Indian Journal of Experimcntal Biology
Vol. 39. Apri l 200 1. pp. 310-322
Review Article
Role of garlic (Allium. sativum L.) in human and plant diseases
UP Singh ', B Prilhiviraj ' , B K Sarma ', Mandavi Singh2 & A B Rai
'Department of Mycology and Plant Pathology. Institutc of Agricultural Scienccs. Banaras Hindu University,
Varan asi 221005, India
Fax: 9 1-542-3 17074. E mail: ups @ banaras. crnet.in
!Dcpart mcnt of Anatomy. Insti tute of Mcdical Scicnces, I3anaras Hindu Uni ve rsity, Va r3nasi 22 1005. India,
JDepartmen t of Mcd icinal Chemistry, Institutc of Medical Scienccs. Banaras Hindu Univcrsity, Varanasi 221005. India
A n:surgc ncc of intcrest in garlic due to recent rcvelations of its bcnefic ial cffec ts in thc treatmcnt of various human
and plan t diseascs and also due to validat ion of claims made in traditional systems of medici nc has resulted a plcthora of
publications on diffcrcnt a pects of garlic in reCCI1l years. Chcmical constituents of garlic and their variations on the mcthods
of isolatio n havc been discussed in the prcsent rev iew. Effect of ga rlic and its constituents against vario us human anel plant
pathogenic and sap rophyt ic microorga nisms has also been reviewcd.
Garlic (A lliulIl sativulII L.) is used worldwide as a
food add itive, spice and medicine. In Ayurveda l , it
has been described as a gastric sti mu lant. It aids
digesti on and is given in tlatulence. It has special
influence over the bronchial and pulmonary secreti ons
and in promotion of fl ow of menses. Garlic is used as
a tonic, carminati ve and stimulant. In large doses, it is
an irritant and produces flatulenc e, headache, nau sea
and even diarrhoea. As a local stim ul ant and ilTitant, it
causes red ness of th e skin and vesication. It is appli ed
to the nose of hysterical patients when in a state of
swooning. Gi ven wi th common salt, it rel ieves colic
pain and nervous headache. It is used as a vermi fu ge
to ex pel round worms. It causes diuresis and hence
used in dropsy . In cold catarrh of chi ldren, brui sed
garlic is applied to the chest as a poulti ce or lini ment.
It is also used as a remedy to bites of venomous
reptiles. The rubificent action of garlic is enh anced by
addition of mustard powder. It is rubbed over
ringworm for relief. Garli c juice boiled wi th salad oil
gives reli ef from earache. It is beneficia l in several
forms of atonic dyspepsia and is effecti ve in the
treatment of tubercu losis.
Many of these effects have been substantiated by
modern research and garli c has been proved to eli cit
antimicrobiaI 2. 5 , antihypertensive 6 , hypo lipidemic7-'J,
. 10, anti'd 'la betl.c 11 -15 ,an d'Insecliclc
.. Ia116
Ilepatoprotectlve
and
antitumor
propert ies.
Immunomod ulati on
activities of garlic have also been reponed 17. Garli c
ex trac t has also been shown to reduce serum
cholesterol levels l R. I ') and increase blood coag ul ati on
.
' 8'-'0 . A ntlun
. f ga l aCli"vlty 0 f' gar I'Ie bit'
u )s- ,.'-3 an d
ttme
aqueous extract 0 f· ·Its Ieaves-,~ '-'5 are a Iso on reco rcI. I n
view of the variety of bioactivities th at garlic and its
various preparations ex hibit, it is co nsidered
appropriate to comp ile the various findin gs in a
systematic manner and an attempt in this direction has
been made in this bri ef review.
ClJell/ical constituents of ga rlic - Garlic is a rich
source of organosulphur compounds showing a
va ri ety of bi ological activi ti es. The chemical
constituen ts from garlic cloves (b ul bs) vary with the
isolation procedure and obviously many of the
compounds report ed from this source have been
proved to be artifacts. Thus, while ga rlic oil obtained
by steam disti ll ation of garlic cloves was proved to be
essentially cl iall yl di sulphide ( 1) accompanied by
lesser amounts of diallyl tri-and tetra-sulphides26 .
Ext rac ti on of garli c with ethyl alcoho l at room
temperature yields ox ide of dially l disulphid e (2)
called all ici n27. Extraction of garlic with ethanol at
subzero temperature yields 28 an adourl ess am ino acid,
(+)-S-allyl-L-cysteine sul foxide (3) whi ch is named
alli in (Fi g. I). Odourl ess alliin has been proved to be
th e precursor of allici n, the main odorous principl e of
garlic and co nversion of the forme r to latter takes
place under th e influence of an enzy me, allinase
whi ch comes in contact wi th alli in on ly when garlic
bul bs arc CLl t or crushed. It is for this reaso n that the
bul bs are odourless unless cut or bruised .
All in<lse, a pyricloxal-phosphate-depclldent enzyme, which is responsible for conversion or alliin (3) to
allicin (2) has becn isolated in a fai rl y pure state from
29
AI/it/Ill tt/bCroSIIJ1/
and thc mecha ni sm or thi s
transformation has been establi shed 2XJo . Allinasc
breaks down alliin to 2-propcnesu lphenic acid (-t ).
