Andrographolide

Andrographolide: A Comprehensive Reference Article

1. Identity and Chemical Characterization

1.1 Names and Classification

Andrographolide is a colorless and crystalline labdane diterpenoid lactone (α-alkylidene γ-butyrolactone) with a very bitter taste; it was first isolated from Andrographis paniculata in the year 1911 by Gorter. It is chemically designated as (4S,E)-4-hydroxy-3-(2-((1R,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylenedecahydronaphthalen-1-yl)ethylidene)dihydrofuran-2(3H)-one, or alternatively 3α,14,15,18-tetrahydroxy-5β,9βH,10α-labda-8,12-dien-16-oic acid γ-lactone. Its molecular formula is C₂₀H₃₀O₅.

The parent plant, Andrographis paniculata, belongs to the family Acanthaceae and its constituents are reported to possess a wide range of biological properties. Andrographolide is identified as the major bioactive constituent of the plant. The molecular stereochemistry, bond distances, and bond angles of andrographolide were determined by X-ray crystallographic analysis.

1.2 Botanical Source

Andrographis paniculata, known as the "King of Bitters" due to its intensely bitter taste, is an annual herbaceous plant native to South and Southeast Asia, including India, Sri Lanka, China, and Thailand, growing in moist, shady environments. It is an annual and herbaceous plant belonging to the family Acanthaceae which grows throughout tropical and subtropical Asia, Southeast Asia, and India.

The plant is known by a variety of names across different traditions. It is known as Kalmegh in Ayurveda, Creat, King of Bitters, Green Chiretta, or Indian Chiretta in English-speaking countries, and chuān xīn lián (穿心蓮) in Pinyin Chinese. Kalamegha, as andrographis is known in Ayurveda, literally means 'black cloud,' perhaps attesting to andrographis being traditionally harvested just before winter. Andrographis is also known as bhunimba, meaning 'neem of the earth,' referring to its bitter neem-like taste and effects.

1.3 Plant Parts Used and Common Preparations

Andrographolide is a diterpene lactone constituent found in the dried above-ground parts of Andrographis paniculata (Burm. f.) Nees, and has shown potential as a natural chemical treatment for various human ailments, including viral infections and immune system enhancement.

Commercial preparations include standardized dry extracts in tablet or capsule form, crude powdered herb preparations, and water-soluble chemical derivatives of andrographolide. Andrographolide is insoluble in water and non-polar solvents; 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. In China, injections of andrographolide derivatives have been used for the treatment of various diseases, such as upper respiratory tract infections, pneumonia, hand, foot and mouth disease, and COVID-19. The majority of clinical trials used products standardized to 4 or 5 mg andrographolide per tablet.

A monograph of Herba Andrographidis (Chuanxinlian) is included in the Chinese Pharmacopoeia, which reports that this decoction can "remove heat, counteract toxicity, and reduce swellings."

2. Traditional and Historical Use

2.1 Ayurvedic Medicine (India)

Andrographis paniculata has a long history in both Ayurvedic medicine and Traditional Chinese Medicine. It has been used as a medicine since India's Ayurvedic medicine began around 3,000–4,000 BCE. Even though it has been used for thousands of years, this versatile herb is still popular among the more than 70% of Indians who use Ayurveda.

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.

Across various cultures, it was commonly used for conditions like fevers, sore throats, and digestive issues such as dysentery and irregular stools. It is also an important constituent of at least 26 Ayurvedic formulas.

2.2 Traditional Chinese Medicine (TCM)

Andrographis paniculata 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.

Traditional Chinese Medicine utilized it to "clear heat" and "dry dampness," often for manifestations in the lungs and digestive organs.

2.3 Broader Traditional and Folkloric Use

It is a traditional herbal treatment for diseases and ailments such as diarrhea, dysentery, cholera, pneumonia, swollen lymph nodes, leprosy, bronchitis, sore throats, tuberculosis, chicken pox, coughs, headaches, ear infection, inflammation, burns, and mumps. Andrographis was also used as a treatment for malaria, as a replacement for quinine.

