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MohdSayeedAkhtar
MallappaKumaraSwamy Editors
Anticancer
Plants:
Properties and
Application
Volume 1
ISBN 978-981-10-8547-5 ISBN 978-981-10-8548-2 (eBook)
https://doi.org/10.1007/978-981-10-8548-2
Library of Congress Control Number: 2018942942
© Springer Nature Singapore Pte Ltd. 2018
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Singapore
Editors
Mohd Sayeed Akhtar
Department of Botany
Gandhi Faiz-e-Aam College
Shahjahanpur, Uttar Pradesh, India
Mallappa Kumara Swamy
Department of Crop Science
Faculty of Agriculture
Universiti Putra Malaysia
Serdang, Selangor, Malaysia
sayeedbot@gmail.com
xv
17 Use ofPlant Secondary Metabolites asNutraceuticals
forTreatment andManagement ofCancer:
Approaches andChallenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
Zahid H. Siddiqui, B. Hareramdas, Zahid K. Abbas,
Talat Parween, and Mohammad Nasir Khan
18 Usefulness ofOcimum sanctum Linn. inCancer Prevention:
AnUpdate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
Naveen Kaushal, Suresh Rao, Preety Ghanghas, Soniya Abraham,
Thomas George, Sueallen D’souza, Jeffey M. Mathew,
Jessica Chavali, Mallappa Kumara Swamy,
and Manjeshwar Shrinath Baliga
19 Phytochemicals withAnticancer Potential:
Methods ofExtraction, Basic Structure,
andChemotherapeutic Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
Gulrez Nizami and R. Z. Sayyed
20 Anticancer Plants andTheir Conservation
Strategies: An Update . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455
Vankayalapati Vijaya Kumar, Mallappa Kumara Swamy,
and Mohd. Sayeed Akhtar
21 Anticancer Plants: Chemistry, Pharmacology,
andPotential Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485
V. D. Ravichandra, C. Ramesh, Mallappa Kumara Swamy,
B. Purushotham, and Gudepalya Renukaiah Rudramurthy
22 Botany, Chemistry, andPharmaceutical Significance
ofSida cordifolia: ATraditional Medicinal Plant . . . . . . . . . . . . . . . . 517
Hassan Ahmed, Abdul Shukor Juraimi, Mallappa Kumara Swamy,
Muhammad Saiful Ahmad-Hamdani, Dzolkii Omar,
Mohd Yusop Rai, Uma Rani Sinniah, and Mohd Sayeed Akhtar
23 Anticancer Properties ofNatural Compounds
onProstate Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539
Priyadarshini and Abhishek Negi
24 Phytochemicals Against Cancer Stem Cells . . . . . . . . . . . . . . . . . . . . . 559
Kok Hoong Leong, Kin Weng Kong, and Lip Yong Chung
Contents
sayeedbot@gmail.com
431© Springer Nature Singapore Pte Ltd. 2018
M. S. Akhtar, M. K. Swamy (eds.), Anticancer Plants: Properties and Application,
https://doi.org/10.1007/978-981-10-8548-2_19
Chapter 19
Phytochemicals withAnticancer Potential:
Methods ofExtraction, Basic Structure,
andChemotherapeutic Action
GulrezNizami andR.Z.Sayyed
19.1 Introduction
Phytochemicals or secondary metabolites are chemical compounds formed during
the normal plantmetabolic processes and useful in theprotection of plants (Watson
etal. 2001; Ning etal. 2009). Most of these phytochemicals possess animportant
medicinal properties and have beenfound to havemany applications in pharmaceuti-
cal industries. Free radical-scavenging molecules such as avonoids, tannins, alka-
loids, quinones, amines, vitamins, and other metabolites possess anti- inammatory,
anticarcinogenic, antibacterial, and antiviral activities (Sala etal. 2002). People have
been relying on thenatural source (plants) of treatments for various diseases even
today that is still the case especially in rural areas, where traditional healers outnum-
ber thewestern doctors. Most medicines used by thewestern doctors are also derived
from natural plants. Most phytochemicals have antioxidant activity and protect
human cells against oxidative damages. Plants with antioxidant properties are used
for minimizing the severity of the inammation- related diseases, and a health-pro-
moting effect of antioxidants from plants is thought to arise from their protective
effects by counteracting reactive oxygen species (ROS) (Wong etal. 2006). Studies
also have looked at the intake of specic phytochemicals and found a link to reduce
cancer risk. One study found that only specic avonoid subgroups were associated
indecreasing therisk of breast cancer. They have found thatthe reduced risk of can-
cer was notas strong byindividual phytochemicals when compared with that ofthe
foods rich in severalphytochemicals. The consumption of cruciferous vegetables
such as broccoli, cabbage, and cauliower has been associated with a decreased risk
G. Nizami
Department of Chemistry, Mohammad Ali Jauhar University, Rampur, Uttar Pradesh, India
R. Z. Sayyed (*)
Department of Microbiology, PSGVP Mandal’s Arts, Science and Commerce College,
Shahada, Maharashtra, India
sayeedbot@gmail.com
432
of prostate, lung, breast, and colon cancers. Isothiocyanate found in cruciferous veg-
etables, especially sulforaphane in broccoli, has been studied extensively and is
believed to offer some degrees of cancerprevention. Foods containing phytochemi-
cals are already apart of our daily diet (Daffre etal. 2008). In fact, most foods con-
tain phytochemicals except for some rened foods, such as sugar or alcohol. Some
foods, such as whole grains, vegetables, beans, fruits, and herbs, contain many phy-
tochemicals. The easiest way to get more phytochemicals is to eat more fruit (blue-
berries, cranberries, cherries, and apple) and vegetables (cauliower, cabbage,
carrots, and broccoli). It is recommended to take daily at least ve to nine servings
of fruits or vegetable. Fruits and vegetables are also rich in minerals, vitamins, and
ber and low in saturated fat. Phytochemicals are naturally present in many foods,
but it is expected that through bioengineering, new plants can be developed, which
will contain higher levels. This would make it easier to incorporate enough phyto-
chemicals intoour dailyfood.
The present chapter describes the importance of some plants of the genera
Philenoptera (family Fabaceae), Xanthocercis (family Fabaceae), and Euphorbia
(family Euphorbiaceae) and crucifer (family Cruciferae) and their signicance in
the treatment of cancer and other diseases with respect to their chemical structure
and methods of extraction. Moreover, anticancer properties of some important phy-
tochemicals like crocetin, cyanidins, diindolylmethane (DIM) or indole-3-carbinol
(I3C), epigallocatechin-3-gallate, setin, genistein, gingerol, kaempferol, broccoli,
and lycopene have also been discussed.
