Current Medicinal Chemistry, 2004, 11, 1451-1460 1451

Antimicrobial and Chemopreventive Properties of Herbs and Spices

P.K. Lai* and J. Roy*

Department of Bioscience, Salem International University, Salem West Virginia 26426, USA

Abstract: Herbs and spices have been used for generations by humans as food and to treat ailments. Scientific
evidence is accumulating that many of these herbs and spices do have medicinal properties that alleviate
symptoms or prevent disease. A growing body of research has demonstrated that the commonly used herbs and
spices such as garlic, black cumin, cloves, cinnamon, thyme, allspices, bay leaves, mustard, and rosemary,
possess antimicrobial properties that, in some cases, can be used therapeutically. Other spices, such as saffron, a
food colorant; turmeric, a yellow colored spice; tea, either green or black, and flaxseed do contain potent
phytochemicals, including carotenoids, curcumins, catechins, lignan respectively, which provide significant
protection against cancer. This review discusses recent data on the antimicrobial and chemopreventive
activities of some herbs and spices and their ingredients.
Keywords: Herbs, Spices, Antimicrobial agents, Chemoprevention, Garlic, Diallyldisulfide, Black Cumin, Thymoquinone,
Saffron, Turmeric, Curcumin, Tea.

INTRODUCTION asthma, is an alkaloid found in the Chinese herb, Ma

Huang. Hippocrates said: “Let your food be your medicine,
Herbs and spices are commonly used in cooking in order and your medicine be your food.” Certainly, herbs and
to add flavor, aroma and visual appeal to food. These spices have a great role in the well-being and health of a
botanicals, also known as nature’s pharmacy, have been used person. Every culture has its unique way of using spices and
as traditional medicines in many parts of the world for herbs for medical benefits. According to the United States
generations. There is no clear distinction between herbs and Code of Federal Regulations, most herbs and spices are
spices. In general, herbs are non-woody plants, and are leafy categorized as ‘GRAS’, i.e. generally recognized as safe for
material in their fresh state. The word herb comes from the human consumption. It is important to point out that herbs
Latin “herba”, meaning grass, green stalks or blades. Spices are not necessarily harmless. Contrary to common belief,
are usually made from seeds, although they can also come many such plants are toxic and may be extremely dangerous.
from bark, root, fruit, or flower of plants, and are generally Moreover, a herb may be harmless when used as food, but
used as dried products. In addition, one can differentiate may have toxicity when used as medicine because of the
herbs from spices on the basis of growing condition, color relative higher dose administered, or because it can interact
and taste. Herbs are usually grown in temperate or cooler with other pharmaceutical medications [2, 3].
climate, whereas spices are grown in the tropics. In general,
Recent research has taken into consideration all aspects
herbs are green and have pleasant taste, whereas spices are
related to the use of traditional herbal remedies towards the
brown, black or red in color with pungent smell. However,
development of modern medicines. Over the years,
some plants can be both herb and spice. For example,
investigations on the curry spice, turmeric, have identified
cilantro (leaves) is herb and coriander (seeds) is spice. Some
curcumin, an active anticancer agent, which is now in Phase
herbs are spices but not all spices come from herbs.
I clinical trials for colon cancer [4]. There are review articles
In addition to their nutritional values, the therapeutic that discuss the relation of herbs and spices to cancer
roles played by herbs and spices are recognized by many prevention, cholesterol lowering effects, antimicrobial
developed countries, including Japan, Germany, USA and effects, and overall protection of human health [5-9].
Canada. The medicinal values of herbs and spices are Research on several herbs, such as garlic, flaxseed, green tea,
strongly promoted in Canada. The uses of natural health rosemary, sage, thyme, turmeric, and saffron, indicated that
products are given legal status [1]. The Canadian they can reduce high blood cholesterol, provide some
Government continues to develop a regulatory framework protection against cancer, and stimulate the immune system
that ensures all Canadians will have ready access to natural [6]. Studies on flavonoids in tea, and anthocyanins in tart
health products that are safe, effective, and of high quality, cherries, have been presented as examples of how to advance
while respecting the freedom of choice as well as our knowledge of the active components in natural products
philosophical and cultural diversity. [7]. Natural anti-inflammatory compounds have been found
Some modern drugs owe their origins to natural herbal in green tea, turmeric and rosemary [8]. Globally, scientists
ingredients, for example, Ephedrine, for the treatment of have been examining the antimicrobial properties of herbs
and spices for over a century [9].
Apart from numerous general cook-books on herbs and
*Address correspondence to this author at the Department of Bioscience, spices, there are several books on their traditional medicinal
Salem International University, Salem West Virginia 26426, USA; E-mail:
roy@salemiu.edu uses [10-13]. Safety data on herbs, contra-indications, side

0929-8673/04 $45.00+.00 © 2004 Bentham Science Publishers Ltd.

