Andrographolide: A Review on Experimental Clinical Trials and Applications

Authors

  • Divya Teli Department of Pharmaceutical Chemistry, L.M. College of Pharmacy, 380009 Ahmedabad, India Author
  • Dixa A. Vaghela Department of Pharmaceutical Chemistry, L.M. College of Pharmacy, 380009 Ahmedabad, India Author
  • Amit Chaudhri Department of Pharmaceutical Chemistry, L.M. College of Pharmacy, 380009 Ahmedabad, India Author
  • Hetvi K. Solanki Department of Pharmaceutical Chemistry, L.M. College of Pharmacy, 380009 Ahmedabad, India Author
  • Keshav Jetha Department of Pharmaceutical Chemistry, L.M. College of Pharmacy, 380009 Ahmedabad, India Author
  • Vivek P. Chavda Department of Pharmaceutical Chemistry, L.M. College of Pharmacy, 380009 Ahmedabad, India Author

DOI:

https://doi.org/10.62767/jecacm501.5474

Keywords:

Andrographis paniculata, anti-oxidant, immunity enhancer, hepatoprotective, cardioprotective, anti-inflammatory, anti-cancer

Abstract

Throughout human history, plants have been used for medicinal purposes. Plants can synthesise a vast range of chemical compounds that possess biological activities and can be employed as medicines. Andrographis paniculata is an Asian medicinal herb and a well-known Chinese herbal remedy. It is referred to as “king of bitters” in English, “Chiretteverte” and “Roi des amers” in French, “Kariyatu” in Gujarati, and “Kirayat” or “Kalpanath” in Hindi. In India, it is commonly known as "kalmegh". Traditionally, it has been used to treat lung infections, cold, fever, diarrhoea, flu, syphilis, rabies, upper respiratory infections, leptospirosis, leprosy, malaria, sinusitis, HIV/AIDS, and TB, among other conditions. A chemical constituent present in the leaves of Andrographis paniculate, a diterpenoid labdane also known as andrographolide, was identified as a key bioactive component of A. paniculata in 1951. It is believed to be responsible for the various biological applications like anti-oxidant, immunity enhancer, hepatoprotective, cardioprotective, anti-inflammatory, anti-cancer, and upper respiratory tract infection. Since 1984, andrographolide and its analogues have been studied for anti-inflammatory activities using contemporary drug development strategies. The anticancer properties of andrographolide have been investigated on several cancer models, yielding promising results. This manuscript primarily focuses on the clinical aspects of andrographolide. We aim to elucidate its applications, preclinical findings, and clinical studies.

References

Chavda VP, Kumar A, Banerjee R, et al. Ayurvedic and Other Herbal Remedies For Dengue: An Update. Clinical Complementary Medicine and Pharmacology 2022; 2(3): 100024.

Chavda VP, Patel AB, Mistry KJ, et al. Nano-Drug Delivery Systems Entrapping Natural Bioactive Compounds for Cancer: Recent Progress and Future Challenges. Frontiers in Oncology 2022; 12: 867655.

Chavda VP, Gajjar N, Shah N, et al. Darunavir ethanolate: Repurposing an anti-HIV drug in COVID-19 treatment. European Journal of Medicinal Chemistry Reports 2021; 3: 100013.

Chavda VP, Patel AB, Vihol D, et al. Herbal Remedies, Nutraceuticals, and Dietary Supplements for COVID-19 Management: An Update. Clinical Complementary Medicine and Pharmacology 2022; 2(1): 100021.

Khadela A, Chavda VP, Postwala H, et al. Epigenetics in Tuberculosis: Immunomodulation of Host Immune Response. Vaccines 2022; 10(10): 1740.

Akbar S. Andrographis paniculata: A review of pharmacological activities and clinical effects. Alternative Medicine Review 2011; 16(1): 66-77.

Hossain MS, Urbi Z, Sule A, et al. Andrographis paniculata (Burm. f.) Wall. ex Nees: A Review of Ethnobotany, Phytochemistry, and Pharmacology. The Scientific World Journal 2014; 2014: 274905

Kumar RA, Sridevi K, Kumar NV, et al. Anticancer and immunostimulatory compounds from Andrographis paniculata. Journal of Ethnopharmacology 2004; 92(2–3): 291–295.

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

Calabrese C, Berman SH, Babish JG, et al. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytotherapy Research 2000; 14(5): 333–338.