SINGH et al.: ROLE OF GARLIC IN HUMAN & PLANT DISEASES
,..--"'-U<.W.!...................""-!.!..n. .
Allium sati vum_!---"E1"-'=<!H-'-'r.....
.t~.- -..
3 11
CH2 = CH - CH2 -S - S - CH2 - CH = CH2
1
CH2 = CH - CH2 i S - S - C1-I2 - CH = CH2
2
0
ElOH<OOC
~=-=-~'---.
CH2 = CH - CH2 - S - C1-I2 - CH - COOH
I
~
3
0
NH2
Fig. I-Variation in chemical constituents of garl ic due to change in isolat ion proced ure
CH2 = CH - CH2 - S - Cl-i2 - CH - COOH
I
~
3
CH2=CH-CH2-S-0H
0
NH2
/k:'
NH3
CH3-CO-COOH
4
2 x CH2 = CH - CH2 - S - OH
4
-H20
• CH2 = CH - CH2 - S - S - CH2 - CH = C H2
J.
2
0
Scheme I
ammonia and pyruvic ac id . Two molecules of
sulphenic acid then react together to give allici n by
loss of a molecu le of water (Scheme I).
Subsequent research has revealed that cysteine
sulfoxide fraction of garlic consists of 85% alliin (3)
along with 2% S-propylcysteine sulfoxide (5) and
13% S-methyl cysteine su lfox ide (6). Action of
allinase on this mixture affords, besides allicin,
allylmethanethi osulfinate (7), methyl methanethiosulfin ate (8) and other mixed or sy mmetrical
thi osu lfinates of th e ge neral structure, R-S(O)-S-R'
where Rand R' represent anyone of methyl, propyl
or all yl groups. Obviously all these thios ul finates are
found to be present in garl ic extract 3t . Lawso n &
coworkers.l2 have show n that in addition to
endogenous allii n (3), a reserve for alli in ex ists in the
precursor compound, y-glutamyl-S-allyl cystei ne (9)
and is present in a signifi ca nt quantity in freshlypicked garl ic cloves.
Analysis of garli c ex tracts)) using GC-MS revea led
the presence of mixture (2.4 : I) of two co mpounds
(79%) which have been proved to be 3-vi nyl-[4H]1,2-di thiin (10) and 3-v inyl-[6 H]- I,2-dithiin (11)
(Scheme II ), on the bas is of comprehensive spectral
analysis. Compou nds (10) and (11) are regarded as
dehydration prod ucts of all icin (2) and th eir formation
is considered to take place during gas chromatography
according to the eq uati on:
o
/N~
f
~C /S~ C02H
6
o
f
H3C /S ,S/ C~
8
9
C6 H IOS20
~
C(, HgS2 + H20
Mechanistically speaking, allicin first breaks down
into 2-propene sulfenic ac id (4) and thioacro lein (12).
While two molecul es of sulfenic acid regenerate a
molecule of allicin by loss of a molecule of water, two
molecul es of thi oacrolein undergo Diels-A lder
cyclisation to give cyclic 1,2 dithiins (Scheme II ).
Thioacroleins may also cycl ise in a different
manner to give 2-vinyl-[4H]-I,3-dithiin (13 ; Scheme
II ) which is al so found to be present in the fracti on.
Other volati le co mponents of garli c ex tract detected
by GC-MS analysi s have been proved to be allyl
alcohol (5.4%), methyl all yl disu lphide (1.2 %), diallyl
INDIAN J EXP. BIOL., APRIL 2001
312
disulphide (5.7%), dimethyl trisulphide (2.4%), allyl
methyl trisulphide (1.5 %), diallyl trisulphide (1.0%)
and sulfur dioxide JJ . Volatiles identified in garl ic oils
are suprisingly few and it has been considered that
investigation of volatiles using modern techniques
such as HPLC or capillary GC-MS would
considerably extend the list of components. In fact, a
temperature-programmed GC-MS analysis of garlic
essential oil has revealed a group of previously
unknown
cyclic
and
acyclic
organo-su lphur
compounds of which the compounds 14 - 17 are
particularly important because of their Jipo-oxyginase
inhibitory activity . Interestingly, most of these
compounds are generated upon heating pure samples
J4
of diallyl disulphide •
Allicin (2) undergoes self-decomposition even at
room temperature and decomposition products may
condense spontaneously to give a variety of
compounds. One of these compounds of importance is
ajoene (both E and Z varieties) which is well known
for its anti thrombotic properties. Taking a cue from
the self-condensation of methyl methane thiosulFinate
10 2,3,5-trithiahexane 5-oxide, the structure of ajoene
is settled as 4,5,9-trithiadodeca-1 ,6, II-triene-9-oxide
(18) and it is prepared by heating allicin (2) with a
mixture of water and acetone. Three molecules of
allicin give two molecules of ajoene (E and Z) and
one molecule of water. The mechanism of formation
of ajoenes from (2) has also been postuiatedZ6
(Scheme 1IJ).