Some accounts of history report that andrographis helped to contain an Indian flu epidemic in 1919, which occurred shortly after the Spanish flu epidemic of 1918, though this claim has not been proven in controlled research.

3. Key Constituents and Active Compounds

3.1 Phytochemical Profile of the Parent Plant

Andrographis paniculata contains diterpene lactones, glycosides and flavonoids, alkaloids, phenols, catechins, saponins, and tannins. In addition, it contains andrographolide, neoandrographolide, tetradecanoic acid, phytol, dioctyl ester, squalene, retinoic acid methyl ester, and β-sitosterol.

Andrographolide is the predominant and most pharmacologically characterized constituent. Andrographolide is identified as the major bioactive constituent of the plant. Its promising biological properties along with structural amenability for facile semi-synthetic modifications have led to the generation of structurally diverse bioactive labdane diterpenes by several research groups.

3.2 Related Diterpenoids

Beyond andrographolide itself, the plant contains several related compounds including neoandrographolide, 14-deoxyandrographolide, and 14-deoxy-11,12-didehydroandrographolide. Andrographolide has the pharmacological effects of anti-inflammatory, anti-viral, anti-bacterial, anticancer, and hepatoprotective activity. Research into semi-synthetic derivatives has generated additional molecular entities intended to improve upon andrographolide's pharmacokinetic limitations.

4. Mechanisms of Action

4.1 NF-κB Inhibition

Andrographolide is one of a growing number of biological and biochemical NF-κB inhibitors that have been found to have anti-inflammatory effects by either blocking the signal transduction pathway that leads to NF-κB activation or inhibiting NF-κB binding activity to target genes. Andrographolide has been identified as an NF-κB inhibitor, which inhibits the NF-κB pathway.

The mechanism is notably specific: a study reported that andrographolide makes a covalent adduct with reduced cysteine-62 of the p50 subunit, blocking the binding of NF-κB oligonucleotide to nuclear proteins. Andrographolide suppressed the activation of NF-κB in stimulated endothelial cells, while it had no suppressive effect on IκBα degradation, p50 and p65 nuclear translocation, thus revealing a unique pharmacological mechanism of andrographolide's protective anti-inflammatory actions.

This pathway, when activated, leads to the transcription of multiple genes such as proinflammatory cytokines (IL-1, IL-2, IL-6, IL-8, and TNF-α), Cox-2, iNOS, and cell adhesion molecules (E-selectin, ICAM-1, and VCAM-1). The anti-inflammatory action of andrographolide is associated with its potent downregulation of NF-κB. The wide-spectrum anti-inflammatory activity of andrographolide demonstrates its therapeutic potential against cytokine storms as an alternative to NSAIDs.

4.2 MAPK Signaling Pathway

Andrographolide can inhibit inflammation caused by bacterial infection by regulating the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways, thereby reducing the expression of pro-inflammatory cytokines. 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.

4.3 Additional Transcription Factor and Signaling Targets

Several targets are described for andrographolide, including the interference of transcription factors NF-κB, AP-1, and HIF-1, and signaling pathways such as PI3K/Akt, MAPK, and JAK/STAT. In addition, an increase in the Nrf2 (nuclear factor erythroid 2–related factor 2) signaling pathway also supports its antioxidant and anti-inflammatory properties. Recent evidence suggests that andrographolide's targets can also modulate glucose metabolism.

A comprehensive review elucidates the capacity of andrographolide to inhibit signaling pathways, namely NF-κB, HIF-1, JAK/STAT, PI3K/AKT/mTOR, Wnt/β-catenin, and MAPK pathways, which are involved in cellular processes and responses such as the inflammatory response, apoptosis, and angiogenesis.

4.4 Antiviral Mechanisms

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.

4.5 Anticancer Mechanisms (Preclinical)

In vitro studies demonstrate the capability of the compound of inducing cell-cycle arrest and apoptosis in a variety of cancer cells at different concentrations. Factors required for tumor progression, nourishment, and metastasis are downregulated — cyclins A, D, Cdk2, Cdk4, NF-κB, VEGF, E-selectin, VCAM, Akt, TNF, Bcl2. On the other hand, tumor suppressor elements like p53, caspases, and inhibitory proteins p21, p16, p27 are upregulated.

