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Phytochemicals – biomolecules for prevention and treatment of

human diseases-a review

Abstract:

Manas Kumar Mukhopadhyay; Pratyusha Banerjee and Debjani Nath*

Department of Zoology, University of Kalyani, Nadia,West Bengal, India

* Corresponding author

Email Address: nath_debjani@yahoo.co.in
Ayurveda is the most ancient healthcare system describes thousands of medicinal plants with their medicinal properties. In recent times, developed countries are turning to the use of traditional medicinal systems because the phytochemicals are potent in different therapeutic applications as they show defensive mechanism of action against a number of chronic diseases including cancer, cardiovascular disease, diabetes, neurodegenerative disease. Plant biomolecules are also involved in anti viral as well as antimicrobial activity and also show efficacy in radioprotection. But still there are some difficulties in proper therapeutic administration of phytochemicals due to their low water solubility, low absorptivity and bioavailability. So a strategy of engineered phytochemicals has been developed to enhance solubility, cellular permeability, proteolytic stability and half-life of plant biomolecules. Still further research is required to ensure high yield as well as viability and bioavailibity of the plant biomolecules in different therapeutic application.

Key words: Medicinal plants and herbs, Plant biomolecules, Therapeutic application, Engineered phytochemicals.

1. Introduction:

Ayurveda is the most ancient health care system and is practiced widely in India, Srilanka and other countries. Atharvveda (around 1200 BC), Charak Samhita and Sushrut Samhita (100 - 500 BC) are the main classics that given detailed descriptions of over 700 herbs. In 78 A.D Dioscorides wrote “De Mater ia Medica”, describing thousands of medicinal plants. This treatise included descriptions of many medicinal plants that remain important in modern medicine, not because they continue to be used as crude drug preparations, but because they serve as the source of important pure chemicals that have important use in modern therapy. The physicians of today continue to use many substances and products derived from natural sources, usually for the same
therapeutic benefit as the crude drug. These single chemical entities, i.e., drugs, form the basis for much of our

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ability to control disease. In recent times, there have been increased waves of interest in the field of research in chemistry of natural Products. This level of interest can be attributed to several factors, including unmet therapeutic needs, the remarkable diversity of both chemical structure and biological activities of naturally occurring secondary metabolites, the utility of novel bioactive natural products as biochemical probes, the development of novel and sensitive techniques to detect biologically active natural products, improved techniques to isolate, purify, and structurally characterize these active constituents, in solving the demand for supply of complex natural products. The R & D thrust is focused on development of new innovative/indigenous plant based drugs from the traditional system of medicine. The World Health Organization has also recognized the importance of traditional medicine and has created strategies, guidelines and standards for botanical medicines. Over the past decade, there has been a resurgence of interest in the investigation of natural materials as a source of potential drug substance. This article is aimed at highlighting the invaluable role of plant biomolecules in different therapeutic applications.

2. Importance of phytochemicals:

In recent times, developed countries are turning to the use of traditional medicinal systems that involve the use of herbal drugs and remedies and according to the World Health Organization (WHO), almost 65% of the world’s population has incorporated the value of plants as a methodology of medicinal agents into their primary modality of health care. It is often noted that 25% of all drugs prescribed today come from plants. This estimate suggests that plant-derived biomolecules make up a significant segment of natural product – based pharmaceuticals. Out of many families of secondary metabolites, nitrogen-containing alkaloids have contributed the largest number of drugs ,ranging in effects from anticholinergics (atropine) to analgesics (opium alkaloids) and from antiparasitics (quinine) to anticholinesterases (galantamine) to antineoplastics (vinblastine/vincristine), terpenoids (including steroids) have made an equally important contribution to human health. They range from Na+/K+ pump-inhibiting cardiac glycosides from Digitalis spp., to antineoplastic paclitaxel , antimalarial artemisinin, anti-inflammatory triptolide. The goals of using plants as sources of therapeutic agents are, a) to isolate bioactive compounds for direct use as drugs, e.g., digoxin, digitoxin, morphine, reserpine, taxol, vinblastine, vincristine; b) to produce bioactive compounds of novel or known structures as lead compounds for semisynthesis to produce patentable entities of higher activity and/or lower toxicity, e.g., metformin, nabilone, oxycodon (and other narcotic analgesics), taxotere, teniposide, verapamil, and amiodarone, which are based, respectively, on galegine, morphine, taxol, podophyllotoxin, khellin, and khellin; c) to use agents as
pharmacologic tools, e.g., lysergic acid diethylamide, mescaline, yohimbine; and d) to use the whole plant or

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part of it as a herbal remedy, e.g., cranberry, echinacea, feverfew, garlic, ginkgo biloba, St. John’s wort, saw
palmetto.

Table1. Numbers of medicinal species documented in different countries and regions:

Country

Total no. of native

species

No. of medicinal

species

Reference

Bulgaria

3567

750

[1]

France

4630

900

[1]

Hungary

2214

270

[1]

Korea

2898

1000

[1]

Malaysia

15500

1200

[1]

Nepal

6973

900

[1]

Pakistan

4950

1500

[1]

Phillipines

8931

850

[1]

Srilanka

3314

550

[1]

Thailand

11625

1800

[1]

Vietnam

10500

1800

[1]

Chile

4672

469

[2]

China

27100

11146

[3]

India

17000

7500

[4]

Mexico

30000

2237

[5]

United states

20000

2572

[6]

South Africa

22000

4000

[7]

Table2. Indian medicinal plants and their medicinal property:

Common Name

Scientific Name

Uses

Acacia

Acacia greggi

astringent, demulcent, emollient

Agrimony

Agrimonia eupatoria

blood coagulant

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Pimenta

Pimenta dioica

heals wounds, bruises

Ajwain

Trachyspermum ammi

antibacterial, carminative, digestive

Ashok

Saraca asoca

relieves menstrual pain, diabetes, uterine disorders

Amla

Phyllanthus emblica

Cough, diabetes, laxative, acidity

Ashwagandha

Withania somnifera

relieves stress, nerve disorder, restores normal function of body

Brahmi

Bacopa monnieri

jaundice, anemia, dropsy

Bael

Aegle marmelos

constipation, diarrhea, dysentery

Chirata

Swertia chirata

burn, skin diseases, fever

Guggul

Commiphora wightii

asthma, hydrocele, diabetes

Guluchi

Tinospora cordifolia

jaundice, gout, piles, fever

Kalmegh

Andrographis paniculata

gastritis, fever, weakness

Makoi

Solanum nigrum

dysentery, diuretic, debility

Pashan Bheda

Coleus barbatus

calculus, stones in kidney

Sarpa Gandha

Ranwolfia serpentina

insomnia, hypertension

Tulsi

Ocimum tenuiflorum

expectorant, cough, cold

Vai Vidanka

Embelia ribes

skin disease, helminthiasis

Peppermint

Mentha piperita

pain-killer, digestive

Vringraj

Eclipta alba

anti-inflammatory, leukemia, stress reliever

Chitrak

Plumbargo zeylanica

dyspepsia, inflammation, cough, colic

Harada

Terminalia chebula

leprosy, inflammation, vomiting, insomnia

Neem

Azadirachta indica

analgesic, astringent, epilepsy

Kantakari

Solanum xanthocarpum

appetizer, stomach ache, diuretic

Table 3. Indian medicinal herbs and their property:

