Green Chiretta (Andrographis paniculata): A Comprehensive Reference
1. Identity and Botanical Classification
1.1 Nomenclature
Andrographis paniculata (Burm. f.) Nees, commonly known as creat or green chiretta, is an annual herbaceous plant in the family Acanthaceae, native to India and Sri Lanka. Botanical synonyms include A. paniculata var. glandulosa Trimen. and Justicia paniculata Burm. f.
It is commonly known as the "king of bitter" or green chiretta in English; "Kalmegh" in Hindi; "Chanxinlian" (also romanized as Chuān Xīn Lián) in Chinese; "fah tha lai" in Thai; and "Hempedubumi" in Malaysian. In Ayurveda, the plant is called Kalamegha, literally meaning "black cloud," perhaps attesting to its traditional harvesting just before winter. It is also known as bhunimba, meaning "neem of the earth," a reference to its bitter, neem-like taste and effects. Other English designations include "Indian echinacea" and "King of Bitters."
1.2 Botanical Description and Geographic Range
A. paniculata is an annual herbaceous plant native to India and Sri Lanka; it has been cultivated or naturalized in various other areas of the world, including China, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Thailand, Vietnam, and the Caribbean. It is an erect herb that is very bitter in taste. A plant of the tropics, it is found at elevations up to 1,600 metres.
Approximately 28 species of Andrographis are known and indigenous to Asia; A. paniculata is the most commonly used.
1.3 Common Preparations and Dosage Forms
Both the fresh and dried leaves, and the fresh juice of the whole plant are used as medicine. In modern commerce, the plant is most frequently encountered as:
- Standardized dry extracts in tablet or capsule form. Well-studied proprietary preparations include Kan Jang (also spelled KanJang or Kanjang), a combination product developed by the Swedish Herbal Institute, and KalmCold (also designated AP-Bio®), a standardized leaf extract.
- Crude dried herb powder, used in traditional systems as decoctions, teas, or compressed tablets.
- Andrographolide-enriched injectable derivatives, used primarily in Chinese clinical medicine — a formulation category associated with a distinct and higher adverse-event profile than oral herbal preparations (discussed under Safety).
The Scandinavian SHA-10 formulation contains a defined 4:1 extract with 5.6% andrographolide and 0.5% dehydroandrographolide. Chuanxinlian — the dried aerial part of A. paniculata — is widely distributed in Asia, including China and India, and is used as a traditional Chinese medicine in the treatment of respiratory tract infections, acute dysentery, gastroenteritis, fever and flu, and hypertension.
2. Traditional and Historical Use
2.1 Ayurvedic Tradition (India and Sri Lanka)
Andrographis paniculata has a long history in both Ayurvedic medicine and Traditional Chinese Medicine. Its use as a medicine has been traced to Ayurvedic practice beginning around 3,000–4,000 BCE. In Ayurveda, andrographis was used as a bitter tonic, a remedy against intestinal parasites, and a general stomachic. In Ayurvedic medicine, it is used as an alterative (supporting routes of detoxification), stomachic (supporting digestion), and as an immune supporter.
The leaves are used traditionally in Asian traditional medicine, and particularly in Ayurveda, to treat fever associated with infections. Across various cultures, it was commonly used for conditions like fevers, sore throats, and digestive issues such as dysentery and irregular stools.
2.2 Traditional Chinese Medicine (TCM)
Known as chuan xin lian in Traditional Chinese Medicine, andrographis was traditionally characterized as a bitter, cooling, and drying remedy. It is used in modern Chinese medicine to eliminate toxins (heat), especially in disorders of the lungs, throat, urinary system, and skin. It is frequently used in TCM to eliminate heat and toxins from the body, making it a popular choice for managing respiratory and immune system disorders. Its bitter character is consistent with the TCM theory of bitter herbs cleansing and detoxifying the body.
As a traditional Chinese medicine, Chuanxinlian has been used clinically in the treatment of respiratory tract infections, acute dysentery, gastroenteritis, fever and flu, hypertension, and other diseases.
2.3 Broader Regional Use
It is a traditional herbal treatment for diseases and ailments such as diarrhea, dysentery, cholera, pneumonia, swollen lymph nodes, leprosy, bronchitis, and sore throats; other traditional uses include treatment for tuberculosis, chicken pox, coughs, headaches, ear infections, inflammation, burns, and mumps. Andrographis was also used as a treatment for malaria, as a replacement for quinine. It is traditionally used for the treatment of snake bite, diabetes, dysentery, and malaria. The plant used to be considered an effective remedy against snake bites and is still used locally for this purpose.
