Andrographis

• How It Works

  Andrographis has been mostly studied for the treatment of colds, flu, and upper respiratory infections. Lab studies suggest possible anticancer effects, but this has not been confirmed in humans.

  Andrographis paniculata is used in traditional medicine to treat infectious diseases and fevers. Andrographis exhibits antibacterial, antioxidant, anti-inflammatory, anticancer, and immunostimulating properties. Either alone or in combination with other herbs, andrographis has been shown to reduce 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.

• Purported Uses
  • Colds and Flu
    Either alone or in combination with other herbs, andrographis may reduce duration and severity of cold and flu symptoms.
  • HIV
    In a small trial of patients infected with HIV, andrographolides, the active ingredients in andrographis, increased the number of lymphocytes, suggesting improved immune function. However, the trial was interrupted midway due to an adverse event.
  • Cancer
    In vitro and animal studies suggest antioxidant and anticancer properties. However, it is unclear if this herb has any beneficial effects in humans as a cancer treatment.
  • Rheumatoid arthritis
    A small clinical trial showed that andrographis extract relieved rheumatoid arthritis symptoms. However, further study is needed to confirm this effect.
  • Ulcerative colitis
    In a clinical trial of patients with ulcerative colitis, use of andrographis extract resulted in clinical response or full remission. However, further study is needed to confirm these effects.
• Do Not Take If
  • You are taking chemotherapy drugs: Andrographis has antioxidant effects and may interfere with the actions of chemotherapy drugs.
  • You are taking drugs that are substrates of cytochrome P450: Although clinical relevance is yet to be determined, andrographis may make some of these drugs less effective and may increase the risk of side effects of others.
  • You are taking blood pressure-lowering drugs: Andrographis may have additional hypotensive effects. A study in healthy humans showed transient reductions in blood pressure when taking the suggested dose for common cold and respiratory tract infections.
  • You are taking anticoagulants or antiplatelet drugs: Some lab studies suggest andrographis may interfere with these drugs.
  • You are taking drugs that are substrates of UDP-glucoronosyltransferase (UGT) 2B7: Lab studies suggest andrographolide derivatives may increase the side effects of drugs metabolized by this enzyme.
• Side Effects
  • Headache
  • Fatigue, dizziness
  • Allergic reactions, hypersensitivity, skin rash
  • Lymph node pain or swelling
  • Nausea, diarrhea, vomiting
  • Altered taste

  Case reports

  • Anaphylaxis and allergic reactions: Caused by several different A. paniculata preparations. Methanol extracts may increase this allergy risk.
  • Anaphylactic reaction: In an HIV patient on-study during week 4
  • Enlarged lymph nodes: With very high doses
  • Acute kidney injury: Following intravenous administration of andrographolides. Symptoms included flank pain, decreased urine output, and nausea or vomiting
• Brand Name

  Kan Jang, Kold Kare, KalmCold, Paractin

• Scientific Name

  Andrographis paniculata

• 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. Andrographis is promoted in supplemental form for cancer prevention, cancer treatment, and to counter chemotherapy toxicity in humans. Formulations containing standardized extracts of andrographis are also marketed for colds and flu.

  In vitro and animal studies indicate that andrographis has antimicrobial ⁽²³⁾, anti-inflammatory ⁽²⁶⁾, antioxidant ⁽²⁷⁾, anticancer ^(13) (18), and antimetastatic ⁽¹⁵⁾ properties.

  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 found useful in treating symptoms of upper respiratory infection ⁽⁵⁾. A few meta-analyses suggest possible benefit with A. paniculata to reduce cough frequency and severity ^(45) (46).

  Andrographis has also been evaluated for ulcerative colitis. In one trial, those receiving A. paniculata extract at higher doses were more likely to achieve a clinical response compared with placebo ⁽⁴⁷⁾. Another study found it as effective as mesalamine in treating ulcerative colitis ⁽⁶⁾.

  In other preliminary studies, andrographis extracts reduced rheumatoid factors and relieved rheumatoid arthritis symptoms ⁽⁷⁾. In patients with modest hypertriglyceridemia, a high-dose andrographis extract reduced triglyceride levels in a manner comparable to gemfibrozil ⁽⁴⁸⁾.

  In preclinical cancer studies, andrographolide exhibited activity against multiple myeloma stem cells ⁽⁴⁹⁾, reversed 5-FU resistance in human colorectal cancer cells ⁽⁵⁰⁾, and modulated P-glycoprotein-mediated multidrug resistance ⁽⁵¹⁾.