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Common name

Scientific name

Uses

Lemon Balm

Melissa officinalis

digestion, stomach spasms, anti-viral

Angelica

Angelica sylvestris

gastritis, cramps, digestion

Chickweed

Stellaria media

itching, irritation, rashes

Cleavers

Galium aparine

skin diseases, diuretic

Couch grass

Cynodon dactylon

rheumatism, cystitis, gout

Dandelion

Taraxacum officinale

dissolves kidney and gallstones, diuretics

Elderberry

Sambucus canadensis

bronchitis, cold, cough

Garlic

Allium sativum

anti-microbial, cardiovascular treatment

Ginger

Zingiber officinale

motion sickness, vomiting, flatulence, diarrhea

Lavender

Lavandula angustifolia

stress reliever, boosts spirits, stomach disorders

Red Clover

Trifolium pratense

rejuvenatory, skin nourishing

Rosemary

Rosmarinus officinalis

improves blood supply to brain

Thyme

Thymus pulegioides

antifungal, anti-bacterial, expectorant

Yarrow

Achillea millefolium

wound cleansing, blood coagulation, digestive

3. List of phytochemical based therapeutic approaches:

Table 4: Phytochemicals and their chemopreventive activity:

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Binding

phytochemical

Molecular targets

Chemopreventive effect

Refferences

3′,4′,7-

trihydroxyisoflavone

PI3 K

Cyclin- dependent kinase 2

EGF-induced cell proliferation and

transformaion

[8]

5-deoxykaempferol

SRC

Ribosomal S6 kinase2 (RSK)

PI3K

UVB-induced two-stage skin

carcinogenesis

UVB-induced COX2 and VEGF

expression

[9]

6-gingerol

Leukotriene A4 hydrolase

(LTA4H)

Xenograft tumour volume of human

HCT116 colon cancer cells

[10]

Caffeic acid

FYN

UVB-induced COX2 expression

[11]

Cyanidin

RAF

Mitogen-activated protein kinase kinase 4 (MKK4) MEK1

UVB-induced COX2 expression

[12]

Cryptotanshinone

Signal transducer and

activator of transcription3

Human prostate cancer cell

proliferation

[13]

Deguelin

Heat shock protein 90

Xenograft tumour volume of

[14]

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human

lung, head, neck, stomach and prostate cancer cells

Delphinidin

FYN

RAF,MEK1,ERKs

,MKK4 PI3K

TNF -induced COX2 expression TPA-induced cell transformation UVB-induced COX2 expression

[15]

[16][17]

(-)-Epigallocatechin

gallate

FYN

Insulin- like growth factor-1 receptor

Glucose-regulated protein 78

Heat shock protein 90

-chain-associated protein kinase70

Ras GTPase activating protein SH3 domain binding protein1

EGF-induced cell transformation

Cell proliferation and transformation

Etoposide-induced breast cancer cell death and drug resistance

TCDD-mediated gene induction in hepatoma cells

Leukaemia proliferation

Anchorage-independent growth of human and mouse lung cancer cell lines

[18]

[19]

[20]

[21] [22] [23]

Equol

MEK1

TPA-induced cell transformation

[24]

Fisetin

CDK6

Kinase activity

[25]

Kaempferol

SRC

UVB-induced two stage skin

[26]

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RSK2

PI3K

carcinogenesis

RSK2-mediated cancer cell proliferation

EGF-induced cell transformation

[27] [28]

Luteolin

SRC Protein

kinase C

UVB-induced two-stage skin

carcinogenesis

[29]

Myricetin

FYN

RAF MKK4

MEK1

PI3K

Janus kinase 1

UVB-induced two-stage skin

carcinogenesis

UVB-induced MMP9 activity and expression

TNF -induced VEGF expression

TPA- or EGF-induced cell tranformation

UVB-induced angiogenesis

Cell transformation

[30]

[31] [32] [33] [34] [35]

Procyanidin B2

MEK1

TPA-induced cell transformation

[36]

Quercetin

RAF

MEK1

PI3K

TPA-induced cell transformation

TNF -induced MMP9 activation

Arsenite-induced COX2 expression

[37]

[38] [39]


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Resveratrol

COX2

LTA4H

Human colon cancer cell

proliferation

Xenograft tumour volume of human pancreatic cancer cells

[40]

[41],[42]

In other diseases

Active

phytochemicals

Target site

Biological effect

References

Ajoene

ROS mediated

apoptosis

Leukemic cells Adipocyte

[43][44]

Chlorogenic acid

and saponins

S-Glut-1mediated

transport

Intestinal glucose transport

[45]

Esters of triterpene

alcohols from rice bran oils

HMG Co-A reductase

hepatic cholesterol esterase and

tocotrienols

[46]

Table.5 plants and their antiviral activity:

Plant tested

Minimum Antiviral Activity (Ag/mb)

Herpes simplex

Sindbis

Polio

Asteraceae

Conyza aegyptiaca (L.) Aiton

500

250

500

Bombacaceae

Adansonia digirara L (root- bark)

125

250

250

250

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(leaves)

<62.5

Commelinaceae

Palisora hirsuta (Thunb.) K. Schum.

<62.5

500

250

Davalliaceae

Davallia chaerophyUoides

(Poir.) Steud.

500

-

-

Malvacae

Sida acuta Burm. f.

250

-

-

Moraceae

Ficus ovata Vahl

125

-

250

Rubiaceae

Mitracarpus villosus (Sw.) DC.

125

-

500

Rutaceae

Zanthorvlunt zanthoxvloides

(Lam.) Zepernick & Tiniler

500

-

-

Simarubaceae

Harrisonia abyssinica Oliv

250

-

-

Sapindaceae

Paullinia pinnata L.

125

-

-

Table.6. phytochemicls and their antimicrobial activity:

Common

name

Scientific

name

Compound

Class

Activity

Relative

toxicity

Alfalfa

Medicago

?

?

Gram-positive

2.3

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sativa

organisms

Allspice

Pimenta

dioica

Eugenol

Essential oil

General

2.5

Aloe

Aloe

barbadensis,

Aloe vera

Latex

Complex

mixture

Corynebacterium, Sa

lmonella,Streptococc us, S. aureus

2.7

Apple

Malus

sylvestris

Phloretin

Flavonoid

derivative

General

3.0

Ashwagand

ha

Withania

somniferum

Withafarin A

Lactone

Bacteria, fungi

0.0

Bael tree

Aegle

marmelos

Essential oil

Terpenoid

Fungi

?