19.1.1 Plant Species Containing Anticancer Phytochemicals
Many plant species are known to have phytochemicals which are active against
cancer and other life-threatening diseases. Some species that areeffective against
cancer are discussed below:
19.1.1.1 Xanthocercis andPhilenoptera
BothXanthocercis and Philenoptera genera belong to the Fabaceae family (Rahman
and Choudhary 2001). Trees, herbs, vines, and shrubs of this plant family are native
to all regions of the world and are commonly cultivated (Kinghorn etal. 2003).
Xanthocercis zambesiaca is found in Africa and is known as Muchetuchetu/Musharo
in Shona and as Nyala berry in English. X. zambesiaca is traditionally used to treat
diabetes mellitus and has been scientically proven to have antihyperglycemic
effects (Kaskiw etal. 2009). P. violacea is also found in Africa, known as Mohata in
Shona, Mphata in Sotho, and apple leaf in English. It has been used in traditional
remedies to treat gastrointestinal problems, powdered root bark for colds and snake-
bite treatment and root infusions as hookworm remedy, and most part of the plant
has been used to treat diarrhea (Yan etal. 2009). The extracts were found to be
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active in the ve-cell line panel consisting of MCF7 (breast cancer), HCT116 (colon
cancer), TK10 (renal), UACC62 (melanoma), and PC3 (prostate cancer) by sul-
forhodamine B (SRB) assay at the CSIR. Qualitative phytochemical analysis of
these plant extracts conrmed the presence of tannins, avonoids, steroids, terpe-
noids, alkaloids, and cardiac glycosides from P. violacea extract, while X. zambe-
siaca extract showed the presence of avonoids, saponins, terpenoids, and
glycosides.
19.1.1.2 Euphorbia tirucalli
The historical use of E. tirucalli (family: Euphorbiaceae) in traditional medicine in
the Middle East, India, Africa, and South America was to treat a range of ailments,
including syphilis, asthma, cancer, colic, intestinal parasites, skin diseases, and lep-
rosy (Greer etal. 2005). Consequently, this has prompted scientic interest in its
pharmacological properties. Chromatographic and spectroscopic analyses of
extracts from the photosynthetic stems have identied a range of phenolics and
terpenes, the most prominent of which are the triterpenes, euphol, and tirucallol
(Greer etal. 2005). Leaf/stem extracts have been shown to possess potent antioxi-
dant properties as key factor in combating cellular oxidative stress. Methanol
extracts of E. tirucalli whole plant has positive antioxidant activity, potentially due
to their high phenolic content, and have been deemed an excellent and accessible
source of natural antioxidant activity. The use of E. tirucalli latex in traditional
medicine as a treatment for cancer has attracted the recent interest of the West.
However, this must be treated with caution, as whole plant aqueous extracts have
been shown to interact with antioxidant enzyme systems in human leukocytes via
upregulation of key antioxidant enzyme genes. This leads to increased cytotoxicity,
conrming the need for precise investigations into dose and administration of E.
tirucalli extracts for medicinal purposes (Harborne and Williams 1992). A further
study assessed the anticancer properties of euphol extracted from E. tirucalli latex,
(Stray and Storchova 1991) nding it to exhibit dose- and time-dependent cytotoxic
effects against a signicant number of cell lines, with most prominent effects against
esophageal squamous cell and pancreatic cell carcinomas.
19.1.1.3 Cruciferae Family
Cruciferae family which is one of the largest families in the plant kingdom is rich in
medicinal plants. It includes 338 genera and 3350 species that are distributed world-
wide (Okwu 2005; Peter 2013). Various studies indicate that consumption of large
number of cruciferous vegetables like broccoli, cabbage, kale, and brussels sprouts
are associated with a reduced incidence of cancer (Peter 2013). These contain vari-
ous primary and secondary metabolites. The breakdown products of glucosinolates
are indole-3-carbinol (I3C) and diindolylmethane (DIM). These degradation
products have properties like antibacterial, anticancer, and antifungal properties
19 Phytochemicals withAnticancer Potential: Methods ofExtraction, Basic Structure…
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(Emam and Abd El-Moaty 2009). The present study deals with phytochemical pro-
ling of cabbage for the presence of various phytochemicals. The extract was found
to contain various secondary metabolites like tannins, avonoids, sugars, alkaloids,
phenols, and anthocyanidin. The secondary metabolites, glucosinolates, are the
characteristic compounds of the crucifer family (Shapiro et al. 2001). These are
group of compounds that are hydrolyzed either enzymatically with myrosinase or
nonenzymatically to form primarily isothiocyanates and/or nitriles. Isothiocyanates
were attributed to chemopreventive activity and induce phase II detoxication
enzymes, boost antioxidant status, and protect animals against chemically induced
cancer. For further identication, of its degradation products, thin-layer chromatog-
raphy (TLC) was performed (Patil and Shettigar 2010).
19.1.1.4 Saffron
Saffron is a spice from the ower of the Saffron crocus and a food colorant present
in the dry stigmas of the plant Crocus sativus L. In a recent review article, saffron is
listed as a potential agent for a novel anticancer drug against hepatocellular carci-
noma (Amin etal. 2011; Abdullaev and Espinosa-Aguirre 2004). Saffron and its
ethanolic extracts are also reported for the studies on human lung cancer
(Samarghandian etal. 2010, 2011), pancreatic cancer cell line (Bakshi etal. 2010),
skin carcinoma (Das etal. 2010), colorectal cancer cells (Aung etal. 2007), and
breast cancer (Chryssanthi etal. 2011). Its applications and mechanism of actions
are reviewed by Bathaie and Mousavi (2010), but till now the exact mechanism of
action is not clear. In general, crocetin affects the growth of cancer cells by inhibit-
ing nucleic acid synthesis, enhancing anti-oxidative system, inducing apoptosis,
and hindering growth factor signaling pathways. Nam’s study has shown that croce-
tin is effective for the inhibition of LPS-induced nitric oxide release; for the reduc-
tion of the produced TNF-α, IL-1β, and intracellular reactive oxygen species; for the
activation of NF-κB; and for blockage of the effect of LPS on hippocampal cell
death (Nam etal. 2010). Although some studies beyond those mentioned above are
successfully conducted, more thorough understanding of the mechanism on croce-
tin and its effects are needed.