1452 Current Medicinal Chemistry, 2004, Vol. 11, No. 11 Lai and Roy

Table 1. Some Common Herbs and Spices and their Inhibitory Effects on Microorganisms

Herbs/Spices Major Antimicrobial Active on Microorganism Ref.

Compound(s)
[No.of phytochemicals
identified]

Common Name[No. Botanical Name

of publications in [Family Name]
1970 – 2000]

Allspice (Spice) Pimenta Eugenol Mycotoxigenic Aspergillus , Shigella sonnei and Shigella 24, 39, 41,45
dioica[Myrtaceae] flexneri, S.enertica,L. monocytogenes

Basil (Herb) Ocimum basilicum Linalool, methylchavicol, Bacillus pumilus, B. anthraces, Microsporum gypsecum, 24, 45,46
eugenol, methyl cinnamate Aspergillus fumigatus, A. nigar, Enterbacter aerogenas, P.
[Labiatae] vulgaris, S. aureus, Shigella sonnei and Shigella flexneri

Black Cumin Nigella sativum Thymoquinone, Escherichia coli, Staphylococcus aureus, Candida 15, 18, 33-
dithymoquinone,thymohydr albicans, Pseudomonas aeruginosa and Klebsiella 36,38
(Spice) [Ranunculaceae] oquinone, thymol pneumoniae
[140]

Cinnamon (Spice) Cinnamomum Cinnamaldehyde, Eugenol Mycotoxigenic Aspergillus, Aspergillus parasiticus, 18,19,
cassia[Lauraceae] S.enertica,L. monocytogenes , E.coli
23,39, 48

Clove (Spice) Syzygium Eugenol Mycotoxigenic Aspergillus, Shigella sonnei and Shigella 18,19, 23,24,
aromaticum[Myrta flexneri , S. enterica, E.coli, L. monocytogenes 39, 44,48
ceae] [83]

Garlic (Spice) Allium sativum Allicin,diallyl Salmonella typhymurium, Escherichia coli, 15,16,
disulfide,diallyl Staphylococcus aureus, methicillin-resistant SD.
[880] [Liliaceous] trisulfide,diallyl Aureus(MRSA), Bacillus cereus, Bacillus subtilis, 18, 25,29-31,
tetrasulfide,diallyl mycotoxigenic Aspergillus, Candida albicans, 35-37
monosulfide Pseudomonas aeruginosa and Klebsiella pneumoniae

Mustard (Spice) Brassica Allyl isothiocyanate Mycotoxigenic Aspergillus 39

nigra[Cruciferae]

Oregano (Herb) Origanum vulgare Thymol, Carbacrol Mycotoxigenic Aspergillus, Salmonella spp., Vibrio 23, 24,39-43,
[Labiatae] parahaemolyticus, Shigella sonnei and Shigella flexneri, 48
[116] S.enertica,L. monocytogenes , E.coli

Rosemary (Herb) Rosmarimus Carnosol, rosmanol, Bacillus cereus, Staphylococcus aureus, Vibrio parahaem, 19, 24,41, 47
officianalis essential oils, Borneol, Shigella sonnei and Shigella flexneri
[Labiatae] bornyl acetate, [211]

Thyme (Herb) Thymus vulgaris Thymol, carvacrol, caffeic Vibrio parahaemolyticus Staphalococcus aureus, Bacillus 19-24,40,
acid, tannins subtilis, Escherichia coli. Shigella sonnei and Shigella
[Labiatae] flexneri, S.enertica,L. monocytogenes 41,48

Sage (Herb) Salvia officinalis Thymol, Eugenol Bacillus cereus, Staphylococcus aureus, Vibrio 19, 42,43
[Labiatae] parahaemolyticus
[2]