Basil

Ocimum

basilicum

Essential oils

Terpenoids

Salmonella, bacteria

2.5

Bay

Laurus

nobilis

Essential oils

Terpenoids

Bacteria, fungi

0.7

Betel pepper

Piper betel

Catechols,

eugenol

Essential oils

General

1.0

Black

pepper

Piper nigrum

Piperine

Alkaloid

Fungi, Lactobacillus,

Micrococcus, E. coli, E. faecalis

1.0

Blueberry

Vaccinium sp

p.

Fructose

Monosacchar

ide

E. coli

?

Brazilian

pepper tree

Schinus

terebinthifoli us

Terebinthone

Terpenoids

General

1.0

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Buchu

Barosma

setulina

Essential oil

Terpenoid

General

2.0

Burdock

Arctium

lappa

?

Polyacetylen

e, tannins, terpenoids

Bacteria, fungi,

viruses

2.3

Buttercup

Ranunculus

bulbosus

Protoanemonin

Lactone

General

2.0

Caraway

Carum carvi

?

Coumarins

Bacteria, fungi,

viruses

?

Cascara

sagrada

Rhamnus

purshiana

Tannins

Polyphenols

Viruses, bacteria,

fungi

1.0

Cashew

Anacardium

pulsatilla

Salicylic acids

Polyphenols

P. acnes

?

Ceylon

cinnamon

Cinnamomu

m verum

Essential oils,

others

Terpenoids,

tannins

General

2.0

Chamomile

Matricaria

chamomilla

Anthemic acid

Phenolic acid

M.tuberculosis,

S. typhimurium, S. aureus, helminths

2.3

Chapparal

Larrea

tridentata

Nordihydrogua

iaretic acid

Lignan

Skin bacteria

2.0

Chili

peppers, paprika

Capsicum

annuum

Capsaicin

Terpenoid

Bacteria

2.0

Clove

Syzygium

aromaticum

Eugenol

Terpenoid

General

1.7

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Coca

Erythroxylu

m coca

Cocaine

Alkaloid

Gram-negative and -

positive cocci

0.5

Cranberry

Vaccinium sp

p.

Fructose

Monosacchar

ide

Bacteria

?

Dill

Anethum

graveolens

Essential oil

Terpenoid

Bacteria

3.0

Eucalyptus

Eucalyptus

globulus

Tannin

Polyphenol

Bacteria, viruses

1.5

Fava bean

Vicia faba

Fabatin

Thionin

Bacteria

?

Gamboge

Garcinia

hanburyi

?

Resin

General

0.5

Garlic

Allium

sativum

Allicin, ajoene

Sulfoxide

General

?

Ginseng

Panax

notoginseng

?

Saponins

E. coli, Sporothrix

schenckii,Staphyloco ccus, Trichophyton

2.7

Glory lily

Gloriosa

superba

Colchicine

Alkaloid

General

0.0

Goldenseal

Hydrastis

canadensis

Berberine,

hydrastine

Alkaloids

Bacteria, Giardia

duodenale, trypanosomes

2.0

Gotu kola

Centella

asiatica

Asiatocoside

Terpenoid

M. leprae

1.7

Grapefruit

peel

Citrus

paradisa

?

Terpenoid

Fungi

?

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Green tea

Camellia

sinensis

Catechin

Flavonoid

General

2.0

Hemp

Cannabis

sativa

β-Resercyclic

acid

Organic acid

Bacteria and viruses

1.0

Henna

Lawsonia

inermis

Gallic acid

Phenolic

S. aureus

1.5

Lemon balm

Melissa

officinalis

Tannins

Polyphenols

Viruses

?

Lemon

verbena

Aloysia

triphylla

Essential oil

Terpenoid

Ascaris

1.5

Licorice

Glycyrrhiza

glabra

Glabrol

Phenolic

alcohol

S. aureus, M.

tuberculosis

2.0

Lucky nut,

yellow

Thevetia

peruviana

?

?

Plasmodium

0.0

Marigold

Calendula

officinalis

?

?

Bacteria

2.7

Mountain

tobacco

Arnica

montana

Helanins

Lactones

General

2.0

Oak

Quercus

rubra

Tannins

Polyphenols

?

?

Olive oil

Olea

europaea

Hexanal

Aldehyde

General

?

Onion

Allium cepa

Allicin

Sulfoxide

Bacteria, Candida

?

Orange peel

Citrus

sinensis

?

Terpenoid

Fungi

?

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Oregon

grape

Mahonia

aquifolia

Berberine

Alkaloid

Plasmodium

2.0

Pao d’arco

Tabebuia

Sesquiterpenes

Terpenoids

Fungi

1.0

Pasque-

flower

Anemone

pulsatilla

Anemonins

Lactone

Bacteria

0.5

Peppermint

Mentha

piperita

Menthol

Terpenoid

General

?

Periwinkle

Vinca minor

Reserpine

Alkaloid

General

1.5

Poinsettia

Euphorbia

pulcherrima

?

?

General

0.0

Poppy

Papaver

somniferum

Opium

Alkaloids

and others

General

0.5

Potato

Solanum

tuberosum

?

?

Bacteria, fungi

2.0

Purple

prairie clover

Petalostemu

m

Petalostemumol

Flavonol

Bacteria, fungi

?

Quinine

Cinchona sp.

Quinine

Alkaloid

Plasmodium spp.

2.0

Rauvolfia,

Chandra

Rauvolfia

serpentina

Reserpine

Alkaloid

General

1.0

Rosemary

Rosmarinus

officinalis

Essential oil

Terpenoid

General

2.3

Sainfoin

Onobrychis

viciifolia

Tannins

Polyphenols

Ruminal bacteria

?

Sassafras

Sassafras

?

?

Helminths

2.0

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albidum

Savory

Satureja

montana

Carvacrol

Terpenoid

General

2.0

Senna

Cassia

angustifolia

Rhein

Anthraquino

ne

S. aureus

2.0

Snakeplant

Rivea

corymbosa

?

General

1.0

St. John’s

wort

Hypericum

perforatum

Hypericin,

others

Anthraquino

ne

General

1.7

Sweet flag,

calamus

Acorus

calamus

?

?

Enteric bacteria

0.7

Tansy

Tanacetum

vulgare

Essential oils

Terpenoid

Helminths, bacteria

2.0

Tarragon

Artemisia

dracunculus

Caffeic acids,

tannins

Terpenoid

Viruses, helminths

2.5

Thyme

Thymus

vulgaris

Caffeic acid

Terpenoid

Viruses, bacteria,

fungi

2.5

Tree bard

Podocarpus

nagi

Totarol

Flavonol

P. acnes, other gram-

positive bacteria

?

Valerian

Valeriana

officinalis

Essential oil

Terpenoid

General

2.7

Willow

Salix alba

Salicin

Phenolic

glucoside

?

?

Wintergreen

Gaultheria

procumbens

Tannins

Polyphenols

General

1.0

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Woodruff

Galium

odoratum

?