19.1.1.5 Cyanidin
Cyanidin is a extract of pigment from red berries such as grapes, blackberry, cran-
berry, and raspberry, apples and plums, and red cabbage and red onion. It possesses
antioxidant and radical-scavenging effects which may reduce the risk of cancer. It is
reported to inhibit cell proliferation and iNOS and COX-2 gene expression in colon
cancer cells (Kim et al. 2008). Another study shows that cyanidin-3-glucoside
(C3G) attenuated the benzo[a]pyrene-7,8-diol-9,10-epoxide-induced activation of
AP-1 and NF-κB and phosphorylation of MEK, MKK4, Akt, and MAPKs and
blocked the activation of the Fyn kinase signaling pathway, which may contribute to
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its chemopreventive potential (Lim etal. 2011). C3G blocks ethanol-induced activa-
tion of the ErbB2/cSrc/FAK pathway in breast cancer cells and may prevent/reduce
ethanol-induced breast cancer metastasis. (Xu etal. 2011) Cyanidin-3-O-glucoside,
cyanidin-3-O-rutinoside, and the ethanol extract of their source of freeze-dried
black raspberries selectively caused signicant growth inhibition and induction of
apoptosis in a highly tumorigenic rat esophagus cell line (RE-149 DHD) but not in
a weakly tumorigenic line (RE-149) (Zikri etal. 2009). Cyanidin markedly inhib-
ited UVB-induced COX-2 expression and PGE2 secretion in the epidermal skin cell
line by suppressing NF-κB and AP-1 which are regulated by MAPK.In that study,
MKK-4, MEK1, and Raf-1 are targets of cyanidin for the suppression of UVB-
induced COX-2 expression (Kim etal. 2010). Indole-3-carbinol (I3C) is found in
Brassica vegetables, such as broccoli, cauliower, collard greens. Diindolylmethane
(DIM) is a digestion derivative of indole-3-carbinol via condensation formed in the
acidic environment of the stomach. Both are studied for their anticarcinogenic
effects. I3C has been studied for cancer prevention and therapy for years (Kim and
Milner 2005) for tobacco smoke carcinogen-induced lung adenocarcinoma in A/J
mice, and it was found that the lung cancer preventive effects are mediated via
modulation of the receptor tyrosine kinase/PI3K/Akt signaling pathway, at least
partially. I3C and DIM demonstrated exceptional anticancer effects against
hormone- responsive cancers like breast, prostate, and ovarian cancers (Acharya
etal. 2010). In a recent study, it is concluded that DIM rather than I3C is the active
agent in cell culture studies (Bradlow and Zeligs 2010).
19.1.1.6 Fisetin
Fisetin is a avone found in various plants such as Acacia greggii, Acacia berland-
ieri, Eurasian smoke tree, parrot tree, strawberries, apple, persimmon, grape, onion,
and cucumber (Maher etal. 2011; Arai etal. 2000). Fisetin has been found to allevi-
ate aging effects in the yeast or fruit y (Howitz etal. 2003; Wood etal. 2004) and
exert anti-inammatory effect in LPS-induced acute pulmonary inammation and
anticarcinogenic effects in HCT-116 human colon cancer cells (Geraets etal. 2009;
Lim and Park 2009). Fisetin is also a potent antioxidant and modulates protein
kinase and lipid kinase pathways. Fisetin, along with other avonoids such as luteo-
lin, quercetin, galangin, and EGCG, induced the expression of Nrf2 and the phase II
gene product HO-1in human retinal pigment epithelial (RPE) cells which could
protect RPE cells from oxidative stress-induced death with a high degree of potency
and low toxicity and reduced H2O2-induced cell death. However, Khan etal. (2012)
found dual inhibition of PI3K/Akt and mTOR signaling in human non-small cell
lung cancer cells by setin.
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19.1.1.7 Genistein
Genistein is an isoavone that originates from a number of plants such as lupine,
fava beans, soybeans, kudzu, Psoralea, Flemingia vestita, and coffee. Functioning
as antioxidant and anthelmintic, genistein has been found to have antiangiogenic
effects (blocking formation of new blood vessels) and may block the uncontrolled
cell growth associated with cancer, most likely by inhibiting the enzymes that regu-
late cell division and cell survival (growth factors). Genistein’s activity was chiey
functioned as a tyrosine kinase inhibitor by inhibiting DNA topoisomerase II
(Lopez-Lazaro etal. 2007). In vitro and invivo studies show that genistein has been
found to be useful in treating leukemia (Wang et al. 2008; Sanchez etal. 2009;
Raynal etal. 2008; Yamasaki etal. 2007). Estrogen receptors are overexpressed in
around 70% of breast cancer cases (ER-positive). Binding of estrogen to the ER
stimulates proliferation of mammary cells, with the resulting increase in cell divi-
sion and DNA replication. Estrogen metabolism produces genotoxic waste, which
may cause disruption of cell cycle, apoptosis, and DNA repair, and forms tumor.
19.1.1.8 Gingerol
Gingerol is the active component of fresh ginger with distinctive spiciness. Gingerol
is known for its anticancer effects for tumors in the colon (Jeong etal. 2009), breast,
ovary (Lee etal. 2008; Rhode etal. 2007), and pancreas (Park etal. 2006). A recent
review by Oyagbemi etal. (2010) summarized the mechanisms in the therapeutic
effects of gingerol. In short, gingerol has demonstrated antioxidant, anti-
inammatory, and antitumor promoting properties and decreases iNOS and TNF-
alpha expression via suppression of IκBα phosphorylation and NF-κB nuclear
translocation (Oyagbemi etal. 2010). Treating K562 cells and MOLT4 cells with
gingerol, the ROS levels were signicantly higher than control groups, inducing
apoptosis of leukemia cells by mitochondrial pathway. On human hepatocarcinoma
cells, gingerol, along with 6-shogaol, was found to exert anti-invasive activity
against hepatoma cells through regulation of MMP-9 and TIMP-1, and 6-shogaol
further regulated urokinase-type plasminogen activity.
19.1.1.9 Kaempferol
Kaempferol is a natural avonol isolated from tea, broccoli, witch hazel, grapefruit,
brussels sprouts, apples, etc. Kaempferol has been studied for pancreatic cancer
(Nothlings etal. 2007) and lung cancer (Cui etal. 2008). It has been investigated for
its antiangiogenic, anticancer, and radical-scavenging effects (Gacche etal. 2011).
