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Andrographis

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Scienti c Name
Andrographis paniculata, synonym Justicia paniculata.
Family: Acanthaceae.

Background
The leaves of Andrographis paniculata, an annual herb, have been used widely as part of Indian folk medicine and Ayurveda for
centuries. The Chinese and Thai herbal medicine systems have also incorporated this herb, renowned in these traditions mostly for
its "bitter" properties as a treatment for digestive problems and for a variety of febrile illnesses. More recently, this herb, in its
standardized extract form, has become popular in Scandinavia as a remedy for upper respiratory infections (URI) and in uenza.
Also known as: Andrographolide, Bhunimba, Bidara, Carmantina, Carmantine, Chiretta, Chirette Verte, Chirreta, Chuan Xin Lian,
Chuanxinlian, Creat, chinace d'Inde, Fa-Tha-Lai-Jone, Gubak, Herba Andrographitis, Indian Echinacea, Justicie, Kalmegh,
Kalamegha, Kariyat, King of Bitters, Kirta, Mahalita, Nabin Chanvandi, Poogiphalam, Roi des Amers, Sadilata, Sambilata, Shivaphala,
Supari, Takila, Vizra Ufar, Yavatikta.
History

People Use This For

Orally, andrographis is used for preventing and treating the common cold, in uenza, swine u, pharyngotonsillitis, allergies, sinusitis,
and to treat HIV/AIDS. Andrographis is also used orally for anorexia, atherosclerosis, snake and insect bites, bronchitis, cachexia,
prevention of cardiovascular disease, cholera, colic, diabetes, diarrhea, atulence, gastritis, gonorrhea, hemorrhoids, hepatomegaly,
drug-induced hepatotoxicity, and other hepatic disorders. Other uses include myocardial ischemia, jaundice, leprosy, leptospirosis,
malaria, familial Mediterranean fever, pharyngitis, pneumonia, pruritus, pyelonephritis, rabies, skin wounds, skin diseases, syphilis,
tuberculosis, tonsillitis, and ulcers. Andrographis is also used as an astringent, antiseptic, antidote, analgesic, antipyretic, antiin ammatory, antithrombotic, expectorant, anthelmintic, laxative, and tonic.

Safety
LIKELY SAFE ...when used orally and appropriately, short-term (2748, 31220, 31223, 31231). A speci c combination product
containing andrographis extract and Siberian ginseng (Kan Jang, Swedish Herbal Institute) has been safely used in short-term
clinical trials lasting 4-7 days (2744, 2748, 2773, 2774, 10441, 10795, 13016). One clinical trial used this combination product in
low doses for up to 3 months (2772).
CHILDREN: POSSIBLY SAFE ...when used orally and appropriately, short-term. Andrographis, in combination with other herbs, has
been used in children with apparent safety for up to one month (12381, 12382).
PREGNANCY: POSSIBLY UNSAFE ...when used orally. Andrographis is thought to have abortifacient effects (12); avoid using.
LACTATION: Insuf cient reliable information available; avoid using.

Effectiveness

See detailed evidence summary

POSSIBLY EFFECTIVE
Common cold. Some clinical research shows that taking a speci c andrographis extract, in combination with Siberian ginseng (Kan
Jang, Swedish Herbal Institute) orally, signi cantly improve symptoms of the common cold when started within 72 hours of
symptom onset. Some symptoms can improve after 2 days of treatment. It typically takes 4-5 days of treatment before there is
maximal symptom relief (2744, 2773, 2774, 5784, 10795, 12380). Some research suggests that this combination of andrographis
and Siberian ginseng relieves cold symptoms better than Echinacea or placebo in children (12381). Other clinical research suggests
that taking a speci c andrographis extract (KalmCold) 200 mg daily for 5 days increases the number of patients who respond to
treatment compared with placebo, and symptoms seem to be reduced by approximately two-fold (31222).
Preliminary clinical research suggests that taking andrographis (Kan Jang, Swedish Herbal Institute) prophylactically might decrease
the risk of developing a cold by about 50% after 2 months of continuous treatment (2772); however, more evidence is needed.
Pharyngotonsillitis. Some clinical research shows that high dose andrographis 6 grams daily is comparable to acetaminophen after 3
and 7 days of treatment for reducing fever and sore throat associated with pharyngotonsillitis (2748).
Ulcerative colitis. Preliminary clinical research suggests that taking andrographis extract 1200-1800 mg daily for 8 weeks reduces
symptoms of mild to moderate ulcerative colitis compared to placebo (31231). Preliminary clinical research also suggests that
taking andrographis extract 1200 mg daily for 8 weeks is as effective as mesalamine for reducing symptoms in patients with
ulcerative colitis (31223).
INSUFFICIENT RELIABLE EVIDENCE to RATE
Familial Mediterranean fever. Preliminary clinical research suggests that a combination of andrographis, Siberian ginseng,