Coumarin

General

3.0

Yarrow

Achillea

millefolium

?

?

Viruses, helminths

2.3

Table 7.Phytochemicals with their radioprotective activity:

Plants with family

Radioprotective efficacy

References

Aegle marmelos

Rutaceae

To promote digestion, treat colic, diarrhoea and dysentery,

intermittent fever, melancholia and heart palpitation. A. marmelos provided protection against radiation-induced sickness and mortality in mice.

[47]

Acanthopanax

senticosus

Araliaceae

To restore normal functioning of spleen and kidneys. Also

used as a remedy for bronchitis, heart ailments and rheumatism Pre-irradiation administration of Shigoka extract rendered maximum survival (80%), while post- irradiation administration exhibited 30% survival.

[48]

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Ageratum

conyzoides L. Asteraceae

In India A. conyzoides leaves are applied to cuts and sores,

while the juice is considered as antilithic. An alcoholic extract of A. conyzoides shoe efficacy inastrointestinal and bone marrow related death .

[49]

Allium cepa L

Alliaceae

.Administration of the dried bulb of Allium cepa was

active against x-irradiation.

[50]

Allium sativum L.

Gaertn

Alliaceae

Radioprotective efficacy of aged garlic extract (containing

compounds such as S-allylcysteine, S- allylmercaptocysteine, allixin and selenium which are stable, highly bioavailable and possess significant antioxidant and anticarcinogenic )has been reported.

[51]

Aloe arborescens

Liliaceae

Acts as a cell proliferant, healer, demucent and allergy

reducer. Topically it is used for skin ulcers, burns, irritations and bites An extract of Aloe arborescens provided protection to mouse skin against soft x-irradiation by scavenging hydroxyl radicals and reducing alterations in enzyme activity.

[52]

Archangelica

officinalis

Hoffm.Umbelliferae

Administration of a combination of Archangelica

officinalis and Ledum palustre extracts before irradiation rendered 70% survival.

[53]

Angelica sinensis

(Oliver) Diels

Apiaceae

The polysaccharide fraction, containing a ferulic acid, of

Angelica sinensis increased survival in irradiated mice by promoting haemopoietic stem cell proliferation.

[54]

Curcuma longa

Linn. Zingiberaceae

Pharmacological activities include antiinflammatory, anti-

HIV, antibacteria, antitumour, antioxidant and nematocidal effects. Curcumin (diferuloylmethane) has been reported to render radioprotective effect.

[55]

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Ginko biloba Linn.

Cycadaceae

Ethanolic extract of dried leaves reported to be effective on

clastogenic factors from plasma of human subjects exposed to irradiation and on rat cerebellar neuronal cell culture against hydroxyl radical induced apoptosis.

[56,57]

Hypericum

perforatum Linn. Hypericaceae

Hypericum perforatum aqueous extract protected bone

marrow and intestinal mucosa against x-ray in a concentration and time-dependent manner.

[58-61]

Lycium chinense

Solanaceae

Administration of root extract prior to x-irradiation

significantly improved the recovery of leukocyte,

erythrocyte and thrombocyte counts and haematocrit.

[62]

Mentha arvensis

Linn. Lamiaceae

It has carminative, antiseptic, refrigerant, stimulant,

emmenagogue and diuretic properties .Pre-irradiation treatment with chloroform extract protected mice against gastrointestinal and bone marrow death .

[63]

Moringa oleifera

Lam. Moringaceae

M. oleifera is used in Ayurveda to treat asthma, gout,

rheumatism, inflammation, epilepsy, cardiac and circulatory disorders, nervous debility and healing of wounds. Pre-treatment with a leaf extract significantly reduced the percent of aberrant cells in metaphase chromosomes to normal range by day 7 post-irradiation in mice.

[64]

Piper longum Linn.

Piperaeae

The ethanolic extract was found to protect mice against the

radiation induced decline in WBC, bone marrow cells a- esterase positive cells and GSH.

[65]

Syzygium cumini

L. Skeels Myrtaceae

In Ayurveda, S. cumini is used to treat bronchitis, asthma,

dyspepsia, diabetes, ulcers and blood impurities. Treatment of human peripheral blood lymphocytes with S. cumini leaf extract before γ-radiation significantly reduced

[66]

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4.

Potential therapeutic applications of phytochemicals:

4.1. Therapeutic application in cancer:

Several proteins have been identified as specific targets of some phytochemicals (TABLE 4). Representative signalling pathways targeted by various phytochemicals include the MAPK pathways, the oncogenic AKT pathway and proteins involved in cell cycle progression [12,17,24,32].

4.1.1 Interfering with the MAPK signaling pathways:

MEK1 is an important downstream component of oncogenic RAS signalling and potentially a good target for disrupting MAPK signalling. The development of pharmacological inhibitors of MEK1, such as PD [37] [29], has shown that MEK1 possesses a unique binding pocket adjacent to its ATP-binding site,and computer modelling has indicated that several phytochemicals, including quercetin[37], myricetin[33] and equol[24], could dock with this allosteric pocket. An analogue of resveratrol (RSvL2) was shown to strongly bind MEK1. The mechanism of allosteric inhibition of MEK is attributed to the inhibitor being able to stabilize the inactive conformation of the activation loop and deform the catalytic site.

4.1.2 Suppressing AKT signaling:

AKT and mTOR mainly reprogramme metabolic pathways in cancer cells, it is also thought to be involved in pathways that control the availability of nutrients acting through AMP activated protein kinase (AMPK), which controls glucose and lipid metabolism by sensing changes in nutrient and extracellular energy levels. This suggests that the AKT-mediated oncogenic pathway could be regulated by nutrients. PI3K is an upstream regulator of AKT–mTOR signalling and also interacts with several phytochemicals. Based on X-ray crystallography, quercetin and myricetin have been shown to directly bind and suppress PI3K activity [39,45].

4.1.3 Intervening with cell cycle progression:

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Regulating cancer cell proliferation is crucial for chemoprevention. Cyclin-dependent kinases (CDKs), the essential proteins for cell cycle progression, bind with cyclins to form CDK–cyclin complexes [68]. Many CDK inhibitors (CDKIs), such as the p21 and p27 proteins, attenuate formation of these complexes and block cell cycle progression [19]. Several phytochemicals can function as CDKIs. Such as metabolite of the soybean isoflavone daidzein, is a direct inhibitor of CDK2 and CDK4 [51].

4.2. Therapeutic application in Diabetes:

Tea and several plant polyphenols were reported to inhibit a-amylase and sucrase activity, decreasing postprandial glycemia[69]. Individual polyphenols, such as β-catechin,epicatechin [70] ,epigallocatechin, epicatechin gallate, isoflavones from soyabeans, tannic acid, glycyrrhizin from licorice root, chlorogenic acid and saponins also decrease S-Glut-1 mediated intestinal transport of glucose [ 45]. Saponins delay the transfer of glucose from stomach to the small intestine.The water-soluble dietary fibres, guar gum, pectins and polysaccharides slow the rate of gastric emptying and thus absorption of glucose. The α-glucosidase inhibitors (acarbose and the others) are presently recommended for the treatment of obesity and diabetes. Phytochemicals have been shown to demonstrate such activity [71]. Plant phenols induce vasorelaxation by the induction of endothelial nitric oxide synthesis or increased bioavailability and the NO-cGMP pathway [30, 29].