* Information on phytochemicals: chromadex.com/T nav/phytochem.html

effects, other herbal classifications of commercial uses and ANTIMICROBIAL AGENTS FROM HERBS AND
general information, are available in a published handbook SPICES
[14]. In addition, there is a international scientific journal
dedicated to herbs, spices and medicinal plants edited by Dr. Most herbs and spices are invaluable ingredients in
Lyle E. Craker, University of Massachusetts, Amherst, and cooking and food preparation. Interestingly, most have been
published by Haworth Press. We present here a review on found to have antimicrobial properties. There are documents
the antimicrobial and cancer chemopreventive properties of recording the consumption of garlic as food ingredient or as
herbs and spices with specific references to mostly those medicine for over 4500 years [15]. However, herb or spice-
used in Asia. resistant bacterial strains have never been reported, and is in
Antimicrobial, Chemopreventive Herbs and Spices Current Medicinal Chemistry, 2004, Vol. 11, No. 11 1453

stark contrast to resistance often seen in pathogens treated Pseudomonas aeruginosa [29] Klebsiella pneumoniae [29],
with modern antibiotics. Though garlic has been cultivated Staphylococcus aureus, methicillin-resistant S. aureus
and used for thousands of years, its antibacterial properties (MRSA), Candida spp. and Aspergillus spp. [30], E. coli
were first mentioned in 1858 by Louis Pasteur [16]. Cowan [31] and human enteric bacteria [32].
[17] reviewed the plant products reported to have
Crude extracts of black cumin (Nigella sativa) have been
antimicrobial properties. He tabulated many plant products,
tested for antimicrobial effectiveness against different
of which herbs and spices are also listed, along with their
bacterial isolates [33,34]. The diethyl ether extract of Nigella
bioactive phytochemicals, extraction methods and activity
sativa seeds caused concentration-dependent inhibition of the
against pathogens. Some of the commonly used
gram-positive S. aureus, gram-negative P. aeruginosa and
antimicrobial herbs and spices are shown in Table 1.
E. coli; and, a pathogenic yeast, C. albicans. The extract
Researchers in different parts of the world have studied showed antibacterial synergism with streptomycin and
the antimicrobial activities of indigenous herbs and spices gentamycin, but are additive to erythromycin, doxycycline,
for over a century. Zaika [9] has reviewed the antimicrobial nalidixic acid, and ampicillin.
effectiveness of spices and herbs. Recent results of one
A combination of garlic and black cumin has been
Indian study[ 18] indicated that clove, cinnamon, black
traditionally used for different infectious diseases, including
cumin, garlic have potent antimicrobial activities against
urinary tract infections [35]. An in vitro investigation [35]
Bacillus subtilis, Escherichia coli and Saccharamyces
revealed that a combination of fresh extract of allium
cereiviae. The inhibitory activity of spices has also been
sativum (garlic) and nigella sativum (black cumin) had more
reported by Italian [19, 20], German [21], Australian [22]
antibacterial sensitivity on the isolates of the urinary tract
and Polish [23] investigators.
infection, compared to the individual extract or drugs, such
Fabio et. al. [19] used the growth of psycrotropic food- as cefalexin, cotrimoxazole, and nalidixic acid. One of us
borne bacteria, such as Aeromonas hydrophilia, Listeria [36] performed experiments to determine the chemical
monocytogenes and Yersinia eterocolitica to evaluate the constituents responsible for the antimicrobial effects present
antibacterial activities in spices, including clove, cinnamon, in a traditional medicine containing extracts of garlic and
oregano, rosemary, sage and thyme. Thyme essential oil black cumin. By use of gas chromatography, mass
gave the greatest inhibition against A. hydrophila. Marino spectrometry and high performance liquid chromatography,
and colleagues [20] also showed that the oil from thyme in allicin, diallyldisulfide, 1,3-dithiin, and other related
full flower was the most effective against the growth of disulfides were identified in water extract of garlic.
different strain of gram-negative and gram-positive bacteria. Likewise, thymoquinone, p-cymene, catechol, and pinene
A comparative study, using 52 plant oils & extracts, were identified in a volatile oil preparation of black cumin.
including herbs and spices, was made by the Australian Recent studies using diallyldisulfide and thymoquinone
investigators [22], whose results supported the notion that indicated that these two have antimicrobial properties, when
herbs and spices may have a role as pharmaceuticals and used singularly or in combination against E. coli * .
preservatives. A very recent investigation [16] evaluated the Thymoquinone was also found to be active against many
antimicrobial effects of 17 spices and herbs on Shigella pathogens (Table 1) including S. aureus *. Table 1 lists
sonnei and Shigella flexneri. Of the 17, cloves, thyme, some commonly used herbs and spices, their major active
oregano, allspice, basil, rosemary and marjoram showed phytochemicals and their inhibitory effect on various
positive effect on both organisms [24]. A recent review by microorganisms.
Polish investigators revealed that the essential oils of herbs
*Roy, J.; Sarker, D., Square Pharmaceutical Company,
and spices, such as thyme, oregano, mint, cinnamon and
2003, unpublished results.
clove, were found to possess the relatively stronger
antibacterial properties against food-borne bacteria and fungi
[23]. STRUCTURAL ASPECTS OF ANTIMICROBIAL
Antimicrobial properties of garlic (allium sativum) PHYTOCHEMICALS IN HERBS AND SPICES
constituents, especially organo-sulfur compounds of garlic
extracts, have been extensively studied since the pioneering Plant’s composition can be broadly divided into two
work of Cavallito in 1947 [25]. Garlic, on crushing or categories of chemical compounds: First, the products of
maceration, produces the principal bioactive compound, primary plant metabolism, such as carbohydrates, proteins,
allicin, through enzymatic conversion of alliin [15]. Allicin & fats, and second, those of secondary metabolites such as
was found to exhibit antimicrobial activity against a wide phenolics, phenolic acids, quinones, flavonoids, tannins,
range of Gram-negative & Gram-positive bacteria including coumarins, terpenoids and alkaloids. Many of these
multidrug–resistant enterotoxicogenic strains of E. coli [26, secondary metabolites provide defense mechanism to plants
27]. Based on several decades of research on the against predation by microorganism, insects and herbivores.
antimicrobial activities of garlic, Cavallito [28] opined that Representative chemical structures of antimicrobial
some bacteria are totally unable to develop resistance against phytochemicals in herbs and spices are shown in (Fig. 1).
allicin and crushed garlic. However, allicin is thermally The chemical structures in (Fig. 1) suggest that most
unstable and is a precursor of many alkyl & alkene sulfides, antimicrobial phytochemicals in herbs & spices consist of
disulfides, dithiines, ajoens derivatives, some of which substituted phenolic ring. The –OH groups in phenolic
exhibit antimicrobial activities. The in vitro antibacterial compounds are thought to be related to their inhibitory
activities of garlic oil, and its naturally occurring action [49]. There is also evidence that increased number of
diallylsulfide compounds, have been investigated against –OH groups in the compound exhibits more toxicity to
1454 Current Medicinal Chemistry, 2004, Vol. 11, No. 11 Lai and Roy

