Exploring Medicinal Properties of Andrographis

by Michael Stanclift, ND

Introduction

Many clinicians who know andrographis (Andrographis paniculata) know its anticancer properties; however, its antimicrobial mechanisms have recently caught researchers’ eyes.^1-3 Andrographis has been used for its medicinal benefits in traditional Chinese medicine and Ayurveda for centuries, mostly for effects related to infections and/or the immune system.^1,3 Based on computer models, some researchers hypothesize andrographolide, a major bioactive compound of andrographis, might have a role in the current COVID-19 pandemic.^2,3 Andrographis demonstrates antiviral activity against a number of a diverse range of viruses, and possesses anti-inflammatory properties.¹

While andrographis has many mechanisms and has been studied for numerous disease states, in this article we will mainly focus on the antimicrobial and anti-inflammatory actions. The information in this article is intended for use by licensed healthcare professionals for educational purposes only and should not be used to treat and/or diagnose any medical condition(s).

Mechanisms of action

Antibacterial

Andrographolide inhibits quorum sensing of Pseudomonas aeruginosa, a gram-negative multidrug-resistant pathogen.¹ It is bacteriostatic and prevents biofilm formation of gram-positive Staphylococcus aureus.⁴ In vitro studies also show activity against Salmonella, Shigella, E. coli, Streptococcus pyogenes, Legionella pneumophila, and Bordetella pertussis.⁵

Antiviral

Andrographolide is antiviral to a multitude of DNA and single-stranded RNA viruses including:²

DNA viruses

• Herpes simplex (HSV)
• Human papilloma (HPV)
• Epstein-Barr (EBV)
• Hepatitis B (HBV)

(+)ssRNA viruses

• Hepatitis C (HCV)
• Chikungunya (CHIKV)
• Dengue (DENV)

(-)ssRNA viruses

• Influenza
• Human immunodeficiency (HIV)

Andrographolide can potentially inhibit the main protease (Mpro) of SARS-CoV-2; however, this has only been tested through computer modeling.⁶ If this mechanism pans out clinically, it might help patients already infected with SARS-CoV-2.⁶ 

In a 5-day randomized, double-blind, placebo-controlled trial (n = 158) 1200 mg/day andrographis extract significantly decreased intensity of symptoms of uncomplicated common cold at day 2 and day 4 of treatment.⁷ The highest odds ratios for decreases in symptoms observed were for sore throat (OR = 2.3 at day 2; OR = 3.59 at day 4), nasal secretion (OR = 2.51 at day 2; OR = 3.27 at day 4), and earache (OR = 3.11 at day 4).

Antioxidant

Andrographolide mitigates oxidative stress through activating nuclear factor erythroid 2-related factor 2 (Nrf2), a regulator of antioxidant proteins.¹ This pathway is important in oxidative stress modulation in diabetes, osteoporosis, and neurodegenerative diseases.¹ Andrographolide has direct antioxidant properties that are even more potent than vitamin C.⁸ Andrographis extract inhibits reactive oxygen species (ROS) formation and exhibits up to an 80% reduction in lipid peroxidation in in vitro models.^5,8 In vitro models show andrographolide protects mitochondria from oxidative stres, and ameliorates mitochondrial dysfunction.⁸

Anti-inflammatory and Immunomodulatory

Andrographolide exhibits important and broad anti-inflammatory actions, including pulmonary and virally induced inflammation with in vitro/vivo experiments.¹ It can prevent lipopolysaccharide (LPS)-incited lung injury, inflammatory cell recruitment, and proinflammatory cytokine production.¹ Andrographolide reduces pro-inflammatory responses from macrophages, shifting the response from M1 (pro-inflammatory) to M2 (pro-resolution) phenotype.^9,10

Andrographolide exerts anti-inflammatory and immunomodulatory effects by inhibiting/lowering in vitro/vivo:¹

• Mitogen-activated protein kinase (MAPK)
• Nuclear factor-κB (NF-κB)
• Inducible nitric oxide synthase (iNOS)
• Signal transducer and activator of transcription 2 (STAT3) activation
• Macrophage inflammatory protein 2 (MIP-2)
• Interleukins 1β and 6 (IL-1β, IL-6)
• Interferon gamma (IFN-γ)
• Tumor necrosis factor-alpha (TNF-α)
• NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation⁹

While inflammatory processes are important for fighting infections, containing their extent is imperative to prevent secondary infectious effects, such as the cytokine storm that contributes to acute respiratory distress syndrome (ARDS) with COVID-19.¹²