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schisandra, and licorice (ImmunoGuard, Inspired Nutritionals) reduces the duration, frequency, and severity of attacks of familial
Mediterranean fever in children (12382).
In uenza. Preliminary clinical research suggests that patients with in uenza who take a speci c andrographis extract in
combination with Siberian ginseng (Kan Jang, Swedish Herbal Institute) have symptom relief more quickly compared to patients
taking amantadine. Patients who take this combination also seem to have a reduced risk of post-in uenza complication such as
sinusitis or bronchitis (10441).
Rheumatoid arthritis. Preliminary clinical research suggests that taking andrographis extract 90 mg for 14 weeks does not reduce
symptoms of rheumatoid arthritis when compared to placebo but does reduce symptoms when compared to pretreatment (31220).
More evidence is needed to rate andrographis for these uses.

Dosing & Administration

Adult
Oral:
General: In India, the andrographis herb is known as Kalmegh, green chiretta, or Maha-tita ("King of bitters") and is the
main ingredient of a common home remedy known as alui, which is used for fever and as a "bitter" for digestive
problems. Andrographis is also used in many Ayurvedic formulas, including SG-I Switradilepa, which is used to treat
vitiligo. Although not well substantiated in clinical trials, typical amounts of leaf preparation are 500-3,000mg taken
three times daily. According to secondary sources, for digestive problems, a typical dose of tea is one teaspoon of herb
per one cup of water, steeped for 5-10 minutes, taken with meals. According to secondary sources, a 300mg Kan Jang
tablet containing 4% andrographolides is taken four times daily to treat colds (for a total daily dose of 48mg
andrographolides).
Rheumatoid arthritis: A standardized extract of A. paniculata containing 30mg of andrographolides was given by
mouth three times daily for 14 weeks with a lack of bene t compared to placebo (31220).
Ulcerative colitis: 400mg of a standardized extract (HMPL-004) containing 8-10% andrographis by weight has been
used three times daily for eight weeks (31223). 1,200mg or 1,800mg of Andrographis paniculata ethanol extract daily
has been taken in three divided doses for eight weeks (31231).
Upper respiratory infection treatment: 3-6g (containing 48-500mg of the andrographolide constituents) divided into
three or four daily doses, has been taken by mouth for 4-10 days particularly for respiratory infections (31213, 2748,
31233, 12380, 31242, 2744, 12382, 13016). 100mg of Andrographis paniculata extract (KalmCold) twice daily after
dinner and breakfast for ve days has been used (31222). 1,200mg of Kan Jang daily has been taken (duration unclear)
(31213).
Upper respiratory infection prevention: 200mg of andrographis has been taken by mouth daily as two standardized
Kan Jang tablets for three months (31213, 31241). Use appears to be safe for up to two weeks. Higher doses may be
unsafe, leading to signi cant side effects (6767).

Children
General: According to secondary sources, in India, andrographis leaves and juice are mixed with cardamom, clove, and
cinnamon. These Ayurvedic formulas are used to treat colic and other stomach ailments in infants.
Upper respiratory infection treatment: 3-6g of andrographis, containing 180-360mg of andrographolide constituents,
divided into three to four daily doses, have been taken by mouth for seven days (2748).