Kaempferol displayed moderate cytostatic activity of 24.8–64.7μM in the cell lines
of PC3, HeLa, and K562 human cancer cells. Kaempferol has been studied as aryl
hydrocarbon receptor (AhR) antagonist showing inhibition of ABCG2
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upregulation, thereby reversing the ABCG2-mediated multidrug resistance, which
may be useful for esophageal cancer treatment. Lycopene is a bright red pigment
and phytochemical from tomatoes, red carrots, watermelons, and red papayas. It
demonstrates antioxidant activity and chemopreventive effects in many studies,
especially for prostate cancer. Poorly soluble in water, lycopene has high solubility
in organic solvents. Its anticancer property is attributed to activating cancer preven-
tive enzymes such as phase II detoxication enzymes (Giovannucci etal. 1995).
Lycopene was found to inhibit human cancer cell proliferation and to suppress insu-
lin-like growth factor-I-stimulated growth. This may open new avenues for lyco-
pene study on the role of the prevention or treatment of endometrial cancer and
other tumors. Lycopene also possesses inhibitory effects on breast and endometrial
cancer cells (Nahum etal. 2001), prostate cancer cells (Giovannucci etal. 1995),
and colon cancer cells. However, in a study conducted by Erdman and group using
xenocraft prostate tumors into rats, it was found that the tumors grew more slowly
in those given whole dried tomato powder but not in those given lycopene, which
may indicate that lycopene may be an important component in tomato but not the
only component in tomato that actively suppressing the growth of the prostate can-
cer (Canene-Adams etal. 2007).
19.2 Extraction Processes ofPhytochemicals
General methods of extraction of phytochemicals are discussed below.
19.2.1 Solvent Extraction
Various solvents have been used to extract different phytoconstituents. The plant
parts are dried immediately either in an articial environment at low temperature
(50–60°C) or dried preferably in shade so as to bring down the initial large moisture
content to enable its prolonged storage life. The dried berries are pulverized by
mechanical grinders and the oil is removed by solvent extraction. The defatted
material is then extracted in a Soxhlet apparatus or by soaking in water or alcohol
(95% v/v). The resulting alcoholic extract is ltered, concentrated in vacuum or by
evaporation, treated with HCl (12N), and reuxed for at least 6h. This can then be
concentrated and used to determine the presence of phytoconstituents. Generally,
the saponins do have high molecular weight, and hence their isolation in the purest
form poses some practical difculties. The plant parts (tubers, roots, stems, leaves,
etc.) are washed, sliced, and extracted with hot water or ethanol (95% v/v) for sev-
eral hours. The resulting extract is ltered and concentrated in vacuum, and the
desired constituent is precipitated with ether. Exhaustive extraction (EE) is usually
carried out with different solvents of increasing polarity in order to extract as much
as possible the most active components with highest biological activity.
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19.2.2 Supercritical Fluid Extraction (SFE)
This is the most technologically advanced extraction system. Supercritical uid
extraction (SFE) involves use of gases, usually CO2, by compressing them into a
dense liquid. This liquid is then pumped through a cylinder containing the material
to be extracted. From there, the extract-laden liquid is pumped into a separation
chamber where the extract is separated from the gas, and the gas is recovered for
reuse. Solvent properties of CO2 can be manipulated and adjusted by varying the
pressure and temperature that one works at. The advantages of SFE are the versatil-
ity it offers in pinpointing the constituents you want to extract from a given material
and the fact that your end product has virtually no solvent residues left in it (CO2
evaporates completely). The downside is that this technology is quite expensive.
There are many other gases and liquids that are highly efcient as extraction sol-
vents when put under pressure.
19.2.2.1 Coupled SFE-SFC
In this system, a sample is extracted with a supercritical uid and then placed in the
chromatographic system, and the extract is directly chromatographed using super-
critical uid.
19.2.2.2 Coupled SFE-GC andSFE-LC
In this system, a sample is extracted using a supercritical uid which is then depres-
surized to deposit the extracted material in the inlet part or a column of gas or liquid
chromatographic system, respectively. SFE has characteritic features such as robust-
ness of sample preparation, reliability, high yield, less time consuming, and also has
potential for coupling with a number of chromatographic methods.
19.2.3 Microwave-Assisted Extraction
Applications of innovative, microwave-assisted solvent extraction technology
known as microwave-assisted processing (MAP) include the extraction of high-
value compounds from natural sources including phytonutrients, nutraceutical and
functional food ingredients, and pharmaceutical actives from biomass. Compared to
conventional solvent extraction methods, MAP technology offers some combina-
tion of the following advantages: (1) improved products, increased purity of crude
extracts, improved stability of marker compounds, and possibility to use less toxic
solvents and (2) reduced processing costs, increased recovery and purity of marker
compounds, very fast extraction rates, and reduced energy and solvent usage. With
microwave-derived extraction as opposed to diffusion, very fast extraction rates and
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greater solvent exibility can be achieved. Many variables, including the microwave
power and energy density, can be tuned to deliver desired product attributes and
optimize process economics. The process can be customized to optimize for com-
mercial/cost reasons, and excellent extracts are produced from widely varying sub-
strates. Examples include, but are not limited to, antioxidants from dried herbs,
carotenoids from single cells and plant sources, taxanes from taxus biomass, essen-
tial fatty acids from microalgae and oilseeds, phytosterols from medicinal plants,
polyphenols from green tea, avor constituents from vanilla and black pepper,
essential oils from various sources, and many more.
19.2.4 Solid-Phase Extraction
This involves sorption of solutes from a liquid medium onto a solid adsorbent by the
same mechanisms by which molecules are retained on chromatographic stationary
phases. These adsorbents, like chromatographic media, come in the form of beads
or resins that can be used in column or in batch form. They are often used in the
commercially available form of syringes packed with medium (typically a few hun-
dred milligrams to a few grams) through which the sample can be gently forced with
the plunger or by vacuum. Solid-phase extraction media include reverse phase, nor-
mal phase, and ion exchange media. This is a method for sample purication that
separates and concentrates the analyte from solution of crude extracts by adsorption
onto a disposable solid-phase cartridge. The analyte is normally retained on the
stationary phase, washed and then evaluated with different mobile phases. If an
aqueous extract is passed down a column containing reverse-phase packing mate-
rial, everything that is fairly non-polar will bind, whereas everything polar will pass
through (Greer etal. 2005).
