• This record comes from PubMed

Biological properties of andrographolide, an active ingredient of Andrographis Paniculata: a narrative review

. 2021 Jul ; 9 (14) : 1186.

Status PubMed-not-MEDLINE Language English Country China Media print

Document type Journal Article, Review

Links

PubMed 34430627
PubMed Central PMC8350652
DOI 10.21037/atm-20-7830
PII: atm-09-14-1186
Knihovny.cz E-resources

Andrographolide is a labdane diterpenoid isolated from Andrographis paniculata and traditionally used in Chinese and Indian medicine. Reported effects include anti-bacterial, anti-inflammatory and anti-cancer functions. Most of the studies support the hypothesis that andrographolide supplementation stimulates immune system, so the observed effects migh in fact be secondary to the stimulation of defense reactions. As andrographolide is involved in regulation of inflammation, it is not surprising that it is also evaluated in inflammation-mediated diseases such as ulcerative colitis. Anticancer effects of the andrographolide have been tested on various cancer panels. Colon cancer, breast cancer, and head and neck carcinomas were the most investigated, followed by prostate cancer and glioblastoma. The results looked promising. However, problems with solubility and low level of active substance in natural extract leads to preparation of chemical analogs. Objective of this short review is to summarize current knowledge of the biological effects of andragrapholide. We conclude that despite documented effects and some partly characterized mechanisms of action, more research is clearly needed. At present, the doses, types of treatment and possible negative side effects are not yet established. In addition, various isolations and compound formulas have been used for treatment of various diseases, making final conclusions problematic.

See more in PubMed

Singha PK, Roy S, Dey S. Antimicrobial activity of Andrographis paniculata. Fitoterapia 2003;74:692-4. 10.1016/S0367-326X(03)00159-X PubMed DOI

Panraksa P, Ramphan S, Khongwichit S, et al. Activity of andrographolide against dengue virus. Antiviral Res 2017;139:69-78. 10.1016/j.antiviral.2016.12.014 PubMed DOI

Li M, Zhang T, Zhu L, et al. Liposomal andrographolide dry powder inhalers for treatment of bacterial pneumonia via anti-inflammatory pathway. Int J Pharm 2017;528:163-71. 10.1016/j.ijpharm.2017.06.005 PubMed DOI

Carretta MD, Alarcón P, Jara E, et al. Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation. Eur J Pharmacol 2009;602:413-21. 10.1016/j.ejphar.2008.11.011 PubMed DOI

Pandey G, Rao CH. Andrographolide: its pharmacology, natural bioavailability and current approaches to increase its content in Andrographis paniculate. Int J Complement Alt Med 2018;11:355-60. 10.15406/ijcam.2018.11.00425 DOI

Kim AY, Shim HJ, Shin HM, et al. Andrographolide suppresses TRIF-dependent signaling of toll-like receptors by targeting TBK1. Int Immunopharmacol 2018;57:172-80. 10.1016/j.intimp.2018.02.019 PubMed DOI

Guo BJ, Liu Z, Ding MY, et al. Andrographolide derivative ameliorates dextran sulfate sodium-induced experimental colitis in mice. Biochem Pharmacol 2019;163:416-24. 10.1016/j.bcp.2019.03.019 PubMed DOI

Levita J, Nawawi A, Mutalib A, et al. Andrographolide: A review of its anti-inflammatory activity via inhibition of NF-kappaB activation from computational chemistry aspects. Int J Pharm 2010;6:569-76. 10.3923/ijp.2010.569.576 DOI

Parichatikanond W, Suthisisang C, Dhepakson P, et al. Study of anti-inflammatory activities of the pure compounds from Andrographis paniculata (burm.f.) Nees and their effects on gene expression. Int Immunopharmacol 2010;10:1361-73. 10.1016/j.intimp.2010.08.002 PubMed DOI

Zhu Q, Zheng P, Chen X, et al. Andrographolide presents therapeutic effect on ulcerative colitis through the inhibition of IL-23/IL-17 axis. Am J Transl Res 2018;10:465-73. PubMed PMC

Jing M, Wang Y, Xu L. Andrographolide Derivative AL-1 Ameliorates Dextran Sodium Sulfate-Induced Murine Colitis by Inhibiting NF-κB and MAPK Signaling Pathways. Oxid Med Cell Longev 2019;2019:6138723. 10.1155/2019/6138723 PubMed DOI PMC

