Review of Related Literature

Pomelo

Shaddock, common name for a tree of the rue family, that, like

other members of the citrus genus, is native to Indonesia and has long

been cultivated in southern Europe. Shaddock is readily distinguished from

most other citrus species by large leaves and a broad-winged leafstalk. It

has very large white flowers, and the large fruit, also called shaddock,

sometimes weighing 4.5 kg (10 lb) or even 6 kg (14 lb), is roundish and

pale yellow. The bitter rind is thick, white, and spongy within; the pulp is

greenish and watery, and slightly acid and aromatic. It is a pleasant,

cooling fruit, often used for preserves. Finer and smaller than the

shaddock proper is the grapefruit, a variety larger than an orange that

bears its fruit in clusters. Both the shaddock and the grapefruit are also

called pomelo, or pummelo.

Scientific classification: The shaddock belongs to the family Rutaceae. It is

classified as Citrus maxima.

Grapefruit

Grapefruit, also called Pomelo, (Citrus paradisi), citrus tree of the - family and its

edible fruit. The grapefruit tree grows to be as large and vigorous as

an orange tree; a mature tree may be from 4.5 to 6 metres (15 to 20 feet) high.

The foliage is very dense, with leaves dark and shiny green and nearly glabrous.

Flowers are large, white, borne singly or in clusters in the axils of the leaves;

petals are similar to those of sweet orange but usually larger. Lemon-yellow

when ripe, the fruit ranges from 100 to 150 mm

Pomelo Benefits:

The benefits of pomelo fruit are listed below.

1. Prevents Urinary Tract Infection:

Urinary Tract infection is a bacterial infection that affects the urinary

system that creates stores and removes urine. Increased consumption of

pomelo juice helps to fight this particular frequent swelling in pregnant women.

The Vitamin C present in pomelo increases the acid level in urine and shirks the

development of bacteria in the urinary tract.

2. Promotes healing:

Wound recovery practise suggests recovering strength of wounded tissue

by replacing the dead tissue with a healthy tissue. Enzyme in Vitamin C helps in
the development of Collagen, a protein that fortifies skin making it skin flexible

and initiating wound recovery.

3. Healthy gums:

Bleeding and loose gums might be a symbol of Vitamin C

deficiency. Collagen development is not just essential for skin, but also

essential for creating healthy and balanced gums and teeth. Pomelo

helps to make the gums stronger and keeps teeth problems at bay.

4. Heart health:

Pomelo has a high content of potassium, which like Vitamin C plays an

important role in supporting the heart. This essential mineral regulates blood

pressure levels. Abundant in pectin, pomelo juice clears the arterial deposits

accumulated in the body, thereby reducing the impurities and benefiting

people with hypertension. Pomelo also reduces the cholesterol count in the

body and promotes good cholesterol.

5. Prevents anaemia:

Research has shown that Vitamin C enhances the absorption of iron in

body. Iron deficiency often leads to anaemia i.e. shortage of blood in body.

Having a diet rich in Vitamin C helps to combat iron loss and improves blood

circulation.
6. Wards off cold and flu:

Eating fresh pomelo fruit or drinking pomelo juice, can help prevent toxins

and free radical cells from building up in the body. Too many free radicals in the

body can cause health conditions like cold, flu, asthma, bacterial infection,

allergies and so on. Vitamin C is one of the nutrients which stimulates the action

of antibodies and immune cells which guard the body against bacteria that

cause cold and flu.

7. Fights cancer:

The skin of pomelo is very rich in bioflavonoids which fights cancer and

helps to reduce pancreatic, intestinal and breast cancer. It also stops cancer

from spreading by enabling the body to eliminate excess oestrogen. Fiber,

present in pomelo protects from colon cancer.

8. Fights Anti ageing:

Pomelo, like grapefruits contain spermadine which protect the cell from

processes related to ageing and cell damage. It combats wrinkles and skin

ageing and makes the skin appear youthful, fair and soft. It not only removes

free radicals that harm the skin, but also assists the body to boost the production

of collagen.

9. Weight loss:

Fiber is extremely significant for weight loss. Foods high in fiber stays in the

stomach for a longer time and reduces regular hunger pangs. They also need
more chewing time giving the body longer time to feel satisfied and reducing

the risk of too much eating. This fruit also has properties which help to burn the

fat reducing the starch and sugar content in the body.

