Pradeep
Sahu1*, Munglu Matlam1, Ravindra Dhar Dubey1, Shweta Paroha2, Shilpi
Chatterji1, Shekhar Verma1 and Tanushree Chatterjee1
1Institute of
Pharmacy, RITEE, Chhatauna, Mandir
Hasaud, Raipur, Chhattisgarh, India.
2Siddhi Vinayaka Institute of Technical
Sciences, Mangla, Bilaspur,
Chhattisgarh, India.
ABSTRACT:
The use of and search for drugs and dietary
supplements derived from plants have accelerated in recent years. Ethno
pharmacologists, botanists, microbiologists, and natural-products chemists are
combing the Earth for phytochemicals and leads
which could be developed for treatment of infectious diseases. While 25 to 50%
of current pharmaceuticals are derived from plants. Traditional healers have
long used plants to prevent or cure infectious conditions; Western medicine is
trying to duplicate their successes. Plants are rich in a wide variety of
secondary metabolites, such as tannins, terpenoids,
alkaloids, and flavonoids, which have been found in
vitro to have antimicrobial properties. This review attempts to summarize the
current status of botanical screening efforts, as well as in vivo studies of
their effectiveness and toxicity. The structure and antimicrobial properties of
phytochemicals viz; Simple phenols and
phenolic acids (spp.2) Quinones (spp.3)
Flavones, flavonoids, and flavonol (spp.3),
Tannins (spp.7) coumarins, (spp.1), Terpenoids
and Essential Oils (spp.19), Alkaloids (spp.9) Lectins
and polypeptides (spp.5) ,mixture
(spp.4), other compounds (spp.1) and new antimicrobial plant origins (spp.7)
are also addressed. Since many of these
compounds are currently available as unregulated botanical preparations and
their use by the public is increasing rapidly, clinicians need to consider the
consequences of patients self-medicating with these preparations.
1. INTRODUCTION:
A microorganism
also spelled micro organism or micro-organism or microbe is an organism that is microscopic (usually too small to be seen by the naked human eye). The
study of microorganisms is called microbiology,
a subject that began with Anton van Leeuwenhoek's
discovery of microorganisms in 1675, using a microscope of his own design.
Microorganisms are very diverse;
they include bacteria, fungi, archaea, and protists; microscopic plants (called green algae); and
animals such as plankton and the planarian. Some
microbiologists also include viruses, but
others consider these as non-living. Most microorganisms are
unicellular (single-celled), but this is not universal, since some multicellular organisms are microscopic, while some unicellular protists
and bacteria, like Thiomargarita namibiensis, are macroscopic and visible to the naked eye. Microorganisms live in all
parts of the biosphere where there is liquid water, including soil, hot springs, on the ocean floor, high
in the atmosphere and deep inside rocks within
the Earth's crust.
Microorganisms are critical to
nutrient recycling in ecosystems as they act as decomposers.
As some microorganisms can fix nitrogen, they
are a vital part of the nitrogen cycle, and
recent studies indicate that airborne microbes may play a role in precipitation and weather.
Microbes are also exploited by people in biotechnology,
both in traditional food and beverage preparation, and in modern technologies
based on genetic engineering. However, pathogenic microbes are harmful, since
they invade and grow within other organisms, causing diseases that kill
millions of people, other animals, and plants.1
2. GENERAL PRINCIPLES OF ANTIMICROBIAL
THERAPY
Antimicrobial
agents are among the most commonly used and misused of all drugs. The
inevitable consequence of the widespread use of antimicrobial agents has been
the emergence of antibiotic-resistant pathogens, fueling an ever-increasing
need for new drugs. However, the pace of antimicrobial drug development has
slowed dramatically, with only a handful of new agents, few of which are novel,
being introduced into clinical practice each year. Reducing inappropriate
antibiotic use is thought to be the best way to control resistance. Although
awareness of the consequences of antibiotic misuse is increasing,
overprescribing remains widespread, driven largely by patient demand, time
pressure on clinicians, and diagnostic uncertainty. If the gains in the
treatment of infectious diseases are to be preserved, clinicians must be wiser
and more selective in the use of antimicrobial agents. In
the strictest sense, antibiotics are antibacterial substances produced by
various species of microorganisms (bacteria, fungi, and actinomycetes)
that suppress the growth of other microorganisms. Common usage often extends
the term antibiotics.2
3. NATURAL PRODUCT AS ANTIMICROBIAL ACTIVITY:
Plants have an
almost limitless ability to synthesize aromatic substances, most of which are
phenols or their oxygen-substituted derivatives. Most are secondary
metabolites, of which at least 12,000 have been isolated, a
number estimated to be less than 10% of the total. In many cases,
these substances serve as plant defense mechanisms against predation
by microorganisms, insects, and herbivores. Some, such as terpenoids, give plants their odors; others (quinones and tannins) are responsible for plant
pigment. Many compounds are responsible for plant flavor (e.g., the terpenoid capsaicin from chili peppers), and some of the
same herbs and spices used by humans to season food yield useful
medicinal compounds.3,4
3.1 Phenolics and Polyphenols:
3.1.1. Simple phenols and phenolic acids:
Some of the simplest bioactive phytochemicals
consist of a single substituted phenolic ring. Cinnamic and caffeic acids are
common representatives of a wide group of phenylpropane-derived
compounds which are in the highest oxidation state. The common
herbs tarragon and thyme both contain caffeic acid,
which is effective against viruses, bacteria, and fungi. Catechol
and pyrogallol both are hydroxylated
phenols, shown to be toxic to microorganisms. Catechol
has two OH groups, and pyrogallol has
three. The site(s) and number of hydroxyl groups on the phenol group
are thought to be related to their relative toxicity to
microorganisms, with evidence that increased hydroxylation results
in increased toxicity. In addition, some authors have found that
more highly oxidized phenols are more inhibitory. The mechanisms thought to be
responsible for phenolic toxicity to microorganisms include enzyme inhibition by the
oxidized compounds, possibly through reaction with sulfhydryl groups or through more nonspecific
interactions with the proteins.
