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- Andrographis (Andrographis paniculata)
| Date:
09-15-2011 | HC#
051144-432
|
Re: Pharmacology and Clinical Effects of Andrographis
Akbar
S. Andrographis paniculata: a review
of pharmacological activities and clinical effects. Altern Med Rev. 2011;16(1):66-77.
Andrographis
(Andrographis paniculata) is widely
used in Unani and Ayurveda, traditional medicine systems of India. It is also a
traditional medicine in China, Hong Kong, the Philippines, Malaysia, Indonesia,
and Thailand. Aerial parts are most used, but the whole plant or roots also
have some uses. Traditional administration is by infusions, decoctions, or
powders, alone or with other herbs. Juice is given to infants with loose bowels
or poor appetite. Leaves and root are used to treat general debility,
dyspepsia, and advanced dysentery. Modern commercial preparations are usually
standardized extracts. Andrographis' bioactive compounds include lactones,
diterpenoids, diterpene glycosides, flavonoids, flavonoid glycosides, alkanes,
ketones, and aldehydes. The leaves have two bitter principles, andrographolide
and kalmeghin.
Many
conditions traditionally treated with andrographis are self-limiting. Unani
considers it aperient, anti-inflammatory, emollient, astringent, diuretic,
emmenagogic, carminative, tonic, antihelmintic, and antipyretic. It is said to "purify"
the blood. In China, it is considered bitter, cold, antipyretic, detoxicant,
anti-inflammatory, and detumescent, "reducing blood heat." It is
currently reported to have antibacterial, antifungal, antiviral, choleretic,
hypoglycemic, hypercholesterolemic, and adaptogenic effects.
Indian
systems of medicine use andrographis to stimulate and protect the liver, alone
or in multiherb preparations. One of the latter has been reported effective
against chronic hepatitis B virus. Few studies have used crude andrographis
extracts. Most have used andrographolide or other possible active constituents.
Hepatoprotective effects have been consistently reported. Animal studies have
found andrographolide as protective or more protective than silymarin from milk
thistle (Silybum marianum) against
numerous hepatic injuries, e.g., acetaminophen-, ethanol-, and carbon
tetrachloride (CCI4)-induced. Against the last, the crude extract
was more effective than andrographolide alone, indicating more than one
hepatoprotective compound. One study compared andrographolide, a methanol
whole-plant extract with an equal amount of andrographolide, and an
andrographolide-free methane extract against CCI4-induced liver
damage; all three improved rat liver histology. Andrographis' activity against
agents with different hepatotoxic mechanisms suggests broad hepatoprotectivity.
Large, multi-center clinical studies are warranted.
A
few studies have examined andrographis' effects on hepatic metabolic enzymes.
While it seems clear that the plant and/or its compounds are metabolically
active, variously inducing or inhibiting select microsomes, the evidence is
insufficient to draw conclusions about potential herb-drug interactions.
Studies are needed in healthy humans and in those using medicines that may be
pharmacokinetically altered (See Peer Reviewer's Note 1).
Andrographis
preparations have been used with good results reported for infectious and
non-infectious conditions from epidemic Japanese B encephalitis to viper bites.
Chinese studies report benefits in bacillary dysentery and gastroenteritis with
cure rates better than those of furazolidone or chloramphenicol. Andrographis has
been tested against some bacteria, viruses, and parasites. Crude powder lacked
antibacterial action. Aqueous extracts showed substantial antibacterial
activity, perhaps attributable to the combined effects of andrographolide and
arabinogalactan protein. Andrographolide, neoandrographolide, and
14-deoxy-11,12-didehydroandrographolide (DDA) are all active against herpes simplex
virus 1. An alcohol rhizome extract was active against malarial parasite Ascaris lumbricoides, halting in vitro growth
within 24 hours. A methanol extract significantly inhibited Plasmodium falciparum, as did four
xanthones from andrographis root. These xanthones also inhibited P. berghei in vivo, and Trypanosoma brucei, T. cruzi, and Leishmania
infantum.
Clinical
studies have concentrated on upper respiratory tract infections (URTIs) with most
finding andrographis safe and effective against symptoms (See Peer Reviewer's
Note 2). Two systematic reviews also found it safe and effective for simple
URTIs compared to placebo. Kan Jang, combining andrographis and eleuthero (Eleutherococcus senticosus), tested in
two parallel group randomized, double-blind, placebo-controlled trials (RCTs) in
Sweden, produced highly significant throat symptom relief in both compared to
placebo. An Armenian RCT found significant improvement in other symptoms. In a
Thai RCT, efficacy was comparable to acetaminophen. A major modern use of andrographis
is to prevent and treat the common cold. A three-armed RCT compared standard
cold treatment, standard treatment with Kan Jang, and standard treatment with
echinacea (Echinacea spp.) in
children 4-11 years of age. Those receiving Kan Jang had less severe symptoms,
faster recovery, and needed significantly less standard medication.