4.6 Hepatoprotective Mechanisms

Andrographolide targets various hepatotoxic substances by increasing the activity of liver microsomal enzymes (CYP1A2 and CYP2E1), maintains the stability of detoxification enzymes, and attenuates oxidative stress and cholestasis.

5. Pharmacokinetics and Bioavailability

The therapeutic potential of andrographolide is hindered by its poor oral bioavailability and unpredictable pharmacokinetics, primarily due to its limited water solubility. The poor oral bioavailability of andrographolide may be credited to physicochemical and biopharmaceutical factors such as low water solubility (3.29 ± 0.73 μg/mL) and high hydrophobicity. Rapid biotransformation and efflux by P-glycoprotein (P-gp) also reduce oral bioavailability. About 55% of andrographolide binds with human plasma proteins.

After oral administration of tablets (equivalent to 10 mg/kg) in rats, the absolute bioavailability of andrographolide was found to be 2.67%, with pharmacokinetic parameters consistent with a one-compartment open model. It has poor oral bioavailability because of its rapid biotransformation and efflux by P-glycoprotein.

Human pharmacokinetic data from a specific formulation (Kan Jang) are more informative: following the oral administration of four Kan Jang tablets (a single therapeutic dose equal to 20 mg of andrographolide) to humans, maximum plasma levels of approximately 393 ng/mL were reached after 1.5–2 hours. Half-life and mean residence times were 6.6 and 10.0 hours, respectively, and pharmacokinetics in humans are explained well by an open two-compartment model.

In the termination phase, andrographolide preferentially undergoes biotransformation partly through phase I hydroxylation and phase II conjugation, and is then eliminated via the renal excretion and hepatobiliary system.

Efforts to improve bioavailability have included cyclodextrin complexation: the bioavailability was computed to be 15.87 ± 3.84% and 23.84 ± 5.46% for andrographolide and its andrographolide-2-hydroxypropyl-β-cyclodextrin (AND-2-HyP-β-CYD) complex, respectively.

6. Scientific Evidence by Area of Use

6.1 Upper Respiratory Tract Infections (URTI)

This is the area with the strongest and most consistent human clinical evidence for andrographolide and its parent plant extract.

A meta-analysis involving 33 randomized controlled trials (RCTs) with 7,175 patients found that A. paniculata significantly improved symptoms of cough and sore throat compared to placebo. This 2017 review found that andrographis improved symptoms of acute respiratory tract infections by shortening the duration of cough and sore throat.

Multiple systematic reviews, including those by Coon and Ernst and by Poolsup et al., collectively conclude: "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. A. paniculata may be a safe and efficacious treatment for the relief of symptoms of uncomplicated upper respiratory tract infection; more research is warranted."

The studies included in efficacy reviews used standardized extracts of A. paniculata alone or in combination with Eleutherococcus senticosus, except for one study that used a crude drug preparation. The comparator interventions were placebo or paracetamol. The daily dose of andrographolide ranged from 48 to 360 mg/day in the efficacy review.

Evidence strength: Moderate to good. Multiple well-designed RCTs and several systematic reviews and meta-analyses support efficacy for symptom relief in uncomplicated URTI. Individual trials are of varying methodological quality, and most studies evaluated the whole plant extract rather than isolated andrographolide.

6.2 Rheumatoid Arthritis

There are several clinical trials that demonstrate positive effects of A. paniculata on infectious diseases, hypertriglyceridemia, and autoimmune disorders such as ulcerative colitis and rheumatoid arthritis. A prospective randomized placebo-controlled trial evaluating an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms has been published (Burgos et al., 2009). Andrographolide is the major active labdane diterpenoid derived from Andrographis paniculata, and has multiple pharmacological effects, including hepatoprotection, anti-angiogenesis, anti-thrombosis, and anti-inflammation. Research in a murine adjuvant-induced arthritis model found that andrographolide alleviated arthritis by reducing neutrophil infiltration and NETosis in the ankle joints and relieving systemic inflammation.

