Anticancer and Antimicrobial Potential of Plant-Derived Natural Products

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6
Anticancer and Antimicrobial Potential
of Plant-Derived Natural Products
Wamidh Hadi Talib
Department of Clinical Pharmacy and Therapeutics, University of Applied Science,
Jordan
1. Introduction
Plant use in treating diseases is as old as civilization (Fabricant & Farnsworth, 2001) and
traditional medicines are still a major part of habitual treatments of different maladies
(Alviano & Alviano, 2009). In recent times and due to historical, cultural, and other reasons,
folk medicine has taken an important place especially in developing countries where limited
health services are available. However, the absence of scientific evaluation of medicinal
plants to validate their use may cause serious adverse effects (Souza et al., 2004).
Plants are considered as one of the main sources of biologically active materials. Recent
records reported that medicinal herbs are used by 80% of the people living in rural areas as
primary healthcare system (Sakarkar & Deshmukh, 2011). It has been estimated that about
50% of the prescription products in Europe and USA are originating from natural products
including plants or their derivatives (Cordell, 2002; Newman et al., 2003). Out of the 250,000
– 500,000 plant species on earth, only 1-10 % have been studied chemically and
pharmacologically for their potential medicinal value (Verpoote, 2000). In the Middle East
region 700 species of the identified plants are known for their medicinal values (Azaizeh et
al., 2006).
In spite of the recent domination of the synthetic chemistry as a method to discover and
produce drugs, the potential of bioactive plants or their extracts to provide new and novel
products for disease treatment and prevention is still enormous (Raskin et al., 2002).
Compared with chemical synthesis, plant derived natural products represent an attractive
source of biologically active agents since they are natural and available at affordable prices
(Ghosh et al., 2008). Also plants derived agents may have different mechanisms than
conventional drugs, and could be of clinical importance in health care improvement (Eloff et
al., 1998). Plant materials might be bioactive secondary metabolites that have the potential to
treat different afflictions. Examples of these compounds include phenols, phenolic
glycosides, unsaturated lactones, sulphur compounds, saponins, cyanogenic glycosides and
glucosinolates (Mukherjee et al., 2001; Quiroga et al., 2001). Such plant derived natural
products are the main focus of many scientists to develop new medication for different
diseases like cancer and microbial infection.
Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal
cells (Karp, 1999). The high mortality rate among cancer patients is an indication of the
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Phytochemicals – Bioactivities and Impact on Health
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limited efficiency of the current therapies including radiation, chemotherapy and surgery
(Xu et al., 2009). Cancer development is a multi-step process including induction of genetic
instability, abnormal expression of genes, abnormal signal transduction, angiogenesis,
metastasis, and immune evasion (Boik, 2001). For many years, scientists were searching for
miracle cures for cancer using chemically synthesized or natural pure compounds. In the
last few decades, research has been focused on the use of natural products such as crude
plant extracts or a combination of different phytochemicals for cancer therapy; this trend is
based upon: first, the synergistic effect of the different plant metabolites in the crude extract,
second, is the multiple points of intervention of such extracts (Neergheen, 2009). This is one
of the many faces of using plants in the quest of controlling different diseases. Another face
is the use of such plant products in controlling microbial resistance spread. As a result of the
uncontrolled use of many antibiotics, their efficiency is being threatened by the emergence
of microbial resistance to existing chemotherapeutic agents (Cowan, 1999; Pareke & Chanda,
2007). Bacterial strains such as methicilin-resistant Staphylococcus aureus (MRSA), pencillin-
resistant Streptococcus pneumonia (PRSP), and Vancomycin- resistant enterococci (VRE) in
addition to the development of multidrug-resistant (MDR) bacterial strains (Alanis, 2005)
are just few examples that made the search for new and novel bioactive substances among
the first priorities in the search for antitumor, antibacterial, and antifungal substances
(Ficker et al., 2005).
Realizing all the aforementioned, it is clear that there is a pressing need to participate in the
search for new and novel bioactive agents that would help in providing new avenues in
fighting diseases and reducing suffering. This chapter will provide information about
selected plants that have a potential to provide new anticancer and/or antimicrobial agents.