O OH
CH CH COOH
S S
S S
HO O
Allicin Diallyldisulfide OH
OH
OH OH
O OH Caffeic acid OH Catechin
OH
OCH3

O O

O O
Thymoquinone Thymol Eugenol
Coumarin
Flavone
HO
O OH
HO CO OH OH
HO
OCH2 O HO O
HO O O C OH HOOC
HO O
O
HO C OH
OH
HO H
HO O H
O Carnos ol
OC OH Carnosolic acid
HO C O
HO Hydrolyzable Tannins OH

Fig. (1). General representative structure of antimicrobial phytochemicals in herbs and spices.

microorganism [17]. Quinones, on the other hand, are highly CANCER CHEMOPREVENTIVE HERBS AND
reactive, and are known to complex with amino acid residues SPICES
to inactivate microbial proteins [50]. Similarly, flavonoids
are hydroxylated phenolic compounds linked to additional For decades, the National Cancer Institute and Memorial
aromatic ring(s). Flaonoids are found to be effective against Sloan-Kettering Cancer Center in the United States have
many microbial pathogens. Most of the antimicrobial recognized the cancer preventive potential of herbs and
phytochemicals in herbs and spices have been found to spices. These herbs and spices included members of the
contain phenolic rings. Garlic is one exception among others allium sp., labiatae, zingiberaceae, and the unbelliferae
that contains non-aromatic sulfur compounds (thiosulfinates) family [5]. An excellent compilation of research work on
that acts as antimicrobial. natural agents having anticancer properties, can be found in

Table 2. Common Herbs and Spices and their Chemopreventive Phytochemicals

Common name (Herb Botanical name Active phytochemicals No. of publications Ref.
or Spice) (Family name) [No. of phytochemicals identified] (1970 – 2002)*