4.3. Therapeutic application in Cardiovascular Disease:

The link between flavonoids and atherosclerosis is based partly on the evidence that some flavonoids possess antioxidant properties and have been shown to be potent inhibitors of LDL oxidation in vitro. For example, the phenolic substances in red wine inhibit oxidation of human LDL [40]. Flavonoids have also been shown to inhibit platelet aggregation and adhesion [72] which may be another way they lower the risk of heart disease. Isoflavones in soy foods have been reported to lower plasma cholesterol and also to have estrogenlike effects [73]. Garlic oil or garlic has been shown to be hypolipidemic in humans, with a recent meta-analysis suggesting that one half clove of garlic per day lowered serum cholesterol by approximately 9%.[74]. The same amount of garlic was shown to reduce cholesterol levels and severity of atherosclerosis in cholesterol-fed rabbits. Garlic contains a number of compounds, but those thought to be the most active are diallyl disulfide and its mono S oxide (allicim). The mechanism of hypercholesterolemia may be the inhibition of cholesterol synthesis [19].

4.4. Therapeutic application in neurodegenerative diseases:

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As is the case with major diseases of other organ systems (cardiovascular disease, diabetes and cancers), data from epidemiological studies of human populations suggest that phytochemicals in fruits and vegetables can protect the nervous system against disease. For example, phytochemicals reduced risk for Alzheimer's disease [75].Because of their beneficial effects on the cerebral vasculature, phytochemicals may also reduce the risk of stroke [76] .Dietary supplementation with blueberries protected dopaminergic neurons against dysfunction and degeneration in a rat model of Parkinson's disease [77], improved learning and memory without affecting amyloid pathology in a mouse model of Alzheimer's disease[78] and reduced brain damage and improved functional outcome in a rat model of stroke [79].Apple juice concentrate prevented age-related impairment of cognitive function in mice [80]. Moderate consumption of red wine reduced amyloid pathology in a mouse model of Alzheimer's disease [81].Considerable effort has been aimed at identifying specific molecules responsible for the health benefits conferred by plants. Four different phytochemicals (sulforaphane, resveratrol, curcumin and the cannabinoid THC) which considerable evidence suggests have neuroprotective properties that likely involve a hormetic mechanism of action.

5. Challenges of phytochemical therapy:

Despite the benefits, many phytochemicals have poor water solubility, low absorptivity and bioavailability. The intended therapeutic role of ingested phytochemicals might be different than their in vivo activity once the food matrix is disrupted [46] due to variation in their metabolism and disposition [Fig 1].

5.1 Sources of variation in phytochemical metabolism and disposition

Researchers investigation on the pharmacokinetics of phytochemicals in humans have shown substantial variation .Circulating concentrations of phytochemicals, such as psoralens, lignans, and the flavonoids naringenin and hesperitin, can vary widely among individuals [46, 82]. The process of phytochemical disposition, like that of disposition of drugs and other xenobiotics, involves absorption, metabolism, distribution, and excretion, and each of these parts may contribute to pharmacokinetic variability.

5.1.1 Phytochemical metabolism by gut bacteria

Gut bacteria can hydrolyze glycosides, glucuronides, sulfates, amides and esters [82]. They also carry out reduction, ring-cleavage, demethylation and dehydroxylation reactions.The hydrolysis of glycosides and glucuronides typically results in metabolites that are more biologically active than the parent compounds. In contrast, further bacterial degradation and transformation of aglycones can lead to production of more or less
active compounds, depending on the substrate being metabolized and the products formed. Plant polyphenols,

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including phytoestrogens such as the isoflavones and lignans, are extensively metabolized in the gut by intestinal bacteria.

5.1.2 Phytochemical metabolism by polymorphic phase II conjugating enzymes


Phytochemicals are metabolized in vivo by biotransformation enzymes in a manner similar to that of other xenobiotics. Many classes of phytochemicals are rapidly conjugated with glutathione, glucuronide, and sulfate moieties and excreted in urine and bile. Thus, in theory, polymorphisms in biotransfo rmation enzymes, such as the glutathione S-transferases (GST), UGT, and SULT, have the capacity to affect phytochemical metabolism in the same fashion as they do carcinogens and other xenobiotics
Figure 1: Schematic diagram presenting sources of variation in phytochemical metabolism and disposition.

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6. Approaches in engineering phytochemicals for conjugation:

Novel antioxidant loaded drug delivery systems such as polymeric nanoparticles have been identified as alternatives that should provide longterm delivery at the therapeutic level, prevent antioxidant degradation, and increase pharmacological activity of such antioxidants [82].

6.1. Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactideco- glycolide) (PLGA) nanoparticles:

Thymoquinone (TQ) is a quinone-based phytochemical present in Nigella sativa (Ranunculaceae) black seed oil is a powerful antioxidant and anticancer drug, but its administration is limited due to poor water solubility .In addition, administration of high dosages to rats has resulted in hypoactivity and difficulty in respiration associated with reduced glutathione in the liver and kidney [41]. Another report has shown that TQ was capable of reducing blood glucose levels and inducing allergic dermatitis [83]. To overcome these disadvantages, biodegradable and biocompatible polymeric nanoparticles would be attractive alternatives for TQ delivery as it provides improved TQ solubility, controlled delivery, and enhanced therapeutic properties.

6.2. Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin") for human cancer therapy:


Though curcumin have widespread clinical application in cancer and other diseases, it has limited activity due to poor aqueous solubility, and consequently, minimal systemic bioavailability. Nanoparticle-based drug delivery approaches have the potential for rendering hydrophobic agents like curcumin dispersible in aqueous media. Polymeric nanoparticle encapsulated formulation of curcumin – nanocurcumin have been synthesized – utilizing the micellar aggregates of cross-linked and random copolymers of N- isopropylacrylamide (NIPAAM), with N-vinyl-2-pyrrolidone (VP) and poly (ethyleneglycol)monoacrylate (PEG-A). Nanocurcumin, unlike free curcumin, is readily dispersed in aqueous media and show therapeutic efficacy to free curcumin against a panel of human pancreatic cancer cell lines [84].