10. Prevents osteoporosis:

Uncontrolled osteoporosis can affect posture, bodily movements as well

as flexibility. Treatment for brittle bones calls for a diet rich in calcium and

minerals to encourage new bone development. The pulp of pomelo boosts

bone health and decreases the potential risk of building brittle bones.

11. Aids digestion:

The high Vitamin C content in pomelo retains the elasticity of arteries and

improves the digestive system. Although the food has high ascorbic acid

content, it produces an alkaline reaction once digested. Pomelo is filled with

dietary fiber which assists in preserving normal bowel motions and avoids

haemorrhoids.

Mechanism of Action

Pharmacology:

Constituents: Grapefruit juice appears to irreversibly inhibit the intestinal

cytochrome P450 3A4 system, responsible for the first-pass metabolism of

many medications. The inhibition of this enzyme system leads to an

 elevation in blood serum concentration of the drug when administered

concurrently with grapefruit juice.

Grapefruit juice contains vitamin C, antioxidizers, furanocoumarins

(bergamottin, 6',7'-epoxybergamottin, 6',7'-dihydroxybergamottin),

flavonoids (naringenin, naringin) and sesquiterpen (nootkatone),

bergapten (5-methoxypsoralen), polyamines (e.g. putrescine), and

limonoids. Naringin is the most abundant flavonoid in grapefruit juice,

present in concentrations of up to 1mM/L.

Structures from the limonoids of Mexican grapefruit were identified as

obacunone, nomilin, limonin, deacetylnomilin (DAN), and limonin-17-

beta-D-glucopyranoside (LG).

It has been determined that lime and lemon juices can be regarded as a

group distinct from grapefruit and pummelo juices, while orange juice

appears to belong to a bridging group.

It has been suggested that phenolic compounds can be used as

biomarkers of specific poly-phenol rich food, in particular, naringin for

grapefruit.

The dried peels of white grapefruit (Citrus paradise) contain high amounts

of ascorbic acid and carotenoid content compared to the other fruits in

addition to polyphenols.

Anticancer effects: Grapefruit juice contributes a high amount of

putrescine to the diet, which may slow the cancer process.

 Antioxidant effects: The dried peels of white grapefruit (Citrus paradise)

contain high amounts of polyphenols, ascorbic acid, and carotenoids,

which suggest an antioxidant potential. Bergaptol has shown good

radical scavenging activity at different tested concentrations. Fresh red

grapefruit contains higher quantities of bioactive compounds and has

significantly higher antioxidant potential than blond grapefruit as

determined by oxygen radical scavenging capacity, 1,1-diphenyl-2-

picrylhydrazyl, carotenoid bleaching, and Folin-Ciocalteu assays. Citrus

limonoids identified as obacunone, nomilin, limonin, deacetylnomilin

(DAN), and limonin-17-beta-D-glucopyranoside (LG) found in Mexican

grapefruit possess antioxidant properties such as radical scavenging

activity.

Antiviral effects: Based on laboratory study, grapefruit juice may have

antiviral effects.

Cardiovascular effects: Beneficial cardiovascular effects of grapefruit may

be due to the flavonoid content. Diet supplemented with grapefruit

pectin or red grapefruit has been shown to inhibit hypercholesterolemia

and have a protective effect against atherosclerosis. However, the

grapefruit pectin may have a direct beneficial effect on atherosclerosis

by a mechanism independent of cholesterol levels. The dried peels of

white grapefruit (Citrus paradise) contain high amounts of polyphenols,

ascorbic acid, and carotenoids, which may be beneficial in

 cardiovascular disease. In a case report, a patient receiving nifedipine

and terazosin had markedly lower blood pressure after consumption of

grapefruit juice (no further details provided); however, the mechanism of

action is not fully understood but may be due to the flavonoids (e.g.

naringin).

CYP 450 effects: Bergamottin, the primary furanocoumarin extracted from

grapefruit juice, has been found to be a mechanism-based inactivator of

P450 3A4. Bergamottin has also been found to inhibit the activities of P450s

1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes.

According to one randomized controlled study, bergamottin is likely

responsible for drug interactions with commercial grapefruit juice;

although, 6',7'-dihydroxybergamottin and naringin may be more

important in grapefruit segments because they are present in higher

concentrations. However, bergamottin and reversible inhibition were

clinically shown not to be the primary substance and mechanism

responsible for the inhibition of CYP3A4 activity. The naringin capsule

alone did not alter the pharmacokinetics of nisoldipine, suggesting that a

combination of the active ingredients may be responsible for the

grapefruit-drug interactions.

