Integrative Medicine

Andrographis

Health Care Professional Information

Scientific Name
Andrographis paniculata
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Common Name

Indian Echinacea, Chuan Xin Lin, Kalmegh

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Brand Name

Kan Jang, Kold Kare, KalmCold, Paractin

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Clinical Summary

Andrographis paniculata is a bitter tasting annual plant prevalent in much of Asia. It is often used in combination with other herbs in traditional medicine to treat infectious diseases and associated fevers. It is also used in folk medicine to treat snakebites. The herb and its fractionated extracts have been studied for their antioxidant, antiviral, antibacterial, antiinflammatory, antihypertensive, antineoplastic, anti-ulcerogenic, and analgesic properties.
Dietary supplements containing Andrographis are promoted for cancer prevention, cancer treatment, and to counter the toxicity of chemotherapy in humans, but clinical evidence is lacking.
Formulations containing standardized extracts of andrographis are also marketed in the West as dietary supplements for cold and flu. Kan Jang, a standardized extract of Andrographis paniculata and Eleutherococcus senticosus, has been studied in manufacturer-sponsored clinical trials for relief of respiratory symptoms from cold and flu (1) (2) (3) (4).
An Andrographis extract was effective in treating the symptoms of upper respiratory infection (5)and another study found it as effective as mesalamine in treating ulcerative colitis (6). Andrographis extract also reduced rheumatoid factors and relieved rheumatoid arthritis symptoms (7)and has been studied in an early phase trial for male fertility (8).

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Purported Uses
  • Immunostimulation
  • Inflammation
  • Influenza
  • Colds
  • Cancer
  • HIV
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Constituents

Diterpenoid lactones: Andrographolides
(10) (11)

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Mechanism of Action

The active constituents of Andrographis paniculata are diterpenoid lactones known as Andrographolides (10) (11). Andrographolides inhibited IL-6 expression and IL-6-mediated signals in human prostate cancer cells, and suppressed tumor growth of DU145 human prostate tumors in mice (12); migration and invasion of human colorectal cancer Lovo cells through suppression of mRNA and matrix metalloproteinase (MMP)-7 protein levels (13); and MMP-2 activity in human HT29 colon cancer cells (14). An in vitro study found that andrographolide reduced the invasiveness of human A549 non small cell lung cancer (NSCLC) cells by suppressing the PI3K/Akt/AP-1 signaling pathway and inhibiting MMP-7 expression (15). Andrographolides were shown to cause apoptosis of human hepatoma cancer cells through the induction of c-Jun N-terminal kinase (16) and through the activation of caspases in vitro (17). They inhibited E-selection expression resulting in the decreased adhesion of gastric cancer cells to endothelial tissues (18). Andrographolides also inhibited tumor cell growth by stimulating cytotoxic T-lymphocyte production through IL-2 and IFN-gamma secretion (19) (25). An in vitro study also found that Andrographolide enhanced doxorubicin-induced cell death in several human cancer cell lines, mainly through JAK-STAT suppression (20). Andrographis paniculata extract exhibited selective antioxidant (21), antiviral (22), antimicrobial (23), and antimalarial (24) activities. In addition, they were shown to inhibit HIV-induced dysregulation of cell cycle and to increase CD4+ lymphocyte levels in HIV-1 patients (10). Andrographolides also demonstrated anti inflammatory activity by inhibiting nitric oxide production and cyclooxygenase-2 expression (26). In animal models, Andrographis demonstrated antioxidant (27) and anti-angiogenic (28) properties, and reduced cyclophosphamide induced toxicity by inhibiting proinflammatory cytokines (29) (30). In mouse hepatocyte, Andrographis induced mRNA expression of P450 subfamily members, CYP1A1 and CYP1A2, in a concentration-dependent manner (31). In other studies, Andrographis extract demonstrated a calcium channel inhibition effect that can cause smooth muscle relaxation and a decrease in blood pressure and heart rate (32), as well as relaxation of uterus (33). It also showed antiplatelet effects by inhibiting thrombin (34) and platelet activating factor (35). When given orally to mice, Andrographis extract was shown to neutralize snake venom (9).