A. paniculata has also traditionally been used in India and China for the common cold and influenza. The claim that andrographis halted the 1919 Indian flu epidemic has been reported in some historical accounts but has not been proven.
3. Key Constituents and Active Compounds
3.1 Phytochemical Profile
Chemically, A. paniculata has major constituents including diterpenoids, lactones, flavonoid glycosides, diterpene glycosides, and flavonoids. Active compounds extracted with ethanol or methanol from the whole plant, leaf, and stem include over 20 diterpenoids and over ten flavonoids.
Andrographolide (C20H30O5) is the major diterpenoid in A. paniculata, making up about 4%, 0.8–1.2%, and 0.5–6% in dried whole plant, stem, and leaf extracts respectively. Andrographolide, a major ent-labdane diterpenoid of A. paniculata, is the largest contributor of many pharmacological activities. Other ent-labdane diterpenoids — such as neoandrographolide and 14-deoxyandrographolide — flavonoids, quinic acids, and xanthones are also reported for their significant contributions.
The other main diterpenoids are deoxyandrographolide, neoandrographolide, 14-deoxy-11,12-didehydroandrographolide, and isoandrographolide. The plant also contains diterpene lactones, glycosides and flavonoids, alkaloids, phenols, catechins, saponins, and tannins; additionally it contains andrographolide, neoandrographolide, tetradecanoic acid, phytol, dioctyl ester, squalene, retinoic acid methyl ester, and β-sitosterol.
3.2 Individual Compound Bioactivities
Among the andrographolide analogues: 14-deoxy-11,12-didehydroandrographolide is immunostimulatory, anti-infective, and anti-atherosclerotic; neoandrographolide is anti-inflammatory, anti-infective, and anti-hepatotoxic; and 14-deoxyandrographolide is immunomodulatory and anti-atherosclerotic. Among the less abundant compounds, andrograpanin is both anti-inflammatory and anti-infective; 14-deoxy-14,15-dehydroandrographolide is anti-inflammatory; isoandrographolide, 3,19-isopropylideneandrographolide, and 14-acetylandrographolide are tumor suppressive; and arabinogalactan proteins are anti-hepatotoxic.
4. Established Mechanisms of Action
4.1 NF-κB Pathway Inhibition
Nuclear factor-κB (NF-κB) is an important intracellular nuclear transcription factor; many complicated diseases are closely related to the NF-κB-mediated signaling pathway, which can affect the body's inflammatory response, immune response, apoptosis regulation, and stress response. Andrographolide dose-dependently inhibits the release and mRNA expression of TNF-α, IL-6, and IL-1β in LPS-stimulated macrophage cells; the nuclear level of p65 protein is decreased with andrographolide treatment.
Andrographolide suppresses the activation of NF-κB in stimulated endothelial cells while having no suppressive effect on IκBα degradation, p50, and p65 nuclear translocation, thus revealing a unique pharmacological mechanism of its protective anti-inflammatory actions.
4.2 JAK/STAT and MAPK Pathway Modulation
Recent research has shown that andrographolide can exert anti-inflammatory effects via multiple pathways and multiple targets, mediated by NF-κB, JAK/STAT, T cell receptor, and other signaling pathways. Andrographolide can reduce the amount of inflammatory swelling in experimental mice by blocking the JAK2/STAT3 signaling pathway and inhibiting the release of pro-inflammatory cytokines and mediators.
4.3 COX-2 and iNOS Inhibition
Andrographolide and its derivatives modulate inflammatory pathways by suppressing NF-κB, COX-2, iNOS, and proinflammatory cytokines, while enhancing lymphocyte proliferation and interleukin-2 expression.
4.4 Immunomodulation
Andrographolide regulates the immune system, treats cardiovascular and cerebrovascular diseases, protects the liver, and the gallbladder. Andrographis paniculata is recognized for its role in immune system modulation, supporting a healthy immune response. The herb also exhibits anti-inflammatory effects, with andrographolides demonstrating the ability to interfere with enzymatic activities involved in inflammatory pathways.
4.5 Antiviral Properties
Several bioactive compounds from A. paniculata, including andrographolide, neoandrographolide, dehydroandrographolide, 14-deoxy-11,12-didehydroandrographolide, and 14-deoxyandrographolide, as well as synthetic derivatives, have been shown to have significant antiviral activity against HIV, influenza A, and HSV-1 without any significant cytotoxic effect at virucidal concentrations. Andrographolide isolated from ethanol extracts showed promise in the treatment of HIV infections.