19.2.5 Chromatographic Fingerprinting andMarker
Compound Analysis
Chromatographic ngerprint of a herbal medicine (HM) is a chromatographic pat-
tern of the extract of some common chemical components of pharmacologically
active and/or chemical characteristics. This chromatographic prole should be fea-
tured by the fundamental attributions of “integrity” and “fuzziness” or “sameness”
and “differences” so as to chemically represent the HM investigated. It is suggested
that with the help of chromatographic ngerprints obtained, the authentication and
identication of herbal medicines can be accurately conducted (integrity) even if the
amount and/or concentrations of the chemically characteristic constituents are not
exactly the same for different samples of this HM (hence, “fuzziness”) or the chro-
matographic ngerprints could demonstrate both the “sameness” and “differences”
between various samples successfully. Thus, we should globally consider multiple
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constituents in the HM extracts and not individually consider only one and/or two
marker components for evaluating the quality of the HM products. However, in any
HM and its extract, there are hundreds of unknown components, and many of them
are in low amount. Moreover, there usually exists variability within the same herbal
materials. Hence it is very important to obtain reliable chromatographic ngerprints
that represent pharmacologically active and chemically characteristic components
of the HM.In the phytochemical evaluation of herbal drugs, TLC is being employed
extensively for the following reasons: (1) it enables rapid analysis of herbal extracts
with minimum sample cleanup requirement, (2) it provides qualitative and semi-
quantitative information of the resolved compounds, and (3) it enables the quanti-
cation of chemical constituents. Fingerprinting using HPLC and GLC is also carried
out in specic cases. In TLC ngerprinting, the data that can be recorded using a
high-performance TLC (HPTLC) scanner includes the chromatogram, retardation
factor (Rf) values, the color of the separated bands, their absorption spectra, and
shoulder inection(s) of all the resolved bands. All of these, together with the pro-
les on derivatization with different reagents, represent the TLC ngerprint prole
of the sample. The information so generated has a potential application in the iden-
tication of an authentic drug, in excluding the adulterants and in maintaining the
quality and consistency of the drug. HPLC ngerprinting includes recording of the
chromatograms, retention time of individual peaks, and the absorption spectra
(recorded with a photodiode array detector) with different mobile phases. Similarly,
GLC is used for generating the ngerprint proles of volatile oils and xed oils of
herbal drugs (Xie et al. 2006). Furthermore, the recent approaches of applying
hyphenated chromatography and spectrometry such as high-performance liquid
chromatography-diode array detection (HPLC-DAD), gas chromatography-mass
spectroscopy (GC-MS), capillary electrophoresis-diode array detection (CE-DAD),
high-performance liquid chromatography-mass spectroscopy (HPLC-MS), and
high-performance liquid chromatography-nuclear magnetic resonance spectros-
copy (HPLC-NMR) could provide the additional spectral information, which will
be very helpful for the qualitative analysis and even for the online structural
elucidation.
19.2.6 Advances inChromatographic Techniques
19.2.6.1 Liquid Chromatography
19.2.6.1.1 Preparative High-Performance Liquid Chromatography
There are basically two types of preparative HPLC.One is low-pressure (typically
under 5bars) traditional PLC, based on the use of glass or plastic columns lled
with low-efciency packing materials of large particles and large size distribution.
A more recent form of PLC, preparative high-performance liquid chromatography
(preparative HPLC), has been gaining popularity in pharmaceutical industry.
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The aim is to isolate or purify compounds, whereas in analytical work the goal is to
get information about the sample. Preparative HPLC is closer to analytical HPLC
than traditional PLC, because its higher column efciencies and faster solvent
velocities permit more difcult separation to be conducted more quickly. In analyti-
cal HPLC, the important parameters are resolution, sensitivity, and fast analysis
time, whereas in preparative HPLC, both the degree of solute purity and the amount
of compound that can be produced per unit time, i.e., throughput or recovery, are
important. This is very important in pharmaceutical industry of today because new
products (natural, synthetic) have to be introduced to the market as quickly as pos-
sible. Having available such a powerful purication technique makes it possible to
spend less time on the synthesis conditions (Dass 2007).
19.2.6.1.2 Liquid Chromatography-Mass Spectroscopy (LC-MS)
In pharmaceutical industry LC-MS has become the method of choice in many stages
of drug development. Recent advances include electrospray, thermospray, and ion
spray ionization techniques which offer unique advantages of high detection sensi-
tivity and specicity; liquid secondary ion mass spectroscopy, later laser mass spec-
troscopy with 600MHz, offers accurate determination of molecular weight proteins
and peptides. Isotopes pattern can be detected by this technique (Narod etal. 1998).
19.2.6.1.3 Liquid Chromatography-Nuclear Magnetic Resonance (LC-NMR)
The combination of chromatographic separation technique with NMR spectroscopy
is one of the most powerful and time-saving methods for the separation and struc-
tural elucidation of unknown compound and mixtures, especially for the structure
elucidation of light- and oxygen-sensitive substances. The online LC-NMR tech-
nique allows the continuous registration of time changes as they appear in the chro-
matographic run automated data acquisition, and processing in LC-NMR improves
speed and sensitivity of detection. The recent introduction of pulsed eld gradient
technique in high resolution NMR as well as three-dimensional technique improves
application in structure elucidation and molecular weight information. These new
hyphenated techniques are useful in the areas of pharmacokinetics, toxicity studies,
drug metabolism, and drug discovery process (Christophoridou etal. 2005).
19.2.6.2 Gas Chromatography
19.2.6.2.1 Gas Chromatography Fourier Transform Infrared Spectrometry
Coupling capillary column gas chromatographs with Fourier transform infrared
spectrometer provides a potent means for separating and identifying the compo-
nents of different mixtures (Chaimbault 2014).
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19.2.6.2.2 Gas Chromatography-Mass Spectroscopy
Gas chromatography equipment can be directly interfaced with rapid scan mass
spectrometer of various types. The ow rate from capillary column is generally low
enough that the column output can be fed directly into ionization chamber of
MS.The simplest mass detector in GC is the ion trap detector (ITD). In this instru-
ment, ions are created from the eluted sample by electron impact or chemical ion-
ization and stored in a radio frequency eld; the trapped ions are then ejected from
the storage area to an electron multiplier detector. The ejection is controlled so that
scanning on the basis of mass-to-charge ratio is possible. The ion trap detector is
remarkably compact and less expensive than quadrupole instruments. GC-MS
instruments have been used for identication of hundreds of components that are
present in natural and biological system (Narod etal. 1998).