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Pharmacokinetics

Andrographolide is readily absorbed orally. A single dose of 20mg resulted in maximum plasma levels in 2 hours and has a half-life of 6.6 hours. It is 55% protein bound in the plasma (36).

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Adverse Reactions

Common adverse effects include headache, fatigue, allergic reactions, lymphadenopathy, pain in the lymph nodes, nausea, diarrhea and altered taste (10) (11). Cases of rash or anaphylactic reaction have been reported (10).

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Herb-Drug Interactions
  • Cytochrome P450 substrates
    Andrographis extract inhibits 1A2, 2C9, 3A4 (37); some compounds of Andrographis were shown to induce CYP1A1 (39). These two properties can affect the intracellular concentration of drugs metabolized by these enzymes.
  • Anticoagulants and antiplatelet drugs
    Data from animal studies indicate possible inhibition of platelet aggregation (34) (35). But an animal study showed that andrographis extract does not interact with warfarin when used concomitantly (38). Patients taking anticoagulant or antiplatelet medications should use andrographis products with caution.
  • Chemotherapy drugs
    Andrographolide may have antioxidant effects (21). This can interfere with the actions of some chemotherapy drugs.
  • Blood pressure lowering drugs
    Andrographis may have additive hypotensive effect (32).
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Herb Lab Interactions

May elevate liver enzymes (6).

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Literature Summary and Critique

Tang T. et al. Randomised clinical trial: herbal extract HMPL-004 in active ulcerative colitis - a double-blind comparison with sustained release mesalazine. Aliment Pharmacol Ther. 2011 Jan;33(2):194-202.
This was an 8-week randomized, double-blind, parallel group study that compared the efficacy of an Andrographis extract (HMPL-04) to slow-release mesalamine granules in 120 patients with mild-to-moderate active ulcerative colitis. Assessments of clinical response were made at baseline and every 2 weeks, and colonoscopy was performed at baseline and at 8 weeks. Clinical response was defined as remission (no symptoms), partial remission (50% reduction in symptoms), or improvement (25% reduction in symptoms). Secondary endpoints were based on colonoscopy findings of inflammation and mucosal appearance, and histological improvement at biopsy. At week 8, remission was observed in 74% (p<0.001) and 28% of the HMPL-04 treated patients (n=60), and 71% (p<0.001) and 24% of the mesalamine-treated patients (n=60), respectively. But the differences were not statistically significant.
The authors concluded that HMPL-04 may be an effective alternative to mesalamine treatment for ulcerative colitis.

Saxena RC, et al. A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold) in patients with uncomplicated upper respiratory tract infection. Phytomedicine. 2010 Mar;17(3-4):178-85.
This randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy of an Andrographis extract in patients with uncomplicated upper respiratory tract infection (URTI). Patients (n=223) were randomized into groups to receive either Andrographis extract (n=112) or placebo (n=111). Patients self-evaluated and scored symptoms of cough, expectoration, nasal discharge, headache, fever, sore throat, earache, malaise/fatigue, and sleep disturbances using a Visual Analogue Scale. For both groups, mean symptom scores showed a significantly decreasing trend (p<0.05) from day 1 to 3, but from day 3 to 5, most of the symptoms in the placebo group either remained unchanged or worsened. However, in the Andrographis extract group, all symptoms (except earache) continued to show a significantly decreasing trend (p<0.05) from days 3 to 5. By day 5, improvement in overall symptom scores in the Andrographis extract group was significantly better than placebo (p<0.05), a decrease of 155.49+7.26 points vs 73.52+6.98 points, respectively. A few minor adverse effects were observed, with no significant difference between groups. The investigators concluded that Andrographis extract was effective in reducing the symptoms of URTI.