2. The history of traditional medicine
For thousands of years and in different parts of the world, medicinal plants have been used
to treat different diseases (Palombo, 2009). Fossil records documented the use of medicinal
plants by humans before 60,000 years (Fabricant & Farnsworth, 2001). Nowadays plants
continue to be the major source of medicine in rural regions of developing countries (Chitme
et al., 2003) and it has been estimated that about 80% of peoples in developing countries are
still using medicinal plants for their health care ( Kim, 2005).
The Eastern region of the Mediterranean has been characterized by high inventory of
medicinal herbs used by local traditional healers to treat different ailments (Azaizeh et al.,
2006). Research on medicinal plant treasures is based on present day and historical systems
of traditional and local medicine (Al-Qura’n, 2009). During the Ottoman Empire and
following the Byzantine traditions, hospitals were run by physician who used pharmacists
to gather medicinal plants and prepare remedies originating from classical Greek and folk
medicinal practice (Littlewood et al., 2002).
A comprehensive study on practitioners and herbalist in Palestine revealed that
approximately 129 plant species are still prescribed to treat different diseases including
liver, digestive tract, respiratory system, skin, cancer and other diseases (Azaizeh et al.,
2003). On the other hand, the high diversity of plant species in Jordan encouraged many to
study the distribution and use of medicinal plants in this country. More than 100 herbalists
were interviewed in an extensive survey for Jordanian medicinal plants indicated the
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Anticancer and Antimicrobial Potential of Plant-Derived Natural Products
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presence of 150 herbal plants used in folkloric medicine (Abu-Irmaileh & Afifi, 2003).
Seventy nine plant species are still in use in traditional medicine in the Showbak region
(south of Jordan) while forty six are part of the popular medicine in the Ajloun Heights
region (north of Jordan) and some of the plants are used in both regions ( Aburjai et al.,
2007; Al-Qura’n, 2009). Most of the practitioners were not licensed and have no scientific
information about medicinal plants (Abu-Irmaileh & Afifi, 2003; Azaizeh et al., 2003).
The diversity of plants in the Mediterranean region is declining, were recent estimates
reported less than 200-250 plant species are used to treat different ailments in the Arab
traditional medicine (Said et al., 2002; Abu-Irmaileh & Afifi, 2003; Saad et al., 2005),
compared to more than 700 species which were identified for their medicinal uses in
previous decades (Azaizeh et al., 2006). The high rate of plant extinction on the earth
necessitates an increase in the efforts to study plant natural products for their potential to
provide treatment for different afflictions.
3. Cancer biology
DNA damage causes conversion of normal cell into a cancer cell. Cancer cells lack the ability
to communicate with their neighboring cells. The first cancer cell starts to divide producing
daughter cells, which in turn divide to produce more and more cancer cells. As cancer cells
divide, they develop malignant characteristics including metastasis, immune system
evasion, and induction of blood vessels formation (angiogenesis). Continuous cell division
of cancer cells lead to the formation of tumors. In solid tumors, blood vessels become
structurally and functionally abnormal; this abnormality leads to heterogeneous blood flow
which creates chronically hypoxic and acidic regions in the core of the solid tumor (Brown &
Wilson, 2004). These hypoxic regions lead to the activation of angiogenesis and cell survival
genes in addition to other genes that induce drug resistant (Chen et al., 2003). Furthermore,
the low pH microenvironment of cancer cells in the tumor core may prevent the active
uptake of some anticancer drugs (Mahoney et al., 2003).
The two traditional therapies (chemotherapy and radiation) are not greatly efficient in
treating hypoxic cancer cells (Tannock et al., 1998). The killing effect of ionizing radiation
depends on the presence of oxygen which is absent or very low in the tumor core and the
poor vascularization minimizes the delivery of chemotherapeutic agents (Brown & Wilson,
2004). This makes the poorly vascularized regions of tumors a major obstacle
to effective
treatment and opens the door to other therapies that may use different mechanisms to
targets highly resistant cancer cells.
4. Oncogenes and tumor suppressor genes
Two sets of genes are controlling cancer development. Oncogenes are the first set of genes
and are involved in different cell activities including cell division. However, overexpression
of these genes transforms a normal cell into a cancer cell. On the other hand, the second set
of genes (tumor suppressor genes) inhibits cancer cell formation by different mechanisms.
