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Andrographis (Andrographis paniculate)

Andrographis paniculata is a bitter-tasting annual plant prevalent in much of Asia and has been used in traditional Asian medicine to treat infectious diseases and fevers.

Andrographis (Andrographis paniculate)

Uses

Andrographis exhibits 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. 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.

Chemistry/Pharmacology

The herb contains several beneficial compounds including flavonoids, diterpenoids, and polyphenols. The most bioactive component is a diterpenoid called andrographolide. This is also the compound that has been studied most extensively because of its potential anti-cancer effect.

Clinical Studies

In vitro and animal studies indicate that andrographis has antimicrobial, anti-inflammatory, antioxidant, anticancer, and antimetastatic properties.

Kan Jang, a standardized extract of Andrographis paniculata and Eleutherococcus senticosus, has been studied in manufacturer-sponsored clinical trials for the relief of respiratory symptoms from cold and flu. An andrographis extract was found useful in treating symptoms of upper respiratory infection. A few meta-analyses suggest possible benefits with A. paniculata to reduce cough frequency and severity.

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. Another study found it as effective as mesalamine in treating ulcerative colitis. In other preliminary studies, andrographis extracts reduced rheumatoid factors and relieved rheumatoid arthritis symptoms. In patients with modest hypertriglyceridemia, a high dose andrographis extract reduced triglyceride levels in a manner comparable to gemfibrozil. In preclinical cancer studies, andrographolide exhibited activity against multiple myeloma stem cells, reversed 5-FU resistance in human colorectal cancer cells, and modulated P-glycoprotein-mediated multidrug resistance.

Biomechanical Mechanism

Sources/Articles

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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