Ajoene may also be prepared synthetically from
diallyl disulfide. Peracetic acid oxidation of diallyl
disulfide (1) gives allicin (2) which on refluxing with
aqueous acetone for 4 hr gives a mixture containing
ajoenes. Removal of nonpolar fract ion by washing of
this mixture with pentane and subsequent extraction
with CHzCl z yields mixture (4:1) of Z-ajoene (18a)
and E-ajoene (18b). The synthetic material is
indistinguishable from ajoene obtained from garlic.
When an ether-soluble fraction of methanolic
extract of garlic is stored in aqueous methanol for 4
days at 25°C and then successively extracted with
hexane and methylene chloride, ajoene has been
found to be present in the latter fraction. Hexanesoluble fraction contains several divalent sulfur
compounds and these are identified as diallyl
disulphide
(1),
diallyl
trisulphide,
diallyl
letrasulphide, allicin (2), and cyclic dithiin (10) and 2vinyl-[4H]- 1,3-dithiin (13). A compound isolated
from oil-macerated garlic by s ilica gel column
chromatography and preparative TLC, has been
identified as Z-4,5,9-trithiadeca 1,6-diene-9-oxide
(19) from NMR and MS analyse 5.
Essential oi l of garlic, an item of commercial
importance, is obtain ed mainly by steam distillation
of garlic and this product differs from garlic extract
prepared at room temperature. In place of allicin (2),
ajoenes (18) and a variety of dialkyl thiosulphinates,
known to be present in garlic extract, the essential oil
of garlic has been reported to contain a mixture of
diallyl and allyl methyl sulphides, disulphides and
trisulphides and other minor components J5 .
In addition to organosulphur compounds, peptides,
steroidal saponins, f1avones and other phytochemicals
12
11
10
12
s~
I s
- C
13
12
Scheme II
313
SINGH et al.: ROLE OF GARLIC IN HUMAN & PLANT DISEASES
15
~S'S~S""S~
16
17
Z - ajoene ( cis fonn)
a
E - ajoene ( trans fonn)
b
18
19
HO
20
Glc
0 11
2
21 : Rl=H. R =Gal-(1-44) p-Glc-(1-43)-p-Glc-(1-43)-p-Glc-(1-42)-Glc
1
22: R =OH . R2 = p-GaH1-44)-p-Glc
Scheme III
INDIAN J EXP. BIOL., APRIL 200 1
314
6
Cii
as by synthes is . In additio n, several other tri- and di peptides have also been isolated 36 . T he presence of
fl avono l, querceti n (20) has also been detected in
37
garli c . Reports of isolati o n of bioactive steroidal
saponi ns fro m garlic are there but the structures of all
of these sapo nin s could not be retri eved from the
rather obscure jo urnals20 .38.39. T wo of the saponins
repon ed earli er38, have been identified as (21) and
(22).
60
>
.~
~
C/)
;f!.
40
o
100
50
200
150
Concentration
(~g
250
300
ml")
Fig. 2-Effect of ajocne on the survival of second stage juveniles
of Heferodem cajalli.
have also been isolated fro m garlic. Seven dipeptides
iso lated from the concentrated aqu eous extract of
garli c have been identifi ed as Ser-Tyr, Gly-Tyr, PheTy r, As n-Tyr, Ser-Phe, Gl y- Phe and As n-Phe from
seq uence anal ys is, FAB mass spectral analysis as well
Effect of garlic 0 11 fU l/gi - Antifungal ac ti vity of
garlic started with the testing of garlic bulb ex tract
against so me fun gi. Appleton and T anse/ I fi rst used
garli c extract against some zoopathogenic fungi with
signifi cant g rowth inhibi tion. Later, Baro ne and
Tanselo have reported the isolati on, puri fication,
identifi catio n, synthes is and kin eti cs o f acti vity of the
inhibitory principl e of A. sativlfJl1 o n some Cal/dida
spec ies and postul ated a hypoth esis for its mode of
action. Effect of aqueous garlic ex tract on fun gi
causing mycotic di seases in human beings has also
22
been investigated . In a preliminary experiment,
fun gicidal effect of garlic leaf extract has been
24
reported by Mi shra and Di xit . Effect of aqueous
ex tract o f garlic leaf o n chickpea s.eeds and wilt and
stem rot of chickpea caused by Fusarium oxysp orlll11
SIXTH DAY
THIRD DAY
c:=J
Tota l hatche-
~ Dead
420
36 0
300
"-
i!
1
24
E
:J
Z
180
120
60
W
W+G
50
100
200
300
W
W+G
50
100
( onc(!ntr ation (pg IT1C1~
Fig. 3-Effect of ajoene on th e egg hatchi ng of Heferode m caj alli.
200
300
SLNGH
el
al.: ROLE OF GARLIC LN HUMAN & PLANT DISEASES
f. Sp. ciceri and Sclerotinia sclerotiorum has been
seen. It has been observed that germination of treated
chickpea seeds is delayed and seedlings arising from
them do not show wilt symptoms25 • Possible use of
garlic leaf extract in controlling plant diseases under
field conditions has been suggested.