Rajagopal S, Kumar RA, Deevi DS, et al. Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata. Journal of Experimental Therapeutics and Oncology 2003; 3(3): 147–158.

Jayakumar T, Hsieh CY, Lee JJ, et al. Experimental and Clinical Pharmacology of Andrographis paniculata and Its Major Bioactive Phytoconstituent Andrographolide. Evidence-Based Complementary and Alternative Medicine 2013; 2013: 846740.

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. Clinical Rheumatology 2009; 28(8): 931–946.

Sandborn WJ, Targan SR, Byers VS, et al. Andrographis paniculata Extract (HMPL-004) for Active Ulcerative Colitis. American Journal of Gastroenterology 2013; 108(1): 90–98.

Chiu PWY, Yue GGL, Cheung MK, et al. The effect of Andrographis paniculata water extract on palliative management of metastatic esophageal squamous cell carcinoma—A phase II clinical trial. Phytotherapy Research 2023; 37(8): 3438-3452.

Yan Y, Fang LH, Du GH. Andrographolide. In Natural Small Molecule Drugs from Plants. Springer Singapore: Gateway East, Singapore, 2018; pp. 357–362.

Owen AE, Louis H, Ejiofor EU, et al. Natural Andrographolide Isolated from Andrographis paniculata as Potent Epileptic Agent: Spectroscopy, Molecular Structure, and Molecular Docking Investigation. Chemistry Africa 2023; 6: 2445-2461.

Smith AB, Toder BH, Carroll PJ, et al. Andrographolide: an X-ray crystallographic analysis. Journal of Crystallographic and Spectroscopic Research 1982; 12(4): 309–319.

Lomlim L, Jirayupong N, Plubrukarn A. Heat-accelerated degradation of solid-state andrographolide. Chemical & Pharmaceutical Bulletin 2003; 51(1): 24-26.

Srivastava N, Akhila A. Biosynthesis of andrographolide in Andrographis paniculata. Phytochemistry 2010; 71(11–12): 1298–1304.

Chao WW, Lin BF. Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian). Chinese Medicine 2010; 5(1): 17.

Rajani M, Shrivastava N, Ravishankara MN. A rapid method for isolation of andrographolide from andrographis paniculata nees (kalmegh). Pharmaceutical Biology 2000; 38(3): 204–209.

Hao M, Lv M, Xu H. Andrographolide: Synthetic Methods and Biological Activities. Mini-Reviews in Medicinal Chemistry 2020; 20(16): 1633–1652.

Suresh K, Goud NR, Nangia A. Andrographolide: Solving Chemical Instability and Poor Solubility by Means of Cocrystals. Chemistry – An Asian Journal 2013; 8(12): 3032–3041.

Boopathi CA. Andrographis SPP.: A Source of Bitter Compounds for Medicinal Use. Ancient Science of Life 2000; 19(3–4): 164–168.

Mishra SK, Sangwan NS, Sangwan RS. Phcog Rev.: Plant Review Andrographis paniculata (Kalmegh): A Review. Pharmacognosy Reviews 2007; 1(2): 283-298.

Bhatnagar SS, Santapau H, Desa JD, et al. Biological activity of Indian medicinal plants. I. Antibacterial, antitubercular and antifungal action. Indian Journal of Medical Research 1961; 49: 799–813.

Kumar G, Singh D, Tali JA, et al. Andrographolide: Chemical modification and its effect on biological activities. Bioorganic Chemistry 2019; 95: 103511.

Patil R, Jain V. Andrographolide: A Review of Analytical Methods. Journal of Chromatographic Science 2021; 59(2): 191–203.

Okhuarobo A, Ehizogie Falodun J, Erharuyi O, et al. Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology. Asian Pacific Journal of Tropical Disease 2014; 4(3): 213–222.

Naik S, Hule A. Evaluation of Immunomodulatory Activity of an Extract of Andrographolides from Andographis paniculata. Planta Medica 2009; 75(08): 785–791.

Li M, Yang X, Guan C, et al. Andrographolide sulfonate reduces mortality in Enterovirus 71 infected mice by modulating immunity. International Immunopharmacology 2017; 55: 142–150.

Peng G, Zhou F, Ding R, et al. Modulation of lianbizi injection (andrographolide) on some immune functions. Zhongguo Zhong Yao Za Zhi 2002; 27(2): 147–150.