Black tea (herb) Camellia sinenesis Flavonols, catechins, l-theanine 51-55,

80
(Temstroemiaceae) Theaflavins

Flaxseed Linum usitatissimum(Linaceae) Lignans, a-tocopheral, b-carotene [114] 1085 57, 71-
74

Garlic (spice) Allium sativum Allicin, diallyldisulfide, [173] 880 59-67

Green tea (herb) Camellia sinenesis (-) Epigallocatechin gallate & other catechins 51-55,69
(Temstroemiaceae)

Rosemary (herb) Rosmarinus officinalis(Lamiaceae) Carnosol, Pinene, camphene, borneol, [211] 177 53, 75-
79

Saffron (spice) Crocus sativus (Iridaceae) Crocetin, dimethylcrocetin, crocin, b-carotene, 106 80-91
safranal, procin, all trans retinoic acid [50]

Turmeric (spice) Curcuma longa (Zingiberaceae) Curcumin, [71] 255 92-99

* ref: www.newcrops.uq.edu.au
Antimicrobial, Chemopreventive Herbs and Spices Current Medicinal Chemistry, 2004, Vol. 11, No. 11 1455

“Natural Compounds in Cancer Therapy” [51] edited by carnosol/carnosic acid, act as inhibitors of DNA adduct
Boik, and published by Oregon Medical Press in 2001. formation induced by benzo(a)pyrene or alfatoxin B1 [77].
Craig et. al.,[6] and Wargovich et. al., [8] have also Studies in animal model indicated a significant increase in
summarized the cancer preventive effectiveness of spices and liver glutathione-S-transferase and quinine reductase, when
herbs in their review articles on health and common herbs. rosemary extract and carnosol were administered
The phytochemicals in garlic, green tea, milk thistle, red intraperitoneally [78]. Topical application of rosemary –
grapes and turmeric, have been evaluated by use of different extract to mouse skin inhibited the skin tumorigenesis [79].
carcinogenesis models with encouraging results. The active
A commonly available spice, saffron (Crocus sativus L.),
chemopreventative phytochemicals in the herbs and spices
has been thoroughly investigated for its cancer preventive
included flavonoids, terpenoids, lignans, sulfides,
and tumoricidal properties. Saffron has been used as a food
polyphenolics, carotenoids, saponins, and curcumins. A few
flavoring spice, as a perfume, and as a dye, or ink. In
herbs and spices that have active chemopreventive
traditional medicine, and in modern pharmacy, saffron is
phytochemicals are provided in Table 2.
reputed to be useful in the treatment of numerous human
Various studies have shown that garlic and organosulfur diseases. A comprehensive review [80] that discusses the
compounds, especially diallyldisulfide, can slow the cancer chemopreventive activities of saffron, and its main
development of cancers of the skin, esophagus, stomach, ingredients, has been published recently.
colon, liver, lung and the mammary glands [58-67].
Saffron has three main pharmacogically active
Epidemiological studies suggest that a high intake of raw
metabolites: (a) crocins, the water-soluble carotenoids that
and cooked garlic may provide a protective effect against
give the saffron color, (b) Picrocrocin is responsible for the
stomach and colorectal cancers [65]. Maurya and Singh
bitter taste and (c) Saffranal is the volatile oil that gives the
reported [66] that diallyl sulfide, an organosulfur compound
characteristic odor and aroma of saffron. In vivo and in vitro,
in garlic, could inhibit chemically induced neoplasia of the
saffron and its components possess anti-carcinogenic and
stomach and lung in mice. According to the US Food and
antitumor activities [81-90]. In experimental models, saffron
Drug Administration, garlic is classified as GRAS. There is
extract could inhibit and/or retard tumorgenesis in vivo [81-
no data in the National Toxicity Program on garlic [67],
87]. Several hypotheses on the main constituents in saffron
although Caporaso reported in 1983 that the maximum
and their mechanism(s) of anti-carcinogenic and tumor
tolerable dose of fresh aqueous garlic extract was 25 ml, and
effects have been proposed. One mechanism was that the
that greater amounts caused severe burning sensations in the
active constituents inhibited cellular DNA and RNA
esophagus and stomach, as well as vomiting [68].
synthesis, but not protein synthesis [80, 83]. A second
The health effects of tea have been extensively proposed mechanism suggested that the active ingredients
investigated. Green tea contains bioactive chemicals such as inhibited the free radical chain reaction [80, 89, 90], while
catechins and polyphenols, which are thought to contribute other proposals included the metabolic conversion of
to the beneficial effects. The (-) epigallocatechin gallate naturally occurring carotenoids to retinoids that exert anti-
(EGCG) in tea is now acknowledged as a cancer preventive tumor effects [90], the interaction of carotenoids with
in Japan [69]. A recent human study [70] showed that black topoisomerase II [85], and the induction of apoptosis [80].
tea, containing L-theanine, a precursor of the non-peptide
Research over the last 50 years indicated that curcumin, a
antigen ethylamine, could primed peripheral blood T cells to
polyphenolic ingredient in turmeric, can prevent, and can be
mediate a memory response on re-exposure to ethylamine,
used to treat, cancer [92]. Chemically, curcumin is a
and secreted interferon-γ (IFN-γ) in response to bacteria.
diferuloylmethane, a compound known to have very little to
Such priming may enhance innate immunity to bacteria and
no toxicity in humans. Studies indicated that curcumin acted
other microbes, as well as tumors that share nonpeptide
as a protective agent against chemical carcinogenesis [93],
antigens with bacteria. Bukowski and colleagues [70]
and inhibited the growth of Helicobacter pylori associated
proposed that it might be possible to further purify L-
with gastric and colon cancer [94]. Indeed, curcumin appears
theanine from tea, and use it as a drug to boost the defense
to have chemotherapeutic potential for colon [95, 96] and
against infection.
colorectal cancer [97]. Recently, an interesting in vitro
Flaxseeds are known as linseeds, used to sprinkle on experiment shows that curcumin, can inhibit the
cereals, salads and desserts as nutritional booster. It is also a proliferation of multiple myeloma cells from humans [98].
good source of lignans known as “phytoestrogens”, which These researchers from the MD Anderson Cancer Center in
are studied for its chemopreventative properties. A number Houston, Texas, found that the trancription factor, NF-kB,
of research publications [57, 71-74] suggest that lignans are was constitutively active in all human multiple myeloma
natural cancer protective compounds. The investigations by cell lines examined. Curcumin, down-regulated NF-kB in all
Thompson have shown that flaxseed’s lignan, cell lines, as detected by use of the electrophoretic mobility
secoisolariciresinol diglucoside (SDG) has a colon cancer gel shift assay. By immunocytochemistry staining they also
protective effect [73, 74]. A study using flaxseed- extract has showed that the nuclear retention of p65 was prevented. All
also shown to protect liver cells against carbon tetrachloride multiple myeloma cell lines showed constitutively active
– induced necrosis [75]. Whereas SDG lignan is also IkB kinase (IKK) and IkBα phosphorylation. Curcumin
considered a powerful antioxidant, rosemary herb is known suppressed the constitutive IkBα phosphorylation through
as one of nature’s most powerful antioxidants [76]. inhibition of the IKK activity [98]. Curcumin also down-
Rosemary also has anti-carcinogenic properties. In vitro regulated the expression of the NF-kB-regulated gene
studies, involving human liver and bronchial cell models, products, including IkBα, Bcl-2, Bcl-xL, cyclin D1, and
have shown that rosemary extract or its active components, interleukin-6. The downregulation led to suppression of
1456 Current Medicinal Chemistry, 2004, Vol. 11, No. 11 Lai and Roy