Chicken infected with Candida albicans have been
41
successfully treated by garlic • Antifungal activity of
garlic has also been reported against seven species of
Candida and two species of Cryptococcus present in
42
human serum • Intravenous administration of garlic
extract inhibits the growth of Cryptococcus
43
neojormans present in plasma and cerebral fluid .
Effects of ajoene and other fractions of garlic
against Aspergillus niger and Candida aLbicalls have
been studied by Yoshida et al. 2. Out of six fractions ,
ajoene has shown strongest activity against the growth
of A. niger and C. albicans at a concentration of <20
Jlg/mL. Ajoene which is hi ghly inhibitory to C.
glabrata. C. tropicalis. Trichophyton mentagrophytes.
Tricosporon beigelii and Saccharomyces cerevisiae
has been found to be superior to allicin. Scanning
electron microscopic study has revealed severe
/
20
>-,6;
15 -
...,
(f)
(f)
>,
u
0
:...
Cll
.......c:
0
10
-
....
:v
.0
E
;::l
Z
<Q;
5
&
~:
h.
V
o V
Control
5
10
Concentration (ppm)
Fig. 4-Effect of ajoene on heterocyst fonnation in Nostoc
calcicola.
315
damage of cell wall of ajoene-treated hyphae and
conidia of A. niger and it has been postulated that like
other antifungal agents, ajoene also acts on the cell
2
wall of fungi •
Effect of ajoene on spore germination of some
plant pathogenic fungi, viz .. Alternaria solani. A.
tenuissima, A.
tntlcma.
ALternaria
species,
Colletotrichum species, Curvularia species, Fusarium
lini. F. oxysporum. F. semitectum and F. udum has
been noticed in vitro by Singh et al. 3 and it has been
observed that at 100 JlglmL concentration, spore
germination of some fungi is completely inhibited.
While working on the effect of ajoene on
44
Plzytophthora drechsleri f.sp. cajani, Singh et al.
have noticed differential response of this chemical on
different developmental stages of the fungus . For
instance, while mycelial growth is completely
inhibited at 25 Jlg/mL, maximum effect is observed
on sporangium formation and its germination at a
very low concentration (2.5 and 3.5 Jlg/mL).
Zoospore germination is affected at slightly higher
concentration (20 Jlg/mL). Treated zoospores produce
2-4 germ tubes and is not dose-dependent.
Fromthing and Bulmer23 have also noti ced
inhibitory effect of aqueous extract of garlic on
Cryptococcus neoJormans. Effect of garlic, its
constituents and commercial garlie supplement
45
products has also been studied on several fungi, viz .•
Trichophyton mentagrophytes. T. rubrum. T.
tonsurans. T. schoenleinii. Microsporum audouinii.
M. canis. Aspergillus jumigatus, Candida albicans
and C. stellatoidea and their efficacy is compared
with ketoconazole. Allicin is generally less effective
than ketoconazole, but is superior to latter against
Aspergillus Jumigatus and Candida spp. Ajoenes
(E&Z) are effective against C. stellato ides, but less
effective against C. albicalls. In general, the
antifungal effects of garlic compounds have been
correlated with their allicin content.
Effect of garlic extract as well as of ajnene in the
field and glasshouse has been observed by some
workers 46 -48 . Reimers et al. 46 noticed the effect of
ajoene on 10 phytopathogenic fungi including three
powdery mildews, viz., Oidium Lycopersicul11.
Sphaerotheca Juliginea and S. pinnosa var. roseae and
two yeasts . The results of in vitro tests indicate that
minimum inhibitory dose for growth depends on
organism, method and nutritional medium used and it
varies from 2-200 ppm. Cladosporiu111 JULVU111.
Verticillium dahliae and Erwinia amylo vora are the
INDIAN J EXP. BIOL.. APRIL 2001
316
47
most sensitive species. Singh et al. have studied the
effect of ajoene on conidial germination of Erysiphe
pisi as well as on powdery mildew development in
growth chamber. According to them only higher
doses of ajoene affect conidial germination and
production of mu ltiple germ tubes of E. pisi. The
post-inoculation treatment of pea leaves with ajoene is
as effective as commercially available fungicides
against the development of powdery mildew of pea.
46
The observations made by Reimers et al. and Singh
47
eL al.
indicate that ajoene acts not only on
germination of spores, but also on other stages of
49
fungaJ development or growt.h. Bitsch has reported
strong reduction in mildew (Sphaerotheca) on
cucumbers upon repeated spraying of garlic tea
(aqueous infusion of garlic).
Effect of garlic on bacteria-Several workers studied
the antibacterial activity of garlic extracts and
attributed this activity to diallyl sulphide, unstable
sulphur in alkyl polysulphides, a bacteriophage and
acrolein or some similar unsaturated aldehydes.
Phytoncides, a chemically undefined group of
27 5o
substances, have been reported to be antibacteriaI . .