Standardization & Formulation

Most clinical studies have tested products standardized to the andrographolide fraction. According to secondary
sources, some commercial products are standardized to contain 4% andrographilides. The most widely tested products
are the two Kan Jang preparations produced by Swedish Herbal Institute, one of which is a single herb preparation
containing the extract SHA-10 standardized to contain 5.25mg andrographolide and deoxyandrographolide per tablet,
and the other which is a combination product containing SHA-10 in combination with the Eleutherococcus senticosus
extract SHE-3 (31213, 2744).
A 6% w/w andrographolide has been used in a clinical study (2748, 12380, 31213). In other clinical research, 5-25mg of
andrographolide and deoxyandrographolide with or without 2% of eleutheroside B and eleutheroside E in each tablet
has been used (12380).
One study used a standardized extract, HMPL-004 (Hutchison Medipharma, Ltd), containing 8-10% andrographis by
weight (31223).
A puri ed dried extract of A. paniculata Wall ex Nees (Acanthaceae) in a 10:1 ratio (herbal drug:extract) has also been
used in research, and one tablet contained 30mg of total andrographolides (30% w/w), standardized to roughly 0.2%
w/w of neoandrographolide and 3% w/w of 14-deoxyandrographolide (31220).
In other research, the brand KalmCold has been used and contained >30.0% w/w andrographolide, >0.30% w/w
isoandrographolide, >1.0% w/w neoandrographolide, >0.30% w/w andrograpanin, >0.05% w/w skullcap avone I,
>0.05% w/w 7-O-methylwogonin, and =5.0% w/w 14-deoxy-11,12-didehydroandrographolide (31222).

Adverse Effects

Report an Adverse Reaction to Andrographis

General: According to available research, andrographis at commonly recommended

doses appears to be safe and well tolerated. Adverse effects reported in trials to date are mild, infrequent, and self-limiting.
However, most trials have been brief (two weeks or less), and the safety of long-term use remains unclear.

Cardiovascular
Dermatologic
Endocrine
Gastrointestinal
Genitourinary
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Hematologic
Immunologic
Musculoskeletal
Neurologic/CNS
Pulmonary/Respiratory
Other

Toxicology
Based on a Phase I dosing trial in HIV patients (6767), it appears that dose-related toxicity becomes common and is signi cant
at a dosage level between 5-10mg/kg, with effects including allergic reaction (two cases), fatigue (six cases), headache (six
cases), lymph node pain (three cases), lymphadenopathy (two cases), nausea (one case), diarrhea ( ve cases), and metallic
taste (six cases). There are three reports of anaphylactic reactions to andrographis documented in the literature (13016).
Long-term use of andrographis preparations (beyond two weeks) lacks suf cient evidence to comment on potential toxicity.

Interactions with Drugs

ANTICOAGULANT/ANTIPLATELETDRUGS
Interaction Rating =ModerateBe cautious with this combination.
Severity=High Occurrence=Possible Level of Evidence = D

Theoretically, concomitant use with andrographis might enhance therapeutic effects and increase the risk of bleeding (2758, 2759).
ANTIHYPERTENSIVEDRUGS
Interaction Rating =ModerateBe cautious with this combination.
Severity=Moderate Occurrence=Possible Level of Evidence = D

Theoretically, concomitant use with andrographis might enhance therapeutic effects and increase the risk of hypotension (2755,
2760).
IMMUNOSUPPRESSANTS
Interaction Rating =ModerateBe cautious with this combination.
Severity=High Occurrence=Possible Level of Evidence = D

Theoretically, andrographis might interfere with immunosuppressive drugs because of its immunostimulant activity (2766).
Immunosuppressant drugs include azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), daclizumab
(Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus
(Rapamune), prednisone (Deltasone, Orasone), and other corticosteroids (glucocorticoids).