5. Scientific Evidence by Area of Use
5.1 Upper Respiratory Tract Infections (Common Cold, Influenza, URTI)
This is the area with the strongest and most consistent body of human clinical evidence for green chiretta.
In a systematic review (Coon and Ernst, 2004), seven double-blind controlled trials (n = 896) met the inclusion criteria for evaluation of efficacy; all trials scored at least three out of a maximum of five for methodological quality on the Jadad scale. The authors of that review concluded that Andrographis paniculata may be an effective treatment with few adverse effects and that further research is justified.
A separate systematic review (Poolsup et al., 2004) aimed to assess the efficacy of A. paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection using a meta-analysis of randomized controlled trials; four studies met inclusion criteria and were reviewed, with a total of 433 patients from three trials included in the statistical analysis. The difference in effects between A. paniculata and placebo was 10.85 points (95% CI 10.36–11.34, P < 0.0001) in favour of A. paniculata.
A 2017 systematic review and meta-analysis (published in PLOS ONE) aimed to evaluate the clinical effectiveness and safety of A. paniculata for symptoms of acute RTIs; the herb had traditionally been used in Indian and Chinese herbal medicine for cough, cold, and influenza. This 2017 meta-analysis indicated possible support for efficacy and safety, but cautioned that the trials reviewed were of poor quality and thus not conclusive.
A key individual trial involved the proprietary extract KalmCold (AP-Bio®): a randomized, double-blind, placebo-controlled clinical study was conducted to evaluate the efficacy of KalmCold in patients with uncomplicated upper respiratory tract infection; assessment involved quantification of symptom scores by Visual Analogue Scale across nine self-evaluated symptoms including cough, nasal discharge, headache, fever, sore throat, and malaise. A total of 223 patients were randomized to receive either KalmCold (200 mg/day) or placebo. The comparison of overall efficacy of KalmCold over placebo was found to be significant (p ≤ 0.05) and it was 2.1 times (52.7%) higher than placebo.
A subsequent larger phase III trial examined AP-Bio® at 200 mg/day and 400 mg/day: participants were randomized in a ratio of 1:1:1 to receive either AP-Bio® 200 mg/day, AP-Bio® 400 mg/day, or placebo for 7 days; the primary outcome measure was Wisconsin Upper Respiratory Symptom Survey (WURSS-21) score; secondary outcome measures included nasal mucous weight, nasal muco-ciliary clearance function, and IL-8 in nasal wash; 300 participants were enrolled. AP-Bio® at 200 mg/day and 400 mg/day (versus placebo) significantly managed common cold symptoms on Day 3 with no safety concerns; it also showed a trend in decreasing nasal mucous weight, tissue paper counts used, and interleukin-8 on Day 3.
The Kan Jang (KanJang) combination product was also investigated: Kanjang® tablets (standardized Andrographis paniculata extract) have proven effective in the initial treatment of common cold and sinusitis.
Evidence assessment: The human clinical evidence for reduction of symptoms and duration of uncomplicated upper respiratory tract infection is the most robust available for this plant. Multiple randomized, double-blind, placebo-controlled trials and several systematic reviews support a modest-to-moderate beneficial effect. Limitations include generally small sample sizes, heterogeneity of preparations and dosages across studies, and methodological quality concerns noted in systematic reviews.
5.2 Ulcerative Colitis
A. paniculata has in vitro inhibitory activity against TNF-α, IL-1β, and NF-κB. A pilot study of the extract HMPL-004 suggested similar efficacy to mesalamine for ulcerative colitis. A randomized, double-blind, placebo-controlled trial evaluated HMPL-004 in 224 adults with mild-to-moderate ulcerative colitis, with patients randomized to 1,200 mg or 1,800 mg daily or placebo for 8 weeks.
In total, 45% and 60% of patients receiving A. paniculata 1,200 mg and 1,800 mg daily, respectively, were in clinical response at week 8, compared with 40% of those who received placebo (P = 0.5924 for 1,200 mg vs. placebo; P = 0.0183 for 1,800 mg vs. placebo). In addition, 34% and 38% receiving 1,200 mg and 1,800 mg daily, respectively, were in clinical remission at week 8, compared with 25% of those receiving placebo. Patients with mildly to moderately active ulcerative colitis treated with HMPL-004 at a dose of 1,800 mg daily were more likely to achieve clinical response than those receiving placebo.
