Andrographis (Andrographis paniculata)

Traditional Indications

Andrographis is alterative, anthelmintic, bitter, febrifuge, stomachic and tonic. Andrographis is also known as Green chireta. Green chireta has a long history of traditional medicinal use in India, various parts of South-East Asia, Central America and the Caribbean (1). The leaf extract is a traditional remedy for the treatment of infectious disease, fever-causing diseases, colic pain, loss of appetite, irregular stools and diarrhoea (2).

Andrographis paniculata has traditionally been used in Indian and Chinese herbal medicine for cough, cold and influenza, suggesting a role in respiratory tract infections (RTIs) (3). In Traditional Chinese Medicine Andrographis paniculata is known as 穿心蓮 Chuān Xīn Lián. Chuān Xīn Lián is said to be bitter and cold and enters the Lung, Stomach, Large Intestine, Liver and Bladder meridians and to clear heat and dry damp, purges fire and remove toxicity and is prescribed to treat common cold fever, swollen sore throat, aphthous ulcers, whooping cough, diarrhoea and dysentery, heat strangury, abscess and insect bites (4)

Pharmacognocy

The major constituents of Andrographis paniculata are diterpenoids, flavonoids and polyphenols. Single compounds include the major one in terms of bioactive properties and abundance andrographolide. Andrographolide analogues is immunostimulatory, anti-infective and anti-atherosclerotic, neoandrographolide is anti-inflammatory, anti-infective and anti-hepatotoxic. 14-deoxyandrographolide is immunomodulatory and anti-atherosclerotic. Andrograpanin is anti-inflammatory and anti-infective, 14-deoxy-14,15-dehydroandrographolide is anti-inflammatory; isoandrographolide, 3,19-isopropylideneandrographolide and 14-acetylandrographolide are tumour suppressive; arabinogalactan proteins are anti-hepatotoxic. The four flavonoids from A. paniculata, namely 7-O-methylwogonin, apigenin, onysilin and 3,4-dicaffeoylquinic acid are anti-atherosclerotic (5).

Andrographis contains diterpenolactones which inhibits liver Phase I cytochrome P450 desired in cases of excess Persistent Organic Pollutants and to assist bitranfromation in bioaccumulation (6).

Andrographis paniculata constituent Andrographolide derivatives display analgesic, antipyretic and anti-inflammatory effects of in experimental animals (7). Andrographis paniculata downregulates proinflammatory cytokine production and augments cell mediated immune response in metastatic tumour-bearing mice (8). Andrographis paniculata showed potent anti-inflammatory effect on pathogen-induced pelvic inflammatory disease (PID) in rats, with a potential mechanism of inhibiting the NF-κB signal pathway (9). NF-κB has long been considered a prototypical proinflammatory signalling pathway, largely based on the activation of NF-κB by proinflammatory cytokines such as interleukin 1 (IL-1) and tumour necrosis factor α (TNFα), and the role of NF-κB in the expression of other proinflammatory genes including cytokines, chemokines, and adhesion molecules (10). Other studies suggest Andrographolide exerts an anti-inflammatory effect by inhibiting the activation of NF-κB/MAPK signalling pathway and the induction of proinflammatory cytokines (11). Andrographolide has the potential to bind with crucial proteins to block the TNF-induced NF-κB signalling pathway responsible for cytokine storm in C-19 patients (12).

A study investigating the immunomodulatory effects of andrographolide on both innate and adaptive immune responses. Andrographolide can modulate the innate and adaptive immune responses by regulating macrophage phenotypic polarization and Ag-specific antibody production. MAPK and PI3K signalling pathways may participate in the mechanisms of andrographolide regulating macrophage activation and polarization. Andrographis paniculata extract was found to be effective in preventing liver damage which was evident by morphological, biochemical and functional parameters (13).