Andrographolide inhibits osteoclast differentiation and triggers apoptosis and cell cycle arrest of fibroblast-like synoviocytes.

Evidence strength: Preliminary. Animal data are supportive; limited human RCT data exist. The rheumatoid arthritis clinical trial showed promising findings but the evidence base remains small.

6.3 Ulcerative Colitis

The anti-inflammatory ability of andrographolide suggests its potential therapeutic effect against ulcerative colitis (UC). In UC patients, elevated serum concentrations of proinflammatory factors including TNF-α, IL-1β, IL-6, and IL-23, as well as increased percentages of Th17 cells, were detected compared to healthy donors. Andrographolide can restrain the activation of the IL-23/IL-17 axis and the production of downstream proinflammatory cytokines, thereby inhibiting the inflammatory response; reducing the levels of serum proinflammatory factors such as TNF-α, IL-1β, IL-6, and IL-23; and inhibiting the Th17-cell immune response in patients with UC.

A 2012 randomized controlled trial found that Andrographis paniculata extract (HMPL-004) significantly improved symptoms in people with mild to moderate ulcerative colitis. One clinical analysis concluded that patients were more likely to achieve a significant improvement in active ulcerative colitis in the andrographis group than with placebo.

Ulcerative colitis is a recurring inflammatory bowel disease in which oxidative stress plays a role in its progression. A study evaluated the protective effect of andrographolide against UC via the Nrf2/HO-1 pathway and demonstrated significant protective effects in animal models.

Evidence strength: Preliminary but promising. At least one published human RCT supports benefit in mild-to-moderate active UC. Mechanistic data from cell and animal studies are extensive. Larger, higher-quality human trials are needed.

6.4 Multiple Sclerosis (MS)

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 analysed. The study found that A. paniculata significantly reduces fatigue in patients with RRMS receiving interferon beta in comparison to placebo and interferon beta treatment alone.

Clinical studies have demonstrated that andrographolide could be useful in therapy for a wide range of diseases such as osteoarthritis, upper respiratory diseases, and multiple sclerosis.

Evidence strength: Very preliminary. Only a small single trial with 22 analyzed patients; results need replication in larger, adequately powered trials.

6.5 Osteoarthritis

A 2019 study found that people with mild to moderate osteoarthritis in their knee joints saw significant reductions in pain after taking a supplement containing andrographolide for 28 days. The presence of a placebo group means the result is considered more reliable. However, further research is needed to better understand the potential benefits.

Evidence strength: Preliminary. A single placebo-controlled trial with positive results; replication in larger trials is required before firm conclusions can be drawn.

6.6 Hepatoprotection

In terms of hepatotoxicity, from the application of andrographolide in liver diseases, andrographolide appears to have a good repairing effect on hepatotoxicity, and there is no evidence that it induces liver damage at therapeutic doses. It has been described that andrographolide has a hepatoprotective role.

Evidence strength: Primarily preclinical and mechanistic. Animal and in vitro data are consistent, but dedicated human clinical trials evaluating hepatoprotection as a primary endpoint are lacking.

6.7 Antimicrobial and Antiviral Activity

Recent investigations have highlighted the anti-infective potential of andrographolide and its derivatives, with demonstrated antiviral, antibacterial, and antimalarial activities. In anti-infective research, andrographolide and its derivatives play important roles by inhibiting pathogen-induced inflammation, modulating the immune system, and scavenging oxidative stress.

Co-treatment with A. paniculata in concert with standard supportive care for influenza reduced the severity of symptoms, shortened treatment duration, and decreased the risk of developing post-influenza complications.

Evidence strength: Moderate in vitro and animal evidence; limited but promising human data specifically for influenza and URTI. COVID-19 applications are being actively investigated but human evidence remains early-stage.