19.2.6.3 Supercritical Fluid Chromatography (SFC)
Supercritical uid chromatography is a hybrid of gas and liquid chromatography
that combines some of the best features of each. This technique is an important third
kind of column chromatography that is beginning to nd use in many industrial,
regulatory, and academic laboratories. SFC is important because it permits the sepa-
ration and determination of a group of compounds that are not conveniently handled
by either gas or liquid chromatography. These compounds are either nonvolatile or
thermally labile so that GC procedures are inapplicable or contain no functional
group that makes possible the detection by spectroscopic or electrochemical tech-
nique employed in LC.SFC has been applied to a wide variety of materials includ-
ing natural products, drugs, foods, and pesticides (Smith etal. 1988).
19.2.6.4 Other Chromato-Spectrometric Studies
The NMR techniques are employed for establishing connectivity between neighbor-
ing protons and establishing C-H bonds. INEPT is also being used for long-range
heteronuclear correlations over multiple bonding. The application of thin-layer
chromatography (TLC), high-performance chromatography (HPLC) and HPLC
coupled with ultraviolet (UV) photodiode array detection, liquid chromatography-
ultraviolet (LC-UV), liquid chromatography-mass spectrophotometry (LC-MS),
electrospray (ES), and Liquid chromatography-nuclear magnetic resonance
(LC-NMR) techniques for the separation and structure determination of antifungal
and antibacterial plant compounds is on the increase frequently (Narod etal. 1998).
Variouschromatographic and spectroscopic techniques in new drug discovery from
natural products are available. Computer modeling has also been introduced in
spectrum interpretation and the generation of chemical structures meeting the
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spectral properties of bioactive compounds obtained from plants. The computer sys-
tems utilize 1H, 13C, 2D-NMR, IR, and MS spectral properties. Libraries of spectra
can be searched for comparison with complete or partial chemical structures.
Hyphenated chromatographic and spectroscopic techniques are powerful analytical
tools that are combined with high-throughput biological screening in order to avoid
re-isolation of known compounds as well as for structure determination of novel
compounds. Hyphenated chromatographic and spectroscopic techniques include
LC-UV-MS, LC-UV-NMR, LC-UV-ES-MS, and GC-MS (Narod etal. 1998).
19.3 Chemical Structures ofAnticancer Phytochemicals
There are more than thousand known phytochemicals. Phytochemicals may have
biological signicance, for example, carotenoids or avonoids, but are not estab-
lished as essential nutrients. There may be as many as 4000 different phytochemi-
cals. Some are responsible for color and other organoleptic properties, such as the
deep purple of blueberries and the smell of garlic. Some of the well-known phyto-
chemicals are lycopene in tomatoes, isoavones in soy, and avonoids in fruits.
Some important class of phytochemicals (Table19.1) is discussed below.
Table 19.1 Summary of plants, anticancer phytochemicals, and plant source
Plant species Phytochemicals
Chemical
compounds Effects
Tomato Lycopene Flavones Effective against prostate
cancer
Tea, broccoli, witch hazel,
grapefruit, brussels sprouts, apples
Kaempferol Flavones Reduced the pancreatic
cancer
Ginger Gingerol Flavonoids Checked the colon
cancer, breast, and
ovarian tumors
Fava beans, soybeans, kudzu Genistein Isoavone Anthelmintic and
antiangiogenic effects
Smoke tree, parrot tree,
strawberries, apple, persimmon,
grape, onion, cucumber
Fisetin Flavones Reduced the lung cancer
Grapes, blackberry, cranberry,
raspberry, or apples and plums, red
cabbage and red onion
Cyanidin Glucoside Antioxidant, anticancer
properties
Saffron crocus, the plant Crocus
sativus L.
Crocetin Alkaloid Active against
hepatocellular carcinoma,
lung cancer
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19.3.1 Alkaloids
These are the largest group of secondary chemical constituents made largely of
ammonia compounds comprising basically of nitrogen bases synthesized from
amino acid building blocks with various radicals replacing one or more of the
hydrogen atoms in the peptide ring, most containing oxygen (Table19.2). The com-
pounds have basic properties and are alkaline in reaction, turning red litmus paper
blue. In fact, one or more nitrogen atoms that are present in an alkaloid, typically as
1°, 2°, or 3° amines, contribute to the basicity of the alkaloid. Degree of basicity
varies considerably, depending on the structure of the molecule and the presence
and location of the functional groups that react with acids to form crystalline salts
without the production of water. Solutions of alkaloids are intensely bitter. In nature,
the alkaloids exist in large proportions in the seeds. Basic structures of some phar-
macologically important plant derived alkaloids and roots of plants and often in
combination with vegetable acids. Alkaloids arehaving pharmacological applica-
tions as anesthetics and CNS stimulants; more than 12,000 alkaloids are known to
exist in about 20% of plant species and only few have been exploited for medicinal
purposes (Wrobleski etal. 2004). The name alkaloid ends with the sufx -ine, and
plant-derived alkaloids in clinical use include the analgesics morphine and codeine,
the muscle relaxant (+)-tubocurarine, the antibiotics sanguinane and berberine, the
anticancer agent vinblastine, the antiarrhythmic ajmaline, the pupil dilator atropine,
and the sedative scopolamine (Table19.2).
19.3.2 Glycosides
Glycosides in general, are dened as the condensation products of sugars (including
polysaccharides) with a host of different varieties of organic hydroxy (occasionally
thiol) compounds (invariably monohydrate in character), in such a manner that the
hemiacetal entity of the carbohydrate must essentially take part in the condensation.
Glycosides are colorlessand crystalline substances containing carbon, hydrogen,
and oxygen (some contain nitrogen and sulfur), water-soluble phytoconstituents,
Table 19.2 Structure of some pharmacologically important anticancer phytochemicals
Phytochemicals type Name of phytochemicals
Alkaloids Caffeine, morphine, codeine
Glycosides Α-Terpineol, cinnamyl acetate, eugenol taxifolin-7-o-β glucoside
Flavonoids Flavan, avone, dihydroavone
Phenolics Caffeic acid, chlorogenic acid
Terpenes Cubebene
Anthraquinone Luteolin, methyl luteolin
Tannins Gallic acid, genistein, glycitein, daidzein
Glycetein R1=H, R2=OCH3, R3=OH
Daidzein R1=R2=H, R3=OH
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and found in the cell sap. Chemically, glycosides contain a carbohydrate (glucose)
and a non-carbohydrate part (aglycone or genin); alcohol, glycerol, or phenol repre-
sents aglycones. Glycosides are neutral in reaction and can be readily hydrolyzed
into its components with ferments or mineral acids. Glycosides are classied on the
basis of type of sugar component, chemical nature of aglycone, or pharmacological
action. Glycosides are purely bitter principles that are commonly found in plants of
the Genitiaceae family and though they are chemically unrelated but possess the
common property of an intensely bitter taste. The bitters act on gustatory nerves,
which results in increased ow of saliva and gastric juices (Table19.2) (Londono
etal. 2010).