Tumor suppressor genes are underexpressed in cancer cells while, oncogenes are
overexpressed. Table 1 summarizes the main oncogenes and tumor suppressor genes and
their role in cancer development. Oncogenes and their products represent good targets for
cancer therapy. Other targets include enzymes involved in cell division like topoisomerases
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that unwind the DNA during replication. The diversity of plant derived natural products
can provide therapeutic products attacking different targets in cancer cells.
Oncogenes Functions of their proteins
Bcl-2
Inhibits apoptosis and protect cancer cell from
free radicals.
c-myc
Initiate cell division and inhibits differentiation.
HER-2/neu( c-erb-2)
Facilitates signal transduction, expressed in 33%
of breast cancers.
MDM2
Protect cancer cells from apoptosis by binding
and inhibiting p
53
(tumor suppressor gene that
induces apoptosis in damaged cells).
ras
Facilitate tumor invasion by stimulation of
collagenase production and inhibits apoptosis by
increasing MDM2 expression.
fos and jun Promote uncontrolled proliferation by their
participation in cell cycle initiation.
Tumor suppressor genes Functions of their proteins
Bax
An inducer of apoptosis
Cx32, Cx 43 and other connexin
producing genes
Inhibits carcinogenesis by restoring
communication between cells through gap
junctions.
p
53
Initiates DNA repair and induce apoptosis in
cells that cannot be repaired.
Reference: Boik, 2001
Table 1. The main oncogenes and tumor suppressor genes.
5. The use of plants in cancer therapy
Cancer is one of the major causes of death and the number of cancer patients is in continuous
rise. Every year 2-3 % of deaths recorded world wide arise from different types of cancer
(Madhuri & Pandey, 2009). The available treatment methods include surgery, chemotherapy,
and radiation (Tannock et al., 1998). The increasing costs of conventional treatments
(chemotherapy and radiation) and the lack of effective drugs to cure solid tumors encouraged
people in different countries to depend more on folk medicine which is rooted in medicinal
plants use (Wood-Sheldon et al., 1997). Such plants have an almost unlimited capacity to
produce substances that attract researchers in the quest for new and novel chemotherapeutics
(Reed & Pellecchia, 2005). Although some plant products are used in cancer therapy, plant
derived anticancer agents represent only one-fourth of the total treatments options. Since 1961,
nine compounds originating from plants have been approved for use in cancer therapy in the
United States. These agents are vinblastine, vincristine, navelbine, etoposide, teniposide, taxol,
taxotere, topotecan, and irinotecan (Lee, 1999). In an extensive study, the anticancer properties
of 187 plant species were evaluated. Among them, only 15 species have been used to treat
cancer clinically (Kintzios, 2006). It was observed that different plants contain different
bioactive compounds and these vary with area, climate and mode of agricultural practice if
they are not present in wild environment.
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Herbivory, pathogens and competition are the driving forces that induce plant species to
develop chemical defense compounds. These plant origin compounds are good models for
elucidation of their functional roles in medication and treatment of different afflictions
(Wood-Sheldon et al., 1997). For example, the lignin in the roots of Anthriscus sylvestris
showed an insecticidal activity (Kozawa et al., 1982). Poisonous plants exposed to frequent
grazing by animals are commonly rich in alkaloids which have many biological activities
including anticancer potential (Kintzios, 2006). However, the growth regulatory properties
of some plant metabolites allow them to act as chemotherapeutical agents. Flavonoids from
Scutellaria baicalensis act on cyclin-dependent kinases to inhibit cancer cell proliferation (Dai
& Grant, 2003; Chang et al., 2004).
Thirteen distinct groups of plant-derived natural products with antitumor properties were
documented (Kintzios, 2006). Among them, alkaloids (Facchini, 2001), phenylpropanoids
(Dixon & Paiva, 1995) and terpenoids (Trapp & Croteau, 2001) are well known for their
antitumor potentials.