Iruretagoyena MI, Tobar JA, González PA, et al. Andrographolide Interferes with T Cell Activation and Reduces Experimental Autoimmune Encephalomyelitis in the Mouse. Journal of Pharmacology and Experimental Therapeutics 2005; 312(1): 366–372.

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. Translational Research 2016; 170: 57–72.

Handa S, Sharma A. Hepatoprotective activity of andrographolide from Andrographis paniculata against carbontetrachloride. Indian Journal of Medical Research 1990; 92: 276–283.

Ye JF, Zhu H, Zhou ZF, et al. Protective Mechanism of Andrographolide against Carbon Tetrachloride-Induced Acute Liver Injury in Mice. Biological & Pharmaceutical Bulletin 2011; 34(11): 1666–1670.

Tang C, Gu G, Wang B, et al. Design, Synthesis, and Biological Evaluation of Andrographolide Derivatives as Potent Hepatoprotective Agents. Chemical Biology & Drug Design 2014; 83(3): 324–333.

Chen SR, Li F, Ding MY, et al. Andrographolide derivative as STAT3 inhibitor that protects acute liver damage in mice. Bioorganic & Medicinal Chemistry 2018; 26(18): 5053–5061.

Roy P, Das S, Auddy RG, et al. Engineered Andrographolide Nanoparticles Mitigate Paracetamol Hepatotoxicity in Mice. Pharmaceutical Research 2013; 30(5): 1252–1262.

Das S, Pradhan GK, Das S, et al. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage. Chemico-Biological Interactions 2015; 242: 281–289.

Mishra A, Shaik HA, Sinha RK, et al. Andrographolide: A Herbal-Chemosynthetic Approach for Enhancing Immunity, Combating Viral Infections, and Its Implication on Human Health. Molecules 2021; 26(22): 7036.

Zhang J, Zhu D, Wang Y, et al. Andrographolide Attenuates LPS-Induced Cardiac Malfunctions Through Inhibition of IκB Phosphorylation and Apoptosis in Mice. Cellular Physiology and Biochemistry 2015; 37(4): 1619–1628.

Zhang Q, Hu L, Li H, et al. Beneficial effects of andrographolide in a rat model of autoimmune myocarditis and its effects on PI3K/Akt pathway. The Korean Journal of Physiology & Pharmacology 2019; 23(2): 103.

Liang E, Liu X, Du Z, et al. Andrographolide Ameliorates Diabetic Cardiomyopathy in Mice by Blockage of Oxidative Damage and NF-κB-Mediated Inflammation. Oxidative Medicine and Cellular Longevity 2018; 2018: 9086747.

Lin KH, Asokan SM, Kuo WW, et al. Andrographolide mitigates cardiac apoptosis to provide cardio‐protection in high‐fat‐diet‐induced obese mice. Environmental Toxicology 2020; 35(6): 707–713.

Woo AYH, Waye MMY, Tsui SKW, et al. Andrographolide Up-Regulates Cellular-Reduced Glutathione Level and Protects Cardiomyocytes against Hypoxia/Reoxygenation Injury. Journal of Pharmacology and Experimental Therapeutics 2008; 325(1): 226–235.

Xie S, Deng W, Chen J, et al. Andrographolide Protects Against Adverse Cardiac Remodeling After Myocardial Infarction through Enhancing Nrf2 Signaling Pathway. International Journal of Biological Sciences 2020; 16(1): 12–26.

Shu J, Huang R, Tian Y, et al. Andrographolide protects against endothelial dysfunction and inflammatory response in rats with coronary heart disease by regulating PPAR and NF-κB signaling pathways. Annals of Palliative Medicine 2020; 9(4): 1965–1975.

Mishra K. Andrographolide: Regulating the Master Regulator NF-κB. Indian Journal of Clinical Biochemistry 2021; 36(1): 117–119.

Liu T, Zhang L, Joo D, et al. NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy 2017; 2: 17023.

Ricciotti E, FitzGerald GA. Prostaglandins and Inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology 2011; 31(5): 986–1000.

Li X, Yuan W, Wu J, et al. Andrographolide, a natural anti-inflammatory agent: An Update. Frontiers in Pharmacology 2022; 13: 920435.

Fujiwara N, Kobayashi K. Macrophages in inflammation. Current Drug Targets - Inflammation & Allergy 2005; 4(3): 281–286.