6.8 Anticancer Activity

Andrographolide is the major bioactive constituent of Andrographis paniculata, a well-known plant of Ayurveda and TCM, and has shown credible anticancer potential. Andrographolide has shown credible anticancer potential in various investigations around the globe. In vitro studies demonstrate the capability of the compound of inducing cell-cycle arrest and apoptosis in a variety of cancer cells at different concentrations.

Inhibiting these pathways enables andrographolide to exhibit anticancer effects against breast, colorectal, and lung cancer (preclinically).

Evidence strength: Preclinical only. All meaningful anticancer evidence to date is from cell cultures and animal models. There are no published clinical trials evaluating andrographolide as an anticancer agent in humans.

6.9 Metabolic and Anti-diabetic Activity

Recent evidence suggests that andrographolide targets can modulate glucose metabolism. Andrographis paniculata contains andrographolide as its main active compound, known for its wide-ranging pharmacological effects, including anti-inflammatory, anti-cancer, anti-obesity, and anti-diabetic properties.

Evidence strength: Primarily preclinical. Anti-diabetic and anti-obesity claims are based on animal and in vitro studies; human clinical evidence is lacking at this time.

6.10 Neuroprotection and Stroke

Andrographolide has antioxidant and anti-inflammatory bioactivities. In vitro and in vivo studies showed that it exerts neuroprotection at low doses. Studies demonstrate that andrographolide produced neuroprotective effects against cerebral ischemia with associated inhibition of microglia activation, possibly caused by the suppression of NF-κB activation, leading to a reduction in the production of cytokines including TNF-α and IL-1β, and pro-inflammatory factors such as PGE2.

As a potent anti-inflammatory drug with neuroprotective activities, the favorable effects of andrographolide to treat ischemic stroke in humans warrant further basic and clinical investigations.

Evidence strength: Preclinical only. No human clinical trials have yet established neurological efficacy.

7. Dosage and Dosage Forms

Dosages reported in published studies span a wide range depending on the indication and formulation. The following figures are drawn from identified clinical studies and reviews:

• The key summary of the recommended dosage for andrographolide in uncomplicated URTI treatment is 30 mg/day for children and 60 mg/day for adults. The dose for adult patients with pharyngotonsillitis could be increased to 180 mg/day, but not exceed 360 mg/day.
• The daily dose of andrographolide in URTI clinical trials ranged from 48 to 360 mg/day in the efficacy reviews and from 11 mg/day to 10 mg/kg per day for studies included in safety reviews.
• In human pharmacokinetic studies with the Kan Jang formulation, a single therapeutic dose equaling 20 mg of andrographolide produced maximum plasma levels of approximately 393 ng/mL reached after 1.5–2 hours.
• In the multiple sclerosis pilot trial, the dose used was 170 mg of A. paniculata dried extract tablet.
• The recommended starting dose cited for use in patients with mild COVID-19 is 180 mg/day of andrographolide, based on the dose used in patients experiencing a URTI with inflammation.

Forms available include standardized tablet or capsule preparations (typically standardized to a defined percentage of andrographolide content), crude herb powders, tinctures, decoctions prepared from dried aerial parts, and, in China, injectable andrographolide derivative preparations used in clinical settings.

8. Safety Considerations and Adverse Effects

8.1 General Tolerability

A systematic review and meta-analysis including ten RCTs and three intensive monitoring studies found that the incidence of serious adverse events (AEs) was very rare, with a pooled incidence from RCTs of 0.02 per 1000 patients. However, the incidence of non-serious AEs was considered very common, at approximately 102.6 per 1000 patients. The most common non-serious AEs were related to gastrointestinal disorder and skin and subcutaneous disorder.

Previous studies have shown that the ADRs of AP herbal preparations include nausea, vomiting, diarrhea, abdominal pain, dizziness, epistaxis, and rash.

One study in HIV-positive patients and healthy volunteers, which used a high dose of andrographolide, was terminated early because of a large number of adverse events. Adverse events in the remaining trials were described as mild, infrequent, and reversible.