Ma L, Liu X, Liang H, et al. Effects of 14-alpha-lipoyl andrographolide on quorum sensing in Pseudomonas aeruginosa. Antimicrob Agents Chemother 2012;56:6088-94. 10.1128/AAC.01119-12 PubMed DOI PMC

Richards JJ, Ballard TE, Huigens RW, 3rd, et al. Synthesis and screening of an oroidin library against Pseudomonas aeruginosa biofilms. Chembiochem 2008;9:1267-79. 10.1002/cbic.200700774 PubMed DOI

Wu CM, Cao JL, Zheng MH, et al. Effect and mechanism of andrographolide on the recovery of Pseudomonas aeruginosa susceptibility to several antibiotics. J Int Med Res 2008;36:178-86. 10.1177/147323000803600123 PubMed DOI

Cheung HY, Cheung SH, Li J, et al. Andrographolide isolated from Andrographis paniculata induces cell cycle arrest and mitochondrial-mediated apoptosis in human leukemic HL-60 cells. Planta Med 2005;71:1106-11. 10.1055/s-2005-873128 PubMed DOI

Park JH, Lee JH, Kim CJ, et al. Extracellular protease in Actinomycetes culture supernatants inhibits and detaches Staphylococcus aureus biofilm formation. Biotechnol Lett 2012;34:655-61. 10.1007/s10529-011-0825-z PubMed DOI

Lazazzera BA. Quorum sensing and starvation: signals for entry into stationary phase. Curr Opin Microbiol 2000;3:177-82. 10.1016/S1369-5274(00)00072-2 PubMed DOI

Guo X, Zhang LY, Wu SC, et al. Andrographolide interferes quorum sensing to reduce cell damage caused by avian pathogenic Escherichia coli. Vet Microbiol 2014;174:496-503. 10.1016/j.vetmic.2014.09.021 PubMed DOI

Zhang L, Bao M, Liu B, et al. Effect of Andrographolide and Its Analogs on Bacterial Infection: A Review. Pharmacology 2020;105:123-34. 10.1159/000503410 PubMed DOI

Wen L, Xia N, Chen X, et al. Activity of antibacterial, antiviral, anti-inflammatory in compounds andrographolide salt. Eur J Pharmacol 2014;740:421-7. 10.1016/j.ejphar.2014.06.053 PubMed DOI

Wang D, Guo H, Chang J, et al. Andrographolide Prevents EV-D68 Replication by Inhibiting the Acidification of Virus-Containing Endocytic Vesicles. Front Microbiol 2018;9:2407. 10.3389/fmicb.2018.02407 PubMed DOI PMC

Islam MT. Andrographolide, a New Hope in the Prevention and Treatment of Metabolic Syndrome. Front Pharmacol 2017;8:571. 10.3389/fphar.2017.00571 PubMed DOI PMC

Lee KC, Chang HH, Chung YH, et al. Andrographolide acts as an anti-inflammatory agent in LPS-stimulated RAW264.7 macrophages by inhibiting STAT3-mediated suppression of the NF-κB pathway. J Ethnopharmacol 2011;135:678-84. 10.1016/j.jep.2011.03.068 PubMed DOI

Gupta SC, Kunnumakkara AB, Aggarwal S, et al. Inflammation, a Double-Edge Sword for Cancer and Other Age-Related Diseases. Front Immunol 2018;9:2160. 10.3389/fimmu.2018.02160 PubMed DOI PMC

Zhang Y, Kong W, Jiang J. Prevention and treatment of cancer targeting chronic inflammation: research progress, potential agents, clinical studies and mechanisms. Sci China Life Sci 2017;60:601-16. 10.1007/s11427-017-9047-4 PubMed DOI

Bonomi M, Patsias A, Posner M, et al. The role of inflammation in head and neck cancer. Adv Exp Med Biol 2014;816:107-27. 10.1007/978-3-0348-0837-8_5 PubMed DOI

Sowers JL, Johnson KM, Conrad C, et al. The role of inflammation in brain cancer. Adv Exp Med Biol 2014;816:75-105. 10.1007/978-3-0348-0837-8_4 PubMed DOI

Wu B, Chen X, Zhou Y, et al. Andrographolide inhibits proliferation and induces apoptosis of nasopharyngeal carcinoma cell line C666-1 through LKB1-AMPK-dependent signaling pathways. Pharmazie 2018;73:594-7. PubMed

Peng T, Hu M, Wu TT, et al. Andrographolide suppresses proliferation of nasopharyngeal carcinoma cells via attenuating NF-κB pathway. Biomed Res Int 2015;2015:735056. 10.1155/2015/735056 PubMed DOI PMC

