Agriculture Reference
In-Depth Information
extract of the leaves has been found to contain an isoprenylated flavone, nimbaflavone, which was
characterized from its spectroscopic data to be 8,3′-diisoprenyl-5,7-dihydroxy-4′-methoxyflavone.237
237
Rutin and quercetin-3-rhamnoside are the main constituents of the polar fraction of the alcoholic
extract of the leaves.
Pharmacological Studies —
The extracts of
A. indica
have been shown to possess antipyretic,
analgesic, and anti-inflammatory activities.
238
The leaf decoction decreased the parasite count in
chloroquine-sensitive strains of
Plasmodium berghei
injected in mice and inhibited the growth of
P. falciparum
.
239,240
The antimalarial activity has been estimated to be equivalent to half the thera-
peutic dose of chloroquine sulfate on a dry weight basis. It had earlier been reported that the leaf
extract of
A. indica
showed no antiparasitic activity when tested (
in vitro
) against
Plasmodium ber-
ghei
drawn from infected albino rats.
239
Etkin, however, found that preincubation of plasmodium-
carrying blood with aqueous leaf extract of the herb led to lack of infection in mice.
241
Furthermore,
a field evaluation of patients using extracts of neem in self-medication for the treatment of malaria
showed that the drug does indeed have antimalarial activity.
242
The antimalarial activity of neem may be considered as established; what is unclear is the mech-
anism of its action. It does appear that the activity of this herb may not be due to a direct antipara-
sitic activity per se, but to a possible drug-catalyzed parasite-host interaction. Etkin and others have
studied the significance of the oxidation-reduction or “redox” status of red blood cells on parasites
and host cell biochemistry during malarial infection. They observed that increased levels of red
cell oxidation attendant on plasmodial infection was a consistent feature of malaria. The suggestion
has been put forward that while plasmodial parasites might be responsible for generating oxidants,
excessive oxidation may in the long run be detrimental to continued and successful malarial infec-
tion.
243-245
An approximate redox balance must therefore be maintained to ensure red cell integrity
and proper metabolic functioning, which is also essential for the development of the
Plasmodium
parasite. In effect, under a drug-induced physiological condition where excess oxidation occurs and
cannot be compensated, a variety of damaging effects will ensue, resulting in the destruction of
both red blood cells (hemolysis) and the malaria parasites.
It has been shown that an aqueous extract of
A. indica
leaf significantly increased the generation
of methemoglobin (by the oxidation of hemoglobin) and the conversion of compound GSH to its
oxidized counterpart (GSSG) in
in vitro
studies using normal red cell hemolysates in dilute hemo-
globin suspensions.
245
Similar oxidant effects on hemoglobin and GSH have been observed
in vivo.
The antimalarial activity of
Azadirachta
is therefore believed probably due to redox perturbation in
the form of the imposition of substantial oxidant stress during malaria treatment. The aqueous leaf
extract inhibits NADPH-cytochrome c (P-450) reductase activity in rats with a significant increase
in microsomal protein. The aniline hydroxylase activity and the phenobarbitone metabolism are also
enhanced by the administration of 400 mg/kg of the extract per os.
246
The ubiquitous flavonoids quer-
cetin-3-rhamnoside and quercetin-3-rutinoside (rutin) have been suggested as the active constituents.
Azadirachta
extract possesses modest
in vitro
antimalarial activity against drug-resistant
strains of
Plasmodium falciparum
.
247
It has been shown that two of the constituents of neem, quer-
cetin and the limonoid gedunin, exhibited activity against
P. falciparum
in vitro,
with IC
50
values
of 6.4 and 0.8 µg/ml, respectively.
248
It has also been suggested that the beneficial therapeutic
effects of the neem tree claimed by patients might be due to the anti-inflammatory and immuno-
modulatory activities of the plant.
249
There is extensive literature on other pharmacological proper-
ties of
Azadirachta,
and what is summarized in the following paragraph is only a random selection
from the major publications.
An aqueous extract of the leaves was found to act on isolated guinea pig ileum with a histamine-
like effect. It had a biphasic action on the blood pressure of a dog; following an intravenous injec-
tion, an initial increase in blood pressure was observed, followed by a prolonged decrease followed
by accelerated breathing.
250
It also exhibited hypoglycemic and antihyperglycemic effects in dogs;
when administered intravenously, it prevented both adrenalin- and glucose-induced hyperglycemia,