Andrographis (Andrographis paniculata)
1. Identity: Botanical Classification, Names, and Forms
Taxonomy and Botanical Description
Andrographis paniculata Wall (family Acanthaceae) is one of the most popular medicinal plants used traditionally for the treatment of an array of diseases. It is an annual herb, and approximately 28 species of Andrographis are known and indigenous to Asia, with A. paniculata being the most commonly used. A. paniculata is native to Taiwan, Mainland China, and India, and is also commonly found across tropical and subtropical Asia and Southeast Asia, including Cambodia, Caribbean islands, Indonesia, Laos, Malaysia, Myanmar, Sri Lanka, Thailand, and Vietnam.
Common Names and Synonyms
The plant carries a wide variety of common names reflecting its cultural reach:
- English: Known as Creat, King of Bitters, Green Chiretta, or Indian Chiretta in English-speaking countries.
- Ayurvedic / Indian: Commonly known as Kalmegh, derived from its bitter taste and medicinal properties.
- Chinese (Pinyin): Chuān Xīn Lián in Traditional Chinese Medicine.
- Malay: Hempedu bumi.
Plant Parts Used and Preparation Forms
The aerial part of the plant contains a large number of chemical constituents, mainly lactones, diterpenoids, diterpene glycosides, flavonoids, and flavonoid glycosides. The leaves are used traditionally in Asian traditional medicine and particularly Ayurveda to treat fever associated with infections. The plant is commercially available in multiple preparation forms, including standardized dried extracts (most common in clinical research), raw dried leaf powder, aqueous (water) extracts, ethanolic extracts, tablets, capsules, liquid tinctures, and traditional decoctions. An ethanol extract of A. paniculata yields an herbal mixture containing mainly diterpene lactones including andrographolide; andrographolide, used as a marker compound, comprises less than 10% of the mixture.
2. Traditional and Historical Use
Ayurvedic Medicine (India)
The bitter taste of the herb indicates its choleretic action, and as such it was traditionally applied for liver problems in both Ayurvedic and TCM. In Ayurveda, the ancient healing system of India, andrographis was used as a bitter tonic, a remedy against intestinal parasites, and a general stomach remedy. In Ayurvedic medicine, it is used as an alterative (supporting the routes of detoxification), stomachic (supporting digestion), and as an immune supporter. It is native to India and Sri Lanka and is widely used as a traditional medicine in Bangladesh, China, and Indonesia; it is traditionally used for the treatment of snake bite, diabetes, dysentery, and malaria. The leaf extract is a traditional remedy for the treatment of infectious disease, fever-causing diseases, colic pain, irregular stools, and diarrhea.
Traditional Chinese Medicine (TCM)
Andrographis paniculata, in addition to its significance in Ayurveda, plays a prominent part in Traditional Chinese Medicine, where it is known as "Chuan Xin Lian." 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. A. paniculata is a traditional herb used in ancient China and other parts of eastern Asia for a very long history to treat various disorders, including rheumatoid arthritis, fever, upper respiratory tract infection, diarrhea, and cancer.
Other Regional Traditions and Historical Scope
The plant has been used traditionally for the treatment of an array of diseases such as cancer, diabetes, high blood pressure, ulcer, leprosy, bronchitis, skin diseases, flatulence, colic, influenza, dysentery, dyspepsia, and malaria for centuries in Asia, America, and Africa. Ethnobotanically, it has been used for treating snake bites, scabies, bug bites, skin eruptions, gonorrhoea, bronchitis, malaria, jaundice, diabetes, leprosy, dysentery, anthelmintic, fever, cardiac diseases, and hepatic diseases.
Scientific review of the plant has covered its pharmacological properties such as common cold, anti-inflammatory, antihyperglycemic, hepatoprotective, antibacterial, antiviral, antiparasitic, anticancer, immunomodulatory, cardiovascular, antihyperlipidemic, sexual dysfunction, contraceptive, safety, and toxicity effects.