β-Carotene >

Crocetin > COOH

HOOC

CH3O OCH3
Curcumin > O O
HO CH CH C CH2 C CH CH OH

Generalized Structure of ligans >

O
S
S S
S OH
Allicin OH
OH Dillyldisulfide
OH
HO O
OH OH
HO O
OH
O C OH

OH OH OH O
OH
OH Epicatechin
Epigallocatechin-3-gallate

OH
HO O

Theaflavins > OH

HO O O

OH
OH
OH

Fig. (2). Representative structure of chemopreventative phytochemicals.

cellular proliferation, and cell cycle arrest at the G1/S phase. crocetins, carnosol, and curcumin. The conjugated double
Curcumin also binds to aminopeptidase N (APN), an bonds, either in open chains or in rings, and polyphenolics,
enzyme that spurs tumor invasiveness and angiogenesis, and are the structural characteristics of these phytochemicals.
irreversibly inhibits its activity [99]. The direct interaction Some of the specific as well as generalized chemical
between curcumin with APN was confirmed in vitro and in structures are shown in (Fig. 2).
vivo by use of surface plasmon resonance analysis and an Carotenoids, especially beta-carotene, are well known
APN-specific antibody competition assay. It is important to biological antioxidants that protect cells and tissues from the
note that curcumin is pharmacologically a very safe damaging effects of free radicals. Studies performed in in
compound. Human clinical trials gave no dose-limiting vitro models revealed that carotenoids inhibited carcinogen-
toxicity when curcumin was administered at doses up to induced neoplastic transformation, inhibited plasma
10g/day [92]. membrane lipid oxidation, and caused unregulated
expression of connexin 43 [100]. On the other hand,
STRUCTURAL ASPECTS OF CHEMOPREVENTIVE according to some researchers, the antitumor activity of
PHYTOCHEMICALS OF HERBS & SPICES carotenoids could be associated with decreasing the fluidity
of the lipid bilayer [101]. It is to be noted that suppression
Chemopreventive phytochemicals are structurally of membrane fluidity is the mechanism whereby tamoxifen–
heterogeneous. However, their antioxidant properties play an related compounds exert their anti-cancer action.
important role in the chemoprevention of oncogenesis. The The anticancer properties of lignans have been
major chemopreventive phytochemicals of herbs & spices summarized by Thomson [57]. It is interesting to note that
included carotenoids, flavonoids, catechins, lignans, there are structural similarities among lignans,
Antimicrobial, Chemopreventive Herbs and Spices Current Medicinal Chemistry, 2004, Vol. 11, No. 11 1457

diethylstilbesterol, isoflavanoid phytoestrogens, and has been discussed. The review emphasizes the additive and
tamoxifen with weak estrogenic/antiestrogenic activity [58]. supra-additive effects of a plant’s multiple constituents.
The exact mechanism of action is uncertain, but the According to the author, synergy may occur through
mechanism whereby lignan blocks cell division may be pharmacokinetic and /or pharmacodynamic interactions.
related to its inhibition of microtubule assembly in the
Simple example of synergistic antibacterial effects of
mitotic apparatus [102].
spices was observed when citric acid (found in lemon) was
Catechins in green tea and the fermented products in added to the spices [112]. Black pepper is also a
black tea are all polyphenolic in nature. According to one "bioavailability enhancer", meaning that it acts
recent report, the cytotoxic action of plant-derived synergistically to increase the rate at which cells, including
polyphenols may involve mobilization of endogenous microorganisms, absorb phytotoxins [113]. The major
copper and consequent prooxidant action[103]. antimicrobial phytochemicals, identified in thyme and
The phytochemicals that are structurally completely oregano, are thymol and carvacrol. Thymol is also available
unrelated to traditional antioxidants, but act as in other herbs and spices (Table 1). A recent study [114]
chemoprevention, are organic sulfides and polysulfides. using thymol, carvacrol and potassium sorbate on E. coli
Diallyl sulfide in garlic was found to inhibit the phase I and S. aureus indicated the synergistic effects when used as
enzyme, cytochrome P450. Similarly diallyl disulfide can a mixture. Ternary mixture of these three compounds
increase phase II enzymes, including glutathione-S- drastically reduced the individual inhibitory concentration.
transferase, quinone reductase and UDP-glucurosyltransferase
[8]. Studies on natural garlic led to the identification of γ- TRADITIONAL HERBAL REMEDIES AND DRUG