Andrographis
appears to be anti-thrombotic and may have benefits in cardiovascular disease. An
aqueous root extract dose-dependently decreased systolic blood pressure in vivo.
Another extract significantly inhibited ex vivo platelet aggregation in 63
patients with cardio- or cerebrovascular diseases in three hours, with even
more significant benefits at one week. Further study is needed of andrographis'
potential uses as suggested by pharmacological studies, such as for myocardial
infarction, ischemia, and after balloon angioplasty. Similarly, several
significant antihyperglycemic effects in diabetic rats with both water and
alcohol extracts demand further study. Improved glucose utilization and
increased insulin release have been proposed as mechanisms of action.
—Mariann
Garner-Wizard
Peer
Reviewer's Note 1:
It
should be mentioned that the results of in vitro studies on isolated cells
(which are valuable when the mechanisms behind the estimated pharmacological
activity are studied) could not have any clinical significance. Direct
pharmacokinetic studies of drugs sensitive to cytochrome P450 (CYP) enzymes provide
more convincing evidence regarding possible drug-herb interactions, when they
are applied concomitantly. Such a possibility of an interaction between
warfarin and Kan Jang (a combination
of Andrographis paniculata and Eleutherococcus senticosus) has been studied in rats
[Hovhannisyan et al., 2006].1 The authors found that Kan Jang had no
significant influence on the pharmacokinetics and pharmacodynamics of warfarin,
indicating there should also be no interactions of Kan Jang with other drugs
sensitive to CYP1A2, CYP2C9, and CYP3A4 enzymes (CYPs predominantly used in
metabolism of warfarin). Each day for 5 days, 2 groups of rats (n = 54) were
given an oral dose of Kan Jang (equivalent to 17 mg/kg andrographolide) or
water. Sixty minutes after dosing, the animals were administered 2 mg/kg
warfarin and at 0, 2, 4, 6, 8, 12, 24, 30, and 48 hours after that 6 animals
from each group were sacrificed, blood samples taken, and the concentration of
warfarin was measured by high-performance liquid chromatography (HPLC). The
concentration of warfarin in the Kan Jang treatment group was slightly higher
than in the control group during the first 6-7 hours following administration
and attained its maximum value earlier than control. However, the mean Cmax
values, elimination half-life, and mean residence time between the two groups
were not statistically significant. Prothombin time (PT) measurements (mean PTmax
and AUCPT 0-∞ [area under the concentration-time curve]) were not
statistically different between the two groups.
In a
similar study, extremely high doses of Andrographis
paniculata extract (APE) (1 and 2 g/kg of rats' body weight) and its major
component, andrographolide (AG) (77 and 154 mg/kg), were investigated on the
pharmacokinetics of theophylline (a substrate of CYP1A2 enzyme) [Chien et al.,
2010].2 The results indicated that the clearance of theophylline was
significantly increased and the AUC was reduced in both AG and APE pretreated
groups at low-dose theophylline administration (1 mg/kg). The authors suggest
that patients who want to use CYP1A2-metabolized drugs such as caffeine and
theophylline should be advised of the potential herb-drug interaction [Chien et
al., 2010].2 However, this precaution is based on the assumption
that patients have to take andrographis in doses at least 10-20 times higher
than it is normally prescribed for the treatment of common cold. The daily dose
of andrographolide in humans is about 1 mg/kg of body weight.
Peer
Reviewer's Note 2:
The results of a literature search of Clinical Efficacy of Andrographis in the
treatment of Acute Upper Respiratory Tract Infections using MEDLINE,
PubMed, Iowa Drug Information System, International Pharmaceutical Abstracts,
the Cochrane Library Database, MICROMEDEX, and the Natural Medicines
Comprehensive Database:
- Andrographis paniculata in
individual preparations – only 3 studies (two RCTs and one nonrandomized
trial),
- Kan Jang fixed combination
of Andrographis paniculata
and Eleutherococcus senticosus – 12 studies (ten RCTs and two
nonrandomized trials).
References
1Hovhannisyan AS,
Abrahamyan H, Gabrielyan ES, Panossian AG. The effect of Kan Jang extract on
the pharmacokinetics and pharmacodynamics of warfarin in rats. Phytomedicine. 2006;13(5):318-323.
2Chien CF, Wu YT, Lee
WC, Lin LC, Tsai TH. Herb-drug interaction of Andrographis paniculata extract and andrographolide on the
pharmacokinetics of theophylline in rats. Chem
Biol Interact. 2010;184(3):458-465.
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