• Purported Uses
  • Immunostimulation
  • Inflammation
  • Colds, flu
  • Cancer
• Mechanism of Action

  The active constituents of andrographis are diterpenoid lactones known as andrographolides ^(10) (11). They exhibit anti-inflammatory activity by inhibiting nitric oxide production and cyclooxygenase-2 expression ⁽²⁶⁾. In mouse hepatocytes, 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 decrease blood pressure and heart rate ⁽³²⁾, as well as relaxation of the 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⁾. In addition, andrographolides inhibit HIV-induced dysregulation of cell cycle and increased CD4+ lymphocyte levels in HIV-1 patients ⁽¹⁰⁾.

  Andrographolides also demonstrate anticancer effects in preclinical studies. Activity against multiple myeloma cells may occur via TLR4/NF-kappaB signaling pathway inhibition ⁽⁵²⁾. In human colorectal cancer cells, reversal of 5-FU resistance was attributed to elevated BAX expression ⁽⁵⁰⁾. In addition, migration and invasion was inhibited through suppression of mRNA and matrix metalloproteinase (MMP)-7 protein levels ⁽¹³⁾, while MMP-2 activity was also identified ⁽¹⁴⁾. Inhibition of IL-6 expression and IL-6-mediated signals occurs in human prostate cancer cells ⁽¹²⁾. In non-small cell lung cancer cells andrographolides reduced invasiveness by suppressing the PI3K/Akt/AP-1 signaling pathway and inhibiting MMP-7 expression ⁽¹⁵⁾. Apoptosis in human hepatoma cells occurred via c-Jun N-terminal kinase induction ⁽¹⁶⁾ and caspase activation ⁽¹⁷⁾. Decreased adhesion of gastric cancer cells to endothelial tissue was attributed to inhibition of E-selection expression ⁽¹⁸⁾. Inhibition of tumor cell growth may also occur by stimulating cytotoxic T-lymphocyte production via IL-2 and IFN-gamma secretion ⁽¹⁹⁾. Andrographolides also enhanced doxorubicin-induced cell death in several human cancer cell lines, mainly through JAK-STAT suppression ⁽²⁰⁾.

• Adverse Reactions

  Headache, fatigue, vertigo, skin rash, hypersensitivity, lymphadenopathy, pain in the lymph nodes, nausea, vomiting, diarrhea, altered taste  ^{(10) (11) (44) (45) (46) (47) (53)}

  Case reports

  • Anaphylaxis and allergic reactions: Caused by several different A. paniculata preparations. Methanol extraction may increase risk of allergenicity ⁽⁵⁴⁾.
  • Anaphylactic reaction: In an HIV patient on-study during week 4 ⁽¹⁰⁾ .
  • Lymphadenopathy: With very high doses ⁽⁵³⁾.
  • Acute kidney injury: Following intravenous administration of andrographolides. Symptoms included flank pain, decreased urine output, and nausea or vomiting ⁽⁴¹⁾.
• Herb-Drug Interactions
  • Cytochrome P450 substrates: Laboratory studies indicate andrographis extract inhibits 1A2, 2C9, 3A4 ⁽³⁷⁾. Some andrographis compounds also induce CYP1A1 ⁽³⁹⁾. Although clinical relevance is yet to be determined, these properties can affect the intracellular concentration of drugs metabolized by these enzymes.
  • Anticoagulants, antiplatelets: Although laboratory studies indicate possible inhibition of platelet aggregation ^(34) (35), one study in rats suggests that andrographis extract does not interact with warfarin when used concomitantly ⁽³⁸⁾. Patients taking anticoagulant or antiplatelet medications should use caution and consult their treating physician if considering the use of andrographis products.
  • Chemotherapy drugs: Andrographolides have been shown to have antioxidant effects ⁽²¹⁾, which may interfere with the actions of some chemotherapy drugs.
  • Blood pressure-lowering drugs: Laboratory studies indicate that andrographis may have additive hypotensive effects ⁽³²⁾. In healthy subjects, A. paniculata at the normal therapeutic dose for the common cold and respiratory tract infections modulated various clinical parameters, including transient reductions in blood pressure ⁽⁵⁵⁾.
  • UDP-glucoronosyltransferase (UGT) 2B7: Laboratory studies indicate that andrographolide derivatives inhibit UGT2B7, and can increase the side effects of drugs metabolized by this enzyme ⁽⁴²⁾.
  • Aminophylline: Andrographis inhibits CYP1A2, which is involved in metabolizing aminophylline, resulting in increased risk of side effects from this drug ⁽⁴³⁾.
• Herb Lab Interactions

  May elevate liver enzymes ⁽⁶⁾.

