Agriculture Reference
In-Depth Information
electron chain complexes, the resultant increase in nitric oxide (NO) in different parts of rats' brains was
prevented by simultaneous treatment with the water and ethanol extracts of
A. paniculata
or androgra-
pholide; the water extract exhibited greater antioxidant activity than the ethanol extract.
192
The antioxidant
activity of the aqueous extract on liver defense systems in lymphoma-bearing AKR mice has also been
investigated. The aqueous extract significantly increased the activities of catalase (CAT), superoxide dis-
mutase (SOD), and glutathione-S-transferase enzymes and reduced lactate dehydrogenase activity.
193
A
methanol extract inhibited formation of reactive oxygen species (ROS)
in vitro
and completely inhibited
carrageenan-induced inflammation. Andrographolide pretreatment significantly attenuates accumula-
tion of phorbol-12 myristate-13-acetate (PMA)-induced formation of ROS and N-formyl-methionyl-
leucyl-phenylalanine (fMLP)-induced adhesion of rat neutrophils.
194
A double-blind, placebo-controlled
study has shown that the king of bitters also had a reproducible effect on rheumathoid arthritis.
195
The antihyperglycemic and hypoglycemic properties of
A. paniculata
have been invesigated in
several animal models and controlled clinical studies. It appears that the water extract does not exert
any hypoglycemic effect on nondiabetic animals, whereas the methanolic extract and androgra-
pholide showed reduction in serum glucose of both diabetic and normal laboratory animals. Chronic
administration of the extract for 6 weeks showed no effect on the fasting blood glucose level but
significantly prevented orally administered glucose-induced hyperglycemia in nondiabetic rabbits
without affecting epinephrine-induced hyperglycemia. However, in chemically induced diabetic
laboratory animals, it significantly reduced the serum blood sugar levels.
187
It has been suggested
that the hypoglycemic effect of
A. paniculata
may be due to insulin release from pancreatic β-cells
through ATP (adenosine triphosphate)-sensitive potassium channels, similar to other insulinotro-
pic antidiabetic agents.
In vitro
experiments indicated that inhibition of alpha-glucosidase and
alpha-amylase enzyme could be the mechanism by which the ethanol extract of
A. paniculata
and
andrographolide produce a hypoglycemic effect. It is highly possible that the hypoglycemic and
antihyperglycemic activities of the extract and andrographolide may involve different mechanisms
in normal and diabetic conditions. Water extract seems to be a more suitable candidate for use as a
dietary supplement as it does not affect fasting blood glucose levels of nondiabetic animals.
For its use in the treatment of hypertension,
A. paniculata
aqueous extract produced a dose-
dependent fall in systolic blood pressure of both spontaneously hypertensive rats (SHRs) and
normotensive Wistar-Kyoto rats, with a corresponding significant decrease in plasma angiotensin-
converting enzyme (ACE) activity and lipid peroxidation in kidneys in extract-treated SHRs. It
was also observed that the decreases in ACE activity and lipid peroxidation were not significantly
altered in normotensive Wistar-Kyoto rats, which suggests that the hypotensive effect in hyperten-
sive and normotensive rats is not mediated through identical mechanisms.
187,196
Other studies have
supported this observation and validated the use of the aqueous extracts of
Andrographis
in the
treatment of cardiac insufficiency and myocardial ischemic-reperfusion injury.
On reproductive systems, the current evidence suggests that
A. paniculata
affects the productive
system in both male and female animals, but the results are too inconsistent, with some findings
directly contradicting others, to reach any definitive conclusion about the reproductive effects of
A.
paniculata
and its possible role in human fertility.
Toxicity —
Andrographis
is well tolerated in mild doses, and no acute toxicity has been reported
in clinical studies. The LD
50
of the alcohol extract and andrographolide is 1.8 g/kg and 11.46 g/kg in
mice, respectively. In a study of HIV-positive patients, a dose of 1500-2000 mg of andrographolides
was given daily for 6 weeks. Side effects led to the early discontinuation of the study despite some
improvements in CD4+ counts. Because of the inconsistency in the effect on the reproductive system,
it would be advisable for both men and women to avoid this herb during desired conception and for
women during pregnancy. Concurrent use of
A. paniculata
with a prescription should be carefully
monitored because of reports of possible drug-herb interaction. It was found that some of the com-
ponents of
A. paniculata
interact with theophylline and retard its elimination when theophylline was
administered at a high dose. The study suggested that patients who want to use CYP1A2-metabolized