3. Key Constituents and Active Compounds
Diterpenoid Lactones
Among the phytochemical constituents, andrographolide, neoandrographolide, and didehydroandrographolide are the most prominent diterpenoid lactones. Andrographolide, in particular, is recognized as the principal active compound and has been extensively studied for its wide pharmacological spectrum. Other notable diterpenoid compounds include andrograpanin, andrographiside, bis-andrographolide, isoandrographolide, 14-deoxy-11-oxoandrographolide, 14-deoxy-11,12-didehydroandrographolide, and 14-deoxyandrographolide.
Andrographolide is a labdane diterpene isolated from the leaves of Andrographis paniculata, a Chinese herbal medicine used for the treatment of viral infections and inflammatory diseases. Andrographolide is insoluble in water and non-polar solvents, and this low water solubility limits its therapeutic use. Some chemical derivatives of andrographolide are soluble in water and can be more widely used in clinical practice.
Other Chemical Classes
Diterpenes, flavonoids, xanthones, noriridoides, and other miscellaneous compounds have been isolated from the plant. In total, 344 compounds, including terpenoid lactones, flavonoids, phenolic acids, triterpenes, and volatile compounds have been summarized in the literature, out of which more than half of the compounds have no reported pharmacological activity.
4. Mechanisms of Action
NF-κB Pathway Inhibition
The most extensively characterized mechanism of andrographolide is its modulation of the nuclear factor-kappa B (NF-κB) signaling pathway, a master regulator of inflammation. Andrographolide is a multitarget anti-inflammatory compound that interferes with signaling pathways including NF-κB, PI3K/Akt, MAPK, and JAK/STAT pathways, as well as other signaling cascades. It effectively decreases inflammation by impeding the activation of NF-κB through modifying the p50 subunit at cysteine 62 via covalent means.
Binding of NF-κB to the promoter site of several inflammatory genes activates them to secrete proinflammatory cytokines and chemokines. Plant-derived natural compounds like andrographolide could be useful in inflammatory disorders as it directly inhibits the binding of NF-κB with DNA at the promoter site. It is concluded that andrographolide exerts its anti-inflammatory effects by inhibiting NF-κB binding to DNA, and thus reducing the expression of proinflammatory proteins, such as COX-2.
Cytokine Suppression
Andrographolide dose-dependently inhibited the release and mRNA expression of TNF-α, IL-6, and IL-1β in LPS-stimulated RAW264.7 cells. The nuclear level of p65 protein was decreased in the andrographolide treatment group. A. paniculata extract has in vitro inhibitory activity against TNF-α, IL-1β, and NF-κB.
Antiviral Mechanisms
For example, andrographolide can inhibit inflammation caused by bacterial infection by regulating the MAPK and NF-κB signaling pathways, thereby reducing the expression of pro-inflammatory cytokines. In antiviral activity, andrographolide can inhibit viral replication and regulate the expression of Nrf2 and its downstream genes, reducing lung inflammation caused by viral infection.
Additional Mechanisms
Andrographolide can reduce the amount of inflammatory swelling by blocking the JAK2/STAT3 signaling pathway and inhibiting the release of pro-inflammatory cytokines and mediators. Research indicates that andrographolide exhibits strong hepatoprotective, antioxidant, anti-inflammatory, immunomodulatory, antibacterial, antipyretic, anti-diabetic, and anti-cancer activities.
5. Scientific Evidence by Area of Use
5.1 Upper Respiratory Tract Infections and Common Cold
This is the most thoroughly studied clinical application of Andrographis paniculata and carries the strongest body of human evidence among all its uses.
Seven double-blind, controlled trials (n = 896) met the inclusion criteria for evaluation of efficacy in one systematic review. All trials scored at least three, out of a maximum of five, for methodological quality on the Jadad scale. Collectively, the data suggest that A. paniculata is superior to placebo in alleviating the subjective symptoms of uncomplicated upper respiratory tract infection. There is also preliminary evidence of a preventative effect.
Four studies met inclusion criteria in another meta-analysis, with a total of 433 patients reported in three trials included in the statistical analysis. Andrographis paniculata fixed combination with Acanthopanax senticosus was more effective than placebo, with a mean difference of 2.13 points (95% CI 1.00–3.26 points, P=0.0002) on the symptom severity score. The difference in effects between A. paniculata and placebo was 10.85 points (95% CI 10.36–11.34 points, P<0.0001) in favour of A. paniculata.