A 12-month double-blind placebo-controlled pilot study concluded that Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis (14).
A systematic review and meta-analysis analysing the use of Andrographis paniculata for symptomatic relief of acute respiratory tract infections (ARTI) in adults and children concluded that Andrographis paniculata appears beneficial and safe for relieving ARTI symptoms and shortening time to symptom resolution and that in light of antimicrobial resistance (AMR) being a substantial threat to public health well-designed trials evaluating the effectiveness and potential to reduce antibiotic using Andrographis are warranted (15).
The active constituent Andrographolide inhibits influenza A virus and reduces inflammatory cytokines expression induced by infection (16).

Sequence analysis indicates that the novel CoV has an insertion of a furin cleavage site (PRRAR) in its S protein. Furin cleavage site plays a critical role in SARS-CoV-2 replication and pathogenesis (17). Furin protease inhibitors may be promising antiviral agents for prevention of SARS-CoV-2 infection and treatment of C-19. Comorbidities associated with C-19 including obesity, diabetes, and hypertension are associated with increased circulating furin levels, therefore addressing comorbidities through diet and lifestyle modifications, and pharmacological treatment is indicated to reduce C-19 pathogenicity. Natural furin inhibitors may prove highly useful to inhibit viral entry and propagation (18). Natural furan inhibitors include the phytochemicals andrographolide and neoandrographolide from Andrographis paniculata (19).

Synergistic effects of acyclovir and 3, 19-isopropylideneandrographolide on herpes simplex virus wild types and drug-resistant strains have been demonstrated (20).

Andrographolide showed potential antibacterial activity against most of the tested Gram-positive bacteria. Among those, Staphylococcus aureus was found to be most sensitive (21). Andrographolide isolated from callus culture of Andrographis paniculata showed broad spectrum of growth inhibition activity against Staphylococcus aureus, Streptococcus thermophilus, Bacillus subtilis, Escherichia coli, Mycobacterium smegmatis, Klebsiella pneumonia and Pseudomonas aeruginosa (22).

Andrographis paniculata extracts inhibit quorum sensing, virulence and biofilm formation in Pseudomonas aeruginosa and exhibit anti-inflammatory activities, therefore it represents itself as a prospective therapeutic agent against Pseudomonas aeruginosa infection (23). Andrographis paniculata inhibits the production of virulence factors of Pseudomonas aeruginosa to achieve anti-infective effects (24).

Andrographis paniculata extract inhibit growth, biofilm formation in multidrug resistant strains of Klebsiella pneumoniae (25) Andrographis paniculata extract inhibit growth, biofilm formation in multidrug resistant strains of Klebsiella pneumoniae (25).