Zhang QQ, Ding Y, Lei Y, et al. Andrographolide suppress tumor growth by inhibiting TLR4/NF-κB signaling activation in insulinoma. Int J Biol Sci 2014;10:404-14. 10.7150/ijbs.7723 PubMed DOI PMC

Dai J, Lin Y, Duan Y, et al. Andrographolide Inhibits Angiogenesis by Inhibiting the Mir-21-5p/TIMP3 Signaling Pathway. Int J Biol Sci 2017;13:660-8. 10.7150/ijbs.19194 PubMed DOI PMC

Kumar RA, Sridevi K, Kumar NV, et al. Anticancer and immunostimulatory compounds from Andrographis paniculata. J Ethnopharmacol 2004;92:291-5. 10.1016/j.jep.2004.03.004 PubMed DOI

Jada SR, Matthews C, Saad MS, et al. Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G(1) arrest and apoptosis. Br J Pharmacol 2008;155:641-54. 10.1038/bjp.2008.368 PubMed DOI PMC

Banerjee M, Chattopadhyay S, Choudhuri T, et al. Cytotoxicity and cell cycle arrest induced by andrographolide lead to programmed cell death of MDA-MB-231 breast cancer cell line. J Biomed Sci 2016;23:40. 10.1186/s12929-016-0257-0 PubMed DOI PMC

Khan I, Khan F, Farooqui A, et al. Andrographolide Exhibits Anticancer Potential Against Human Colon Cancer Cells by Inducing Cell Cycle Arrest and Programmed Cell Death via Augmentation of Intracellular Reactive Oxygen Species Level. Nutr Cancer 2018;70:787-803. 10.1080/01635581.2018.1470649 PubMed DOI

Suriyo T, Pholphana N, Rangkadilok N, et al. Andrographis paniculata extracts and major constituent diterpenoids inhibit growth of intrahepatic cholangiocarcinoma cells by inducing cell cycle arrest and apoptosis. Planta Med 2014;80:533-43. 10.1055/s-0034-1368399 PubMed DOI

Khan I, Mahfooz S, Saeed M, et al. Andrographolide Inhibits Proliferation of Colon Cancer SW-480 Cells via Downregulating Notch Signaling Pathway. Anticancer Agents Med Chem 2021;21:487-97. 10.2174/1871520620666200717143109 PubMed DOI

Chen X, Zhang J, Yuan L, et al. Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake. Molecules 2017;22:1444. 10.3390/molecules22091444 PubMed DOI PMC

Chiu SP, Batsaikhan B, Huang HM, et al. Application of Electric Cell-Substrate Impedance Sensing to Investigate the Cytotoxic Effects of Andrographolide on U-87 MG Glioblastoma Cell Migration and Apoptosis. Sensors (Basel) 2019;19:2275. 10.3390/s19102275 PubMed DOI PMC

Yang SL, Kuo FH, Chen PN, et al. Andrographolide suppresses the migratory ability of human glioblastoma multiforme cells by targeting ERK1/2-mediated matrix metalloproteinase-2 expression. Oncotarget 2017;8:105860-72. 10.18632/oncotarget.22407 PubMed DOI PMC

Dai L, Wang G, Pan W. Andrographolide Inhibits Proliferation and Metastasis of SGC7901 Gastric Cancer Cells. Biomed Res Int 2017;2017:6242103. 10.1155/2017/6242103 PubMed DOI PMC

Khan I, Mahfooz S, Ansari IA. Antiproliferative and Apoptotic Properties of Andrographolide Against Human Colon Cancer DLD1 Cell Line. Endocr Metab Immune Disord Drug Targets 2020;20:930-42. 10.2174/1871530319666191125111920 PubMed DOI

Banerjee A, Banerjee V, Czinn S, et al. Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells. Oncotarget 2017;8:26142-53. 10.18632/oncotarget.15393 PubMed DOI PMC

Bundela S, Sharma A, Bisen PS. Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine. PLoS One 2015;10:e0141719. 10.1371/journal.pone.0141719 PubMed DOI PMC

Wang S, Li H, Chen S, et al. Andrographolide induces apoptosis in human osteosarcoma cells via the ROS/JNK pathway. Int J Oncol 2020;56:1417-28. 10.3892/ijo.2020.5032 PubMed DOI PMC