Burgos RA, et al. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. Clin Rheumatol. 2009 Aug;28(8):931-46.
This randomized, double-blind, placebo-controlled trial investigated the efficacy of Andrographis extract tablets (ParactinÒ) in patients (n=60) with active rheumatoid arthritis (RA). After a 2 week washout period, patients received either Andrographis extract (n=30) or placebo (n=30) for 14 weeks. The primary outcome measure was pain intensity, evaluated by a horizontal visual analog pain scale (VAPS). By week 14, joint pain intensity decreased in the treatment group, however this difference was not statistically significant compared to placebo. However, by week 1, the treatment group experienced a statistically significant decrease in other RA symptoms (tender joints [p=0.001], number of swollen joints [p=0.02], total grade of swollen joints [p=0.010], number of tender joints [p=0.033], total grade of swollen joints [p=0.01], total grade of tender joints [p=0.002], and health assessment quality survey [p<0.001]) compared to placebo. A significant reduction in rheumatoid factors IgA (p=0.101) and C4, (p=0.031) was also observed in the treatment group compared to placebo. The authors concluded that Andrographis may be a useful complementary treatment for RA, however a longer and larger trial is needed to confirm these results.

Spasov AA, Ostrovskij OV, Chernikov MV, Wikman G. Comparative controlled study of Andrographis paniculata fixed combination, Kan Jang and an Echinacea preparation as adjuvant, in the treatment of uncomplicated respiratory disease in children. Phytother Res 2004;18(1):47-53.
A three arm study was conducted comparing Kan Jang preparation with Immunal, an Echinacea-based preparation, as adjuvants to a standard regimen of warm drinks, mouth gargles and paracetamol prn in children aged 4 to 11 suffering from the common cold over 10 days. 130 children were randomized to receive either standard treatment, or standard treatment with either Kan Jang or Immunal. Adjuvant treatment with Kan Jang was more effective than Immunal. Cold symptoms were less severe in the Kan Jang group, particularly in the amount of nasal secretion and congestion reported. Kan Jang accelerated recovery time compared to Immunal which did not demonstrate the same efficacy. There was less use of standard medication in the Kan Jang group, and treatment was well tolerated.