Interactions with Herbs & Supplements

ANTICOAGULANT/ANTIPLATELET HERBS AND SUPPLEMENTS: Theoretically, concomitant use of andrographis with herbs that
have anticoagulant or antiplatelet activity might enhance therapeutic effects and increase the risk of bleeding (2758, 2759). These
include angelica, clove, danshen, garlic, ginger, ginkgo, Panax ginseng, horse chestnut, red clover, turmeric, and others.
HERBS AND SUPPLEMENTS WITH HYPOTENSIVE EFFECTS: Theoretically, concomitant use with andrographis might enhance
therapeutic effects and increase the risk of hypotension (2755, 2760). Some of these products include andrographis, casein
peptides, cat's claw, coenzyme Q-10, sh oil, L-arginine, lycium, stinging nettle, theanine, and others.

Interactions with Foods

None known.

Interactions with Lab Tests

None known.

Interactions with Diseases

AUTOIMMUNE DISEASES: Andrographis might have immunostimulant effects (2766). Theoretically, andrographis might
exacerbate autoimmune diseases by stimulating immune activity. Advise patients with autoimmune diseases such as multiple
sclerosis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or others to avoid or use andrographis with caution.
BLEEDING CONDITIONS: In vitro and in vivo evidence suggests that andrographis may inhibit platelet aggregation (2758, 2759).
Although this has not been observed in humans, theoretically, andrographis may increase the risk of bleeding in patients with
bleeding disorders. Use with caution.
HYPOTENSION: Animal research suggests that andrographis might reduce blood pressure (2755, 2760). Although this has not been
observed in clinical research, theoretically, andrographis might increase the risk of blood pressure becoming when used by patients
with hypotension. Use with caution.