8.2 Andrographolide Derivative Injections

ADRs of andrographolide derivative injections include those of skin and mucous membranes (rash, itching, edema, flushing), digestive system (nausea, vomiting, abdominal pain, diarrhea), blood system (thrombocytopenia, leukopenia), circulatory system (chest tightness, palpitations), respiratory system (dyspnea, cough), and nervous system (dizziness, headache, convulsion, coma). A total of 262 studies were included in one systematic review. In 9490 participants using andrographolide derivative injections, 383 (4.04%) reported ADRs.

8.3 Hepatotoxicity Assessment

From the application of andrographolide in liver diseases, andrographolide appears to have a good repairing effect on hepatotoxicity, with no evidence that it can induce liver damage. A study pointed out that the lethal dose of andrographolide-2-hydroxypropyl-β-cyclodextrin is greater than 2000 mg/kg, and it has no adverse effects on animal growth, circulating blood cells, and liver and kidney function at tested doses.

8.4 Acute Toxicity

Toxicology studies are limited, but andrographis does not appear to be acutely toxic. Acute lethal doses (median lethal dose) in mice are reported to be more than 40 g/kg for andrographolide. Ames, chromosome aberration, and micronucleus in vitro tests on a standardized extract of A. paniculata demonstrated no evidence of mutations or clastogenicity, and no evidence of acute toxicity was observed in the female rats studied.

8.5 Reproductive and Fertility Concerns

The reproductive safety profile of andrographolide is a matter of notable scientific discussion, with conflicting data across studies. A preliminary study reported that oral administration of herb powder to male albino rats for 60 days resulted in cessation of spermatogenesis and regression of Leydig cells, suggesting an antiandrogenic effect. Andrographolide administered to male rats at doses of 25 and 50 mg/kg body weight for 48 days showed testicular toxicity and sperm abnormalities. On the other hand, extract of A. paniculata containing 6.1% andrographolide did not produce testicular toxicity in male rats when administered at doses of 20, 200, and 1000 mg/kg for 60 days. A phase I clinical study of A. paniculata fixed combination showed no adverse effects on male semen quality and fertility in healthy human subjects.

In female rats, A. paniculata aqueous extract at 1 g/kg for 4, 6 and 8 weeks caused infertility by lowering reproductive hormones including Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), estrogen, and progesterone.

Results from embryonic stem cell test (EST) research showed that andrographolide exhibited reproductive toxicity signals according to established prediction models. Overall, the reproductive toxicity data from animal studies are mixed and conflicting, and the human data are very limited. For pregnant women and children, it seems prudent to recommend against the use of andrographis because there is little data from studies in these populations to exclude risk of harm.

8.6 Potential Drug Interactions

The therapeutic potential of andrographolide in cardiovascular diseases is thought to be associated with the inhibition of LPS/IFN-γ-induced iNOS and MMP-9 expressions in rat vascular smooth muscle cells. Andrographolide inhibited p65 Ser536 phosphorylation, reduced nuclear translocation of p65, and diminished p65 κB oligonucleotide binding. These mechanisms — alongside the compound's known effects on platelet function, blood pressure, and immune modulation — suggest the theoretical potential for interactions with anticoagulant, antiplatelet, antihypertensive, and immunosuppressive agents, though dedicated human drug interaction studies for andrographolide specifically are not yet available in the published literature.

Herbal preparations of AP have been used in many countries to treat respiratory tract infections, colitis, early stages of COVID-19, and to relieve symptoms of arthritis. Results of previous systematic reviews showed that herbal preparations of AP were beneficial and safe for relieving symptoms of RTIs and shortening time to symptom resolution.

Summary of Evidence Landscape

Andrographolide is among the better-studied botanical compounds in terms of mechanistic pharmacology. Its most robustly evidenced clinical application is in uncomplicated upper respiratory tract infections, where multiple RCTs and systematic reviews support symptom relief and shorter symptom duration. Evidence for ulcerative colitis, rheumatoid arthritis, and multiple sclerosis-related fatigue is promising but rests on a small number of human studies. Preclinical evidence for anticancer, neuroprotective, anti-diabetic, and hepatoprotective activities is extensive but has not yet been translated into conclusive human clinical data. Bioavailability limitations of the native molecule represent an ongoing pharmaceutical challenge, and various formulation strategies are under active investigation.