Yang SH, Wang SM, Syu JP, et al. Andrographolide induces apoptosis of C6 glioma cells via the ERK-p53-caspase 7-PARP pathway. Biomed Res Int 2014;2014:312847. 10.1155/2014/312847 PubMed DOI PMC

Wei RJ, Zhang XS, He DL. Andrographolide sensitizes prostate cancer cells to TRAIL-induced apoptosis. Asian J Androl 2018;20:200-4. 10.4103/aja.aja_30_17 PubMed DOI PMC

Yang T, Yao S, Zhang X, et al. Andrographolide inhibits growth of human T-cell acute lymphoblastic leukemia Jurkat cells by downregulation of PI3K/AKT and upregulation of p38 MAPK pathways. Drug Des Devel Ther 2016;10:1389-97. 10.2147/DDDT.S94983 PubMed DOI PMC

Deng Y, Bi R, Guo H, et al. Andrographolide Enhances TRAIL-Induced Apoptosis via p53-Mediated Death Receptors Up-Regulation and Suppression of the NF-кB Pathway in Bladder Cancer Cells. Int J Biol Sci 2019;15:688-700. 10.7150/ijbs.30847 PubMed DOI PMC

Yang PY, Hsieh PL, Wang TH, et al. Andrographolide impedes cancer stemness and enhances radio-sensitivity in oral carcinomas via miR-218 activation. Oncotarget 2017;8:4196-207. 10.18632/oncotarget.13755 PubMed DOI PMC

Lu WJ, Lin KH, Hsu MJ, et al. Suppression of NF-κB signaling by andrographolide with a novel mechanism in human platelets: regulatory roles of the p38 MAPK-hydroxyl radical-ERK2 cascade. Biochem Pharmacol 2012;84:914-24. 10.1016/j.bcp.2012.06.030 PubMed DOI

Yu CC, Chen CA, Fu SL, et al. Andrographolide enhances the anti-metastatic effect of radiation in Ras-transformed cells via suppression of ERK-mediated MMP-2 activity. PLoS One 2018;13:e0205666. 10.1371/journal.pone.0205666 PubMed DOI PMC

Zhang M, Xue E, Shao W. Andrographolide promotes vincristine-induced SK-NEP-1 tumor cell death via PI3K-AKT-p53 signaling pathway. Drug Des Devel Ther 2016;10:3143-52. 10.2147/DDDT.S113838 PubMed DOI PMC

Mao W, He P, Wang W, et al. Andrographolide sensitizes Hep-2 human laryngeal cancer cells to carboplatin-induced apoptosis by increasing reactive oxygen species levels. Anticancer Drugs 2019;30:e0774. 10.1097/CAD.0000000000000774 PubMed DOI

Su M, Qin B, Liu F, et al. Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway. Drug Des Devel Ther 2017;11:3333-41. 10.2147/DDDT.S140354 PubMed DOI PMC

Chen YP, Liu YW, Lee D, et al. Biodegradable andrographolide-eluting nanofibrous membranes for the treatment of cervical cancer. Int J Nanomedicine 2019;14:421-9. 10.2147/IJN.S186714 PubMed DOI PMC

Xiang DC, Yang JY, Xu YJ, et al. Protective effect of Andrographolide on 5-Fu induced intestinal mucositis by regulating p38 MAPK signaling pathway. Life Sci 2020;252:117612. 10.1016/j.lfs.2020.117612 PubMed DOI

Gong C, Ni Z, Yao C, et al. A High-Throughput Assay for Screening of Natural Products that Enhanced Tumoricidal Activity of NK Cells. Biol Proced Online 2015;17:12. 10.1186/s12575-015-0026-6 PubMed DOI PMC

Sheeja K, Kuttan G. Andrographis paniculata downregulates proinflammatory cytokine production and augments cell mediated immune response in metastatic tumor-bearing mice. Asian Pac J Cancer Prev 2010;11:723-9. PubMed

Sheeja K, Kuttan G. Modulation of natural killer cell activity, antibody-dependent cellular cytotoxicity, and antibody-dependent complement-mediated cytotoxicity by andrographolide in normal and Ehrlich ascites carcinoma-bearing mice. Integr Cancer Ther 2007;6:66-73. 10.1177/1534735406298975 PubMed DOI

Soo HL, Quah SY, Sulaiman I, et al. Advances and challenges in developing andrographolide and its analogues as cancer therapeutic agents. Drug Discov Today 2019;24:1890-8. 10.1016/j.drudis.2019.05.017 PubMed DOI