19.3.3 Flavonoids
Flavonoids are important group of polyphenols widely distributed among the plant
ora. Structurally, they are made of more than one benzene ring in its structure (a
range of C15 aromatic compounds), and numerous reports support their use as anti-
oxidants or free radical scavengers (Angelini et al. 2010). The compounds are
derived from parent compounds known as avans. Over 4000 avonoids are known
to exist and some of them are pigments in higher plants. Quercetin, kaempferol, and
quercitrin are common avonoids present in nearly 70% of plants. Other groups of
avonoids include avones, dihydroavons, avans, avonols, anthocyanidins
(Table 19.2), calchones and catechin, and leucoanthocyanidins (Londono et al.
2010).
19.3.4 Phenolics
Phenolics, phenols, or polyphenolics (or polyphenol extracts) are chemical compo-
nents that occur ubiquitously as natural color pigments responsible for the color of
fruits of plants. Phenolics in plants are mostly synthesized from phenylalanine via
the action of phenylalanine ammonia lyase (PAL). They are very important to plants
and have multiple functions. The most important role may be in plant defense
against pathogens and herbivore predators and thus is applied in the control of
human pathogenic infections. They are classied into (1) phenolic acids, (2) avo-
noid polyphenolics (avonones, avones, xanthones, and catechins), and (3) non-
avonoid polyphenols. Caffeic acid is regarded as the most common of phenolic
compounds distributed in the plant ora followed by chlorogenic acid known to
cause allergic dermatitis among humans. Phenolics essentially represent a host of
natural antioxidants, used as nutraceuticals and found in apples, green tea, and red
wine for their enormous ability to combat cancer, and are also thought to prevent
heart ailments to an appreciable degree and sometimes are anti-inammatory
agents. Other examples include avones, rutin, naringin, hesperidin, and chloro-
genic (Table19.2) (Dai and Mumper 2010).
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19.3.5 Terpenes
Terpenes are among the most widespread and chemically diverse groups of natural
products. They are ammable unsaturated hydrocarbons, existing in liquid form
commonly found in essential oils, resins, or oleoresins. Terpenoids include hydro-
carbons of plant origin of general formula (C5H8)n and are classied as mono-, di-,
tri-, and sesquiterpenoids depending on the number of carbon atoms. Examples of
commonly important monoterpenes include terpinen-4-ol, thujone, camphor, euge-
nol, and menthol. Diterpenes (C20) are classically considered to be resins, and
Taxol, the anticancer agent, is the common example. The triterpenes (C30) include
steroids, sterols, and cardiac glycosides with anti-inammatory, sedative, insecti-
cidal, or cytotoxic activity. Common triterpenes, such as amyrins, ursolic acid, and
oleanolic acid, and sesquiterpene (C15), like monoterpenes, are major components
of many essential oils. The sesquiterpene acts as irritants when applied externally,
and when consumed internally, their action resembles that of gastrointestinal tract
irritant. A number of sesquiterpene lactones have been isolated, and broadly they
have antimicrobial (particularly antiprotozoal) and neurotoxic action. The sesqui-
terpene lactone, palasonin, isolated from Butea monosperma has anthelmintic activ-
ity, inhibits glucose uptake, and depletes the glycogen content in Ascaridia galli
(Jiang etal. 2016) (Table19.2).
19.3.6 Anthraquinones
These are derivatives of phenolic and glycosidic compounds. They are solely
derived from anthracene giving variable oxidized derivatives such as anthrones and
anthranols. Other derivatives such as chrysophanol, aloe-emodin, rhein, sali-
nosporamide, luteolin, and emodin have in common a double hydroxylation at posi-
tions C1 and C8. To test for free anthraquinones, powdered plant material is mixed
with organic solvent and ltered, and an aqueous base, e.g., NaOH or NH4OH
solution, is added to it. A pink or violet color in the base layer indicates the presence
of anthraquinones in the plan (Table19.2) (Shami 2015).
19.3.7 Tannins
These are widely distributed in plant ora. They are phenolic compounds of high
molecular weight. Tannins are soluble in water and alcohol and are found in the
root, bark, stem, and outer layers of plant tissue. Tannins have a characteristic fea-
ture to tan, i.e., to convert things into leather. They are acidic in reaction, and the
acidic reaction is attributed to the presence of phenolics or carboxylic group. They
form complexes with proteins, carbohydrates, gelatin, and alkaloids. Tannins are
divided into hydrolyzable tannins and condensed tannins. Hydrolyzable tannins,
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upon hydrolysis, produce gallic acid and ellagic acid, and depending on the type of
acid produced, the hydrolyzable tannins are called gallotannins or ellagitannins. On
heating, they form pyrogallic acid. Tannins are used as antiseptic and this activity is
due to the presence of the phenolic group. Common examples of hydrolyzable tan-
nins include theaavins (from tea), daidzein, genistein, and glycitein (Table 19.2)
(Rhazi etal. 2015).
19.4 Action ofPhytochemicals
19.4.1 Antioxidant Agents
In normal conditions, the human body possesses many defense mechanisms against
oxidative stress, including antioxidant enzymes and nonenzymatic compounds
(Kahkonen etal. 1999). The natural antioxidant mammalian mechanism sometimes
become insufcient, and then the excess of free radicals can damage both the struc-
ture and function of a cell membrane in a chain reaction leading to many degenera-
tive diseases (Wong et al. 2006). Antioxidants reduce the oxidative stress in cells
and are therefore useful in the treatment of many human diseases, including cancer,
cardiovascular diseases, and inammatory diseases (Gacche etal. 2011). Natural
plants are a cheap source for the extraction of antioxidant compounds, thus provid-
ing important economic advantage. The DPPH radical is a stable organic free radi-
cal with an absorption maximum band around 515–528nm. It is therefore a useful
reagent for evaluation of antioxidant activity of compounds. In the DPPH test, the
antioxidants reduce the DPPH radical to a yellow-colored compound, diphenyl pic-
ryl hydrazine, and the extent of the reaction depends on the hydrogen-donating
ability of the antioxidants. The methanol extract of both Philenoptera violacea and
Xanthocercis zambesiaca demonstrated a concentration-dependent scavenging
activity by quenching DPPH radicals (Conforti etal. 2008). The hydrogen-donating
activity, measured using DPPH test, showed that the concentration of Xanthocercis
zambesiaca needed for 50% scavenging (SC50) was found to be 2.5mg/ml, for
Philenoptera violacea was >2.5mg/ml (Shirwaikar etal. 2006).