Discussion and Conclusion:

Phytochemicals are potentially involved as protective compounds for a number of chronic diseases. Reactive oxygen species (ROS) or oxidants formed in our body due to exogenous and endogenous factors are found to be responsible for many diseases such as cancer, cardiovascular disease, neurodegenerative diseases, inflammatory disease, ischemia-reperfusion injury and aging. The phytochemicals have the ability to neutralize the free radicals or reactive oxygen species or oxidants responsible for the onset of the diseases. The mechanisms by which the plant biomolecules provide defense against ROS mediated diseases are ROS
scavenging, reduction of peroxides and repair of peroxides membrane, utilization of dietary lipids and

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alternative biological pathways that occur in different type of cancer, multiple system organ failure and diabetes. Synthetic antioxidants are found to be harmful to the health, so as alternative natural antioxidants from plant source are safer to health and have better antioxidant activity. Considerable evidences suggest that plant biomolecules such as 6-gingerol ,Caffeic acid, Cyanidin ,Equol, Fisetin ,Myricetin ,Quercetin have anticancer property[10.11,12,24,25,30,37]. Plant flavonoids show efficacy against cardiovascular disease by inhibiting platelet aggregation and adhesion [68].Some phytochemicals have been shown to be hypolipidemic thus control the plasma cholesterol [21,19].On the other hand few plant biomolecules such as polyohenols (β-catechin, epicatechchin ,tannic acid, saponins etc.) demonstrated to have antidiabetic activity as they decrease or delay the transport of glucose to intestine by a variety of parthways [29,30,45,71]. phytochemicals like sulforaphane, resveratrol, curcumin and the cannabinoid THC show hormetic mechanism of action to prevent a number of neurodegenerative diseases[74-78]. Despite the importance of phytochemicals in prevention of diseases there are some challenges regarding its proper administration in the body because of their low water solubility, low absorptivity, low bioavailability and half life of oral phytochemicals are poor. To deal with such problem a strategy of engineered phytochemicals such as PEG-curcumin, nanocurcumin has developed. Engineered phytochemicals are with improved cellular permeability, proteolytic stability and enhanced half-life of cells. Thus by increasing effective size, solubility in aqueous medium and thereby increasing circulation half life; without disturbing rather enhancing bioactivity engineered phytochemicals are now of immense interest in the area of targeted phytochemical delivery. The latest trend of rethinking the natural sources for health and medicine has created a lot of development but still there is much to be learnt about their metabolism, bioavailability, mode of action and dose-response effect, physical, chemical properties such as solubility, diffusion and temperature effects of the phytochemicals of interest and in some cases the actual compound responsible for health effects are still unknown. So, further research is needed to ensure high yield as well as viability and bioavailibity of the plant biomolecules.

Acknowledgement: Authors are grateful to the Vice-Chancellor, University of Kalyani, Kalyani, Nadia, for his interest and support in this work.

References:

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1. Schippmann U., D. Leaman & A. B. Cunningham. 2006. A comparison of cultivation and wild collection of medicinal and aromatic plants under sustainability aspects, en R. J. Bogers, L. E. Craker & D. Lange (eds.). Medicinal and Aromatic Plants, pp. 75-95. Springer, the Netherlands.
2. Massardo F. & R. Rozzi. 1996. Usos medicinales de la flora nativa chilena. Ambiente & Desarrollo 12:
76-81.
3. He S. A. & Y. Gu. 1997. The challenge for the 21st Century for Chinese botanic gardens, en D. H.
Touchell & K. W. Dixon (eds.). Conservation into the 21st Century, pp. 21-27. Kings Park and Botanic
Garden, Perth
4. Shiva V. 1996. Protecting our biological and intellectual heritage in the age of biopiracy. The Research
Foundation for Science, Technology and Natural Resources Policy, New Delhi.
5. Toledo V. M. 1995. New paradigms for a new ethnobotany: reflections on the case of Mexico, en R. E.
Schultes & S. von Reis (eds.). Ethnobotany: evolution of a discipline, pp. 75-88. Chapman and Hall, London
6. Moerman D. E. 1998. Native North American food and medicinal plants: epistemological considerations, en H. D.V. Prendergast, N. L. Etkin, D. R. Harris & P. J. Houghton (eds.). Plants for food and medicine, pp. 69-74. Proc. Joint Conference of the Society for Economic Botany and the International Society for Ethnopharmacology, Royal Botanic Gardens, Kew.
7. Addae-Mensah I. 2000. Plant biodiversity, herbal medicine, intellectual property rights and industrially developing countries, en H. Lauer (ed.). Ghana: Changing values/changing technologies, pp. 165-182. Council for Research in Values and Philosophy, Washington, DC.
8. Engelman, J. A. & Cantley, L. C. Chemoprevention meets glucose control. Cancer Prevention research. (Phila) 3, 1049–1052 (2010).
9. Sherr, C. J. & Roberts, J. M. CDK inhibitors: positive and negative regulators of G1-phase progression.

Genes Development. 13, 1501–1512 (1999).

10. Shim JH, Su ZY, Chae JI, Kim DJ, Zhu F, Ma WY. Epigallocatechin gallate suppresses lung cancer cell growth through Ras-GTPase-activating protein SH3 domain-binding protein 1. Cancer Prevntion Research (Phila Pa) 2010; 3:670–679.
11. Lee, K. M. et al. Kaempferol inhibits UVB-induced COX-2 expression by suppressing Src kinase activity. Biochemical Pharmacology. 80, 2042–2049 (2010).
12. Cho YY, Bode AM, Mizuno H, et al. A novel role for mixed-lineage kinase-like mitogen-activated
protein triple kinase α in neoplastic cell transformation and tumor development. Cancer Research.2004;

64:3855–64.

13. Manach C, Williamson G, Morand C, Scalbert A, Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. American Journal of Clinical Nutrition
2005; 81(1 Suppl): 230S–242S.

IJSER © 2012 http://www.ijser.org

The research paper published by IJSER journal is about Phytochemicals – biomolecules for prevention and treatment of human diseases-a review 27

ISSN 2229-5518

14. Erlund I, Meririnne E, Alfthan G, Aro A. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. Journal of Nutrition 2001; 131(2):235–241. [PubMed: 11160539]
15. Lee, K. M. 5-deoxykaempferol plays a potential therapeutic role by targeting multiple signaling pathways in skin cancer. Cancer Prevtion. Research. (Phila Pa) 3, 454–465 (2010).
16. Kuijsten A, Arts IC, Vree TB, Hollman PC. Pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside. Journal of Nutrition
2005;135(4):795–801.
17. Funk, C. D. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294, 1871–1875 (2001).
18. Ermakova, S. P. (-)-Epigallocatechin gallate overcomes resistance to etoposide-induced cell death by targeting the molecular chaperone glucoseregulated protein 78. Cancer Research. 66, 9260–9269 (2006).
19. Shim, J. H. et al. Epigallocatechin gallate suppresses lung cancer cell growth through Ras-GTPase- activating protein SH3 domain-binding protein 1. Cancer Prevention Research (Phila Pa) 3, 670–679 (2010).
20. Palermo, C. M., Westlake, C. A. & Gasiewicz, T. A. Epigallocatechin gallate inhibits aryl hydrocarbon receptor gene transcription through an indirect mechanism involving binding to a 90 kDa heat shock protein. Biochemistry 44, 5041–5052 (2005).
21. Dirsch VM, Gerbes AL, Vollmar AM. Ajoene, a compound of garlic, induces apoptosis in human promyeloleukemic cells, accompanied by generation of reactive oxygen species and activation of nuclear factor kappaB. Molecular Pharmacology 1998;53:402–7.
22. Li, M. Direct inhibition of insulin-like growth factor-I receptor kinase activity by (–)-epigallocatechin-3- gallate regulates cell transformation. Cancer Epidemiology. Biomarkers Prevention. 16, 598–605 (2007).
23. Yang JY, Della-Fera MA, Nelson-Dooley C, Baile CA. Molecular mechanisms of apoptosis induced by ajoene in 3T3-L1 adipocytes. Obesity Research 2006;14:388–97.
24. Funk, C. D. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294, 1871–1875 (2001).
25. Shephard SE, Zogg M, Burg G, Panizzon RG. Measurement of 5-methoxypsoralen and 8- methoxypsoralen in saliva of PUVA patients as a noninvasive, clinically relevant alternative to
monitoring in blood. Archives of Dermatological Research 1999;291(9):491–499.