An integrated part of cancer cell development is the resistance to programmed cell death
(apoptosis). Re-establishment of apoptosis in cancer cells is a target mechanism for
anticancer agents (Joshi et al., 1999). Some plant-derived products are known to selectively
induce apoptosis in cancer cells, which represent the ideal property for successful anticancer
agents (Hirano et al., 1995). Identifying the mode of action of anticancer agents of plant
origin provide helpful information for their future use. Thus it is important to screen the
apoptotic potential of plants either in their crude extract form or as pure compounds
(Tarapadar et al., 2001). Due to their multiple intervention strategies, crude plant extracts
have been proposed to prevent, arrest, or reverse the cellular and molecular processes of
carcinogenesis (Neergheen et al., 2009).
Since the distribution of bioactive compounds differs according to the plant used, different
solvents were used to extract these compounds from different plants. The methanol extract
of Scutellaria orientalis showed potent anti-leukemic activity against HL-60 cell line (Ozmen
et al., 2010). The water extract of Rheum officinale exhibited significant antiproliferative
activity by inducing apoptosis in MCF-7 and A549 cell lines (Li et al., 2009). A potent
antiproliferative activity was also reported for the hexane extract of Casearia sylvestris stem
bark against different cancer cell lines (Mesquita et al., 2009) and the butanol extract of
Pfuffia paniculata demonstrated high cytotoxic activity against MCF-7 cell line (Nagamine et
al., 2009). Additionally, the Physalis minima chloroform extract induced apoptosis in human
lung adenocarcinoma cell line (Leong et al., 2009). Out of 76 Jordanian plant species, the
ethanolic extracts of Inula graveolens, Salvia dominica, Conyza canadiensis and
Achillea santolina
showed potent antiproliferative activity against MCF-7 cell line (Abu-Dahab &Afifi, 2007).
The aqueous methanol of Ononis hirta and Inula visocsa showed high ability to selectively
target MCF-7 cancer cells and induced apoptosis (Talib & Mahasneh, 2010a).
A substantial progress has been made in the treatment of cancer since the early years of
anticancer drug research. An example of successful anticancer plant products are the vinca
alkaloids which were isolated from Catharanthus roseus. The first identified vinca alkaloids
were Vincristine and Vinblastine (Duflos et al., 2002). The antitumor activities of these
compounds involve binding to tubulin and disruption of mitotic spindle assembly (Nobili et
al., 2009). Myelosuppression and neurotoxicity were reported as side effects of vinca
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Phytochemicals – Bioactivities and Impact on Health
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alkaloids (Yun-San et al., 2008). Another example of plant products in cancer therapy is taxol
which was extracted from the bark of Taxus brevifolia (Wani et al., 1971). Its cytotoxic activity
is mediated by stabilizing microtubules rather than destabilizing them (Horwitz et al., 1993).
Since taxol drugs have low solubility, they are administered together with solvents which
cause some adverse effects like hypersensitivity and neuropathies (Onetto et al., 1993).
Other anticancer plant products mediate their activities by inhibiting the enzyme DNA
topoisomerase. Plants under this category include camptothecins extracted from the Chinese
tree Camptotheca acuminate (Wall et al., 1966) and Podophyllotoxins extracted from the roots
of the Indian plant Podophyllum peltatum (Nobili et al., 2009).
In spite of the success of previously mentioned anticancer plant products, the development
of multi-drug resistance in cancer chemotherapy still one of the major problems (Xu et al.,
2009). To avoid this problem, researchers focused on other targets including starving cancer
cells by targeting the process of angiogenesis (formation of new blood vessels) which
represent an attractive target since tumors depend on angiogenesis for survival and
metastasis (Griggs et al., 2001). Some plant derived agents showed promising anti-
angiogenic activity such as stilbene combretsatatin- A4 which was isolated from Combretum
caffrum (Young & Chaplin, 2004). Another strategy to target multi-drug resistance cancers is
to use a combination of chemotherapy with other strategies including anaerobic bacteria
which experimentally showed promising results in targeting solid tumors (Dang et al.,
2001). Many plants exhibited promising anticancer activities (Table 2). Such plants may
provide compounds that can change the list of drugs available for cancer treatment in the
future.
Family Species Compounds
Anacardiaceae
Rhus succedanea
Flavones, aldehydes
Annonaceae
Annona chrimola, A. muricata, A.
senegalensis,
Annonaceous acetogenins
A. reticulate, A. squamosa, A. bullata
(lactones)
Goniothalamus gardneri, G. amuyon
and G. giganteus
lactones
Polyathia barnesii
Clerodane diterpenes
Xylopia aromatica
Annonaceous acetogenins
Apiaceae
Anthriscus sylvestris
Lignans
Seseli mairei
Polyacetylenes
Apocynaceae
Alstonia scholaris R. BR.