Wang W, Wang J, Dong S, et al. Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response. Acta Pharmacologica Sinica 2010; 31(2): 191–201.

Mussard E, Cesaro A, Lespessailles E, et al. Andrographolide, A Natural Antioxidant: An Update. Antioxidants 2019; 8(12): 571.

Schieber M, Chandel NS. ROS Function in Redox Signaling and Oxidative Stress. Current Biology 2014; 24(10): R453–R462.

Burgos RA, Alarcón P, Quiroga J, et al. Andrographolide, an Anti-Inflammatory Multitarget Drug: All Roads Lead to Cellular Metabolism. Molecules 2021; 26(1): 5.

Li J, Huang L, He Z, et al. Andrographolide Suppresses the Growth and Metastasis of Luminal-Like Breast Cancer by Inhibiting the NF-κB/miR-21-5p/PDCD4 Signaling Pathway. Frontiers in Cell and Developmental Biology 2021; 9: 643525.

Othman NS, Mohd Azman DK. Andrographolide Induces G2/M Cell Cycle Arrest and Apoptosis in Human Glioblastoma DBTRG-05MG Cell Line via ERK1/2 /c-Myc/p53 Signaling Pathway. Molecules 2022; 27(19): 6686.

Chen Z, Tang WJ, Zhou YH, et al. Andrographolide inhibits non-small cell lung cancer cell proliferation through the activation of the mitochondrial apoptosis pathway and by reprogramming host glucose metabolism. Annals of Translational Medicine 2021; 9(22): 1701.

Wang S, Li H, Chen S, et al. Andrographolide induces apoptosis in human osteosarcoma cells via the ROS/JNK pathway. International Journal of Oncology 2020; 56(6): 1417–1428.

Lim SC, Jeon HJ, Kee KH, et al. Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells. Oncology Letters 2017; 13(5): 3837–3844.

Nishida N, Yano H, Nishida T, et al. Angiogenesis in Cancer. Vascular Health and Risk Management 2006;2(3): 213–219.

Duan MX, Zhou H, Wu QQ, et al. Andrographolide Protects against HG-Induced Inflammation, Apoptosis, Migration, and Impairment of Angiogenesis via PI3K/AKT-eNOS Signalling in HUVECs. Mediators of Inflammation 2019; 2019: 6168340.

Derbyshire EJ, Calder PC. Respiratory Tract Infections and Antibiotic Resistance: A Protective Role for Vitamin D? Frontiers in Nutrition 2021; 8: 652469.

Rajanna M, Bharathi B, Shivakumar BR, et al. Immunomodulatory effects of Andrographis paniculata extract in healthy adults – An open-label study. Journal of Ayurveda and Integrative Medicine 2021; 12(3): 529–534.

Adiguna SP, Panggabean JA, Atikana A, et al. Antiviral Activities of Andrographolide and Its Derivatives: Mechanism of Action and Delivery System. Pharmaceuticals 2021; 14(11): 1102

Murgia V, Manti S, Licari A, et al. Upper Respiratory Tract Infection-Associated Acute Cough and the Urge to Cough: New Insights for Clinical Practice. Pediatric Allergy, Immunology, and Pulmonology 2020; 33(1): 3–11.

Gupta S, Mishra KP, Ganju L. Broad-spectrum antiviral properties of andrographolide. Archives of Virology 2017; 162(3): 611–623.

Banerjee M, Parai D, Chattopadhyay S, et al. Andrographolide: antibacterial activity against common bacteria of human health concern and possible mechanism of action. Folia Microbiologica 2017; 62(3): 237–244.

Aldurrah Z, Kauli FSM, Rahim NA, et al. Antidepressant evaluation of Andrographis paniculata Nees extract and andrographolide in chronic unpredictable stress zebrafish model. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 2023; 271: 109678.

Indirapriyadarshini R, Kanimozhi G, Natarajan D, et al. Andrographolide protects acute ultraviolet-B radiation-induced photodamages in the mouse skin. Archives of Dermatological Research 2023; 315(5): 1197–1205.

Yang ES, Do Y, Cheon SY, et al. Andrographolide suppresses aerobic glycolysis and induces apoptotic cell death by inhibiting pyruvate dehydrogenase kinase 1 expression. Oncology Reports 2023; 49(4): 72.

Carretta MD, Alarcón P, Jara E, et al. Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation. European Journal of Pharmacology 2009; 602(2–3): 413–421.