Clinical application

Andrographis is commonly administered in standardized extracts of andrographolides and often in combination with other herbs.^1,6,13-17

Dose ranges

• 4–4,200 mg per day, usually in divided doses in acute infections^13,14
• 10 mg/kg has been used up to 3 weeks in chronically ill (HIV population)¹⁵

Administration

• 3–5 days (up to 4,200 mg) for acute infections^6,13,14
• 3 weeks (1,500–2,000 mg) for chronic infections¹⁵
• 1–12 months (300–1,800 mg) for chronic inflammatory conditions^1,16,17

Safety/tolerability

• Minor digestive adverse events and elevated liver enzymes are reported in one placebo-controlled study, but the findings did not reach statistical significance (p = 0.197).¹⁷
• Absolute neutrophils increased and a transient significant reduction in blood pressure was observed on the third day of administering 4,200 mg per day in healthy subjects.¹⁴
• Hypersensitivity has been rarely observed in areas where andrographis use is widespread.¹⁸
• Andrographolide has antiplatelet activity and may increase bleeding time when used with drugs of similar effects; however, this interaction appears to be based on theoretical rather than clinical evidence.¹⁹

Conclusion

Andrographis and it major compound, andrographolide, have been largely overlooked in Western medicine despite their safety and a wide therapeutic range. Andrographis’s effects on COVID-19 are theoretical and unknown; however, evidence supports its use in numerous viral infections. Its anti-inflammatory activities act upon multiple pathways, giving it a unique therapeutic profile deserving of clinical attention.

Citations

1. Dai Y et al. Overview of pharmacological activities of Andrographis paniculataand its major compound andrographolide. Crit Rev Food Sci Nutr. 2019;59(sup1):S17-S29.
2. Banerjee A et al. Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19. Life Sci. 2020;255:117842.
3. PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/Andrographolide#section=Coronavirus-Studies. Accessed June 29, 2020.
4. Banerjee M et al. Andrographolide: antibacterial activity against common bacteria of human health concern and possible mechanism of action. Folia Microbiol (Praha). 2017;62(3):237-244.
5. Jayakumar T et al. Experimental and clinical pharmacology of andrographis paniculata and its major bioactive phytoconstituent andrographolide. Evid Based Complement Alternat Med. 2013;2013:846740.
6. Enmozhi SK et al. Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach. J Biomol Struct Dyn. 2020;1-7.
7. Cáceres DD et al. Use of visual analogue scale measurements (VAS) to assess the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study. Phytomedicine. 1999;6(4):217-223.
8. Mussard E et al. Andrographolide, a natural antioxidant: an update. Antioxidants (Basel). 2019;8(12):571.
9. Wang W et al. Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response. Acta Pharmacol Sin. 2010;31(2):191-201.
10. Jantan I et al. Plant-derived immunomodulators: an insight on their preclinical evaluation and clinical trials. Front Plant Sci. 2015;6:655.
11. Guo W et al. Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitis-associated cancer. Autophagy. 2014;10(6):972-985.
12. Ye Q et al. The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. J Infect. 2020;80(6):607-613.
13. Roxas M et al. Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations. Altern Med Rev. 2007;12(1):25-48.
14. Suriyo T et al. Clinical parameters following multiple oral dose administration of a standardized Andrographis paniculata capsule in healthy Thai subjects. Planta Med. 2017;83(9):778-789.
15. Jayakumar T et al. Experimental and clinical pharmacology of Andrographis paniculata and its major bioactive phytoconstituent andrographolide. Evid Based Complement Alternat Med. 2013;2013:846740.
16. Bertoglio JC et al. Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study. BMC Neurol. 2016;16:77.
17. Hancke JL et al. A double-blind, randomized, placebo-controlled study to assess the efficacy of Andrographis paniculata standardized extract (ParActin®) on pain reduction in subjects with knee osteoarthritis. Phytother Res. 2019;33(5):1469-1479.
18. Suwankesawong W et al. Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database. BMC Complement Altern Med. 2014;14:515.
19. Drug Bank. https://www.drugbank.ca/drugs/DB05767. Accessed July 1, 2020.

Michael Stanclift, ND graduated from Bastyr University’s school of naturopathic medicine and practiced in Edinburgh, Scotland, and Southern California. He enjoys educating other healthcare providers and impacting the lives of their many patients. When he’s not working, he spends his hours with his wife and two children.