• References

  • 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.

  • 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.

  • 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.

  • 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.

  • 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;17(3- 4):178-85.

  • 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;33(2):194-202.

  • 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;28(8):931-46.

  • 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.

  • 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 2008;115(2):302-12

  • 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.

  • 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.

  • Chun JY, Tummala R, Nadiminty N, et al. Andrographolide, an herbal medicine, inhibits interleukin-6 expression and suppresses prostate cancer growth. Genes Cancer. 2010; 1(8): 868-876.

  • 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;180(3):344-52.

  • 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;76(16):1827-33.

  • 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;632(1- 3):23-32.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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;79(9):1242-50.

  • 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. 2002;135(2):399-406.

  • 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.

  • Singha PK, Roy S, Dey S. Antimicrobial activity of Andrographis paniculata. Fitoterapia 2003;74(7-8):692-694.

  • 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.

  • 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.

  • 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.

  • Verma N, Vinayak M. Antioxidant action of Andrographis paniculata on lymphoma. Mol Biol Rep. 2008;35(4):535-40

  • Sheeja K, Guruvayoorappan C, Kuttan G. Antiangiogenic activity of Andrographis paniculata extract and andrographolide. Int Immunopharmacol 2007;7(2):211-221.

  • Sheeja K, Kuttan G. Protective effect of Andrographis paniculata and andrographolide on cyclophosphamide-induced urothelial toxicity. Integr Cancer Ther 2006;5(3):244-251.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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 2008;115(3):432-40

  • 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.

  • 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;25(8):1757-63.

  • Chao WW, Lin BF. Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian). Chin Med. 2010;5:17.

  • Zhang WX, Zhang ZM, Zhang ZQ, Wang Y, Zhou W. Andrographolide induced acute kidney injury: analysis of 26 cases reported in Chinese Literature. Nephrology (Carlton). 2014;19(1):21-6.

  • Ma HY, Sun DX, Cao YF, et al. Herb-drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7. Toxicol Appl Pharmacol. 2014;277(1):86-94.

  • Li XP, Zhang CL, Gao P, Gao J, Liu D. Effects of andrographolide on the pharmacokinetics of aminophylline and doxofylline in rats. Drug Res (Stuttg). 2013;63(5):258-62.

  • Suwankesawong W, Saokaew S, Permsuwan U, Chaiyakunapruk N. Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database. BMC Complement Altern Med. 2014;14(1):515.

  • Hu XY, Wu RH, Logue M, et al. Andrographis paniculata (Chuan Xin Lian) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis. PLoS One. 2017;12(8):e0181780.

  • Wagner L, Cramer H, Klose P, et al. Herbal Medicine for Cough: a Systematic Review and Meta-Analysis. Forsch Komplementmed. 2015;22(6):359-368.

  • Sandborn WJ, Targan SR, Byers VS, et al. Andrographis paniculata extract (HMPL-004) for active ulcerative colitis. Am J Gastroenterol. Jan 2013;108(1):90-98.

  • Phunikhom K, Khampitak K, Aromdee C, et al. Effect of Andrographis paniculata Extract on Triglyceride Levels of the Patients with Hypertriglyceridemia: A Randomized Controlled Trial. J Med Assoc Thai. Jul 2015;98 Suppl 6:S41-47.

  • Gunn EJ, Williams JT, Huynh DT, et al. The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma. Leuk Lymphoma. Jun 2011;52(6):1085-1097.

  • Wang W, Guo W, Li L, et al. Andrographolide reversed 5-FU resistance in human colorectal cancer by elevating BAX expression. Biochem Pharmacol. Dec 1 2016;121:8-17.

  • Han Y, Bu LM, Ji X, et al. Modulation of multidrug resistance by andrographolid in a HCT-8/5-FU multidrug-resistant colorectal cancer cell line. Chin J Dig Dis. 2005;6(2):82-86.

  • Gao H, Wang J. Andrographolide inhibits multiple myeloma cells by inhibiting the TLR4/NF-kappaB signaling pathway. Mol Med Rep. Feb 2016;13(2):1827-1832.

  • Rahman H, Kim M, Leung G, et al. Drug-Herb Interactions in the Elderly Patient with IBD: a Growing Concern. Curr Treat Options Gastroenterol. Dec 2017;15(4):618-636.

  • Gunawardana NC. Risk of anaphylaxis in complementary and alternative medicine. Curr Opin Allergy Clin Immunol. Oct 2017;17(5):332-337.

  • Suriyo T, Pholphana N, Ungtrakul T, et al. Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects. Planta Med. Jun 2017;83(9):778-789.