Phenolic compounds possessing a C3
side chain at a lower level of oxidation and containing no oxygen are
classified as essential oils and often cited as antimicrobial as
well. Eugenol is a well-characterized representative
found in clove oil. Eugenol is considered bacteriostatic against both fungi and bacteria.4-7
Morus alba L.; Moraceae, IOA-16:99 Shahtut Leaves p-Cresol, phenol, morin.8
Ocimum sanctum L.; Labiatae, Tulsi
Whole plant 71.3% Eugenol, 3.7% carvacrol
Gastric disorders bronchitis, ear HDCO-23:28 plant 20.4% Methyl eugenol 1.7% ache antiseptic, diaphoretic, hepatic Caryophyllene affections.9
3.1.2 Quinones:
Quinones are aromatic rings with two ketone
substitutions. They are ubiquitous in nature and are
characteristically highly reactive. These compounds, being colored,
are responsible for the browning reaction in cut or injured fruits
and vegetables and are an intermediate in the melanin synthesis
pathway in human skin. Their
presence in henna gives that material its dyeing properties. The switch between
diphenol (or hydroquinone) and diketone (or quinone) occurs
easily through oxidation and reduction reactions. The individual redox potential of the particular quinone-hydroquinone pair is very important in many
biological systems; witness the role of ubiquinone
(coenzyme Q) in mammalian electron transport systems. Vitamin K is a
complex naphthoquinone. Its antihemorrhagic activity may be related to its ease of
oxidation in body tissues. Hydroxylated
amino acids may be made into quinones in
the presence of suitable enzymes, such as a polyphenoloxidase..
In addition to
providing a source of stable free radicals, quinones
are known to complex irreversibly with nucleophilic
amino acids in proteins
often leading to inactivation of the protein and loss of
function. For that reason, the potential range of quinone antimicrobial effects is great. Probable targets in
the microbial cell are surface-exposed adhesins,
cell wall polypeptides, and membrane-bound enzymes. Quinones may
also render substrates unavailable to the microorganism. As with all
plant-derived antimicrobials, the possible toxic effects of quinones must be thoroughly examined.
Terminalia chebula Retz; Harir
Fruit Chebulinic acid, tannic acid Laxative, ulcers,
used in carious Combretaceae, HDCO-70:116 2040%, Anthroquinone chebulagic teeth, pilesacid, Corilagi.
Kazmi et al. described an anthraquinone from Cassia italica,
a Pakistani tree, which was bacteriostatic for Bacillus
anthracis, Corynebacterium
pseudodiphthericum, and Pseudomonas aeruginosa and bactericidal for Pseudomonas pseudomalliae. Hypericin,
an anthraquinone from St. John's wort (Hypericum perforatum), has received much attention in
the popular press lately as an antidepressant, and Duke reported in
1985 that it had general antimicrobial properties.9,10
Cascara sagrada; Obtain from sacred /chittern bark of Rhamnus purshiana Rhamnaceae
containing tannins, polyphenols Anthraquinones
active against viruses bacteria and fungi.
3.1.3 Flavones, flavonoids,
and flavonols:
Flavones are phenolic structures
containing one carbonyl group (as opposed to the two carbonyls in quinones). The addition of a 3-hydroxyl group yields a flavonol Flavonoids are
also hydroxylated phenolic
substances but occur as a C6-C3 unit linked to
an aromatic ring. Since they are known to be synthesized by plants
in response to microbial infection, it should not be surprising that
they have been found in vitro to be effective antimicrobial
substances against a wide array of microorganisms. Their activity is
probably due to their ability to complex with extracellular and
soluble proteins and to complex with bacterial cell walls, as
described above for quinones. More lipophilic flavonoids may
also disrupt microbial membranes.
Catechins, the most reduced form of the C3
unit in flavonoid compounds, deserve special mention.
These flavonoids have been extensively
researched due to their occurrence in oolong green teas. It was
noticed some time ago that teas exerted antimicrobial activity and
that they contain a mixture of catechin compounds.