Two randomized, double-blind clinical studies in patients with ulcerative colitis (N = 120 and N = 224) suggest extracts of andrographis may be as effective as mesalamine; dosages of 1,200 mg or 1,800 mg of A. paniculata extract daily (in 3 divided doses) for 8 weeks were used in the studies.
Evidence assessment: The evidence for ulcerative colitis is preliminary but promising. The larger (N = 224) trial is properly randomized, double-blind, and placebo-controlled, and demonstrated statistically significant clinical response at the higher dose. The clinical remission rates, however, did not reach statistical significance versus placebo. This area warrants further investigation with larger trials.
5.3 Rheumatoid Arthritis
A prospective, randomized, double-blind, placebo-controlled study in patients with rheumatoid arthritis (RA) was performed. Tablets (Paractin) made of an extract of A. paniculata (30% total andrographolides) were administered three times a day for 14 weeks after a 2-week washout period to 60 patients with active RA. The primary outcomes were pain intensity measured using a horizontal visual analog pain scale. In addition, ACR, EULAR, and SF36 clinical parameters were recorded. The intensity of joint pain decreased in the active vs. placebo group at the end of treatment, although these differences were not statistically significant.
In 60 patients with rheumatoid arthritis, andrographolides 30 mg taken 3 times daily over 14 weeks resulted in improved rheumatoid symptoms of swelling and tenderness; reductions in rheumatoid factor and other indices were also associated with treatment compared with placebo.
Evidence assessment: Evidence for rheumatoid arthritis is limited to small, single trials. The primary endpoint of pain reduction did not reach statistical significance in the main RCT. Some secondary inflammatory markers showed improvement. Research in this area is currently limited, and human studies are needed before andrographis can be recommended to treat rheumatoid arthritis.
5.4 HIV and Immune Function
In a small trial of patients with HIV, andrographolides, the active ingredients in andrographis, increased the number of lymphocytes. However, this trial was also the context for significant adverse events (see Safety section), and the study was interrupted. The evidence in this area remains very preliminary.
5.5 COVID-19 (Emerging Evidence)
Amid Thailand's COVID-19 outbreak in December 2020, the country's health ministry approved the usage of the plant extract for a pilot alternative treatment program. In silico studies demonstrated strong binding affinities of andrographolide and related compounds to SARS-CoV-2 targets, including the spike protein, spike protein–ACE-2 receptor complex, and main protease (Mpro). Most COVID-19 evidence remains in silico or from cell culture/animal models; robust human clinical trials are lacking and results in this area should be treated as highly preliminary.
5.6 Diarrhea and Gastrointestinal Infections
Studies have found that A. paniculata has significant antidiarrheal properties. According to one study, an ethanolic extract of A. paniculata treated 88.3% of acute bacillary dysentery cases and 91.3% of acute gastroenteritis cases. Furthermore, andrographolide was found to treat 91% of acute bacillary dysentery cases. These figures derive from older and primarily Asian clinical studies; they have not been replicated in modern controlled trials of comparable rigor and should be interpreted with caution.
6. Body Systems and Health Areas of Association
The pharmacological effects attributed to A. paniculata include anti-inflammatory, antibacterial, antiviral, antihyperglycemic, anticancer, antistress, hepatoprotective, and immunomodulatory activities.
- Immune system: One of the most studied properties of A. paniculata is its ability to modulate the immune system; numerous studies have examined its ability to boost immune cell function, allowing the body to develop a more powerful defense against infections. Because of this function, the herb is used in formulations targeting prevention and treatment of common cold, flu, and other respiratory illnesses.
- Respiratory system: Upper respiratory tract infections represent the most evidenced clinical application (see Section 5.1).
- Gastrointestinal system: Andrographis is also used for digestive problems, blood cleanser, fever, sore throat, and upper respiratory infections.
- Musculoskeletal / inflammatory system: Limited clinical evidence for rheumatoid arthritis and osteoarthritis (see Section 5.3). In vitro research shows it can inhibit human lung cancer cells, colon cancer cells, osteosarcoma cells, and other tumor cells.
- Liver and biliary system: Andrographolide is reported to protect the liver and the gallbladder. Arabinogalactan proteins in the plant have been identified as anti-hepatotoxic.