Mechanism of Action
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Constituents: Andrographolide, a diterpene lactone compound, is believed to be the principal active agent (31214). Other
constituents include a,-unsaturated ?-butyrolactone moiety (31227), bisandrographolide A (31215),
dehydroandrographolide succinate (DAS) (31230), neoandrographolide, andrographiside, 14-deoxy-11,12didehydroandrographolide, deoxyandrographolide, and arabinoglycan proteins. 5-Hydroxy-7,8-dimethoxy (2R)- avanone-5O-beta-D-glucopyranoside, 5-hydroxy-7,8,2',5'-tetramethoxy- avone-5-O-beta-D-glucopyranoside, andrographic acid, and
andrographidine A have also been isolated from Andrographis paniculata (31216). The aerial portion of andrographis,
contains a large number of lactones, diterpenoids, diterpene glycosides, ?avonoids, and ?avonoid glycosides (31224).
General: According to in vitro research, derivatives of andrographolide have inhibitory activity of proprotien convertases,
which are essential for processing protein precursors into bioactive mature products that are also involved in such
pathologies as cancer, Alzheimer's disease, obesity, and bacterial and viral infections (31228).
In an in vitro study using mouse cells, bisandrographolide A extracted from Andrographis paniculata potently activated
transient receptor potential 4 (TRPV4) channels with an EC50 of 790-950nm (31215).
Analgesic effects: In vivo research in mice has shown a lack of analgesic activity using a hot plate test, but did show a
signi cant analgesic effect (p<0.05) in acetic acid-induced writhing (31240).
Antibacterial effects: A research group performed three separate studies to assess the antibacterial effect of Andrographis
paniculata (Burma) Wall. ex Ness (AP) (2764). The rst study lacked any antibacterial activity when using a direct assay of AP
against Salmonella, Shigella, E. coli, group A streptococci, and S. aureus, even in a solution containing 25,000mg/L of crude AP
powder. A second study also found a lack of antibacterial activity based on serum assays using Bacillus spores and ve strains
of each pathogen (Shigella, Salmonella typhi, S. aureus and gr. A streptococci) from 10 healthy individuals that were randomly
administered a single oral dose of 1-6g of AP stem and leaves. Lastly, 0.12-24g/kg of AP were fed to rats daily for six months
and antibacterial activity was reported as undetectable after lung and liver tissue was placed on bacteria containing cultures.
Anti-HIV effects (proposed): 14-dehydroandroandrographolide succinic acid monoester (DASM) may inhibit proteolytic
cleavage of the HIV envelope glycoprotein, thus acting as a protease inhibitor for HIV (in vitro) (31239). In a Phase I dosing
trial in HIV positive patients, investigators reported a signi cant rise in CD4 counts at a dose of 10mg/kg/day; however, this
dose was not well-tolerated by most patients with adverse reactions that included multiple cases of allergic reactions, fatigue,
headache, painful lymphadenopathy, nausea, and diarrhea (6767).
Anti-in ammatory: Andrographolide inhibits NK-kappaB binding to DNA in vitro, reducing expression of a variety of
in ammatory proteins, including COX-2 (31210, 31227). In rat neutrophils, it also appears to exert anti-in ammatory action
via a decrease in gene expression required for neutrophil adhesion and transmigration (31203). In mice with experimental
autoimmune encephalomyelitis, an in ammatory demyelinating disease that serves as an animal model for multiple sclerosis,
andrographolide signi cantly inhibited T-cell and antibody responses to myelin antigens (31209). Andrographolide also
reduced immune-stimulated nitric oxide production in vitro, either through accelerated degradation of the iNOS nitric-oxide
producing protein or by suppressing expression of this protein (31238, 31200). Neoandrographolide has also been shown in
vitro and ex vivo to suppress nitric oxide synthesis in mice (31204). Other in vitro studies suggest that the antiin ammatory/anti-apoptotic action may be mediated by a decrease in free radical production through inhibition of release of
cytochrome C by mitochondria (31208). Andrographolide may also have mast-cell stabilizing activity in rats.
In vitro, methanolic and hydroalcoholic extracts from the leaves and other parts of Andrographis paniculata showed that both
extracts exhibited inhibitory action on all the in ammatory mediators except PGE2 and TNF-alpha (31229). Additionally,
hydroalcoholic extracts from both leaves and other portions showed inhibitory action on IL-1 beta, TXB2, but lacked any
effect towards other mediators. Extracts with successive water also lacked inhibitory effects for all mediators.
Antiplatelet effects: According to in vivo and in vitro research, andrographolide possesses antiplatelet activity by being a
platelet-activating factor antagonist (31232).
Antipyretic effects: In vivo research showed signi cant antipyretic activity (p<0.05) in Brewer's YeastTM-induced pyrexia in
rats (31240).
Antineoplastic effects: Several in vitro studies have indicated that andrographolide has anticancer effects (31212, 31211,
31216). Speci cally, andrographolide and isoandrographolide have ED50 values of 6.5 and 5.1mcg/mL, respectively, when
added to KB cells (31216). Based on their experience with andrographolide and human cancer cells, Zhou et al. postulate that
andrographolide may induce apoptosis in human cancer cells via activation of caspase 8 in the extrinsic death receptor
pathway and subsequently with the participation of mitochondria (31212).
According to in vitro research, the ethanol extract of Andrographis paniculata signi cantly inhibited growth of human acute
myeloid leukemic HL-60 cells with an IC50 value of 14.01mcg/mL after 24 hours of treatment (31211).
According to a review, the anticancer mechanisms for andrographolide include inhibition of cyclins and cyclin-dependent
kinases, metalloproteinases and growth factors, transcription activators and Janus tyrosine kinases-signal transducers,
signaling pathways of phosphatidylinositol 3-kinase and NF-?B, suppression of heat shock protein 90, and the induction of
tumor suppressor proteins p53 and p21 (31227, 31226).
Cardiovascular effects: Studies in dogs have shown a decrease in myocardial reperfusion injury following ischemic events,
possibly mediated by a decrease in the level of free radicals generated by ischemia (31236). Studies in rabbits report that
andrographolide may help reduce restenosis after angioplasty by reducing the secretion of endothelial growth factors that
contribute to restenosis (2782). Rat studies show a possible hypotensive effect as well (31237).
Gastrointestinal effects: In vivo research in mice showed signi cant anti-ulcerogenic activity (p<0.05) in aspirin-induced
ulcerations (31240).
Genitourinary effects: Animal studies have shown possible decreased spermatogenesis by preventing cytokinesis of dividing
spermatogenic cell lines (31201)
Hematologic effects: In vitro studies have demonstrated an antithrombotic effect via inhibition of PAF-induced platelet
aggregation (2759).
Hepatoprotective effects: In mouse models of chemically-induced hepatotoxicity, andrographolide, neoandrographolide, and
andrographiside all reduced levels of lipid peroxidation, glutathione depletion, and enzymatic leakage, possibly through
antioxidant effects (2778). A choleretic effect was seen in rats and guinea pigs with paracetamol-induced liver damage (2761).
In addition, according to several reviews of available research, derivatives of andrographis, including andrographolide and
neoandrographolide possess potent hepatoprotective activity (31225, 31217).
Hypoglycemic effects: Studies in rabbits suggest that a water extract of andrographis can prevent hyperglycemia induced by
oral glucose administration, probably through an effect on glucose absorption from the gut (31235); there is no effect on
fasting blood sugar levels with chronic administration of the extract. A rat study showed increased digestion and absorption
of carbohydrates in rats after the administration of andrographolide. This is believed to be mediated by activation of intestinal
disaccharidases (31234). Recent animal studies report that there may also be an increased glucose metabolism in rats treated
with andrographolide (31207).
In vitro research has found that a Modi ed Kreb-Ringer Solution (KRB) containing glucose and Andrographis paniculata
(Sambiloto), exhibited greater insulin releasing effects as compared to glucose alone after a twenty minute incubation of
BRIN-BD11 in KRB-3 containing 16.7mM glucose plus 0.625-5 mg/mL A. paniculata (p=0.002 to p<0.001, respectively) and
BRIN-BD11 in KRB-1 containing 1.11mM glucose plus 0.625-10mg/mL A paniculata (p=0.019 to p<0.001, respectively)
(31218).
Immunomodulatory properties: Andrographolide alone and the standardized andrographis combination product Kan Jang
were found to increase the formation of TNF-alpha and Beta2MG in vitro; the xed combination was more effective than the
andrographolide alone (31205). In vitro andrographolide also increased TNF-alpha production and cytotoxic activity of
lymphocytes against certain cancer cell lines, as well as demonstrating potential direct anticancer activity by induction of cellcycle inhibitory protein p27 and decreased expression of cyclin-dependent kinase (31206).
According to a review, the formulation Kan Jang possesses immunomodulatory activity of certain cytokines (31221).

