Citrus Phytochemicals Designer Foods Functional Foods Hypernutritious Foods Nutraceuticals Phytochemicals Naturally occurring biologically active components Found in plant Phytonutrient
Plant chemical with known nutrien properties Consumed as part of a usual diet Biologically active or Protect against Disease Health 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 Disease Health Canada, 1998 Chemopreventive agents Micronutrients vitamins, beta carotene, molybdenum, calcium
Polyphenols Flavonoids Tannins Folic acid Contd. Chemopreventive agents (Based on their mechanisms of action) Blocking agents Suppressing agents CANCER CHEMOPREVENTIVE AGENTS 1. BLOCKING AGENTS -- prevent carcinogens
from reaching or reacting with the DNA, the genetic information. 2. SUPPRESSIVE AGENTS -- inhibit the expression of cancer in cells that have already been exposed to a carcinogen. Cancer Producing Compounds Blocking Agents Cells Attacked By Cancer Producing Compounds Suppressing Agents Cancer Wattenburg, 1993 Chemopreventive agents
Blocking agents Flavonoids Indoles Isothiocynates Diallyl sulfides D-limonene MECHANISM OF ACTION (BLOCKING AGENTS) 1. Inhibit the formation of the active carcinogen. 2. Increase the rate at which the active carcinogen is inactivated. 3. Act as scavengers for the active forms of carcinogens. Chemopreventive agents Suppressing agents
D-limonene Diallyl sulfides vitamin D vitamin A and retinoids monoterpenes carotenoids polyphenols protease inhibitors selenium calcium Anticarcingenic 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 THREE-PHASE MECHANISM FOR CHEMICAL CARCINOGENESIS 1. INITIATION - normal cells to latent tumor cells. 2. PROMOTION - latent tumor cells to carcinoma in situ. 3. PROGRESSION - carcinoma in situ to invasive carcinoma. Procarcinogens Phase I enzymes Phase II enzymes Glutathione S-transferase
Limonoids Carcinogens Electrophiles Flavonoids Promotion DNA Damage Lycopene, Lutein, Zeaxanthin and Beta carotene Initiation Oxidative damage Free radicals
Tumor Health Promoting Compounds Carotenoids Lycopene -Prostate Cancer Beta carotene Lutein and zeaxanthin-Blindness Beta cryptoxanthin Carotenoid Concentrations Lycopene- Grapefruit 3362 ug/100 g wet wt (Mangels et al.,1993) 350 ug/100 g wet wt (Gross et al., 1987) Carotenoid Concentrations (ug/100g) Carotenoids
8. pancreas. lung. colon. rectum. LIMONOID GLUCOSIDES 1. Tasteless. 2. Soluble in water. 3. Human consumption (already present in citrus and citrus products in relatively high concentrations). 4. Can be prepared from by-products of juice processing plants (seeds and citrus molasses). Limonoid Concentrations Limonoid glucosides
Limonin 17-beta D-glucopyranoside (54-180 ppm) Oranges-320 ppm Grapefruit -195 ppm Lemon-90 ppm LG 1000 ROLE OF METABOLISM IN CHEMICAL CARCINOGENESIS P-450 PHASE I PRO CARCINOGENS OXIDATIO
N PHASE II REDUCTION HYDROLYSI S ULTIMATE CARCINOGEN DNA DAMAGE GST GSH
GSH-CONJUGATION PRODUCT EXCRETION TUMOR GST-catalyzed Conjugation of CDNB to GSH GST GSH Cl NO2 NO2 1-chloro-2,4-dinitrobenzene GS
NO2 HCl NO2 Dinitrophenyl glutathione INSOLUBLE SOLUBLE Toxic Less toxic GST in Liver for Aglycone Groups Sp Act (mol/min/mg protein) 0.8
0.6 0.4 0.2 0.0 oil AglMix Nomilin Limonin Treatment GST in Intestine for Aglycone Groups