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References
  1. Spasov AA, Ostrovskij OV, Chernikov MV, Wikman G. Comparative controlled study of Andrographis paniculata fixed combination, Kan Jang and an Echinacea preparation as adjuvant, in the treatment of uncomplicated respiratory disease in children. Phytother Res 2004;18(1):47-53.
  2. Kulichenko LL, Kireyeva LV, Malyshkina EN, Wikman G. A randomized, controlled study of Kan Jang versus amantadine in the treatment of influenza in Volgograd. J Herb Pharmacother 2003;3(1):77-93.
  3. Melchior J, Spasov AA, Ostrovskij OV, et al. Double-blind, placebo-controlled pilot and phase III study of activity of standardized Andrographis paniculata Herba Nees extract fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infection. Phytomedicine 2000;7(5):341-350.
  4. Gabrielian ES, Shukarian AK, Goukasova GI, et al. A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis. Phytomedicine 2002;9(7):589-597.
  5. Saxena RC, Singh R, Kumar P, et al. A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold) in patients with uncomplicated upper respiratory tract infection. Phytomedicine. 2010 Mar;17(3- 4):178-85.
  6. Tang T, Targan SR, Li ZS, et al. Randomised clinical trial: herbal extract HMPL-004 in active ulcerative colitis - a double-blind comparison with sustained release mesalazine. Aliment Pharmacol Ther. 2011 Jan;33(2):194-202.
  7. Burgos RA, Hancke JL, Bertoglio JC, et al. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. Clin Rheumatol. 2009 Aug;28(8):931-46.
  8. Mkrtchyan A, Panosyan V, Panossian A, et al. Aphase I clinical study of Andrographis paniculata fixed combination Kan Jang versus ginseng and valerian on the semen quality of healthy male subjects. Phytomedicine 2005;12(6-7):403-409.
  9. Samy RP, Thwin MM, Gopalakrishnakone P, Ignacimuthu S. Ethnobotanical survey of folk plants for the treatment of snakebites in Southern part of Tamilnadu, India. J Ethnopharmacol 2007.
  10. Calabrese C, Berman SH, Babish JG, et al. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytother Res 2000;14(5):333-338.
  11. Kligler B, Ulbricht C, Basch E, et al. Andrographis paniculata for the treatment of upper respiratory infection: a systematic review by the natural standard research collaboration. Explore (NY) 2006;2(1):25-29.
  12. Chun JY, Tummala R, Nadiminty N, et al. Andrographolide, an herbal medicine, inhibits interleukin-6 expression and suppresses prostate cancer growth. Genes Cancer. 2010 August 1; 1(8): 868-876.
  13. Shi MD, Lin HH, Chiang TA, et al. Andrographolide could inhibit human colorectal carcinoma Lovo cells migration and invasion via down- regulation of MMP-7 expression. Chem Biol Interact. 2009 Aug 14;180(3):344-52.
  14. Chao HP, Kuo CD, Chiu JH, et al. Andrographolide exhibits anti- invasive activity against colon cancer cells via inhibition of MMP2 activity. Planta Med. 2010 Nov;76(16):1827-33.
  15. Lee YC, Lin HH, Hsu CH, et al. Inhibitory effects of andrographolide on migration and invasion in human non-small cell lung cancer A549 cells via down-regulation of PI3K/Akt signaling pathway. Eur J Pharmacol. 2010 Apr 25;632(1- 3):23-32.
  16. Ji L, Liu T, Liu J, et al. Andrographolide inhibits human hepatoma-derived Hep3B cell growth through the activation of c-Jun N-terminal kinase. Planta Med 2007;73(13):1397-1401.
  17. Zhou J, Zhang S, Ong CN, Shen HM. Critical role of pro-apoptotic Bcl-2 family members in andrographolide-induced apoptosis in human cancer cells. Biochem Pharmacol 2006;72(2):132-144.
  18. Jiang CG, Li JB, Liu FR, et al. Andrographolide inhibits the adhesion of gastric cancer cells to endothelial cells by blocking E-selectin expression. Anticancer Res 2007;27(4B):2439-2447.