These compounds inhibited in vitro Vibrio
cholerae, Streptococcus mutans, Shigella,
and other bacteria and microorganisms. The catechins
inactivated cholera toxin in Vibrio and
inhibited isolated bacterial glucosyltransferases
in S. mutans, possibly due to complexing activities described for quinones
above. This latter activity was borne out in vivo tests of
conventional rats. When the rats were fed a diet containing 0.1% tea
catechins, fissure caries (caused by S. mutans) was reduced by 40%.
Flavonoid compounds exhibit inhibitory
effects against multiple viruses. Numerous studies have documented the effectiveness
of flavonoids such as swertifrancheside,
glycyrrhizin (from licorice), and chrysin
against HIV. More than one study has found that flavone
derivatives are inhibitory to respiratory syncytial
virus (RSV). Kaul et al. provide a summary
of the activities and modes of action of quercetin,
naringin, hesperetin,
and catechin in in vitro
cell culture monolayers. While naringin was not inhibitory to herpes simplex virus type
1 (HSV-1), poliovirus type 1, parainfluenza
virus type 3, or RSV, the other three flavonoids
were effective in various ways. Hesperetin reduced
intracellular replication of all four viruses; catechin
inhibited infectivity but not intracellular replication of RSV and
HSV-1; and quercetin was universally effective in
reducing infectivity. The authors propose that small structural
differences in the compounds are critical to their activity and
pointed out another advantage of many plant derivatives: their low
toxic potential. The average Western daily diet contains
approximately 1 g of mixed flavonoids;
pharmacologically active concentrations are not likely to be harmful
to human hosts.
An isoflavone found in a West African legume, alpinumisoflavon, prevents schistosomal
infection when applied topically, Phloretin,
found in certain serovars of apples, may have
activity against a variety of microorganisms, Galangin
(3,5,7-trihydroxyflavone), derived from the perennial herb Helichrysum aureonitens,
seems to be a particularly useful compound, since it has shown
activity against a wide range of gram-positive bacteria as well as
fungi and viruses, in particular HSV-1 and coxsackie
B virus type 1.
Camelia sinensis L.; Theaceae,
Chai Leaves Caffeine, theaine,
Theobromine, Astrigent,
diuretic stimulant Assam Tea Chowk Ltd. Chlorgenic acid, Myricetin, Epi-gallotannins, 3 galactosides
of flavones and flavonols.
Delineation of
the possible mechanism of action of flavones and flavonoids
is hampered by conflicting findings. Flavonoids lacking
hydroxyl groups on their -rings are more active against microorganisms
than are those with the OH groups; this finding supports the idea
that their microbial target is the membrane. Lipophilic
compounds would be more disruptive of this structure. However,
several authors have also found the opposite effect; i.e., the more
hydroxylation, the greater the antimicrobial activity, this latter finding
reflects the similar result for simple phenolics
(see above). It is safe to say that there is no clear predictability
for the degree of hydroxylation and toxicity to microorganisms.11-18
3.1.4 Tannins.
Tannin is a general descriptive name for a group of
polymeric phenolic substances capable of tanning
leather or precipitating gelatin from solution, a property known as
astringency. Their molecular weights range from 500 to
3,000 and
they are found in almost every plant part: bark, wood, leaves,
fruits, and roots they are divided into two groups, hydrolyzable and condensed tannins. Hydrolyzable tannins are based on gallic
acid, usually as multiple esters with D-glucose, while the more numerous
condensed tannins (often called proanthocyanidins)
are derived from flavonoid monomers
Tannins may be formed by condensations of flavan
derivatives which have been transported to woody tissues of plants.
Alternatively, tannins may be formed by polymerization of quinone units. This group of compounds has
received a great deal of attention in recent years, since it was
suggested that the consumption of
tannin-containing beverages, especially green teas and red wines,
can cure or prevent a variety of ills.
Many human
physiological activities, such as stimulation of phagocytic
cells, host-mediated tumor activity, and a wide range of
anti-infective actions, have been assigned to tannins. One of their molecular actions is to
complex with proteins through so-called nonspecific forces such as
hydrogen bonding and hydrophobic effects, as well as by covalent
bond formation Thus, their
mode of antimicrobial action, as described in the section on quinones, may be related to their ability to inactivate
microbial adhesins, enzymes, cell envelope
transport proteins, etc. They also complex with polysaccharide. The
antimicrobial significance of this particular activity has not been
explored. There is also evidence for direct inactivation of
microorganisms: low tannin concentrations modify the morphology of
germ tubes of Crinipellis perniciosa Tannins in plants inhibit insect growth
and disrupt digestive events in ruminal animals.
