cancer and Chronic Disease Prevention Bhimu Patil...

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