Extract, indole alkaloids
Ervatamia divaricata, E. microphylla,
E. heyneana
Alkaloids
Plumeria rubra
Alkaloids (iridoids), lignans
Araliaceae
Dendropanax arboreus
Oxylipins (linoleic acid
derivatives)
Panax ginseng, P. quinquefolius, P.
vietnamensis
Saponins, polysaccharides,
polyacetylenic alcohols
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Aristolochiaceae
Aristolochia elegans, A. versicolar
Sesquiterpene lactones
Asclepiadaceae
Calotropis procera, C. gigantea
Glycosides
Asteraceae
Neurolaena lobata
Sesquiterpene lactones
Bigoniaceae
Kigelia pinnata
Dichloromethane extracts
Burseraceae
Bursera simaruba, B. permollis, B.
morelensis, B. microphylla, B. klugii, B.
schlechtendalii
Lignans
Caesalpiniaceae
Caesalpinia sappan
Ethyl acetate extracts
Campanulaceae
Platycodon grandiflorum
Polysaccharides
Capparaceae
Polanisia dodecandra
Flavonols
Celastraceae
Glyptopetalum sclerocarpum
Terpenoids
Maytenus boaria, M. guangsiensis, M.
ovatus, M. senegalensis, M.
wallichiana and M. emarginata
Triterpenes
Combretaceae
Bucida buceras
Flavanones, diterpenes
Terminalia arjuna
Flavones, tannins
Compositae
Eupatorium cannabinum
Lactones
E. cuneifolium, E. rotundifolium, E.
semiserratum, E. altissimum
Flavones
Hellenium microcephalum, H. hoopesii
Sesquiterpene lactones
Xanthium strumarium
Alkaloids
Inula viscosa Flvonoids and alkaloids
Inula graveolens, Achillea santolina,
Conyza canadiensis
Ethanol extract
Conifereae J. virginiana, J. chinensis Podophyllotoxin (lignans)
Cucurbitaceae
Cucurbita moschata, Mormodica
charantia
Proteins
Cupressaceae
Chamaecyparis lawsonianna, Thujopsis
dolabrata
Alkaloids
Ericaceae
Vaccinium macrocarpon, V. smallii
Triterpenes, flavonol,
glycosides
Eriocaulaceae
Paepalanthus latipes
Naphthoquinones
Euphorbiaceae
Emblica offcinalis
Aqueous extracts,
Norsesquiterpenoid,
glycosides
Euphorbia amygdaloides, E. helioscopic,
E. lathyris, E. mongolica, E. pubescens
Jatrophane diterpenoids
Jatropha curcas, J. macrorhiza
Jatrophane diterpenoids and
triterpenoids
Mallotus phillipinensis
Rottlerin, phloroglucinol
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derivatives
Phyllanthus acuminatus, P. amarus, P.
emblica, P. urinaria
Glycosides
Fabaceae
Ononis sicula, Ononis hirta
Aqueous methanol extract
Flacourtiaceae
Caesaria sylvestris
Clerodane diterpenes
Guttiferae
Garcinia hunburyi
Processed extract
Hernandiaceae Hernandia sp. Lignans
Hyacynthaceae
Scilla scilloides, S. peruviana
Glycosides
Hypericaceae
Hypericum perforatum, H. drummondii
Polycyclic diones
Iridaceae
Crocus sativus
Carotenoids
Lamiaceae
Hyptis martiusii, H. verticillata
Diterpenes, lignans
Origanum vulgare, O. majorana
Quinines, quinine glycosides
Rabdosia ternifolia, R. trichocarpa, R.
macrophylla
Diterpenoids, lactones
Salvia sclarea
Lectins, Ursolic acid
(carboxylic acids)
Salvia pinardi
Aqueous methanol extract
Salvia przewalskii
Quinones
Salvia dominica
Ethanol extract
Scutellaria barbata, S. lateriflora, S.
baicalensis
Flavonoids, flavones
Lauraceae
Cinnanomum camphora
Cinnamaldehydes
Leguminosae
Acacia catechu, A. victoriae, A.