A 2017 systematic review and meta-analysis published in PLOS ONE (Hu et al.) searched both English and Chinese databases from inception to March 2016 and is among the most comprehensive reviews available. A. paniculata improved cough (n = 596, SMD: −0.39, 95% CI [−0.67, −0.10]) and sore throat (n = 314, SMD: −1.13, 95% CI [−1.37, −0.89]) when compared with placebo. A. paniculata (alone or plus usual care) had a statistically significant effect in improving overall symptoms of ARTIs when compared to placebo, usual care, and other herbal therapies. Evidence also suggested that A. paniculata (alone or plus usual care) shortened the duration of cough, sore throat, and sick leave/time to resolution when compared with usual care.
Authors of a further systematic review concluded that Andrographis paniculata may be an effective treatment with few adverse effects and that further research is justified. The conclusions are in line with the evidence presented and appear appropriately cautious. Current evidence suggests that A. paniculata extract alone or in combination with A. senticosus extract may be more effective than placebo and may be an appropriate alternative treatment of uncomplicated acute upper respiratory tract infection.
Evidence strength: Moderate. Multiple RCTs and several systematic reviews consistently point to benefit for symptom reduction and duration in uncomplicated upper respiratory tract infections. Limitations include heterogeneity in extract standardization, dosage, and outcome measures across trials, as well as a high proportion of Chinese-language trials with variable reporting quality.
5.2 Ulcerative Colitis
A randomized, double-blind, placebo-controlled trial evaluated the efficacy of A. paniculata extract (HMPL-004) in 224 adults with mild-to-moderate ulcerative colitis. Patients were randomized to A. paniculata extract 1,200 mg or 1,800 mg daily or placebo for 8 weeks. In total, 45% and 60% of patients receiving 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 and P=0.0183 for 1,800 mg vs. placebo). Patients with mildly to moderately active ulcerative colitis treated with A. paniculata extract (HMPL-004) at a dose of 1,800 mg daily were more likely to achieve clinical response than those receiving placebo.
A pilot study of A. paniculata extract (HMPL-004) 1,200 mg/day suggested similar efficacy to mesalamine for ulcerative colitis. In one trial, those receiving A. paniculata extract at higher doses were more likely to achieve a significant improvement in active ulcerative colitis than placebo.
Evidence strength: Preliminary to moderate. Results from two controlled trials suggest benefit at higher doses (1,800 mg/day), particularly for clinical response in mild-to-moderate disease, but further replication in larger, independently conducted trials is needed before firm conclusions can be drawn.
5.3 Rheumatoid Arthritis
In one human clinical trial, 60 participants with active rheumatoid arthritis took a daily dose of 300 mg of andrographis over a 14-week period. Patients receiving andrographis reported a decrease in tenderness and swelling of their joints compared to the placebo group. However, there was no significant difference in the intensity of their pain. Other preliminary data suggest andrographis extracts can reduce rheumatoid factors and arthritis symptoms.
Evidence strength: Preliminary. One small randomized controlled trial showed partial benefit on joint tenderness and swelling but not on pain intensity; additional, larger trials are required.
5.4 Immunomodulation and HIV
In a small trial of patients with HIV, andrographolides, the active ingredients in andrographis, increased the number of lymphocytes. This finding is preliminary and based on a small sample; the clinical significance has not been established in adequately powered trials.
5.5 Antiviral Activity
Andrographolide is anticancer, anti-inflammatory, antibacterial, immunomodulatory, and antiviral. It is reported to be effective against chikungunya virus (CHIKV), dengue virus (DENV), Epstein–Barr virus (EBV), and influenza A virus (IAV) in laboratory studies. Recent investigations have highlighted the anti-infective potential of andrographolide and its derivatives, with demonstrated antiviral, antibacterial, and antimalarial activities. Derivatives of andrographolide show potent antiviral activity against RNA and DNA viruses, antibacterial activity against Gram-positive and Gram-negative bacteria, antifungal effects, and antiparasitic activity against Plasmodium spp. and Leishmania spp. Nevertheless, poor solubility and limited bioavailability still hinder their clinical translation.