Grapefruit juice may affect hepatic and intestinal CYP3A4 dose-

dependently. One clinical study found that a high dose (double strength

three times per day for three days) of grapefruit juice appeared to inhibit
 hepatic and intestinal CYP3A4 whereas a normal dose (single strength

single dose) appeared to inhibit intestinal but not hepatic CYP3A4. Drug

interactions with grapefruit juice that occur by inhibition of CYP3A

enzymes may also affect the activity of influx (e.g. OATPs) and efflux (e.g.

P-glycoprotein) transporters. Grapefruit also appears to activate P-gp-

mediated efflux of drugs that are substrates of P-glycoprotein, potentially

partially counteracting the CYP3A-inhibitory effects of grapefruit.

Bergaptol and geranylcoumarin were found to be potent inhibitors of

debenzylation activity of CYP3A4 enzyme.

Drugs that are substrates of cytochrome P450 isoform CYP1A2 may not be

inhibited by grapefruit juice in a clinically significant manner.

Enzymatic activity (esterase inhibition): The active components of

grapefruit juice responsible for its esterase-inhibitory effect were identified.

The esterase-inhibitory potential of 10 constitutive flavonoids and

furanocoumarins toward p-nitrophenylacetate (PNPA) hydrolysis was

investigated. The furanocoumarins bergamottin, 6',7

dihydroxybergamottin, and bergapten, and the glycoside flavonoids

naringin and hesperidin, at concentrations found in grapefruit juice or

higher, did not inhibit the hydrolysis of PNPA by purified porcine esterase

and human liver microsomes. However, the flavonoid aglycones morin,

galangin, kaempferol, quercetin, and naringenin showed appreciable

inhibition of PNPA hydrolysis in purified porcine esterase and human and

 rat liver systems. In Caco-2 cells, demonstrated to contain minimal CYP3A

activity, the permeability coefficient of the prodrugs lovastatin and

enalapril was increased in the presence of the active flavonoids

kaempferol and naringenin, consistent with inhibition of esterase activity.

In rats, oral coadministration of kaempferol and naringenin with these

prodrugs led to significant increases in plasma exposure to the active

acids. In addition, in portal vein-cannulated rats, coadministration of

lovastatin with kaempferol (10mg/kg) led to a 154% and a 113% increase

in the portal plasma exposure to the prodrug and active acid,

respectively, compared with coadministration with water. The contribution

of CYP3A inhibition was demonstrated to be minimal.

Intestinal effects: In a case series of 15 patients with atopic eczema,

150mg oral grapefruit seed extract (ParaMicrocidin) three times daily for

one month reduced intestinal Candida spp., Geotrichum spp., and

hemolytic coliforms and slightly inhibited Staphylococcus aureus and

aerobic spore formers. All patients noted improvement in constipation,

flatulence, abdominal discomfort, and night rest after four weeks of

treatment.

Neurologic effects: The effects of the cuticle and epicuticular waxes of

grapefruit on the photodegradation and penetration of chlorpyrifos-

methyl were studied. No pesticide was detected in samples of grapefruit

 pulp. The waxes and cuticle appear to have some effect on the

photodegradation and penetration of chlorpyrifos-methyl.

Renal effects: In a clinical trial of seven healthy subjects with no history of

kidney stones ingesting a soft drink containing grapefruit juice diluted

(10%) in mineral water, grapefruit juice significantly (p=0.021) increased

urinary excretion of citrate (25.8 9.3 vs. 18.7 6.2mg/hour), calcium (6.7

4.3 vs. 3.3 2.3mg/hour, p=0.015), and magnesium (2.9 1.5 vs. 1.0

0.7mg/hour, p=0.003) compared to mineral water ingestion. However, two

large epidemiological studies linked drinking grapefruit juice to an

increased risk of kidney stones.

Weight loss effects: Although the mechanism of grapefruit in weight loss is

unknown, it has been shown to decrease weight as part of a weight-

reduction diet.

Other effects: In vivo study has found that the dietary flavonoids in

grapefruit juice may inhibit the enzyme 11-hydroxysteroid

dehydrogenase, which oxidizes cortisol to inactive cortisone in a

concentration dependent manner.11 High doses were observed to cause

an apparent mineralocorticoid effect and theoretically, some individuals

might increase their potassium clearance if they drink large amounts of

grapefruit juice.