glutamyl-Se-methylselenocysteine (GGMSC) as an effective DEVELOPMENT
anticancer agent with a mechanism of action similar to that
of methylselenocysteine [104] in an experimental animal Every traditional herbal remedy has its own long history
model. of usage and the indigenous knowledge of traditional remedy
has always acted as potential leads in drug development. The
discovery of quinine from cinchona bark is such an example.
INFORMATION ON EXTRACT’S CONCENTRA-
In addition, important modern medicines, such as codeine,
TION AND SYNERGISM
morphine, atropine, vincristine and vinblastin, topotecan,
In general, crude extracts of herbs and spices contain artemisinin and recent development of taxol, an anticancer
dozens of phytochemicals. Though publications relating to drug, have come from the information and research based on
the antimicrobial and chemopreventive actions of herbs and traditional uses of medicinal plants. Traditional medicines
spices are plentiful, information on the minimum play a very important role in the primary health care system
concentration needed for pharmacological activity has not in most of the developing countries [115]. The use of
been standardized. Some reports [105, 106] suggest a typical traditional medicines in the developed world also is on the
solution containing 0.5–4.0% purified spice chemicals (30– rise. However, according to the World Health Organization
2000 pg/ml) is sufficient to inhibit the growth of certain (WHO), research into traditional medicines has been
microbial pathogens. On the other hand, minimum inadequate, and has slowed the development of regulations
inhibitory concentration (MIC) of thyme, oregano, basil, and and public policies regulating their use in developing
rosemary, ranged from 0.5 to 1.0% (wt/vol) depending on countries.
the Shigella strain used [24]. Considerable literature exists One of the major concerns with the promotion and use of
on the uses of garlic in antimicrobial and chemoprevention. herbal traditional medicines is these products are often
One report on garlic suggested the minimum inhibitory promoted by non-professional healers, especially in
concentration to inhibit 90% of growth (MIC90) was 5 developing countries, for every type of disease. In the name
µg/mL for the clinical isolates of H. pylori [107]. On anti- of herbal, a dubious claim is made to cure any disease. The
tumor activity of rosemary herb, an 70% extract, at a consumers are often-time deceived by the term “natural”,
concentration of 50 mg/mL, inhibited KB cells by 87% because many consider natural as harmless. Also fraudulent
[108]. Whole rosemary extract, at a concentration of 6 reports on products used in herbal treatments are not
µg/ml, was found to block th initiation of carcinogenesis in uncommon. Sometimes, herbal medicines are made potent
human bronchial epithelial cell by procarcinogen, by lacing with modern drugs, and the patients are not
benzo[a]pyrene [109]. informed of these added ingredients [116]. For example, a
When crude extracts of herbs and spices are used, it is potion sold as “miracle medicine” for asthma-eczema [117-
thought that the effects, whether antimicrobial or 119] contained betamethasone, a synthetic gluco-
chemopreventive, are the combined effects of multiple corticosteroid. Fraudulence aside, it should be pointed out
bioactive phytochemicals. There is thus a good possibility that herbal medicines are not as safe as is being promoted.
of having spices or herbs synergism. Information on the Many herbal remedies are associated with potential health
occurrence of synergy in herbal extracts is slowly emerging. hazards [120]. A recent report from Oregon Health & Science
Williamson [110] has reviewed synergy and other University suggested that herbal and dietary supplements
interactions in different phytomedicines including Ginko were potential hepatotoxins in higher proportion of patients
biloba, Piper methysticum, Glycyrrhiza glabra, Hypericum with fulminant hepatic failure [121]. Phytochemicals present
perforatum, Valeriana officinalis, Cannbis sativa and Salix in the botanicals are influenced by many factors, including
alba. In another review paper [111], the importance of geographic location, soil and weather conditions and the
pharmacological synergy in psychoactive herbal medicines genetic predisposition of a plant population towards certain
1458 Current Medicinal Chemistry, 2004, Vol. 11, No. 11 Lai and Roy