IJSER © 2012 http://www.ijser.org

The research paper published by IJSER journal is about Phytochemicals – biomolecules for prevention and treatment of human diseases-a review 28

ISSN 2229-5518

26. Byun, S. Luteolin inhibits protein kinase C(epsilon) and c-Src activities and UVB-induced skin cancer.

Cancer Research. 70, 2415–2423 (2010).

27. Samuelsson, B., Dahlen, S. E., Lindgren, J. A., Rouzer, C. A. & Serhan, C. N. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237, 1171–1176 (1987).
28. Undevia SD, Gomez-Abuin G, Ratain MJ. Pharmacokinetic variability of anticancer agents. Nature
Reviews Cancer 2005;5(6):447–458.
29. Fisher, R. P. CDKs and cyclins in transition(s). Current. Opinion on Genetic. Development. 7, 32–38 (1997).
30. Kang, N. J. Equol, a metabolite of the soybean isoflavone daidzein, inhibits neoplastic cell transformation by targeting the MEK/ERK/p90RSK/ activator protein-1 pathway. Journal. Biological. Chemistry. 282, 32856–32866 (2007).
31. Lee, K. M. Kaempferol inhibits UVB-induced COX-2 expression by suppressing Src kinase activity.

Biochemical Pharmacology 80, 2042–2049 (2010).

32. Cho, Y. Y. et al. A regulatory mechanism for RSK2 NH(2)-terminal kinase activity. Cancer Research

69, 4398–4406 (2009).

33. Yang JY, Della-Fera MA, Nelson-Dooley C, Baile CA. Molecular mechanisms of apoptosis induced by ajoene in 3T3-L1 adipocytes. Obesity Research 2006; 14:388–97.
34. Lu, H., Chang, D. J., Baratte, B., Meijer, L. & Schulze-Gahmen, U. Crystal structure of a human cyclin- dependent kinase 6 complex with a flavonol inhibitor, fisetin. Jornal of Medical Chemistry 48, 737–743 (2005).
35. Goldin BR. In situ bacterial metabolism and colon mutagens. Annual Review of Microbiology
1986;40:367–393.
36. Keppler K, Humpf HU. Metabolism of anthocyanins and their phenolic degradation products by the intestinal microflora. Bioorganic Medical Chemistry 2005;13(17):5195–5205
37. Dirsch VM, Gerbes AL, Vollmar AM. Ajoene, a compound of garlic, induces apoptosis in human promyeloleukemic cells, accompanied by generation of reactive oxygen species and activation of nuclear factor kappaB. Molecular Pharmacology 1998; 53:402–7.
38. Rechner AR, Smith MA, Kuhnle G, Gibson GR, Debnam ES, Srai SK, et al. Colonic metabolism of dietary polyphenols: influence of structure on microbial fermentation products. Free Radical Biology
and Medicine 2004; 36(2):212–225.

IJSER © 2012 http://www.ijser.org

The research paper published by IJSER journal is about Phytochemicals – biomolecules for prevention and treatment of human diseases-a review 29

ISSN 2229-5518

39. Atkinson C, Frankenfeld CL, Lampe JW. Gut bacterial metabolism of the soy isoflavone daidzein:
exploring the relevance to human health. Experimental Biology and Medicine (Maywood)
2005;230(3):155–170.
40. Kang, N. J. Delphinidin attenuates neoplastic transformation in JB6 Cl41 mouse epidermal cells by blocking Raf/mitogen-activated protein kinase kinase/ extracellular signal-regulated kinase signaling. Cancer Prevntion Research (Phila Pa) 1, 522–531 (2008).
41. Oi, N. Resveratrol, a red wine polyphenol, suppresses pancreatic cancer by inhibiting leukotriene a4 hydrolase. Cancer Research: 70, 9755–9764 (2010).
42. Undevia SD, Gomez-Abuin G, Ratain MJ. Pharmacokinetic variability of anticancer agents. Nature
Reviews Cancer 2005; 5(6):447–458.
43. Shoji Y and Nakashima H 2004 J. Drug Targ. 12 385
44. Commandeur JNM, Vermeulen NPE. (1996). Cytotoxicity and cytoprotective activities of natural compound. The case of curcumin. Xenobiotica, 26: 667-668.
45. Jung, S. K. Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting
Raf. Biochemistry Pharmacology 79, 1455–1461 (2010).
46. Lee, K. M. 5-deoxykaempferol plays a potential therapeutic role by targeting multiple signaling pathways in skin cancer. Cancer Prevention Research. (Phila Pa) 3, 454–465 (2010).
47. Jagetia ,G.C.,Baliga,S.M.,2002e.The evaluationof the radioprotectiveeffect of chyavanaprasha(an ayurvedic rasayana drug) in the mice exposed to lethal dose of γ-radiation:a preliminary study. Phytotherapy research.
48. Yonezawa M, Katoh N, Takeda A. 1989. Radiation protection by shigoka extract on split dose in mice.

Journal of Radiation Research 30: 247– 254

49. Miyanomae T, Frindel E. 1988. Radioprotection of haemopoiesis conferred by Acanthopanax senticosus

Harms (Shigoka) administered before or after irradiation. Experimental Hematology 16: 801–806.

50. Jagetia GC, Shirwaikar A, Rao SK, Bhilegaonkar PM. 2003d. Evaluation of the radioprotective effect of Ageratum conyzoides Linn. Extract in mice exposed to different doses of gamma radiation. Journal of Pharmacy and Pharmacology 55: 51–58.

51. Bakina EE, Rodina Y, Kinzburskii, Kopytin BM. 1967. Use of P vitamins, quercetin and flavallicep during radiation sickness in rats. Vliyanie Organizm Fiz Khim Faktorov Vnesh Sredy Sb Rab Mater

Nauch Konf 1967: 57–58.