Tarigan TJE, Purwaningsih EH, Yusra, et al. Effects of Sambiloto (Andrographis paniculata) on GLP-1 and DPP-4 Concentrations between Normal and Prediabetic Subjects: A Crossover Study. Evidence-Based Complementary and Alternative Medicine 2022; 2022: 1535703.

JC B, Baumgartner M, Palma R, et al. Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study. BMC Neurology 2016; 16: 77.

Dimpfel W, Schombert L, Keplinger-Dimpfel IK, et al. Effects of an Adaptogenic Extract on Electrical Activity of the Brain in Elderly Subjects with Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled, Two-Armed Cross-Over Study. Pharmaceuticals 2020; 13(3): 45.

Shang Y, Shen C, Stub T, et al. Adverse Effects of Andrographolide Derivative Medications Compared to the Safe use of Herbal Preparations of Andrographis paniculata: Results of a Systematic Review and Meta-Analysis of Clinical Studies. Frontiers in Pharmacology 2022; 13: 773282.

Greco R, Siani F, Demartini C, et al. Andrographis Paniculata shows anti-nociceptive effects in an animal model of sensory hypersensitivity associated with migraine. Functional Neurology 2016; 31(1): 53–60.

Sattayasai J, Srisuwan S, Arkaravichien T, et al. Effects of andrographolide on sexual functions, vascular reactivity and serum testosterone level in rodents. Food and Chemical Toxicology 2010; 48(7): 1934–1938.

Zhang WX, Zhang ZM, Zhang ZQ, et al. Andrographolide induced acute kidney injury: Analysis of 26 cases reported in Chinese Literature. Nephrology 2014; 19(1): 21–26.

Bothiraja C, Pawar AP, Shende VS, et al. Acute and subacute toxicity study of andrographolide bioactive in rodents: Evidence for the medicinal use as an alternative medicine. Comparative Clinical Pathology 2013; 22(6): 1123–1128.

Suebsasana S, Pongnaratorn P, Sattayasai J, et al. Analgesic, antipyretic, anti-inflammatory and toxic effects of andrographolide derivatives in experimental animals. Archives of Pharmacal Research 2009; 32(9): 1191–1200.

Huang H, Cao H, Xing C, et al. Andrographolide induce human embryonic stem cell apoptosis by oxidative stress response. Molecular & Cellular Toxicology 2019; 15(2): 209–219.

Akbarsha MA, Murugaian P. Aspects of the male reproductive toxicity/male antifertility property of andrographolide in albino rats: effect on the testis and the cauda epididymidal spermatozoa. Phytotherapy Research 2000; 14(6): 432–435.

Zhang WX, Zhang ZM, Zhang ZQ, et al. Andrographolide induced acute kidney injury: Analysis of 26 cases reported in Chinese Literature: Andrographolide induced AKI in Chinese Literature. Nephrology 2014; 19(1): 21–26.

Xu J, Xing W, Yuan T, et al. Metabolic changes in the urine of andrographolide sodium bisulfite-treated rats. Human & Experimental Toxicology 2016; 35(2): 162–169.

Sa-ngiamsuntorn K, Suksatu A, Pewkliang Y, et al. Anti-SARS-CoV-2 Activity of Andrographis paniculata Extract and Its Major Component Andrographolide in Human Lung Epithelial Cells and Cytotoxicity Evaluation in Major Organ Cell Representatives. Journal of Natural Products 2021; 84(4): 1261–1270.

Al Batran R, Al-Bayaty F, Al-Obaidi MMJ, et al. Acute Toxicity and the Effect of Andrographolide on Porphyromonas gingivalis-Induced Hyperlipidemia in Rats. BioMed Research International 2013; 2013: 594012.

Worakunphanich W, Thavorncharoensap M, Youngkong S, et al. Safety of Andrographis paniculata: A systematic review and meta-analysis. Pharmacoepidemiology and Drug Safety 2021; 30(6): 727–739.

Kaewdech A, Nawalerspanya S, Assawasuwannakit S, et al. The use of Andrographis paniculata and its effects on liver biochemistry of patients with gastrointestinal problems in Thailand during the COVID-19 pandemic: a cross sectional study. Scientific Reports 2022; 12(1): 18213.

Published

2024-02-29 — Updated on 2024-05-20

Versions

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Issue

Section

Review

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