1. PFAF. Andrographis paniculata 2018 [Available from: https://pfaf.org/user/Plant.aspx?LatinName=Andrographis+paniculata.
2. Okhuarobo A, Falodun JE, Erharuyi O, Imieje V, Falodun A, Langer P. Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology: Asian Pac J Trop Dis. 2014 Jun;4(3):213-22. doi: 10.1016/S2222-1808(14)60509-0.
3. Hu XY, Wu RH, Logue M, Blondel C, Lai LYW, Stuart B, et al. Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis. PLoS One. 2017;12(8):e0181780.
4. Lotus S. Chuan Xin Lian (Green Chiretta or Kariyat or Andrographis) 2018 [Available from: https://www.sacredlotus.com/go/chinese-herbs/substance/chuan-xin-lian-green-chiretta-kariyat-andrographis.
5. Chao W-W, Lin B-F. Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian). Chinese medicine. 2010;5:17-.
6. Mohamed L Ashour FSY, Haidy A Gad, Michael Wink2. Inhibition of Cytochrome P450 (CYP3A4) Activity by Extracts from 57 Plants Used in Traditional Chinese Medicine (TCM). Pharmacogn Mag. 2016.
7. Suebsasana S, Pongnaratorn P, Sattayasai J, Arkaravichien T, Tiamkao S, Aromdee C. Analgesic, antipyretic, anti-inflammatory and toxic effects of andrographolide derivatives in experimental animals. Arch Pharm Res. 2009;32(9):1191-200.
8. 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(3):723-9.
9. Zou W, Xiao Z, Wen X, Luo J, Chen S, Cheng Z, et al. The anti-inflammatory effect of Andrographis paniculata (Burm. f.) Nees on pelvic inflammatory disease in rats through down-regulation of the NF-κB pathway. BMC complementary and alternative medicine. 2016;16(1):483-.
10. Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harbor perspectives in biology. 2009;1(6):a001651-a.
11. Li Y, He S, Tang J, Ding N, Chu X, Cheng L, et al. Andrographolide Inhibits Inflammatory Cytokines Secretion in LPS-Stimulated RAW264.7 Cells through Suppression of NF-κB/MAPK Signaling Pathway. Evidence-based complementary and alternative medicine : eCAM. 2017;2017:8248142-.
12. Rehan M, Ahmed F, Howladar SM, Refai MY, Baeissa HM, Zughaibi TA, et al. A Computational Approach Identified Andrographolide as a Potential Drug for Suppressing COVID-19-Induced Cytokine Storm. Frontiers in immunology. 2021;12:648250.
13. Rana AC, Avadhoot Y. Hepatoprotective effects of Andrographis paniculata against carbon tetrachloride-induced liver damage. Arch Pharm Res. 1991;14(1):93-5.
14. Bertoglio JC, Baumgartner M, Palma R, Ciampi E, Carcamo C, Cáceres DD, 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-.
15. Hu X-Y, Wu R-H, Logue M, Blondel C, Lai LYW, Stuart B, et al. Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis. PLOS ONE. 2017;12(8):e0181780.
16. Ding Y, Chen L, Wu W, Yang J, Yang Z, Liu S. Andrographolide inhibits influenza A virus-induced inflammation in a murine model through NF-κB and JAK-STAT signaling pathway. Microbes and infection. 2017;19(12):605-15.
17. Johnson BA, Xie X, Kalveram B, Lokugamage KG, Muruato A, Zou J, et al. Furin Cleavage Site Is Key to SARS-CoV-2 Pathogenesis. bioRxiv. 2020.
18. Fitzgerald K. Furin Protease: From SARS CoV-2 to Anthrax, Diabetes, and Hypertension. Perm J. 2020;24.
19. Devi KP, Pourkarim MR, Thijssen M, Sureda A, Khayatkashani M, Cismaru CA, et al. A perspective on the applications of furin inhibitors for the treatment of SARS-CoV-2. Pharmacological Reports. 2022;74(2):425-30.
20. Priengprom T, Ekalaksananan T, Kongyingyoes B, Suebsasana S, Aromdee C, Pientong C. Synergistic effects of acyclovir and 3, 19-isopropylideneandrographolide on herpes simplex virus wild types and drug-resistant strains. BMC Complement Altern Med. 2015;15:56.
21. Banerjee M, Parai D, Chattopadhyay S, Mukherjee SK. Andrographolide: antibacterial activity against common bacteria of human health concern and possible mechanism of action. Folia Microbiol (Praha). 2017;62(3):237-44.
22. Chen JX, Xue HJ, Ye WC, Fang BH, Liu YH, Yuan SH, et al. Activity of andrographolide and its derivatives against influenza virus in vivo and in vitro. Biological and pharmaceutical bulletin. 2009;32(8):1385-91.
23. Banerjee M, Moulick S, Bhattacharya KK, Parai D, Chattopadhyay S, Mukherjee SK. Attenuation of Pseudomonas aeruginosa quorum sensing, virulence and biofilm formation by extracts of Andrographis paniculata. Microb Pathog. 2017;113:85-93.
24. Zhang L, Bao M, Liu B, Zhao H, Zhang Y, Ji X, et al. Effect of Andrographolide and Its Analogs on Bacterial Infection: A Review. Pharmacology. 2020;105(3-4):123-34.
25. Sah SK, Rasool U, Hemalatha S. Andrographis paniculata extract inhibit growth, biofilm formation in multidrug resistant strains of Klebsiella pneumoniae. J Tradit Complement Med. 2020;10(6):599-604.