  19. Sheeja K, Kuttan G. Activation of cytotoxic T lymphocyte responses and attenuation of tumor growth in vivo by Andrographis paniculata extract and andrographolide. Immunopharmacol Immunotoxicol 2007;29(1):81-93.
  20. Zhou J, Ong CN, Hur GM, et al. Inhibition of the JAK-STAT3 pathway by andrographolide enhances chemosensitivity of cancer cells to doxorubicin. Biochem Pharmacol. 2010 May 1;79(9):1242-50.
  21. Shen YC, Chen CF, Chiou WF. Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved in its anti-inflammatory effect. Br J Pharmacol. Jan 2002;135(2):399-406.
  22. Wiart C, Kumar K, Yusof MY, et al. Antiviral properties of ent-labdene diterpenes of Andrographis paniculata nees, inhibitors of herpes simplex virus type 1. Phytother Res 2005;19(12):1069-1070.
  23. Singha PK, Roy S, Dey S. Antimicrobial activity of Andrographis paniculata. Fitoterapia 2003;74(7-8):692-694.
  24. Dua VK, Ojha VP, Roy R, et al. Anti-malarial activity of some xanthones isolated from the roots of Andrographis paniculata. J Ethnopharmacol 2004;95(2-3):247-251.
  25. Burgos RA, Seguel K, Perez M, et al. Andrographolide inhibits IFN-gamma and IL-2 cytokine production and protects against cell apoptosis. Planta Med 2005;71(5):429-434.
  26. Liu J, Wang ZT, Ji LL, Ge BX. Inhibitory effects of neoandrographolide on nitric oxide and prostaglandin E2 production in LPS-stimulated murine macrophage. Mol Cell Biochem 2007;298(1-2):49-57.
  27. Verma N, Vinayak M. Antioxidant action of Andrographis paniculata on lymphoma. Mol Biol Rep. Sep 5 2007.
  28. Sheeja K, Guruvayoorappan C, Kuttan G. Antiangiogenic activity of Andrographis paniculata extract and andrographolide. Int Immunopharmacol 2007;7(2):211-221.
  29. Sheeja K, Kuttan G. Protective effect of Andrographis paniculata and andrographolide on cyclophosphamide-induced urothelial toxicity. Integr Cancer Ther 2006;5(3):244-251.
  30. Sheeja K, Kuttan G. Ameliorating effects of Andrographis paniculata extract against cyclophosphamide-induced toxicity in mice. Asian Pac J Cancer Prev 2006;7(4):609-614.
  31. Jaruchotikamol A, Jarukamjorn K, Sirisangtrakul W, et al. Strong synergistic induction of CYP1A1 expression by andrographolide plus typical CYP1A inducers in mouse hepatocytes. Toxicol Appl Pharmacol 2007;224(2):156-162.
  32. Yoopan N, Thisoda P, Rangkadilok N, et al. Cardiovascular effects of 14-deoxy-11,12-didehydroandrographolide and Andrographis paniculata extracts. Planta Med 2007;73(6):503-511.
  33. Burgos RA, Aguila MJ, Santiesteban ET, et al. Andrographis paniculata (Ness) induces relaxation of uterus by blocking voltage operated calcium channels and inhibits Ca(+2) influx.Phytother Res 2001;15(3):235-239.
  34. Thisoda P, Rangkadilok N, Pholphana N, et al. Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation. Eur J Pharmacol 2006;553(1-3):39-45.
  35. Burgos RA, Hidalgo MA, Monsalve J, et al. 14-deoxyandrographolide as a platelet activating factor antagonist in bovine neutrophils. Planta Med 2005;71(7):604-608.
  36. Panossian A, Hovhannisyan A, Mamikonyan G, et al. Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human. Phytomedicine 2000;7(5):351-364.
  37. Pekthong D, Martin H, Abadie C, et al. Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolide. J Ethnopharmacol 2007.
  38. Hovhannisyan 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.
  39. Chatuphonprasert W, Remsungnen T, Nemoto N, Jarukamjorn K. Different AhR binding sites of diterpenoid ligands from Andrographis paniculata caused differential CYP1A1 induction in primary culture in mouse hepatocytes. Toxicol In Vitro. 2011 Dec;25(8):1757-63.
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Consumer Information