confuse, A. auriculiformis A. Cunn.
and A. nilotica
Proteins
Bauhinia racemosa
Methanol extracts
Cassia acutifolia, C. angustifolia, C.
torosa, C. leptophylla
Anathracenes,
polysaccharides, piperidin
(alkaloids)
C. pudibunda Glycyrrhiza glabra, G.
uralensis, G. inflata
Anthraquinones Glycyrrhizic
acid, glycyrrhetinic acid,
flavonoids and
Tamarindus indica
Triterpenoids, Polysaccharides
Liliaceae
Colchicum autumnale, C. speciosum
Crinum asiaticum var. toxicarium
Alkaloids
Linaceae
Linum usitatissimum
Lignans
Viscum cruciatum
Hexanoic acid extracts
Magnoliaceae
M. offcinalis, M. grandiflora, M.
virginiana
Neolignans
Malvaceae
G. herbaceum G., indicum
Cathechin (phenolics)
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Meliaceae
Azadirachta indica
Limonoids (triterpenes)
M
elia azedarach
Limonoids (triterpenes)
M
y
rtaceae
Eugenia jambos
H
y
drol
y
zable tannins
Ochnaceae
Ouratea hexas
p
erma, O. semiserrata
Biflavonoids
Pinaceae
Pseudolarix kaempferi
Triterpene lactones, diterpenes
Pol
yg
alaceae
Polygala vulgaris
Xanthones
Pol
yg
onaceae
Polygonum cuspidatum
Flavonoids, anthraquinones
Ranunculaceae
Nigella sativa
Quinones, fatt
y
acids
Pulsatilla koreana
Li
g
nans, saponins
Rosaceae
Agrimonia pilosa
Tannins, methanolic extracts
Rubiaceae
Nauclea orientalis
An
g
ustine alkaloids
Psychotria. rubra, P. forsteriana Napthoquinones, alkaloids
Rubia cordifolia, R. akane
C
y
clic hexapeptides
Naphthoquinones,
anthraquinones
Rutaceae
Aegle marmelos Correa Fagara
macrophylla
H
y
droalcoholic extract
Alkaloids
Acronychia oblonga, A. porteri, A.
p
edunculata, A. Baueri
Flavonols, alkaloids
Zieridium pseudobtusifolium
Flavonols
Sapindaceae
Koelreuteria henryi
Anthraquinone, stilbene, and
flavonoids
Simaroubaceae
Brucea dysenterica, B. javanica
Quassinoid
g
l
y
cosides,
Alkaloids
Eurycoma harmadiana
Alkaloids, quassinoids
Hannoa chlorantha, H. kleineana Quassinoids, chaparrinones
Solanaceae
Solanum pseudocapsicum
Alkaloids
Scrophulariaceae
Verbascum sinaiticum
Aqueous methanol extract
Theaceae
Camellia sinensis
Pol
y
phenols
Th
y
melaceae
Stellera chasmaejasme
Diterpenes
Tropaeolaceae Wikstroemia foetida, W. uvaursi, W.
indica, Tropaeloum majus
Pol
y
saccharides, Aromatic
plant hormones
Umbellifereae
Angelica archangelica A. keiskei, A.
sinensis,A. gigas, A. acutiloba, A.
radix, A. japonika, A. edulis
P
y
ranocoumarins, chalcones,
polysaccharides
Urticaceae
Ficus carica
Lectins
Verbenaceae
Vitex ro
t
undifolia
Flavonoids
Violaceae
Viola odorata
Nucleotides
References:
(
Kintzios, 2006
)
,
(
Abu-Dahab and Afifi, 2007
)
,
(
Talib and Mahasneh, 2010
)
Table 2. Plants with potential anticancer activity
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6. Plants as a source of antimicrobial agents
The discovery of antibiotics has decreased the spread and severity of a wide variety of
inferior diseases. However, and as a result of their uncontrolled use, the efficiency of many
antibiotics is being threatened by the emergence of microbial resistance to existing
chemotherapeutic agents (Cowan, 1999). While bioactive natural compounds have been
isolated mainly from cultivable microbial strains, an untapped biologically active
metabolites of different resources including plants remains to be investigated (Quiroga et
al., 2001) to alleviate or help responding to current health care situations; such situations
include but not limited to unmet clinical needs, increasing cost of chemotherapy,
mycobacterial reemergence, and the emergence of antibiotic resistant microbial strains such
as MRSA (Alanis et al., 2005) .