Naringenin, the principal flavonoid in grapefruit, inhibited the lipidation

and subsequent secretion of apoB-containing lipoproteins primarily by

 limiting the accumulation of triglycerides in the endoplasmic reticulum

lumen, secondary to microsomal triglyceride transfer protein (MTP)

inhibition.

Pharmacodynamics/Kinetics:

Absorption: Methoxyflavanones from grapefruit appear to be absorbed

from the juice.

Bioavailability: The interaction potential of high amounts of grapefruit

juice with CYP3A4 substrates dissipates within three to seven days after

ingestion of the last dose of grapefruit juice. Cumulative urinary recovery

of naringin and hesperidin in one study indicated low bioavailability

(<25%) of the grapefruit substituents. Bioavailability and unbound fraction

(f(u)) are major determinant factors of calcium antagonist-grapefruit juice

interaction; a drug with smaller bioavailability or lower f(u) is likely to

exhibit a more potent interaction and vice versa.

Metabolism: Absorbed citrus flavanones may undergo glucuronidation

before urinary excretion.

Excretion: The urinary excretion ratio of the endogenous 6 beta-

hydroxycortisol and cortisol ratio was significantly decreased (p=0.036) by

grapefruit juice in one clinical study. In one in vitro study, 6',7'-

dihydroxybergamottin (DHB) rapidly inhibited CYP3A4 activity in a

substrate-independent fashion with maximal inhibition (85%) generally

 occurring within 30 minutes. In contrast, bergamottin (BG) had a slower

onset and exhibited substrate-dependent inhibition.

Median Inhibition Concentration: An in vitro study evaluating the CYP3A4

inhibitory properties of the various substituents found in grapefruit juice

identified bergapten (5-methoxypsoralen) with the lowest IC50 value (19-

36mcM) to be the most potent CYP3A4 inhibitor and proposed that more

than one component of grapefruit juice may be responsible for its CYP3A4

inhibitory activity.

In human liver microsomes, the mean IC50 for grapefruit juice versus

CYP3A (triazolam alpha-hydroxylation) was 0.55%, without preincubation

of inhibitor with microsomes.

The alkyloxy-furanocoumarin analogues were found to inhibit CYP3A4

activity in a dose dependent manner, with observed IC50 values ranging

from 0.13 0.03 to 49.3 1.9mcM.

Bergaptol and geranylcoumarin were found to be potent inhibitors of

debenzylation activity of CYP3A4 enzyme with an IC50 value of 24.92 and

42.93mcM, respectively.

Furanocoumarin dimers showed potent dose-dependent inhibition of

CYP3A4 activity in both liver and intestine; IC50 values ranged from 0.021

0.002 to 0.146 0.041mcM (mean S.D. N=3). Of the four dimmers

evaluated further, all showed time-dependent inhibition of CYP3A4

activity. 88Prop showed moderate inhibition of both CYP2C19 and

 CYP1A2 with IC50 values of 4.42 0.01 and 1.98 0.34 microM, 88Octa was

found to inhibit CYP2C19 (IC50=3.16 0.01mcM) and 58Prop to inhibit

CYP1A2 (IC50=2.39 0.77mcM). Minimal inhibition of CYP2D6 and CYP2C9

was observed (IC50>10mcM).

Rice

Rice, plant that produces an edible grain; the name is also used for the grain

itself. Rice is the primary food for half the people in the world. In many regions it

is eaten with every meal and provides more calories than any other single food.

According to the United Nations Food and Agricultural Organization (FAO), rice

supplies an average of 889 calories per day per person in China. In contrast, rice

provides an average of only 82 calories per day per person in the United States.

Rice is a nutritious food, providing about 90 percent of calories from

carbohydrates and as much as 13 percent of calories from protein.

Of the 20 known species of rice, only two are cultivatedthe widely

grown Asian rice and the hardier African rice. Asian rice, if managed with

modern techniques such as fertilizers, irrigation, and chemical pesticides,

produces significantly more grain per plant than African rice, and for this reason

is the preferred type in the majority of rice-growing countries. African rice,

however, is more productive than Asian rice in traditional farming systems where

modern techniques are not used or poor growing conditions are present. About
50,000 varieties exist within these two species, only a few hundred of which are

cultivated.
 Bibliography

Shaddock." Microsoft Encarta 2009 [DVD]. Redmond, WA: Microsoft

Corporation, 2008.

Microsoft Encarta 2009. 1993-2008 Microsoft Corporation. All rights

reserved.

http://global.britannica.com/EBchecked/topic/241976/grapefruit