Casuarina equistifolia L.; Jangli-saru
Bark Casuarin, 618% Tannins Astrigent,
useful in diarrhoea and Casuarinaceae,
IOA-07:99 dysentery. Emblica officinalis Gaerth.; Amla Fruits Vitamin C, phosphatides,
seeds Acrid, cooling, refrigerant diuretic, Euphorbiaceae,
IOA-11:99 contain tannins, Chebulinic Acids used in diarrhoea, dysentery. Hemidesmus
indicus R. Br.; Anatamul
Roots 0.18% 2-OH, 4 Methyl Demulcant, tonic,
diaphoretic, skin Asclepiadaceae, HDCO-204:76 benzaldehyde, sterols, glucosides,
diseases, syphilis, and blood purifier resinic acid,
tannins. Terminalia arjuna
W.&A.; Arjun Bark Arjunine,
Lactone, Arjunetin Astrigent, bilious affections, heart Combretaceae,
IOA-29:99 tannin. diseases. Lawsonia inermis L.; Lythraceae, Hena:Mehdi Leaves Glucoside, hennotannic acid, Headache, burning of skin, IOA-15:99 Lawsone. Terminalia belerica Roxb.; Bahera Fruit 17% tannins, triterpenoid
dropsy. C. equistifolia L.;
IOA-08:99 Jangli-saru Leaves Decoction used in
colic.8,9
Scalbert reviewed the antimicrobial
properties of tannins in 1991. He listed 33 studies which had
documented the inhibitory activities of tannins up to that point.
According to these studies, tannins can be toxic to filamentous
fungi, yeasts, and bacteria. Condensed tannins have been determined
to bind cell walls of ruminal bacteria,
preventing growth and protease activity. Although this is still
speculative, tannins are considered at least partially responsible
for the antibiotic activity of methanolic extracts
of the bark of Terminalia alata found in Nepal. This activity was
enhanced by UV light activation (320 to 400 nm at 5 W/m2
for 2 h). At least two studies have shown tannins to be inhibitory to
viral reverse transcriptases.19-25
3.1.5 Coumarins:
Coumarins are phenolic substances made of fused
benzene and -pyrone rings. They are responsible for the characteristic
odor of hay. As of 1996, at least 1,300 had been identified. Their
fame has come mainly from their antithrombotic, anti-inflammatory, and vasodilatory activities. Warfarin
is a particularly well-known coumarin which is used
both as an oral anticoagulant and, interestingly, as a rodenticide.
It may also have antiviral effect. Coumarins are
known to be highly toxic in rodents and therefore are treated with caution by
the medical community. However, recent studies have shown a pronounced species-dependent
metabolism, so that many in vivo animal studies cannot be extrapolated to
humans. It appears that toxic coumarin derivatives
may be safely excreted in the urine in humans.
Several other coumarins have antimicrobial properties. R. D. Thornes, working at the Boston Lying-In Hospital in
1954, sought an agent to treat vaginal candidiasis
in his pregnant patients. Coumarin was found in vitro
to inhibit Candida albicans. (During subsequent in
vivo tests on rabbits, the coumarin-spiked water
supply was inadvertently given to all the animals in the research facility and
was discovered to be a potent contraceptive agent when breeding programs
started to fail.) Its estrogenic effects were later described.
As a group, coumarins have been found to stimulate macrophages, which
could have an indirect negative effect on infections. More specifically, coumarin has been used to prevent recurrences of cold sores
caused by HSV-1 in humans but was found ineffective against leprosy. Hydroxycinnamic acids, related to coumarins,
seem to be inhibitory to gram-positive bacteria. Also, phytoalexins,
which are hydroxylated derivatives of coumarins, are produced in carrots in response to fungal
infection and can be presumed to have antifungal activity. General
antimicrobial activity was documented in woodruff (Galium odoratum) extracts. All in all, data
about specific antibiotic properties of coumarins are
scarce, although many reports give reason to believe that some utility may
reside in these phytochemicals. Further research is
warranted.26,-31
3.2 Terpenoides
and Essential Oils:
The fragrance of plants is carried in the so called quinta essentia, or essential oil
fraction. These oils are secondary metabolites that are highly enriched in
compounds based on an isoprene structure. They are called terpenes,
their general chemical structure is C10H16, and they occur as diterpenes, triterpenes, and tetraterpenes (C20, C30, and C40), as well as hemiterpenes
(C5) and sesquiterpenes (C15). When the compounds
contain additional elements, usually oxygen, they are termed terpenoids. Terpenoids are
synthesized from acetate units, and as such they share their origins with fatty
acids. They differ from fatty acids in that they contain extensive branching
and are cyclized. Examples of common terpenoids are methanol and camphor (monoterpenes)
and farnesol and artemisin
(sesquiterpenoids). Artemisin
and its derivative -arteether, also known by the name
qinghaosu, find current use as antimalarials.
In 1985, the steering committee of the scientific working group of the
World Health Organization decided to develop the latter drug as a treatment for
cerebral malaria.
Terpenenes or terpenoids
are active against bacteria), fungi, viruses, and protozoa. In 1977, it
was reported that 60% of essential oil derivatives examined to date were
inhibitory to fungi while 30% inhibited bacteria. The triterpenoid
betulinic acid is just one of several terpenoids (see below) which have been shown to inhibit
HIV. The mechanism of action of terpenes is not fully
understood but is speculated to involve membrane disruption by the lipophilic compounds. Accordingly, Mendoza et al.found that increasing the hydrophilicity
of kaurene diterpenoids by
addition of a methyl group drastically reduced their antimicrobial activity.