Allicin, isolated from garlic by steam distillation of
crushed cloves has been found to be effective against
many gram-positive and gram-negative bacteria
belonging to Staphylococcus, Streptococcus, BaciLLus
and Vibri027. Mechanism of action of allicin has been
reported to be due to its ability to inhibit sulthydryl
contall1l11g enzymes 51 and RNA synthesis in
bacteria52 . Effect of a bacteriostatic concentration of
allicin (0.2 to 0.5 mM) on growth of SalmoneLLa
typhimurium shows a pattern characterised by (i) a lag
of approximately 15 min between addition of allicin
and onset of inhibi tion; (ii) a transitory inhibition
phase whose duration is proportional to allicin
concentration and inversely proportional to culture
density; (iii) a resumed growth phase which shows a
lower rate of growth than in uninhibited controls; and
(iv) an entry into a stationary phase at a lower culture
densi ty 52.
Kinetics of decline of populations of Salmonella
typhimurium and Escherichia coli in the presence of
freshly reconstituted dehydrated garlic powders has
53
been studied by Johnson and Vaughn . According to
them, there is a significant bactericidal property of
this powder on the above mentioned bacteria. Though
the use of garlic for the treatment of tuberculosis with
remarkable cure rate had been reported from Dublin
Hospital and New York city around the turn of
twentieth century, the concentration of the garlic
extract necessary for inhibition of Mycobacterium
tuberculosis and other strains of mycobacteria of 17
different species has been quantitatively assessed by
54
Delaha and Garaguci rather recemly and it has been
observed that minimum inhibitory concentration
(MIC) of garlic extract ranged from 1.34 to 3.35
mg/mL. Inhibitory activity of garlic extract against
some food pathogens, viz.. Staphylococcus aureus,
Sallllonella typhi, Escherichia coli and Listeria
mallocytogenes has been measured by turbidity
method and all the bacterial strains tested have been
4
inhibited by garlic • MIC of the essential oil of garlic
against L. fllallacytagenes is 1: 1280 (v/v units)55.
Like ajoenes, Z-I O-devinyl ajoene (19) also exhibits a
broad spectrum of antibacterial activity and its
activity is comparable to that of Z-ajoene (lSa); but is
superior to that of E-ajoene (lSb)5. This shows that
the replacement of allyl group by methyl group does
not alter the activity .
Effect of garlic 011 mites - Effect of garlic or garlic
products on mites has not been reported earlier. Only
recently acaricidal effect of ajoene has been studied
using spotted mite (TetrallYcllUs urricae Koch) and
complete mortality (100%) has been observed with
0.075 % solution (w/v) after 14 hr of treatment which
is comparable with conventionally used acaricides . At
lower concentration (0.05%), ajoene affects facundity
and juvenile survival (the survival rate being 37.56%
without affecting the
at this concentration
male:female ratio). The results suggest that ajoene,
besides having direct acaricidal effect, can also check
res urgence of the pest. Use of ajoene for the control of
T. urticae under field conditions is quite possiblel 6 .
Effect of garlic 011 Ilematodes - Effect of ajoene
(IS) on survival of second stage juveniles of
Heterodera cajani which causes root knot disease in
pigeonpea (Cajanus cajan (L.) Millsp.) has been
tested in our laboratory and it has been noticed that
survival percentage is reduced to zero at 300 Ilg/mL
of ajoene (Figs. 2,3).
Effect ,of garlic all blue-greell algae - In order to
explore the possibility of use of garlic or its products
for control of plant pathogens in the field conditions,
it is of paramount importance to know their effect on
non-target organisms, particularly, blue-green algae.
With this objective in view, the effect of ajoene on the
growth of Nastac calcicola has been studied in our
university (unpublished work) and it has been
observed that at the concentration of 6-20 ppm, the
growth of alga decreases up to 4th day of incubation
SINGH et al.: ROLE OF GARLIC IN HUMAN & PLANT DISEASES
and thereafter increases up to 14th day while lower
doses do not have any effect.
In another experiment, it has been observed that the
heterocyst formatio n is affected by ajoene. At I ppm,
the number of heterocysts sli ghtly decreases as
compared to control but at 5 and 10 ppm the number
increases significantly in compari son to control (Fig.
4). The use of ajoene against plant pathogens may ,
therefore, indirectly help in nitrogen fixation.
Effect of garlic on rats - With the objective of
finding out whether ajoene, a constituent of garlic, has
any effect on rats, it was injected intraperitonially to
female and male wister rats (unpubli shed work). In
female rats it was injected before and after
fertilization of the ovum at the rate of 10, 20 and 40
mg/kg body weight in sing le and multiple doses. In all
the experimental gro ups, the average number of live
fetuses was higher than those of corresponding
contro ls and the weight of ovaries at full term was
co mparatively increased. In pregnant female rats, at
full term, when the fetuses were removed, the weight
of viscera, like liver, spleen and kidney, was found to
be nearly similar to those of contro ls, whereas in
nonpregnant female rats , the weight of these viscera
was comparatively reduced . In male rats the weight of
li ver, spleen, kidney and testes was reduced in treated
groups as compared to control male rats.