A. paniculata and its active compounds possess favorable antiviral, anti-inflammatory, immunomodulatory, and antipyretic activities that could be beneficial for treatment of respiratory viral diseases.
Evidence strength: Largely preclinical (in vitro and animal). Human clinical evidence for direct antiviral indications (such as influenza or dengue) outside of general URTI symptom management remains limited.
5.6 Antimalarial Activity
Andrographolide was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages of Plasmodium. In antimalarial activity, andrographolide in combination with curcumin has shown significant antiplasmodial activity against Plasmodium falciparum in research settings.
Evidence strength: Preclinical only. No robust human clinical trials have evaluated andrographis as an antimalarial agent; evidence is limited to in vitro and animal studies.
5.7 Hepatoprotective Effects
In animal research, andrographolide co-administration substantially reduced toxicant-induced hepatic damage. Acetaminophen-induced intoxication increased malondialdehyde (MDA) levels and declined cellular endogenous antioxidant enzymes such as catalase, superoxide dismutase, and glutathione, where andrographolide treatment amended their levels. Histopathological evaluation further verified that andrographolide protected hepatocytes from damage.
Andrographolide has the pharmacological effect of anti-inflammatory, anti-viral, anti-bacterial, anticancer, and hepatoprotective activity.
Evidence strength: Preclinical. Evidence of hepatoprotection comes predominantly from animal and in vitro studies. Human clinical trials specifically evaluating hepatoprotective endpoints are lacking.
5.8 Multiple Sclerosis-related Fatigue
One study investigated the effect of A. paniculata on relapse rate and fatigue in relapsing-remitting multiple sclerosis (RRMS) patients receiving interferon beta. Using 170 mg of A. paniculata dried extract tablet, twenty-five patients were enrolled and twenty-two were ultimately analysed and randomised to the active or placebo group. This study found that A. paniculata significantly reduces fatigue in patients with RRMS receiving interferon beta in comparison to placebo and interferon beta treatment alone.
Evidence strength: Very preliminary. This is a single very small pilot trial; results cannot support firm conclusions and require replication in larger studies.
5.9 Anticancer Activity
In vitro (test tube) and animal studies have found potential anti-cancer effects of andrographis. Although andrographolide itself has not received regulatory approval as a stand-alone drug, several andrographolide-containing preparations have been clinically used in certain countries.
Evidence strength: Preclinical only. Extensive in vitro and animal data demonstrate antiproliferative effects across various cancer cell lines, but no robust human clinical trials have confirmed efficacy in oncology settings.
6. Body Systems and Health Areas Associated with Andrographis
- Immune system: One of the most studied properties of Andrographis paniculata is its ability to modulate the immune system. Numerous studies have looked at its ability to boost immune cell function, allowing the body to develop a more powerful defense against infections.
- Respiratory system: Treatment and prevention of upper respiratory tract infections; cough and sore throat relief, as supported by multiple clinical trials.
- Gastrointestinal system: Andrographis is also used for digestive problems, blood cleanser, fever, sore throat, and URIs. Clinical trial evidence also exists for ulcerative colitis.
- Musculoskeletal system: Preliminary evidence from one RCT for rheumatoid arthritis joint tenderness and swelling.
- Hepatobiliary system: Traditional use and substantial preclinical evidence for liver protection; limited human data.
- Cardiovascular system: Reported properties in the literature include antithrombotic and cardioprotective activity. Evidence is largely preclinical.
- Metabolic/Endocrine: Its potential in the treatment of metabolic illnesses such as diabetes has been studied. The plant may help enhance insulin sensitivity and glucose metabolism. Evidence is preclinical or very preliminary clinically.
- Neurological: Small pilot data for fatigue reduction in MS patients; otherwise preclinical.