How It Works

BOTTOMLINE: Andrographis has been primarily studied for the treatment of colds, flu, and upper respiratory infections. It has also demonstrated possible anticancer effects in laboratory studies, but this has not been confirmed in humans.

Andrographis paniculata is used in traditional medicine to treat infectious diseases and fevers. Andrographis possesses antibacterial, antioxidant, anti-inflammatory, anticancer, and immunostimulating properties. Either alone, or in combination with other herbs, andrographis has been shown to reduce the duration and severity of upper respiratory infections such as those associated with the common cold or flu. Andrographis extract may benefit patients with ulcerative colitis. It also reduced symptoms of rheumatoid arthritis. However, patients should use caution before using this herb as it may interact with many drugs.

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Purported Uses
  • Colds and Flu
    Either alone or in combination with other herbs, andrographis may reduce the duration and severity of cold and flu symptoms in humans.
  • HIV
    In a trial of patients infected with HIV, andrographolides, the active ingredients in andrographis were shown to increase the number of lymphocytes, suggestive of an improvement in immune function.
  • Cancer

    Studies done in animals have shown antioxidant activities. It is unclear if this herb has beneficial effects in human as cancer treatment.
  • Rheumatoid Arthritis
    A small clinical trial showed Andrographis extract relieved rheumatoid arthritis symptoms. However, further study is needed to confirm this effect.
  • Ulcerative Colitis
    A clinical trial showed that Andrographis extract achieved a clinical response or full remission of ulcerative colitis. However, further study is needed to confirm these effects.
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Research Evidence

Ulcerative colitis
This was an 8-week randomized, double-blind, parallel group study that compared the efficacy of an Andrographis extract (HMPL-04) to slow-release mesalamine granules in 120 patients with mild-to-moderate active ulcerative colitis. Assessments of clinical response were made at baseline and every 2 weeks, and colonoscopy was performed at baseline and at 8 weeks. Clinical response was defined as remission (no symptoms), partial remission (50% reduction in symptoms), or improvement (25% reduction in symptoms). At week 8, remission was observed in 74% and 28% of the HMPL-04 treated patients, and 71% and 24% of the mesalamine-treated patients, respectively. But the differences were not statistically significant.
The authors concluded that HMPL-04 may be an effective alternative to mesalamine treatment for ulcerative colitis.

Respiratory infections
This randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy of an Andropraphis extract in patients with uncomplicated upper respiratory tract infection (URTI). Two hundred twenty-three patients were randomized into groups to receive either Andrographis extract or placebo. Patients self-evaluated and scored symptoms of cough, expectoration, nasal discharge, headache, fever, sore throat, earache, malaise/fatigue, and sleep disturbances using a Visual Analogue Scale. For both groups, symptom scores showed a significantly decreasing trend from day 1 to 3, but from day 3 to 5, most of the symptoms in the placebo group either remained unchanged or worsened. However, in the Andrographis extract group, all symptoms (except earache) continued to show a significantly decreasing trend from days 3 to 5. By day 5, improvement in overall symptom scores in the Andrographis extract group was significantly better than placebo. The investigators concluded that Andrographis extract was effective in reducing the symptoms of URTI.

Rheumatoid arthritis
This randomized, double-blind, placebo-controlled trial investigated the efficacy of Andrographis extract tablets (ParactinÒ) in 60 patients with active rheumatoid arthritis (RA). After a 2 week washout period, patients received either Andrographis extract or placebo for 14 weeks. By week 14, joint pain intensity decreased in the treatment group, however this difference was not statistically significant compared to placebo.  A significant reduction in rheumatoid factors was also observed in the treatment group compared to placebo. The authors concluded that Andrographis may be a useful complementary treatment for RA, however a longer and larger trial is needed to confirm these results.

Common cold
A three arm study was conducted comparing Kan Jang preparation with Immunal, an Echinacea-based preparation, as adjuvants to a standard regimen of warm drinks, mouth gargles and paracetamol in children aged 4 to 11 suffering from the common cold over 10 days. One hundred and thirty children were randomized to receive either standard treatment, or standard treatment with either Kan Jang or Immunal. Adjuvant treatment with Kan Jang was more effective than Immunal. Cold symptoms were less severe in the Kan Jang group, particularly in the amount of nasal secretion and congestion reported. Kan Jang accelerated recovery time compared to Immunal. There was less use of standard medication in the Kan Jang group, and treatment was well tolerated.

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Do Not Take If
  • You are taking chemotherapy drugs (Andrographis has antioxidant effects and can interfere with actions of chemo drugs).
  • You are taking drugs that are substrates of Cytochrome P450 (Andrographis may make some of these drugs less effective and may increase the risk of side effects of others).
  • You are taking blood pressure reducing drugs (Andrographis may have additive hypotensive effects).
  • You are taking anticoagulants and antiplatelet drugs (Andrographis may interfere with these drugs).
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Side Effects

Side effects are mild and infrequent including

  • headache
  • fatigue
  • allergic reactions
  • lymphadenopathy
  • lymph node pain, nausea, diarrhea
  • altered taste
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Last updated: February 13, 2013
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