metabolic pathways. Beyond phytochemicals, the plants (6). Thymoquinone, a bioactive compound identified in
may accumulate minerals and heavy metals from the soil. the oil of black cumin (Nigella sativa), has a great
Contamination by lead, cadmium, mercury and arsenic has therapeutic potential as an antimicrobial [33-36] and
been reported [122-124]. Contamination is undesirable, but anticancer agent [127]. Further research is necessary to
it is almost unavoidable when the product is produced in find out its toxicity level and its clinical efficacy.
nature, especially when the plants are harvested from the
(7). Finally, Curcumin, a highly conjugated symmetrical
wild. Other factors, such as harvesting method, drying
phenolic compound (Fig. 2) isolated from the
procedure, handling, transport, milling, light and moisture
traditional and commonly used Indian curry spice,
exposure and storage also impact product quality. Hence,
turmeric, is now under clinical trial against different
WHO has developed a strategy to intensify research into the
cancers, including colon cancer [128]. It may turn
safety and effectiveness of traditional medicines between
into a modern drug in the near future.
2000 and 2005.
Towards developing modern medicines from traditional
herbal remedies, researcher should consider the fact that ACKNOWLEDGEMENTS
traditional herbal medicines are often taken as decoction.
Thus researchers need to (a) look at chemical profiling of the This work was supported by US public Health Services
decoction; (b) identify major bioactive compound; (c) find grant P20RR16477 from the National Canter for Research
out any role of synergistic effects or additive effects; (d) Resources. National Institutes of Health, and a seed grant
compare the effect of decoction formulation with the isolated from the Salem International University.
major individualized active compound; and finally, (e) study
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