Antioxidant activity of ga rlic - Garlic oil and some
of its components have been reported to inhibit
lipooxygenase ( LO), one of the enzy mes involved in
arachidonic acid metaboli sm which may be rel ated to
its biological
properti es 34 . Of the different
co mponents of garlic oil that shows significant LO
inhibitory activity, 2-(2',3'-dithia-5'-hexenyl)-3,4dihydro-2H-thiopyran (14), 3-(2',3'-dithia-5'-hexenyl)3,4-dihydro-2H-thiopyran (15), 6-methyl-4,5,8,9(16)
and
4,5,9,10tetrathi adodeca-I , ll-diene
tetrathi atrideca- l , 12-diene (17) display lC 50 values
toward soybean l5 -lipooxygenase enzyme within a
range of 8-37 11M, in comparison to 90 IlM shown by
E- and Zajoenes (18). A stru cture - activity
relationship study made by these authors using garlic
oil components and structurally related synthetic
model compounds reveals that LO inhibitory activity
increases with molec ular weight up to a certain point
and that changes made in the molecules by addition or
removal of unsaturation have only minor influence.
While LO inhibitory activity of garlic oil components
and homologues may be attributed primarily to
the abi lity
of these
lipophilic interactions,
organosulphur co mpounds to bind to LO iron merits
317
further study. Diallyl di sulphide (1) has been reported
to inhibit linear microsomal lipid perox idation
induced by doxorubicin, a well known anticancer
drug. As the oxidative injury caused by doxorubi cin
rest ricts its clinical use, the clinical efficacy of thi s
drug can be improved, if used in combination with
diallyl disulphide 56 • It is interesting to note that most
of the garli c oil components cou ld be obtained simply
by pyrolysis of diallyl di sulfide (1) and, the refore,
their presence is regarded as a consequence of heat
(duri ng steam di stillation) o n alli cin (2) and diall yl
disulfide (1). Obviously, any culinary procedure that
exposes garli c or garlic spiced food to heat generates
compound s with poss ible health benefits assoc iated
with anti ox idant or LO inhibitory activity.
Hypolipidel'nic. hypochoLesterolaemic. antithrombotic alld an tidiabetic properties of garlic - G arlic
preparations have been shown to lower the levels of
serum cholesterol and triglyceride through inhibition
of their biosy nthesis in liver and of oxidation of low
density lipoproteins 7•9 • The garlic constituent, alli in
(3) has hypolipidcmic8 activity and both alliin and Smethyl cysteine sufl oxide are endowed with
an tidi abeti c actions I2 . 13 . A combination of garlic and
ginger has been claimed to be su perior to garlic alone
4
in reducing serum lipids as well as blood glucose' . A
recent study reveals garlic protein to be similar in
composition to soya protein and it exhibits
57
hypolipidemic action • Effects of aspirin and garli c
powder supplementation on some clotting parameters
in rabbi ts show that garlic powder suppl ementation to
cholesterol rich di et is more advantageous than aspirin
alo ne because it has the beneficial effects on both
blood clotting and plas ma cholesterol level58 . Some
stero idal saponins isolated from fresh garlic bulbs also
exhibited inhibitory effect on blood coagulabilit/o.
Beneficial effects of garlic and its preparatio n
against atherosclerosis and coronary thrombosis are
considered to be due to thei r ability to lower serum
cholesterol 19 and inhibit aggregation of blood
platelets59 . Admini stration of aged garlic ex tract over
an extended period significantly reduces epine phrine
and collagen-induced platelet aggregation. While
early work re ports allicin (2), allyl methyl tri sulfide
and di allyl trisultide to be the active const ituents, 2vi nyl-[4H]-1 ,3-dithiin (13) and ajoene (18) have been
proved to be the potent anti thrombotic agents. Unlike
several other inhibitors of platelet aggregation, these
compounds are found to inhibit aggregation induced
60 61
by all known inductors · • In an effort to understand
the structure activity relationship. a comparative study
318
INDIAN J EXP. BIOL., APRIL 200 1
of antithrombotic activity of (E and Z)-ajoene and
synthetic homologues has been made and it has been
found that among the components of garlic oil , Zajoene (18b) is most active. The central carboncarbon double bond and di sulfide groups of ajoene
have been proved to be essenti al fo r activity. On the
bas is of thi s study it has been postulated that platelet
membrane sulphydryl groups participate in a
disulphide exchange reaction with ajoene and the
resultant alteration in the membrane prevents
aggregation. Apitz-Castro et at. 62 have established the
molecular basis of the anti platelet action of ajoene
and it has been shown that it directly interacts with
fibrinogen receptor. One of the re markable features of
ajoene is that its anti aggregatory effect is sy nergistic
with that of prostacyc1in, aspirin and indo methacin 63 .
Dipeptides isolated from concentrated aqueous
extract of garlic show angiotensin I-converting
enzyme inhibitory activity. These are considered to be
responsible, at least in part, for antihyperten sive
activity of garlic in animals and humans 6 . Efficacy of
garlic powder, extract or oi l in treatment of patients
has,
however,
been
with
hyperlipidemi a
questi oned 64 .65 . Efficacy of garli c principles on
hyperlipidemic patients may, however, differ
according to etiology of the disease and thi s aspect
needs further investigation.