Food scientists have found the terpenoids present in
essential oils of plants to be useful in the control of Listeria
monocytogenes. Oil of basil, a commercially available
herbal, was found to be as effective as 125 ppm
chlorine in disinfecting lettuce leaves. Chile peppers are a food item found
nearly ubiquitously in many Mesoamerican cultures. Their use may reflect more
than a desire to flavor foods. Many essential nutrients, such as vitamin C, provitamins A and E, and several B vitamins, are found in chiles. A terpenoid constituent,
capsaicin, has a wide range of biological activities in humans, affecting the
nervous, cardiovascular, and digestive systems as well as finding use as an
analgesic. The evidence for its antimicrobial activity is mixed. Recently, Cichewicz and Thorpe found that capsaicin might enhance the
growth of Candida albicans but that it clearly
inhibited various bacteria to differing extents. Although possibly detrimental
to the human gastric mucosa, capsaicin is also bactericidal to Helicobacter pylori. Another hot-tasting
diterpene, aframodial, from
a Cameroonian spice, is a broad-spectrum antifungal. The ethanol-soluble
fraction of purple prairie clover yields a terpenoid
called petalostemumol, which showed excellent
activity against Bacillus subtilis and Staphylococcus
aureus and lesser activity against gram-negative
bacteria as well as Candida albicans. Two diterpenes isolated by Batista et al.were
found to be more democratic; they worked well against Staphylococcus aureus, V. cholerae,
P. aeruginosa,
and Candida spp. When it was observed
that residents of Mali used the bark of a tree called Ptelopsis
suberosa for the treatment of gastric ulcers,
investigators tested terpenoid-containing fractions
in 10 rats before and after the rats had ulcers chemically induced. They
found that the terpenoids prevented the formation of
ulcers and diminished the severity of existent ulcers. Whether this activity
was due to antimicrobial action or to protection of the gastric mucosa is not
clear. Kadota et al.found
that trichorabdal A, a diterpene
from a Japanese herb, could directly inhibit H. pylori.32-38
Allium cepa L.; Liliaceae, Piyaz Leaves Methylallyl, diallyl dimethyl, Expectorant
IOA-01:99 propanethiol, phloroglucinol,
propanethio. Allium
sativum L.;
Liliaceae, Lasan Bulb Allicin 0.060.1%, diallyl
Carminative, coughs in fevers, IOA-02:99 catechols, protocatechuic acid juice used in skin diseases, ear Allistin I & II, ajoene, allyl aches, atonic dysepsia, colic propyl sulfide 39,40
A.sativum L.;
IOA-03:99 Lasan Leaves. Citrus sinensis
L.; Rutaceae, Musambi
Rind Tangetin, Sinensetin,
Limonene Carminative, tonic used for acne IOA-09:99 decyclicaldehyde,
Linalool diterpineol. Lantana camara
L.; Verbenaceae, Ghaneri
Leaves Essential oil carmene, isocamerene,
Decoction used in malaria, atoxy, IOA-19:99 micramene rheumatism. Eucalyptus sp.; Myrtaceae, Eucalyptus Leaves 0.91.2% oil: Cineole, Pinene Antiseptic, infections of upper IOA-12:99 Sesquiterpene alcohols, Astrgin
respiratory tract, skin diseases, eudesmal, a-phellandrene burns, rheumatism. Syzgium
aromaticum L.; Myrtaceae,
Laung Bud Eugenol, eugeniin, Casuarji-citin
Stimulant, carminative used in IOA-26:99. dyspepsy. S.
aromaticum L.; Myrtaceae,
Dabur Laung Oil Eugenol, vanillin. Syzgium
cumini L.; Myrtaceae, Jamun Bark Jambosine. Astrigent, used for sore throat, IOA-27:99 diarrhoea. S. cumini
L.; IOA-28:99 Leaves Dysentery. Terminalia belerica Roxb. Bahera Fruit 17%
tannins, triterpenoid dropsy. Bael tree; Unripe
or half ripe fruits of Aegle marmelos,
family-Rutaceae containing Essential oil, Terpenoid active against fungi.8, 9
Basil; Fresh and dried leaves of
Ocimum basilicum,
family-Labiatae containing Essential oils, Terpenoids, active against Salmonella, bacteria.
Chili peppers paprika; Dried ripe fruits of Capsicum annuum,
family- Solanaceae containing Capsaicin, Terpenoid,active against Bacteria. Dill; Dried fruits of Anethum graveolens,
family-Umbelliferae containing Essential oil, Terpenoid active against Bacteria. Hops; Dried strobiles of Humulus lupulus, family-Cannabinaceae
containing Lupulone, humulone,
Phenolic acids,(Hemi) terpenoids,
active against general microbes. Rosemary; Flowering tops of leafy twing Rosmarinus officinalis,family-Labiatae
containing Essential oil,Terpenoids active against general microbes. Thyme; Dried leaves
and flowering tops of plant Thymus vulgaris,
family-Lamiaceae containing Caffeic
acids, Terpenoid, active against Viruses, bacteria,
fungi. Turmeric; Dried as well as fresh rhizomes of Curcuma longa, family-Zingiberaceae
containing Curcumin Turmeric oil, Terpenoid, active
against Bacteria.