References

• Suresh Babu, K. et al. (2011). "Andrographolide: A New Plant-Derived Antineoplastic Entity on Horizon." PMC / PubMed Central.
• ScienceDirect Topics: Andrographolide — Overview (Medicine and Dentistry).
• PubMed: "Andrographolide: A natural product template for the generation of structurally and biologically diverse diterpenes." (2019). PMID 31151068.
• PubChem Compound Summary: Andrographolide (CID 5318517). National Library of Medicine.
• PMC: "The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs." (2024). PMC11253928.
• PMC: "Andrographolide: Regulating the Master Regulator NF-κB." (2021). PMC7817737.
• PMC: "Andrographolide and Its Derivatives: A Comprehensive Review of Anti-Infective Properties and Clinical Potential." (2025). PMC12610367.
• PMC: "Multi-Targeting Andrographolide, a Novel NF-κB Inhibitor, as a Potential Therapeutic Agent for Stroke." (2017). PMC5578028.
• PMC: "Andrographolide Inhibits Inflammatory Cytokines Secretion in LPS-Stimulated RAW264.7 Cells through Suppression of NF-κB/MAPK Signaling Pathway." PMC5476883.
• PMC: Hu, X.-Y. et al. (2017). "Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis." PMC5544222.
• NCBI Bookshelf / DARE: Coon JT, Ernst E. "Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy." Planta Med. 2004.
• NCBI Bookshelf / DARE: Poolsup N, et al. "Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection: systematic review of randomized controlled trials." J Clin Pharm Ther. 2004.
• PMC: Shang et al. (2022). "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." PMC8831758.
• Worakunphanich W, et al. (2021). "Safety of Andrographis paniculata: A systematic review and meta-analysis." Pharmacoepidemiol Drug Saf. 30(6):727–739.
• Frontiers in Pharmacology: "Andrographolide, a natural anti-inflammatory agent: An Update." (2022).
• PMC: "Andrographolide, an Anti-Inflammatory Multitarget Drug: All Roads Lead to Cellular Metabolism." (2021). PMC7792620.
• PMC: "Andrographolide presents therapeutic effect on ulcerative colitis through the inhibition of IL-23/IL-17 axis." (2018). PMC5835811.
• PMC: "Protective effect of andrographolide against ulcerative colitis by activating Nrf2/HO-1 mediated antioxidant response." (2024). PMC11317410.
• PMC: "Targeting signaling pathways with andrographolide in cancer therapy (Review)." (2024). PMC11411607.
• PMC: "Enhancing oral bioavailability of andrographolide using solubilizing agents and bioenhancer: comparative pharmacokinetics of Andrographis paniculata formulations in beagle dogs." (2024). PMC10868414.
• PubMed: "Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human." (2000). PMID 11081986.
• PMC: "Molecular encapsulation of andrographolide in 2-hydroxypropyl-β-cyclodextrin cavity: synthesis, characterization, pharmacokinetic and in vitro antiviral activity analysis against SARS-CoV-2." (2021). PMC8351079.
• PMC: "A comprehensive review on disposition kinetics and dosage of oral administration of Andrographis paniculata, an alternative herbal medicine, in co-treatment of coronavirus disease." (2022). PMC9437296.
• PMC: "Andrographolide Ameliorates Rheumatoid Arthritis by Regulating the Apoptosis–NETosis Balance of Neutrophils." (2019). PMC6834122.
• Allan, J.J. et al. (2009). "Reproductive and Fertility Effects of an Extract of Andrographis paniculata in Male Wistar Rats." International Journal of Toxicology.
• PMC: "The Therapeutic Potential of Andrographolide and Its Derivatives in Inflammatory Diseases." (2025). PMC12397499.
• ScienceDirect Topics: Andrographis — Overview (Immunology and Microbiology).
• PMC: "Andrographolide, a Novel NF-κB Inhibitor, Inhibits Vascular Smooth Muscle Cell Proliferation and Cerebral Endothelial Cell Inflammation." PMC4804993.