Effect of ga rlic on A IDS (HIV) viruses all~
mala rial parasites - Apitz-Castro and coworkers 6have observed that ajoene inhibits pl atelet aggregati on
by allosterically inactivati ng the platelet integrin GP
lIb/III , and thi s prompted Tatarintaev et al. 66 to
propose that ajoene may also inhibit both adhesive
interacti ons and fu sio n of leucocytes and may
antagonize integrin-dependent processes in HIYinfected T-Iymphoblasts. Study has shown that ajoene
(18) inhibits platelet aggregat ion, HIY -medi ated
syncytia formation, rep lication of HIY-I (RF) in H9
ce lls and replication of HIY-I (LA Y-BRU). Based on
their results it has been suggested that ad mini strati on
of ajoene in combination with conven tiona l anti -HIY
drugs may be a promising approach for treatment of
AIDS.
Perez et af. 67 have investi gated anti Plasmodium
berghei activity of ajoene on ex perimental mice. They
observed inhibition of malarial parasite following
treatment with ajoene. However, when ajoene was
lI sed as a mixture with a noncllrative dose of
ch loroquine there was a complete prevention of the
deve lopment of parasitemia in mice. It is be lieved that
ajoene sy nergistically enhances antimalari al activity
of chloroquine against plasmodial paras ite. The actual
mechani sm o f action is not yet known.
Hepatoprotective activity and detoxification effects
of garlic - Garlic preparations and organosulphur
compounds present in garlic have been proved to be
responsible
for
protection
of liver against
. . 10 38
acetaminophen and bromobenzene tOXICity· .
Acetaminophen-induced acute cataract and other
occular ti ssue damage in mice could be prevented by
treatment with diallyl disulfide 0), preferab ly in
co mbination with N-acetyl L-cystine. The pl ausible
mechanism fo r thi s detoxifi cation effect has been
68
Cl9
postulated • Khan um and co-workers have observed
that long term feed ing of fresh garlic, or its oi l,
reduces the toxi c effects of azoxy meth ane, a
carcinogen.
Iron
nitrilotriacetate-med iated
nephrotoxicity is dimini shed by one week of oral
pretreatment of male albino wister rats with garlic
70
oi l • Most of the toxin s damage tissues by free radical
formation and garlic principles counter them by th eir
· actions
.
71
detoxi·fyl£lg
.
Allticancer and il1ll1lullolllodulalory activity of
garlic - Several ingred ients of our dietary sys tem are
known to have the potential against occurrence of
cancer in hu man beings. A variety f phytochemicals
present in edible fruits and vegetables has been
proved to inhibit carcinogenesis by ap propri ate
experimental studi es but evaluation of anticancer
acti vity of garlic, its ex tract and of its co nstitu ents has
been done recently despite the reference of garli c as
an effecti ve remedy fo r tumors in Codex Ebers, an
Egyptian Medical Papyrus dating back to around 1550
BC (Ref. 33,72). Kyo et al. 17 have studied the
antitumor activiti es of aged garlic ex tract and
observed that it stimulates the proliferation of mouse
spleen cells and the release of cywk ines , increases
K activities and enhances phagocytosis of peritonea l
macrophages. It also stimu lates the reactivity of
lymphocy tes in response to cy tok ines and mitogens.
Aoed
oarlic ex tract (a rich source of ajoene)
I:>
I:>
signi ficant ly inhibits the growth of sarcoma- 180
(all ogenic) and LLl2 lung carci noma (sy ngenic) cells
transplan ted into mi ce. Increased N K and ki ller
activities of spleen cells have been observed in
sarcoma- 180 bearing mice treated with aged garlic
extract. Aged garlic extract has thus been proved to be
a potent biological response modifi er in NK cell s and
T-Iymphocytes as it inhibits the growth of
transplanted tumors. A protein fraction from aged
garlic extract has also been reported to enhance
SINGH et al.: ROLE OF GARLIC IN HUMAN & PLANT DISEASES
cytotoxicity
and
lymphocytes 73.
proli fe ration
of
human
Direct cytotox ic effect of garlic and its extract has
been studi ed . Dietary (5 % in di et) and subcutaneous
admini stration of garlic extrac t have been re ported to
inhibit the g rowth of Mo rri s hepato ma 3924A in
74
rats . Inhibiti on of growth of murine transition al cell
carcinoma (MBT-2) in mi ce by intrape riton ea l
75
inj ecti on of garlic extract has been reported .
76
Belman
has shown inh ibitio n o f 7,
12dimeth ylbe nzanthrace ne-induced phorbo l-myri stateacetate pro moted skin papillo mas in mice by topical
applicat ion of garlic oil.
Diall y l sulphide and diall y l di sulphide have been
used to de termine inhibitio n of ary l amine Nacetyltransferase (NAT) activity in a human colon
tumor (adenocarcin oma) ce ll line and it has been
observed th at NAT acti vity is inhi bited by these
orga nosul phur co mpounds in a dose-de pe ndent
manne r77 • Modulati o n o f he patic drug- metabo li zi ng
enzy mes in rats treated with dialky l sulphides and
di sulph ides has been studi ed. The res ults suggest a
poss ible protective effect of d ia ll yl d isulfide o n the
first step of carc inogenes is via modul ati on o f enzy mes
78
in vo lved in carci noge n metabo li sm .