3.3 Alkaloids:
Heterocyclic
nitrogen compounds are called alkaloids. The first medically useful example of
an alkaloid was morphine, isolated in 1805 from the opium poppy
Papaver somniferum; the name morphine
comes from the Greek Morpheus, god of dreams. Codeine and heroin are
both derivatives of morphine. Diterpenoid alkaloids,
commonly isolated from the plants of the Ranunculaceae,
or buttercup family, are commonly found to have antimicrobial properties.
Solamargine, a glycoalkaloid
from the berries of Solanum khasianum, and other alkaloids may be useful against
HIV infection as well as intestinal infections associated with
AIDS. While alkaloids have been found to have microbiocidal
effects (including against Giardia and Entamoeba species), the major antidiarrheal effect is probably due to their effects on
transit time in the small intestine. Berberine
is an important representative of the alkaloid group. It is potentially
effective against trypanosomes and plasmodia. The mechanism of
action of highly aromatic planar quaternary alkaloids such as berberine and harmane is
attributed to their ability to intercalate with DNA.41-43
Acorus calamus
L.; Araceae, Bach:Vaj Rhizome Glucoside acorin, alkaloid,
Emetic, stomach-ache, nerve HDCO-166:297
1.53.5% essential oil, methyl dyspepsia, colic, tonic in isoeugenol.
Holarrhena antidysenterica
R.; Kurachi Bark Alkaloids Conessine,
Kurchine, Dropsy, diarrhoea
Apocyanaceae, HDCO-120:235 Kurchicine,
Holarhimine. Nyctanthes
arbortristis L.; Oleaceae,
Harsingar Leaves Alkaloid, resins, glucoside Fever, rheumatism, obstrinate
sciata IOA-20:99. Nyctanthes
arbortristis L.; Oleaceae,
Harsingar Leaves Alkaloid, resins, glucoside Fever, rheumatism, obstrinate
sciata IOA-20:99. Barberry; Bark of Berberis vulgaris,
family-Berberidanceae containing Berberine,
Alkaloid, active against Bacteria, protozoa. Black pepper; Dried ripe or
unripe fruits of Piper nigrum, family-Piperaceae containing
Piperine,Alkaloid,active against Fungi, Lactobacillus,
Micrococcus, E. coli, E. faecalis.
Opium (Poppy); Dried latex from unripe fruits of Papaver
somniferum, family- containing Opium, Alkaloid
and others active against general microbes. Quinine(Cinchona);Dried bark of
stem and roots of Hydrastis Canadensis,
family-Rubiaceae containing Quinine, Alkaloid, active against Plasmodium spp. Rauvolfia, Chandra; Dried roots and rhizomes of Rauvolfia serpentina containing Reserpine, Alkaloid, active against general microbes.8,9
3.4 Lectins
and Polypeptides:
Peptides
which are inhibitory to microorganisms were first reported in 1942. They are often positively
charged and contain disulfide bonds. Their mechanism of action may
be the formation of ion channels in the microbial membrane or competitive
inhibition of adhesion of microbial proteins to host polysaccharide
receptors. Recent interest has been focused mostly on studying
anti-HIV peptides and lectins, but the
inhibition of bacteria and fungi by these macromolecules, such as
that from the herbaceous Amaranthus, has long
been known.
Thionins are peptides commonly found in
barley and wheat and consist of 47 amino acid residues. They are toxic
to yeasts and gram-negative and gram-positive bacteria. Thionins AX1 and AX2 from sugar beet are active against
fungi but not bacteria. Fabatin, a newly
identified 47-residue peptide from fava
beans, appears to be structurally related to -thionins
from grains and inhibits E. coli, P. aeruginosa,
and Enterococcus hirae but not Candida or Saccharomyces.
The larger lectin
molecules, which include mannose-specific lectins
from several plants, MAP30 from bitter melon, GAP31 from Gelonium multiflorum,
and jacalin, are inhibitory to viral
proliferation (HIV, cytomegalovirus), probably by inhibiting viral
interaction with critical host cell components. It is worth
emphasizing that molecules and compounds such as these whose mode of
action may be to inhibit adhesion will not be detected by using most
general plant antimicrobial screening protocols, even with the
bioassay-guided fractionation procedures used by natural-products chemists (see
below). It is an area of ethnopharmacology
which deserves attention, so that initial screens of potentially
pharmacologically active plants and may be made more useful.
44,45
3.5 Mixtures:
The
chewing stick is widely used in African countries as an oral hygiene aid (in
place of a toothbrush). Chewing sticks come from different species of plants,
and within one stick the chemically active component may be
heterogeneous. Crude extracts of one species used for this purpose, Serindeia werneckei,
inhibited the periodontal pathogens Porphyromonas
gingivalis and Bacteroides
melaninogenicus in vitro. The active component
of the Nigerian chewing stick (Fagara
zanthoxyloides) was found to consist
of various alkaloids. Whether these compounds, long utilized in
developing countries, might find use in the Western world is not yet
known.