19.4.2 Anticarcinogenesis
Polyphenols particularly are among the diverse phytochemicals that have the poten-
tial in the inhibition of carcinogenesis (Liu 2004). Phenolic acids usually signi-
cantly minimize the formation of the specic cancer-promoting nitrosamines from
the dietary nitrites and nitrates. Glucosinolates from various vegetable sources such
as broccoli, cabbage, cauliower, and brussels sprouts exert a substantial protective
support against the colon cancer. Regular consumption of brussels sprouts by human
subjects (up to 300g day−1) miraculously causes a very fast (say within a span of
3 weeks) and appreciable enhancement in the glutathione S-transferase, and a
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subsequent noticeable reduction in the urinary concentration of a specic purine
metabolite serves as a marker of DNA degradation in cancer. Isothiocyanates and
the indole-3-carbinols do interfere categorically in the metabolism of carcinogens,
thus causing inhibition of procarcinogen activation and thereby inducing the “phase
II” enzymes, namely, NAD(P)H quinone reductase or glutathione S-transferase, that
specically detoxify the selected electrophilic metabolites which are capable of
changing the structure of nucleic acids. Sulforaphane (rich in broccoli) has been
proven to be an extremely potent phase II enzyme inducer. It predominantly causes
specic cell-cycle arrest and also the apoptosis of the neoplasm (cancer) cells.
Sulforaphane categorically produces d-D-gluconolactone which has been estab-
lished to be a signicant inhibitor of breast cancer. Indole-3-carbinol (most vital and
important indole present in broccoli) specically inhibits the human papillomavirus
(HPV) that may cause uterine cancer. It blocks the estrogen receptors specically
present in the breast cancer cells as well as downregulates CDK6 and upregulates
p21 and p27in prostate cancer cells. It affords G1 cell-cycle arrest and apoptosis of
breast and prostate cancer cells signicantly and enhances the p53 expression in
cells treated with benzopyrene. It also depresses Akt, NF-kappaB, MAPK, and
Bel-2 signaling pathways to a reasonably good extent. Phytosterols block the devel-
opment of tumors (neoplasms) in colon, breast, and prostate glands. Although the
precise and exact mechanisms whereby the said blockade actually takes place are
not yet well understood, yet they seem to change drastically the ensuing cell-
membrane transfer in the phenomenon of neoplasm growth and thereby reduce the
inammation signicantly. Cancer is one of the most prominent diseases in humans.
Plants still remain a prime source of drugs for the treatment of cancer and can pro-
vide leads for the development of novel anticancer agents (Williams et al. 2004).
The pace of research in the continuing discovery of new anticancer agents from
natural product sources has been staggering lately (Rahman and Choudhary 2001).
Recently, intensive research has been focused on developing tumor therapies from
saponins. Xanthocercis zambesiaca extract had saponins and glycosides. Saponins
exhibit potent anticancer activity in several human cancer cells through apoptosis-
inducing pathways (Kinghorn et al. 2003), and glycosides are compounds that
strongly inuence the anticancer activity of the plant extract (Kaskiw etal. 2009).
Xanthocercis zambesiaca have been proven to have isoavones (Yan etal. 2009),
and this compound regulates estrogen levels. It already has been proven that estro-
gen reduces risks of ovarian and endometrial cancer (Liao etal. 2009).
19.4.3 Antimicrobial Activity
Phytoconstituents employed by plants to protect them against pathogenic insects,
bacteria, fungi, or protozoa have found applications in human medicine. Some phy-
tochemicals such as phenolic acids act essentially by helping in the reduction of
particular adherence of organisms to the cells lining the bladder and the teeth, which
ultimately lowers the incidence of urinary tract infections and the usual dental caries.
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Plants can also exert either bacteriostatic or bactericidal activity of microbes
(Calderon-Montano etal. 2011). The volatile gas phase of combinations of cinna-
mon oil and clove oil showed good potential to inhibit growth of spoilage fungi,
yeast, and bacteria normally found on intermediate moisture foods when combined
with a modied atmosphere comprising a high concentration of CO2 (40%) and low
concentration of O2 (<0.05%). A. avus, which is known to produce toxins, was
found to be the most resistant microorganism. It is worthy of note that antimicrobial
activity results of the same plant part tested most of the time varied from researcher
to researcher. This is possible because concentration of plant constituents of the
same plant organ can vary from one geographical location to another depending on
the age of the plant, differences in topographical factors, the nutrient concentrations
of the soil, extraction method as well as method used for antimicrobial study. It is
therefore important that scientic protocols be clearly identied and adequately fol-
lowed and reported (Monte etal. 2014).
19.5 Conclusions andFuture Prospects
Researches on specic phytochemicals in foods and their effects on disease risks are
limited, but there’s enough evidence from the association between foods rich in
phytochemicals and disease risks which strongly suggests that consuming foods
rich in these compounds may help to prevent diseases. However, it isn’t known
whether the health benets are the result of individual phytochemicals, the interac-
tion of various phytochemicals, the ber content of plant foods, or the interaction of
phytochemicals and the vitamins and minerals found in the same foods. The con-
sumption of fruits, vegetables, and whole grains, as well as dietary patterns such as
the Mediterranean diet that emphasize these foods, have been associated with a
reduced risk of several types of cancer including breast, lung, and colon. Increase of
three servings per day of whole grains is associated with a lower risk (17%) of
colorectal cancer. Studies also have looked at the intake of specic phytochemicals
and found a link to areduced cancer risks. One study found that only specic avo-
noid subgroups were associated with a decreased risk of breast cancer. These have
found the reduced risk of cancer wasn’t as strong for individual phytochemicals as
for the foods rich in phytochemicals. The consumption of cruciferous vegetables
such as broccoli, cabbage, and cauliower has been associated with a decreased risk
of prostate, lung, breast, and colon cancers. Isothiocyanate phytochemicals found in
cruciferous vegetables, especially sulforaphane in broccoli, which has been studied
extensively, are believed to offer some degree of prevention. It is quite clear fromthe
above discussion that phytochemicals play avery important role in ghting many
diseases like diabetes, cardiovascular diseases, nervous system disorder, cancer, and
other diseases. Nowadays, the successful treatment for cancer has become a chal-
lenge to the whole world. Almost all the countries are doing several investiga-
tionson the prevention and treatment of cancer, so that the lives of billions of people
can be saved.
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