Garli c has also been fo un d to modul ate
immunological res ponse aga inst cancer. Mi ce inj ec ted
with aqueous garli c ex trac t-treated Ehrli ch carcino ma
cell s acq uire res istan ce against a chall e nge with
79
untreated tumor cell s.
In a human study,
adm in istrat ion of raw garli c (0.5 g per kg body wt/-.
day) for th ree weeks indu ced the inc rease of natural
killer cell activ ity by 140% (Ref. 80) . Diall y l
sul phi de, a cons titue nt of garl ic has been shown to
inhibit carcinogen induced nuclear damage in mouse
co lon epi theli al ce ll s a nd esophagea l cancer in
rats 1.82 . T he cancer preventi ve role of o rganosulphur
compounds of garli c has been reviewed by Sumi yoshi
and Wargovich 83 .
Essential oil of garlic know n to inhi bit
lipooxygenase and cycl ooxygenase enzymes has also
been fo und to inhibit mo use ski n tumor promo ti o n. O f
the di ffere nt com po nent s of garlic oi I tested , di-(Iprope nyl) su lph ide and ajoene have been found to
inhi bit both li pooxyge nase a nd tumor p ro m oti on 8~ .
Scharfenberg et at. 85 have tes ted the cytotox ic effect
of ajoene us in g huma n pri mary fibrob lasts (FS 4), a
permanent, no n-tu mo rgeni c cell line derived fro m
baby hamste r kidney ce ll s (B H K 2 1) a nd a
3 19
tumorogeni c lymphoid ce ll line deri ved from Burkitt
lympho ma (BJA-B) and observed the cytotoxic acti on
in the range 2-50 Ilg/mL de pe nding on the cell
density. Although the exact mechani sm o f cytotox ic
acti o n of aj oene is not known, it is assumed th at it
reacts w ith cellul ar SH fun cti o ns to exhibit its
cytotox ic activity. Z- aj oene (18a) has also been
shown to induce cell death by apoptos is in hu man
HL-60 pro myelocytic leuke mi a ce ll s, MGc-803
gastric mucoid adenocarcino ma cells and Mo lt-4T
86
ly mphocy te le ukemi a cell s .
The re are several firms now in Indi a and abroad
which prepare garlic capsul es that are recomm e nded
fo r the diseases of lungs, athe roscleros is, hi gh blood
pressure, gout, rheumati sm, asthm a, chroni c bronch ial
catarrh , intestinal co mpl ain ts and loss o f appeti te.
These capsules are also claimed to re new the blood,
clean it o f all impuriti es, regul ate diges ti on, re move
all parasites from the intes tines a nd c ure bacterial
in fec tion. Garlic fri ed in mustard o r coconut oil is an
excell ent anti septic suitabl e fo r applicati on in scabi es
and wound s. Its juice mi xed w ith sa lt is applied to
brui ses and is cl aimed to re li eve neuralgi a and
earache. The essenti al oil o f garl ic diluted with edi ble
o il is administered to dogs and other pe ts to expel
parasi tes fro m the di gesti ve trac t as we ll as from other
parts of the body . It has also bee n po inted out that
feed ing o f dogs with a teaspoonful o f fresh garlic
j uice twice a week keeps th e m free fro m paras ites.
In spite of be neficial effects o f garli c aga inst a
varie ty of di seases, it suffers fro m the di sadvantage of
producing bad breath . Inc identall y, the constituten ts
in hu man breath after ingesti on of garli c ha ve been
a nalysed
using
proto n-transfer-reacti on
mass
87
spectro metry by Taucher et at. and th e co mponen ts
have been ide ntifi ed as all y l methy l sulfi de,
all y l methy l di sulfide, diall y l d isul fide, d iall yl
trisul fide, d imethyl sul fide a nd aceto ne. Various
pre parati o ns and fo rmul atio ns of garli c are avail able
in the market but all of them may not be eq ually
useful fo r all kinds o f d iseases. It was observed by
Eric Bloc k30 th at the a nt ith ro mboti c principl es, ajoene
(18) and 2-v inyl-[4H ]-1 ,3-d it hi in (13) are virtu all y
absent in dehydrated garl ic powder, pills, o ils,
ex tracts and oth er proprietary garl ic preparati ons. It is
presumably due to thi s reason that in ma ny of th ese
preparations, essenti al o il of garlic obtain ed by steam
distill ati o ns is used . Again many of the vo latile
compounds know n to have li pooxygenase inh ib itory
or ant ioxida nt activity are present o nl y in essential
oi ls and in produ cts prepared by app li cati on of heat.
320
INDIAN J EXP. BIOL., APRIL 200 1
Thus, while essential oil of garlic lacks most of the
antibacterial and antithrombotic activity of garlic
extract prepared at room temperature, it appears to
possess equally interesting anti tumor and an ti oxidant
properties among other types of biological activities 34 .
Appropriate form ulati ons of garlic for the c ure of
different diseases are, therefore, a necessity. The
research on garlic may go a long way in f inding out
its newer therapeutic values, in validating the claims
made in different systems of medicine and also in
assessi ng its potential in plant di sease contro l.
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