Ayurveda is a type of healing craft
practiced in India but not unknown in the United States. Ayurvedic
practitioners rely on plant extracts, both "pure"
single-plant preparations and mixed formulations. The preparations
have lyrical names, such as Ashwagandha (Withania somnifera
root), Cauvery 100 (a mixture), and Livo-vet.
These preparations are used to treat animals as well as humans. In
addition to their antimicrobial activities, they have been found to
have antidiarrheal, immunomodulatory,
anticancer, and psychotropic properties. In vivo studies of Abana, an Ayurvedic formulation,
found a slight reduction in experimentally induced cardiac
arrhythmias in dogs. Two microorganisms against which Ayurvedic
preparations have activity are Aspergillus
spp. and Propionibacterium acnes.
(The aspergillosis study was performed with mice
in vivo, and it is therefore impossible to determine whether the effects
are due to the stimulation of macrophage activity in the whole
animal rather than to direct antimicrobial effects.) The toxicity of Ayurvedic preparations has been the subject of some
speculation, especially since some of them include metals. Prpic-Majic et al. identified high levels of lead in the
blood of adult volunteers who had self-medicated with Ayurvedic medicines.
Propolis is a crude extract of the
balsam of various trees; it is often called bee glue, since honeybees gather it
from the trees. Its chemical composition is very complex: like the
latexes described above, terpenoids are
present, as well as flavonoids, benzoic
acids and esters, and substituted phenolic acids and
esters. Synthetic cinnamic acids, identical to those
from propolis, were found to inhibit hemagglutination activity of influenza virus. Amoros et al. found that propolis
was active against an acyclovir-resistant mutant of HSV-1,
adenovirus type 2, vesicular stomatitis
virus, and poliovirus. Mixtures of chemicals, such as are found in
latex and propolis, may act synergistically. While
the flavone and flavonol
components were active in isolation against HSV-1, multiple flavonoids incubated simultaneously with the
virus were more effective than single chemicals, a possible explanation
of why propolis is more effective than its individual
compounds. But mixtures are more likely to contain toxic
constituents, and they must be thoroughly investigated and standardized
before approved for use on a large-scale basis in the West.
Papaya
(Carica papaya) yields a milky sap,
often called latex, which is a complex mixture of chemicals. Chief among them
is papain, a well-known proteolytic
enzyme. An alkaloid, carpaine, is also
present. Terpenoids are also present and
may contribute to its antimicrobial properties. Osato
et al.found the latex to be bacteriostatic
to B. subtilis, Enterobacter cloacae, E. coli, Salmonella
typhi, Staphylococcus aureus, and Proteus vulgaris.46-49
3.6 Other Compounds:
Many
phytochemicals not mentioned above have been found to
exert antimicrobial properties. This review has attempted to focus on
reports of chemicals which are found in multiple instances to be
active. It should be mentioned, however, that there are reports of
antimicrobial properties associated with polyamines (in particular spermidine), isothiocyanates, thiosulfinates, and glucosides. Polyacetylenes deserve special mention. Estevez-Braun et
al. isolated a C17 polyacetylene compound
from Bupleurum salicifolium,
a plant native to the Canary Islands. The compound, 8S-heptadeca-2(Z),9(Z)-diene-4,6-diyne-1,8-diol,
was inhibitory to S. aureus and B. subtilis but not to gram-negative bacteria
or yeasts . Acetylene compounds and flavonoids from
plants traditionally used in Brazil for treatment of malaria fever
and liver disorders have also been associated with antimalarial
activity.
Much has been written about the
antimicrobial effects of cranberry juice. Historically, women have been told to
drink the juice in order to prevent and even cure urinary tract
infections. In the early 1990s, researchers found that the
monosaccharide fructose present in cranberry and blueberry juices
competitively inhibited the adsorption of pathogenic E. coli
to urinary tract epithelial cells, acting as an analogue for
mannose. Clinical studies have borne out the protective effects of
cranberry juice. Many fruits contain fructose, however, and
researchers are now seeking a second active compound from cranberry
juice which contributes to the antimicrobial properties of this
juice.50-53
3.7 New Antimicrobials of Plant
Origin:
3.7.1 Garcinia kola,
bitter kola (Guttiferae):
Garcinia kola is found in moist forest and grows as a medium size
tree, up to 12 m high. It is cultivated and distributed throughout west and
central Africa. Medicinal uses include purgative, antiparasitic,
antimicrobial. The seeds are used in the treatment of bronchitis and throat
infections. They are also used to prevent and relieve colic, cure head or chest
colds and relieve cough. Also the plant is used for the treatment of liver
disorders and as a chewing stick. The
constituents includebiflavonoids, xanthones and benzophenones. The
antimicrobial properties of this plant are attributed to the benzophenone, flavanones. This
plant has shown anti-inflammatory, antimicrobial and antiviral properties.