- Cardiovascular system: Aberrant vascular smooth muscle cell proliferation and cerebral endothelial cell dysfunction contribute significantly to the pathogenesis of cardiovascular diseases; andrographolide has been investigated as a novel NF-κB inhibitor with anti-proliferative and anti-inflammatory effects in these cell types.
7. Dosage Forms and Dosages Reported in Clinical Studies
The following dosages reflect those reported in identifiable clinical studies. They are not recommendations.
- In the KalmCold randomized, double-blind, placebo-controlled URTI trial, 223 patients received KalmCold at 200 mg/day.
- In a subsequent phase III trial, participants received AP-Bio® (KalmCold) at either 200 mg/day or 400 mg/day for 7 days.
- In a systematic review, the dose of andrographis used across trials ranged from 48 to 360 mg.
- In two randomized, double-blind clinical studies of ulcerative colitis (N = 120 and N = 224), dosages of 1,200 mg or 1,800 mg of A. paniculata extract daily, given in 3 divided doses, were used for 8 weeks.
- In the rheumatoid arthritis trial, tablets (Paractin) of an extract of A. paniculata (30% total andrographolides) were administered three times a day for 14 weeks.
- Adverse reactions became apparent at an andrographolide dose of 10 mg/kg body weight in a phase I HIV study.
8. Safety Considerations and Drug Interactions
8.1 General Safety Profile of Oral Herbal Preparations
A systematic review and meta-analysis of safety (262 studies including 125 RCTs) found that in 9,490 participants using andrographolide derivative injections, 383 (4.04%) reported adverse drug reactions. In contrast, nine herbal preparations of A. paniculata tested in 10 studies reported adverse drug reactions that were mainly mild to moderate gastrointestinal and skin/subcutaneous tissue disorders. This distinction between injectable andrographolide derivatives and oral herbal preparations is important: the injectable forms carry substantially higher risk.
The adverse drug reactions of andrographolide derivative injections were mainly gastrointestinal, skin and subcutaneous tissue disorders, and anaphylaxis; fifty-five patients experienced life-threatening anaphylactic shock, and three patients died, with causation attributed to the andrographolide derivative injection.
8.2 Adverse Events in Oral Clinical Trials
In a clinical trial, headache, fatigue, rash, bitter/metallic taste, diarrhea, pruritus, and decreased sex drive were reported with andrographis at 10 mg/kg body weight. One participant who was HIV-positive experienced an anaphylactic reaction. In the same trial, elevated liver enzymes were experienced by many subjects. Two cases of urticaria were reported in other trials.
Anaphylaxis and allergic reactions have been caused by several different A. paniculata preparations; methanol extracts may increase this allergy risk. An anaphylactic reaction occurred in one HIV patient during week 4 of a clinical study. Enlarged lymph nodes have been reported with very high doses; acute kidney injury has been reported following andrographolide given intravenously, with symptoms including flank pain, decreased urine output, and nausea/vomiting.
8.3 Reproductive Safety
Feeding sun-dried Andrographis powder to female mice at a dose of 2 g/kg/day for 6 weeks, then mating them with untreated males of proven fertility, inhibited pregnancy in 100% of the tested animals. It has also been reported that the administration of andrographis resulted in abortion in pregnant rabbits. Based on these preclinical findings, use during pregnancy is considered contraindicated in most clinical references.
8.4 Drug Interactions
When administered with anticoagulants, there may be increased risk of bruising and bleeding since andrographis itself inhibits platelet aggregation and prevents blood clots. Reduced drug activity in the case of immunosuppressants might be possible since A. paniculata is shown to be immunostimulatory.
Because andrographis may be an immunostimulant, theoretically it may worsen autoimmune diseases by stimulating immune activity; caution is advised in patients with autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus (SLE), psoriasis, rheumatoid arthritis, or others.
Andrographis has been shown to reduce blood pressure and pulse in animals; theoretically this herb may cause excessively low blood pressure in people with already low blood pressure, although the same effects have not been definitively investigated in humans.
8.5 Preclinical Toxicology
In single-dose toxicity tests, no death or abnormal consequences were observed, and the maximum tolerated dose of A. paniculata extract was 10 g/kg in animal studies. Results from repeated-dose toxicity tests did not reveal any obvious toxic effects from repeated daily intragastric administration of the extract at 1 g/kg for 8 weeks. At a dose of 1 g/kg, the extract did not exert any adverse effects. These results are from animal experiments and cannot be directly extrapolated to human dosing.
References
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