7. Dosage Forms and Dosages Reported in Studies
Andrographis is found commercially as standardized dried extract capsules/tablets, raw leaf powder, aqueous decoctions, and liquid extracts. The following dosages have been reported in specific clinical studies:
- Upper respiratory tract infections (URTI): The dose of andrographis used in controlled trials ranged from 48 to 360 mg. A systematic review and meta-analysis exploring 33 randomised controlled trials involving 7,175 participants used dosages that varied across studies, but on average participants were given 1,200 mg per day, with treatment durations ranging from 3–10 days.
- Ulcerative colitis: A. paniculata extract (HMPL-004) at 1,200 mg or 1,800 mg daily, given for 8 weeks, in a randomized double-blind placebo-controlled trial of 224 adults.
- Rheumatoid arthritis: In a study involving sixty people with rheumatoid arthritis who were given either Andrographis paniculata tablets containing 30 mg of andrographolides or placebo tablets three times a day for 14 weeks.
- Multiple sclerosis fatigue: 170 mg of A. paniculata dried extract tablet was used in a 25-patient pilot study.
It should be noted that the preparation method, degree of standardization, and the specific compound being measured (whole extract vs. andrographolide content) vary considerably across studies, making direct dose comparisons difficult.
8. Safety Considerations and Drug Interactions
General Safety Profile
Results of previous systematic reviews showed that herbal preparations of A. paniculata were beneficial and safe for relieving the symptoms of RTIs and shortening time to symptom resolution. In clinical pharmacokinetic studies of high-dosage regimens, the occasional adverse events experienced by individuals were of mild intensity, infrequent in occurrence, and reversible to the normal baseline. Safety consideration should be given to the individual patient's pertinent health conditions when using this extract in patients with hepatic or kidney dysfunction.
Reported Adverse Effects
Under an intensive monitoring programme in Thailand, 1,873 patients using andrographis oral containing products reported that andrographis could possibly cause various adverse events such as rash, pruritus, breath discomfort, cough, peeling skin, fatigue, nausea, gastric discomfort, anorexia, headache, and palpitation. It should be noted that direct causation has not been substantiated and other contributing factors could be playing a role in adverse events being reported.
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.
Anaphylaxis and allergic reactions have been caused by several different A. paniculata preparations, and methanol extracts may increase this allergy risk. Acute kidney injury following andrographolides given by IV has been reported. Symptoms included flank pain, decreased urine output, and nausea/vomiting. (This concern applies specifically to parenteral administration, not oral preparations.)
Pregnancy and Fertility
Andrographis should be avoided in pregnancy and lactation. Studies on rats have shown andrographis to have a potential antifertility effect in female rodents; this has not been confirmed with human clinical studies, but caution is advised if trying to conceive. Adverse effects, including abortifacient effects, have been documented.
Drug Interactions
When being administered with anticoagulants, there may be an increased risk of bruising and bleeding since andrographis itself inhibits platelet aggregation and prevents blood clots. Andrographis may increase the risk of hypotension when used in conjunction with antihypertensive medication. Reduced drug activity in the case of immunosuppressants might be possible since A. paniculata is shown to be immunostimulatory.
The elimination half-life and mean residence time of theophylline were shortened by 14% and 17%, respectively, in the andrographis pre-treated group when high-dose theophylline was given. Some herbal components contained in andrographis preparations may interact with theophylline and retard its elimination when theophylline is administered at a high dose.
Andrographis may also potentiate the effects of midazolam. Bitters are contraindicated in states of hyperacidity including duodenal ulcers and should be used with caution in oesophageal reflux.
The most widely reported cases of herb-drug interactions today involve the modulation of herbal medicinal components in the drug metabolism system involving cytochrome P450 (CYP)-metabolizing enzymes. The full extent of CYP-mediated interactions with andrographis preparations has not been thoroughly characterized in human clinical studies, and caution is warranted when combining the herb with drugs that have a narrow therapeutic index.
Regulatory Status
Although andrographolide itself has not received regulatory approval as a stand-alone drug, several andrographolide-containing preparations have been clinically used in certain countries. A. paniculata has been used as a complementary treatment for COVID-19 in several Asian countries, reflecting its wide cultural acceptance and ongoing regulatory consideration in parts of Asia.
References
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