Studies show very good antimicrobial and antiviral properties. In addition, the
plant possesses antidiabetic and antihepatotoxic
activities.54
3.7.2 Aframomum melegueta (Zingiberaceae)
Grains of Paradise
This is a spicy edible fruit that is
cultivated and occurs throughout the tropics. It is a perennial herb. The
medicinal uses of Aframomum include
aphrodisiac, measles, and leprosy, taken for excessive lactation and post partem hemorrhage, purgative, galactogogue
and anthelmintic and hemostatic
agent. The constituents are essential oilssuch as gingerol,
shagaol, paradol. Studies
show antimicrobial and antifungal activity and effective against schistosom.54
Key constituents are diterpenic and xylopic acid. In
studies, the fruit as an extracts has been shown to be active as an
antimicrobial against gram positive and negative bacteria. Though it has not
been shown to be effective against E. coli. Xylopic
acid has also demonstrated activity against Candida albicans.55
An evergreen, aromatic tree
growing up to 20 m high with peppery fruit. It is native to the lowland
rainforest and moist fringe forest in the savanna zones of in Africa. Largely
located in West, Central and Southern Africa. Medicinal uses of the plant are,
as a carminative, as a cough remedy, and as a post partum tonic and lactation
aid. Other uses are stomachache, bronchitis, biliousness and dysentery. It is
also used externally as a poultice for headache and neuralgia. It is used with
lemon grass for female hygiene. It is high in copper, manganese, and zinc.
56
3.7.4 Cryptolepis
sanguinolenta Lindl. Schltr. (Periplocaceae):
A shrub that grows in the
rainforest and the deciduous belt forest, found in the west coast of Africa.
Related species appear in the east and southern regions of the continent. Its
main medicinal use is for the treatment of fevers. It is used for urinary tract
infections, especially Candida. Other uses are inflammatory conditions,
malaria, hypertension, microbial infections and inflammatory conditions,
stomach aches colic.
Active principals identified are
indo quinoline alkaloids. Studies show inhibition
against gram negative bacteria and yeast. Additionally studies have shown this
plant to have bactericidal activity. Clinical studies have shown extracts of
the plant were effective in parasitemia. Recent in
vitro study shows activity against bacteria specifically, enteric pathogens,
most notably E. coli (but also staphylococcus, C. coli, C. jejuni, pseudomonous,
salmonella, shigella, streptococcus, and vibrio) and some activity against candida.
It has shown histamine antagonism, hypotensive, and vasodilatory activities. In addition it has demonstrative antihyperglcyemic properties. 57,58
A woody climber that grows wild
in forest margins and savanna. The plant is cultivated. It is used medicinally
for venereal disease, topically on sprained joints and bruises and as a general
tonic for physical and nervous debilities. The constituents include berberine type alkaloids, palmatine,
colombamine, and jateorhizine.
Studies show that the berberine sulfate in the plant
inhibits lieshmania.
It is a shrub or small spreading
tree that is a widely distributed savanna plant. It is found in the forest and
fringe tropical forest. Medicinal uses are as a tonic and fever medicine,
chewing stick, toothaches, dental caries, septic mouth and malaria., diarrhea
and dysentery.59
Key constituents are indole-quinolizidine
alkaloids and glycoalkaloids and sapponins.
There are studies showing the root has antibacterial activity against gram
positive and negative bacteria and antifungal activity. It is most effective
against Corynebacterium diphtheriae,
Streptobacillis sp., Streptococcus sp.,
Neisseria sp., Pseudomonas aeruginosa, Salmonella sp.60
3.7.7 Araliopsis tabouensis (Rutaceae):
4. CONCLUSIONS:
The greatest service which can be rendered
any country is to add a useful plant to its culture. Plants have forever been a
catalyst for our healing. In order to halt the trend of increased emerging and
resistant infectious disease, it will require a multi-pronged approach that
includes the development of new drugs. Using plants as the inspiration for new
drugs provides an infusion of novel compounds or substances for healing
disease. Evaluating plants from the traditional African system of medicine
provides us with clues as to how these plants can be used in the treatment of
disease. Many of the plants presented here show very promising activity in the
area of antimicrobial agents, warranting further investigation. Scientists from
divergent fields are investigating plants a new with an eye to their
antimicrobial usefulness. A sense of urgency accompanies the search
as the pace of species extinction continues. Laboratories of the
world have found literally thousands of phytochemicals
which have inhibitory effects on all types of microorganisms in vitro.
More of these compounds should be subjected to animal and human
studies to determine their effectiveness in whole-organism systems,
including in particular toxicity studies as well as an examination
of their effects on beneficial normal microbiota.
It would be advantageous to standardize methods of extraction and
in vitro testing so that the search could be more systematic and
interpretation of results would be facilitated. Also, alternative mechanisms
of infection prevention and treatment should be included in initial
activity screenings. Disruption of adhesion is one example of an
anti-infection activity not commonly screened for currently.
Attention to these issues could usher in a badly needed new era of
chemotherapeutic treatment of infection by using plant-derived principles.
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Received on 01.12.2010
Accepted on 10.01.2011
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