Microbial resistance occurs mainly in three general mechanisms: prevention of interaction of
the drug with target; direct destruction or modification of the drug; and efflux of the drug
from the cell (Alviano & Alviano, 2009). These mechanisms were used by different
microorganisms and led to the emergence of many pathogenic bacterial strains (Alanis et al.,
2005). With pathogenic fungi, the situation is not so bright also, where Amphotericin B was
for many years the only treatment available for fungal infections. In late 1980s fluconazole
and itracozole was developed as additional therapeutic options (Ficker et al., 2002).
Recently, azole derivatives are most widely used antifungal agents, although resistance for
these drugs is emerging (Groll et al., 1998). All the available antifungal drugs used to date
are not ideal in efficiency, safety, and antifungal spectrum (Di Domenico, 1998).
Combination antifungal therapy was also used to increase the efficiency but there is a real
demand for a next generation of safer and more powerful antifungal agents (Bartoli et al.,
1998). Knowing that modifying known antimicrobial compounds is increasingly difficult
created an urgent and very pressing need for isolation and identification of new bioactive
chemicals from new sources including plants (Barker, 2006).
Plant derived natural products represent an attractive source of antimicrobial agents since
they are natural, have manageable side effects and available at affordable prices (Ghosh et
al., 2008). Also plants derived agents may have different mechanisms than conventional
drugs, and could be of clinical importance in health care improvement (Ellof, 1998).
There are two main classes of plant derived agents.1) phytoalexins which are low molecular
weight compounds produced in response to microbial, herbivorous, or environmental
stimuli (Van Etten et al., 1994). Phytoalexins include simple phenylpropanoid derivatives,
flavonoids, isoflavonoids, terpenes and polyketides (Grayer & Harbborne, 1994). 2)
Phytoanticipins which are produced in plants before infection or from pre-existing
compounds after infection (Van Etten et al., 1994). Phytoanticipins include: glycosides,
glucosinolates and saponins that are normally stored in the vacuoles of plant cells (Osbourn,
1996). The antimicrobial potential of plant derived natural products is well documented.
Schelz and colleagues reported the potential of menthol isolated from peppermint oil to
eliminate the resistance plasmids of bacteria (Schelz et al., 2006). In another study carbazole
alkaloids isolated from Clausena anisata stem bark showed high antibacterial and antifungal
activities (Chakraborty et al., 2003).
Thousands of other phytochemicals having
in vitro antimicrobial activities were also
screened. Such screening programs are essential for validating the traditional use of
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medicinal plants and for providing leads in the search for new antimicrobial agents
(Alviano & Alviano, 2009). A number of studies of the bioactivity of plant extracts have been
conducted and many of these studies showed promising results in developing new
biologically active agents. The methanolic extract of clove Caryophyyllus aromaticus showed
antibacterial activity against many bacterial genera and the highest activity was against
Staphylococcus aureus (Ushimaru et al., 2007). Association of clove extract and antibiotics
showed synergistic antibacterial activity against antibiotic resistant Pseudomonas aeruginosa
(Nascimento et al., 2000). Out of the 50 plants used in Indian traditional medicine, 72%
showed antimicrobial activity including nine plants showed antifungal activity (Srivnivasan
et al., 2001). When some Palestinian plants were tested for bioactivity, out of fifteen used in
traditional medicine, only eight showed antibacterial activity against eight different
bacterial strains (Essawi & Srour, 2000). Butanol extracts of Rosa damascene, Narcissus tazetta,
and Inula viscose exhibited potent antimicrobial activities against different microorganism
including Methicillin-resistant Staphylococcus aureus and Candida albicans (Talib & Mahasneh,
2010b).