AglMix Nomilin Treatment Limonin GST in Intestine for Glucoside Groups Sp Act (mol/min/mg protein) 0.5 0.4 0.3
0.2 0.1 0.0 Water GluMixA GluMixB Treatment Naringin Isolation, Purification and Characterization of
Putative Bioactive Compounds Isolated Citrus Bioactive Compounds Limonoids and Flavonoids Limonoid Aglycone Limonoid Glucosides Phase II Enzymes GST and QR Isolation and
Characterization Bioactive Compounds Animal Studies Cell Culture Phase I Enzymes CYP450s Flavonoids Limonoids Colon Cancer Colon Cancer
Experimental Diets Significantly Reduced Total ACF Number 200 a p<0.05 b TOTAL ACF 150 100 50
0 Basal Diet GFPP IGFPP Naringin Limonin Experimental Diets Significantly Reduced High Multiplicity ACF a 14
p<0.05 12 HMACF 10 b 8 6 4 2 0 Basal Diet
GFPP IGFPP Naringin Limonin Objective To investigate the possibilities of various citrus limonoids and flavonoids to reduce plasma cholesterol Percentage of Hamster Plasma LDL/HDL LDL/HDL Cholesterol Ratio Comparison
d 90% 80% d 70% d d c b 60%
Jun Yu a 50% 40% 30% 20% 10% 0% C1 Lim LG Ng
Ngn Pulp C2 Total Antioxidant capacity ORAC- Oxygen Radical Absorbance Capacity can be measured by COBAS FARA II analyzer ORAC of commercial orange juice and vitamin C from juice 20 ORAC (micromoles Trolox eq./ml) Grape
Grapefruit Tomato Orange Apple 15 10 5 0 Juice
Vit. C Juice Vit. C Juice Vit. C Wang et al., 1996. J. Agric. Food Chem. 14(3):701-705. Juice Vit. C Juice
Vit. C Antioxidant Activity of Fruits 160 ORAC (micromoles of Trolox equvivalents/g of dry matter) 140 120 100 80 60 40 20 0
Strawberry Plum Orange Grapefruit Grapefruit Wang et al., 1996. J. Agric. Food Chem. 14(3):701-705. Tomato Grape Grape Pectin Used traditionally for jelly
preparation Modified pectin can prevent prostate cancer Pectin can reduce levels of serum cholesterol How much we need? To consume about 6g of pectin only about 170 g of grapefruit pulp is sufficient (Baker, 1994) Pectin Content in Different Fruits (% fresh wt) Apples Apricots Bananas Beans Blackberries Carrots
0.51-1.00 0.09-0.28 3.30-4.50 2.8-2.99 0.59 2.34-2.38 0.97 1.00-2.00 Dietary Fiber Dietary fiber denotes all plant cell wall components that cannot be digested by an animals own enzymes.
Pectin gums lignin Cellulose Hemicellulose pentosans Citrus Pectin Health Benefits Modified Citrus Pectin (MCP) prevent cancer metastasis, inhibiting cancer cell proliferation
Hypoglycemic Effect Hypocholesterolemic Effect Hemostasis Modulate human immune function Detoxification Steps in the process of tumor dissemination Schematic representation of aggregation of tumor cell to normal cell and pectin function Raz and LOtan, 1987 Probable mechanism of pectin hypocholesterol effect Farnandez, et al., 1990
Pectin Hypocholesterolemic Action Pectin Hemostasis Function Pectin can shorten the coagulation time of blood and act as an antagonist of heparin when injected intravenously. Pectin sulfate can behave as strong anticoagulant. Parts of the citrus fruit which contain pectin Components of Pectin
Molecular Weight Polygalacturonic Acid Galacturonic Acid Content Methoxyl Esters Neutral Sugar Content Ions Proteins Structure of Pectin Side Chain
Rhamnogalacturonan Linear galacturonan Structure of Pectin Fibroblast Growth Factor Signaling System Factor-Receptor Cell needs to communicate to each other.