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Pharmacokinetics
Absorption: In humans, maximum plasma levels of andrographolide after a typical therapeutic dose of 20mg (four tablets of
Kan Jang preparation) are reached after 1.5-2 hours (31202).
Distribution: After an 80, 160, and 320mg injection of dehydroandrographolide succinate (DAS), an extract of Andrographis
paniculata (Burm f) Nees, in healthy Chinese volunteers, the average C(max) was 4.82, 12.85, and 26.90mg/L, respectively,
and the average AUC(0-12) was 6.18, 16.95, and 40.65mg/L hourly, respectively (31230).
Metabolism: Andrographolide appears to be intensively metabolized in a dose-dependent fashion. Renal excretion does not
play a signi cant role in its elimination. The half-life of andrographolide is approximately 6.6 hours (31202).
Four metabolites and andrographolide administration were isolated from human urine and identi ed using chromatography
and mass spectra techniques (31219).
Excretion: After an 80, 160, and 320mg injection of dehydroandrographolide succinate (DAS), an extract of Andrographis
paniculata (Burm f) Nees, in healthy Chinese volunteers, the average T(max) was 0.94-1.0 hour with a half-life of
approximately 1.51-1.89 hours. Approximately 10.1-15.5% of the intravenous DAS dose from all three groups was excreted
unchanged in urine within 24 hours, and more than 90% of unchanged DAS was excreted between 0-4 hours (31230).

Evidence Table / Discussion

See detailed Evidence Summary

References
See Monograph References
This monograph was last reviewed on 1/6/2012 and last updated on 2/13/2015. Monographs are reviewed at least once per year. If
you have comments or suggestions on something that should be reviewed or included, please tell the editors. For details about our
evidence-based approach, see our Editorial Principles and Process.

2016 Therapeutic Research Center

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