During the past decade there is an increase in the number of immuno-compromised
patients. This is probably due to the alteration of the immune system caused by human
immunodeficiency virus (HIV), cancer chemotherapy, and organ and bone marrow
transplantation in addition to the use of immune suppressors to treat many diseases
(Alexander & Perfect, 1997). The compromised immune system facilitates microbial
infections including systemic mycosis. This leads to extensive use of Amphotericin B and
azole derivatives as antifungal agents. Unfortunately, the wide range use of these antifungal
agents leads to the emergence of drug resistant pathogenic fungi (Alexander & Perfect,
1997). Candida albicans is opportunistic yeast that can cause vaginal, oral, and lung infections
in addition to systemic tissue damage in AIDS patients (Madigan & Martinko, 2006). This
yeast was the target of many researchers to develop new antifungal agents. Out of twenty
four medicinal plants used in traditional medicine in South Africa, two showed high
potential to treat candidiasis (Motsei et al., 2003). Also some indigenous plants of Lebanon
showed antimicrobial activity against Candida albicans and other tested microorganisms
(Barbour et al., 2004).
Successive isolation of antimicrobial compounds from plants depends upon the type of
solvent used in extraction procedure (Parekh & Chanda, 2007). Literature reported the use
of different solvents to extract antimicrobial agents. The ethanol/methanol extracts of
thirty four medicinal plants were more active than aqueous extracts against bacterial
strains belonging to Enterobacteriaceae (Parekh & Chanda, 2007). Methanolic extract of
Terminallia chebula showed higher antibacterial potential compared with aqueous extract
(Ghosh et al., 2008). Mahasneh found that butanol extracts of several plants including:
Lotus halophpilus, Pulicaria gnaphaloides, Capparis spinosa, Medicago laciniata
, Limonium
axillare to exhibit superior antimicrobial activity compared with ethanol and aqueous
extracts (Mahasneh, 2002). The ethanolic extract of 11 plant species from Argentina
showed high antimicrobial activity against a list of microorganisms including methicillin,
oxacillin, and gentamicin resistant Staphylococcus (Zampini et al., 2009). Of 16 plants
studied, the methanolic and aqueous extracts of 10 Yemeni plants exhibited significant
antimicrobial activity against three gram positive, two gram negative bacteria, and one
fungus (Mothana et al., 2009).
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Jordanian plants were the focus of many researchers for their antimicrobial activities.
Butanol, ethanol, petroleum ether, and aqueous extracts were prepared from nine Jordanian
plants. Butanol extract showed superior antimicrobial activity compared with other extracts
(Mahasneh & El-Oqlah, 1999). Of 27 ethanol extracts prepared from indigenous Jordanian
plants, six plants showed promising antimicrobial activity against different test
microorganisms (Al-Bakri & Afifi, 2007). In addition to their broad antimicrobial activities
some Jordanian plants like Sonchus oleraceus and Laurus nobilis exhibited high antiquorum
sensing activities (Al-Hussaini & Mahasneh, 2009). Other Jordanian plants like Crupina
crupinastrum and Achillea biebersteinii showed high antimicrobial activity against bacteria
and fungi (Khalil et al., 2009). Additionally the methanolic extracts of two Jordanian plants
Artemisia herba-alba and Artemisia arborescens showed high antibacterial activity against 32
isolates of Mycoplasma species (Al-Momani et al., 2007).
7. Conclusions
The potential isolation and use of new and novel bioactive products from plant origins is
still very productive playground for the development of new drugs to improve health care
in certain medical fields. It is essential to emphasize that extensive in vitro and in vivo tests
must be conducted to assure the selection of active and nontoxic anticancer and
antimicrobial phytochemicals.
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Phytochemicals - Bioactivities and Impact on Health
Edited by Prof. Iraj Rasooli
ISBN 978-953-307-424-5
Hard cover, 388 pages
Publisher InTech
Published online 22, December, 2011
Published in print edition December, 2011
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Among the thousands of naturally occurring constituents so far identified in plants and exhibiting a long history
of safe use, there are none that pose - or reasonably might be expected to pose - a significant risk to human
health at current low levels of intake when used as flavoring substances. Due to their natural origin,
environmental and genetic factors will influence the chemical composition of the plant essential oils. Factors
such as species and subspecies, geographical location, harvest time, plant part used and method of isolation
all affect chemical composition of the crude material separated from the plant. The screening of plant extracts
and natural products for antioxidative and antimicrobial activity has revealed the potential of higher plants as a
source of new agents, to serve the processing of natural products.
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