No Stimulation No Inhibition Inhibitors (Heparin Mimics) Suramin Suramin analogs pentosan polysulfate Carrageenans Dextran Dextran derivatives
FPLC Elution Profile Variation of Pectin Content and Composition in Different Citrus Species Extraction Rate (% of fresh weight) Pectin Extraction Rate in Different Citrus Species 6.00 F/A L 5.00 4.00 3.00
2.00 1.00 0.00 d lem b a tan a b
org b c gra b Changes of Pectin Content and Composition Due to Harvest Season Extraction Rate (% of fresh weight) Pectin Extraction Rate 6
F A 5 4 3 2 1 0 Aug Sep Nov Jan
Mar May L Variation of Pectin Sugar Content mg/g of Pectin Weight 200 F 180 A L
160 140 120 100 80 60 40 20 0 Aug Sep Nov Jan
Mar May Variation of pectin sugar composition Percentage (% of total sugar wt.) 70 rhamnose mannose arabinose galactose xylose glucose
60 50 40 30 20 10 0 Aug Sep Nov Jan Harvest Month Mar
May In Vitro Effects of Citrus Pectin on the FGF Signaling System Specific bound (% of control) Pectin Inhibit FGF-1 Binding to FGFR1 100 80 60 40 20 0 -20
0 3 30 Pectin Concentration (g/ml) 300 Pectin Inhibit FGF-1 Binding to FGFR1 % of Maximum Binding 120 Pectin Added Heparin Only
Tarragon Cucumber Thyme Chives Barley Berries Foods with cancer preventative properties Case Control and Cohort Studies of All Types of Cancer Fruit Vegetables No. of studies Inverse Positive 55
9 Fruits 29 5 Tomatoes 35 10 Carrots 50
7 Citrus Fruit 26 6 Exploring Potential Drug Interaction with Texas Rio Red Grapefruit Variation of Furocoumarins in Different Varieties 9 different varieties are analyzed for the quantitative and qualitative differences in Furocoumarins. Bottom line: Optimization of
furocoumarin levels. Analytical HPLC Profile of Grapefruit Juice UV6000-240nm 3000 3000 Retention Time DHB mAU WHITE GFJ 2000
mAU 2000 1000 1000 Bergamottin Paradisin A 0 0 10
20 30 0 40 50 60 Minutes UV6000-240nm Retention Time
3000 3000 mAU RED GFJ 2000 m AU 2000 1000 1000
Bergamottin DHB Paradisin A 0 0 10 20 30 0 40
Minutes 50 60 Varieties Used for this Study Rio Red Star Ruby Ray Red Henderson Ruby Red Thompson Pink Duncan Marsh White Pumello
Variation of DHB in different Varieties 9 8 7 6 5 g/ml 4 3 2 1 0 Variation of Bergamottin in different Varieties 4 3.5
3 2.5 2 1.5 1 0.5 g/ml 0 Variation of GF-I-1 in different Varieties. 0.8 0.7 0.6 0.5 g/ml0.4
"And they sung a new song, saying, Thou art worthy to take the book, and to open the seals thereof: for thou . wast. slain, and hast redeemed us to God by thy blood out of every kindred, and tongue,...
defer for a later time . to create object B referred to by object A. ... link synonym allowing the user to use in the context of the current directory a symbolic name instead of a long path name. This...
Plenary Session IV. Goals & Strategies #2: Facilitate Local League Work • Help local Leagues increase membership and new leadership • Increase diversity of ethnicity, age, gender and socio-economic status at all levels of League • Support on-going training and...
Parties Indorser The person who indorses the bill, note or cheque to another Indorsee The person to whom the bill, note or cheque is indorsed Parties Drawee in case of need When in the bill or in any indorsement thereon...
John Dewey. I believe it is the business of every one interested in education to insist upon the school as the primary and most effective instrument of social progress and reform in order that society may be awakened to realize...
Epilepsy - 2014 International League Against Epilepsy (ILAE) updated definition: Recurrent unprovoked seizures (two or more unprovoked seizures at least 24 hours apart). Heightened tendency toward future recurrent unprovoked seizure over the next 10 years (single seizure with abnormal EEG...
5-100 KM. Composition. Mostly Oxygen, Silicon, Aluminum, and Granite. Temperature. Ranges from air temperature to 870 C. Density. 2.7 - 3.3 g/cm3. Mantle! The mantle is below the crust. The mantle is the LARGEST layer of the earth containing about...
Ready to download the document? Go ahead and hit continue!