IJSER © 2012 http://www.ijser.org

The research paper published by IJSER journal is about Phytochemicals – biomolecules for prevention and treatment of human diseases-a review 30

ISSN 2229-5518

52. Reeve VE, Bosnic M, Rosinova E, Boehm-Wilcox C. 1993. A garlic extract protects from ultraviolet B (280–320 nm) induced suppression of contact hypersensitivity. Photochemical Photobiological science

58: 813–817.

53. Sato Y. 1990. Studies on chemical protectors against radiation. XXXI. Protection effects of Aloe arborescens on skin injury induced by x-irradiation. Yakugaku Zasshi 110: 876– 884

54. Narimanov AA, Miakisheva SN, Kuznetsova SM. 1991. The radioprotective effect of extracts of Archangelica officinalis Hoffm. and Ledum palustre L. on mice. Radiobiologiia 31: 391–393. Narimanov AA. 1993.

55. Liu CX, Xiao PG. 1993. Danggui (Angelica sinensis). An Introduction to Chinese Materia Medica.

Beijing Medicinal University and Peking Union Medical University Press: Beijing, 168.

56. Ammon HP. 1993. Mechanism of antiinflammatory actions of curcumin and boswellic acids. Journal of

Ethnopharmacology 38: 113– 119.

57. Chaudhary D, Chandra D, Kale RK. 1999. Modulation of radioresponse of glyoxalase system by curcumin. Journal of Ethnopharmacology 64: 1–7.

58. Agarwal SS, Singh VK. 1999. Immunomodulation: A review of studies on Indian medicinal plants and synthetic peptides. Proc Indian National Academy of Science B65: 79–204.

59. Belinky PA, Aviram M, Mahmood S, Vaya J. 1998. Structural aspects of the inhibitory effects of glabridin on LDL oxidation. Free Radical Biology of Medicine 24: 1419–1429.

60. Kovalenko PG, Antonjuk VP, Maluita SS. 2003. Secondary metabolites production from transformed cells of Glycyrrhiza glabra and Potentilla alba producents of radioprotective compounds. Ukraininca Biorganica Acta 1: 1–17.

61. Shetty TK, Satav JG, Nair CKK. 2002. Protection of DNA and microsomal membranes in vitr o by

Glycyrrhiza glabra L. against gamma radiation. Phytotherapy Research 16: 576–578.

62. Smyshliaeva AV, Kudriashov Iu B. 1992. The modification of a radiation lesion in animals with an aqueous extract of Hypericum perforatum L. Nauchnye Doke Vyss Shkoly Biol Nauki 4: 9–13.

63. Hsu HY, Yang JJ, Ho YJ, Lin CC. 1999. Difference in the effects of radioprotection between aerial and root parts of Lycium chinese. Journal of Ethnopharmacology 64: 101–108.

64. Jagetia GC, Baliga MS. 2002a. Influence of the leaf extract of Mentha arvensis Linn. (mint) on the survival of mice exposed to different doses of gamma radiation. Strahlenther Onkol 178: 91–98

65. Rao AV, Uma Devi P, Kamath R. 2001. In vivo radioprotective effect of Moringa oleifera leaves.

Indian Journal of Experimental Biology 39: 858–863.

66. sunila ES and Kuttan G,2005

IJSER © 2012 http://www.ijser.org

The research paper published by IJSER journal is about Phytochemicals – biomolecules for prevention and treatment of human diseases-a review 31

ISSN 2229-5518

67. Jagetia GC, Baliga MS, Malagi KJ, Kamath SM. 2002. The evaluation of radioprotective effect of triphala (an Ayurvedic rejuvenating drug) in the mice exposed to gamma-radiation. Phytomedicine 9:

99–108.

68. Lee, K.W., Kang, N.J., Rogozin, E.A; Myricetin is a novel natural inhibitor of neoplastic cell transformation and. MEK1. Carcinogenesis 28:1918-1927 (2007).
69. Jung, S. K. Myricetin suppresses UVB-induced skin cancer by targeting Fyn. Cancer Research. 68,
6021–6029 (2008).
70. Molavi B and Mehta J L 2004 Current Opinion on Cardiology 19 488.
71. Kim, J. E. MKK4 is a novel target for the inhibition of tumor necrosis factor-alpha-induced vascular endothelial growth factor expression by myricetin. Biochemical Pharmacology 77, 412–421 (2009).
72. Kwon, J. Y. Delphinidin suppresses ultraviolet B-induced cyclooxygenases-2 expression through inhibition of MAPKK4 and PI-3 kinase. Carcinogenesis 30, 1932–1940 (2009).
73. He, Z.Fyn is a novel target of (-)-epigallocatechin gallate in the inhibition of JB6 Cl41 cell transformation. Moecularl Carcinogenesis 47, 172–183 (2008).
74. Commenges D, Scotet V, Renaud S,2000; Staehelin HB, Perrig-Chiello P, Mitrache C 2005.
75. Flight, I., & Clifton, P. (2006). Cereal grains and legumes in the prevention of coronary heart disease and stroke: a review of the literature. European Journal of Clinical Nutrition, 60 (10), 1145-1159.
76. Stromberg, I, Gemma, C, Vila, J, and Bickford, PC. 2005. “Blueberry and Spirulina-enriched diets enhance striatal dopamine recovery and induce a rapid, transient microglia activation after injury of the rat nigrostriatal dopamine system.” Journal of Experimental Neurology 196(2):298-307.
77. Joseph JA, Denisova NA, Arendash G, Gordon M, Diamond D, Shukitt -Hale B, Morgan D (2003) Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer dis ease model. Nutritional Neuroscience 6:153–162.
78. Wang, B., T. Li Y.H. Ding, R.H Zhang and H.J Wang, 2005: East Asian-Western North Pacific monsoon: A distinctive component of the Asian-Australian monsoon system. In: The Global Monsoon Systemt: Research and Forcast. Ed. by C.-P Chang, Bin Wang and N.-C.G Lau, WMO/TD No. 1266 (TMRP Report No. 70), 72-79.
79. Tchantchou, F., Apple juice concentrate prevents oxidative damage and impaired maze performance in
aged mice. Journal of Alzheimer’s Disease, 2005. 8(3): p. 283
80. Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J. American journal of clinical nutrition... 2006 Dec;84(6):1554.

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81. Jeong, C. H. [6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase.

Cancer Research. 69, 5584–5591 (2009).

82. Cho, Y. Y. A regulatory mechanism for RSK2 NH(2)-terminal kinase activity. Cancer Research. 69,
4398–4406 (2009).
83. Davies, D. R. Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography. Journal of Medical Chemistry 52, 4694–4715 (2009).
84. Bisht S, Feldmann G, Soni S, Ravi R, Karikar C, Maitra A and Maitra A. Polymeric nanoparticle- encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy. Journal of

nanobiotechnology. 53 (2007).

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