Iruretagoyena MI, Tobar JA, González PA, et al. Andrographolide interferes with T cell activation and reduces experimental autoimmune encephalomyelitis in the mouse. J Pharmacol Exp Ther 2005;312:366-72. 10.1124/jpet.104.072512 PubMed DOI

Iruretagoyena MI, Sepúlveda SE, Lezana JP, et al. Inhibition of nuclear factor-kappa B enhances the capacity of immature dendritic cells to induce antigen-specific tolerance in experimental autoimmune encephalomyelitis. J Pharmacol Exp Ther 2006;318:59-67. 10.1124/jpet.106.103259 PubMed DOI

Naik SR, Hule A. Evaluation of immunomodulatory activity of an extract of andrographolides from Andographis paniculata. Planta Med 2009;75:785-91. 10.1055/s-0029-1185398 PubMed DOI

Wang W, Wang J, Dong SF, et al. Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response. Acta Pharmacol Sin 2010;31:191-201. 10.1038/aps.2009.205 PubMed DOI PMC

Nie X, Chen SR, Wang K, et al. Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway. Sci Rep 2017;7:4738. 10.1038/s41598-017-04673-x PubMed DOI PMC

Xu Y, Chen A, Fry S, et al. Modulation of immune response in mice immunised with an inactivated Salmonella vaccine and gavaged with Andrographis paniculata extract or andrographolide. Int Immunopharmacol 2007;7:515-23. 10.1016/j.intimp.2006.12.008 PubMed DOI

Ciampi E, Uribe-San-Martin R, Cárcamo C, et al. Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial. BMC Neurol 2020;20:173. 10.1186/s12883-020-01745-w PubMed DOI PMC

Das S, Mishra KP, Ganju L, et al. Andrographolide - A promising therapeutic agent, negatively regulates glial cell derived neurodegeneration of prefrontal cortex, hippocampus and working memory impairment. J Neuroimmunol 2017;313:161-75. 10.1016/j.jneuroim.2017.11.003 PubMed DOI

Yen TL, Chen RJ, Jayakumar T, et al. Andrographolide stimulates p38 mitogen-activated protein kinase-nuclear factor erythroid-2-related factor 2-heme oxygenase 1 signaling in primary cerebral endothelial cells for definite protection against ischemic stroke in rats. Transl Res 2016;170:57-72. 10.1016/j.trsl.2015.12.002 PubMed DOI

Lu J, Ma Y, Wu J, et al. A review for the neuroprotective effects of andrographolide in the central nervous system. Biomed Pharmacother 2019;117:109078. 10.1016/j.biopha.2019.109078 PubMed DOI

Zhang Z, Jiang J, Yu P, et al. Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment. J Transl Med 2009;7:62. 10.1186/1479-5876-7-62 PubMed DOI PMC

Yu BC, Hung CR, Chen WC, et al. Antihyperglycemic effect of andrographolide in streptozotocin-induced diabetic rats. Planta Med 2003;69:1075-9. 10.1055/s-2003-45185 PubMed DOI

Zhang C, Gui L, Xu Y, et al. Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance. Int Immunopharmacol 2013;16:451-6. 10.1016/j.intimp.2013.05.002 PubMed DOI

Peng S, Gao J, Liu W, et al. Andrographolide ameliorates OVA-induced lung injury in mice by suppressing ROS-mediated NF-κB signaling and NLRP3 inflammasome activation. Oncotarget 2016;7:80262-74. 10.18632/oncotarget.12918 PubMed DOI PMC

Gao F, Liu X, Shen Z, et al. Andrographolide Sulfonate Attenuates Acute Lung Injury by Reducing Expression of Myeloperoxidase and Neutrophil-Derived Proteases in Mice. Front Physiol 2018;9:939. 10.3389/fphys.2018.00939 PubMed DOI PMC

Hidalgo MA, Hancke JL, Bertoglio JC, et al. Andrographoline a new potential drug for the long-term treatment of rheumatoid arthritis disease. In: Matsuno H, editor. Innovative Rheumatology. Rijeka, Croatia: InTech; 2013. p. 247-70.

Yu Z, Lu B, Sheng Y, et al. Andrographolide ameliorates diabetic retinopathy by inhibiting retinal angiogenesis and inflammation. Biochim Biophys Acta 2015;1850:824-31. 10.1016/j.bbagen.2015.01.014 PubMed DOI

Dai Y, Chen SR, Chai L, et al. Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide. Crit Rev Food Sci Nutr 2019;59:S17-29. 10.1080/10408398.2018.1501657 PubMed DOI

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...