Andrographis

In Ayurveda andrographis is kalmegh. It is a main ingredient of at least 26 Ayurvedic formulations for liver disorders ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}.

The fresh and dried leaves and the leaf juice are official drugs in the Indian Pharmacopoeia ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}. The Indian Materia Medica gives the dried leaves with black pepper, a compound infusion with orange peel and coriander, and a compound tincture with myrrh and aloes ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}.

In Chinese medicine andrographis is chuan xin lian (穿心莲) ^{19Reference 19DengDeng, Y. F., Hu, J. Q., Daniel, T. F., & Wood, J. R. I. (n.d.). Andrographis paniculata (N. L. Burman) Wallich ex Nees — species description and distribution — flora. In Wu, Z. Y., & Raven, P. H. (eds.), Flora of China, Vol. 19 (Acanthaceae). http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200021989View study →}. It is a cold herb, and its decoction is used to clear heat, bring down fever and dispel toxins ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}.

It is given for colds and fever, sore throat, sore tongue and snakebite ^{14Reference 14Zeng et al. · 2022Clinical trialAndrographolide: a review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches — reviewView study →}.

In Thailand andrographis is fa tha lai jone, and it has a long history of use for sore throat ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}.

The whole dried plant, called creyat or kariyat, was official in the British Pharmaceutical Codex of 1934 ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}. Martindale described a liquid extract of the whole plant with fennel and ajowan oils, standardised to 0.5% andrographolides ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}.

Western herbalists use it mainly short term for colds and acute respiratory infections, and as a bitter.

A 2004 systematic review of seven double-blind controlled trials (n = 896) found andrographis better than placebo for the symptoms of uncomplicated upper respiratory infection, with preliminary evidence that it may also prevent them ^{1Reference 1Coon et al. · 2004Systematic reviewAndrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy — systematic reviewView study →}.

A meta-analysis from the same year pooled three trials (433 patients). The fixed combination with Eleutherococcus (eleuthero) improved the symptom score by 2.13 points over placebo, and andrographis alone by 10.85 points ^{2Reference 2Poolsup et al. · 2004Meta-analysisAndrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection: systematic review of randomized controlled trials — meta-analysisView study →}.

The largest review, of 33 trials and 7,175 patients, found andrographis improved cough and sore throat compared with placebo, improved overall symptoms, and shortened the time to recovery. Adverse events were minor and mostly digestive ^{3Reference 3Hu et al. · 2017Meta-analysisAndrographis paniculata for symptomatic relief of acute respiratory tract infections in adults and children: a systematic review and meta-analysis — systematic reviewView study →}.

A meta-analysis of herbal cough treatments found strong evidence for andrographis across six trials (standardised mean difference −1.00) ^{4Reference 4Wagner et al. · 2015Meta-analysisHerbal medicine for cough: a systematic review and meta-analysis — meta-analysisView study →}.

In a 2023 trial in 60 adults with acute viral sore throat, both an andrographis spray and a chamomile spray reduced symptoms. The andrographis group responded faster, in 1.9 days against 2.5 ^{5Reference 5Okonogi et al. · 2023RCTEfficacy of Andrographis paniculata spray in acute pharyngitis: a randomized controlled trial — RCTView study →}.

In a trial in 223 patients, 200 mg a day of a leaf extract relieved respiratory symptoms better than placebo ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}. In 152 adults with tonsillitis, 6 g a day of dried leaf and paracetamol both relieved fever and sore throat better than 3 g a day by day 3. By day 7 the three groups did not differ ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}.

Gap: many of the main trials tested the eleuthero combination rather than andrographis alone, doses and extracts vary, and the largest review rated the trials’ quality as poor overall ^{3Reference 3Hu et al. · 2017Meta-analysisAndrographis paniculata for symptomatic relief of acute respiratory tract infections in adults and children: a systematic review and meta-analysis — systematic reviewView study →}.

In vitro, andrographolide and the extract HMPL-004 suppress NF-κB signalling and lower TNF-α and IL-1β. This is the pathway put forward to explain the ulcerative colitis and rheumatoid arthritis results ^{6,13Reference 6Sandborn et al. · 2013RCTAndrographis paniculata extract (HMPL-004) for active ulcerative colitis — randomised controlled trialView study →Reference 13Dai et al. · 2019ReviewOverview of pharmacological activities of Andrographis paniculata and its major compound andrographolide — reviewView study →}.

Pharmacology reviews gather a large body of cell and animal work in which andrographolide dampens inflammatory cytokines and mediators across many tissue models ^{13,14Reference 13Dai et al. · 2019ReviewOverview of pharmacological activities of Andrographis paniculata and its major compound andrographolide — reviewView study →Reference 14Zeng et al. · 2022Clinical trialAndrographolide: a review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches — reviewView study →}.

Gap: no human trial has used inflammatory markers as its main measure. The mechanism comes from cell and animal work and from the disease trials.

In a randomised, double-blind, placebo-controlled trial in 224 adults with mild-to-moderate ulcerative colitis, 60% of patients on HMPL-004 at 1,800 mg a day responded by week 8, against 40% on placebo (p = 0.0183). The 1,200 mg dose did not differ from placebo, and neither dose improved remission significantly ^{6Reference 6Sandborn et al. · 2013RCTAndrographis paniculata extract (HMPL-004) for active ulcerative colitis — randomised controlled trialView study →}.

An earlier trial in 120 patients in China compared HMPL-004 at 1,200 mg a day with slow-release mesalazine at 4,500 mg a day. Response and remission rates did not differ significantly between the two ^{7Reference 7Tang et al. · 2011RCTRandomised clinical trial: herbal extract HMPL-004 in active ulcerative colitis — a double-blind comparison with sustained release mesalazine — randomised controlled trialView study →}.

The extract inhibits TNF-α, IL-1β and NF-κB ^{6Reference 6Sandborn et al. · 2013RCTAndrographis paniculata extract (HMPL-004) for active ulcerative colitis — randomised controlled trialView study →}.

Gap: the phase III HMPL-004 programme, and a maintenance trial, were terminated, so the phase II result was never confirmed at scale. The results apply only to that extract.

In Swiss albino mice, an oral andrographis extract (100–200 mg/kg) given after a toxic dose of paracetamol (150 mg/kg) restored liver enzymes, antioxidant enzymes and liver structure in a dose-dependent way ^{10Reference 10Nagalekshmi et al. · 2011AnimalHepatoprotective activity of Andrographis paniculata and Swertia chirayita — animal model (mouse)View study →}.

Pharmacology reviews attribute this to andrographolide’s antioxidant and anti-inflammatory actions on liver cells ^{13,17Reference 13Dai et al. · 2019ReviewOverview of pharmacological activities of Andrographis paniculata and its major compound andrographolide — reviewView study →Reference 17Hossain et al. · 2014ReviewAndrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacology — reviewView study →}.

In a randomised, double-blind, placebo-controlled trial, 60 patients with active rheumatoid arthritis took an extract standardised to 30% total andrographolides (Paractin) three times a day for 14 weeks ^{8Reference 8Burgos et al. · 2009RCTEfficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial — RCTView study →}.

Joint pain fell more on the extract than on placebo, but the difference was not statistically significant. Within the extract group, tender and swollen joint counts, joint scores and quality-of-life measures improved significantly, and rheumatoid factor, IgA and C4 fell ^{8Reference 8Burgos et al. · 2009RCTEfficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial — RCTView study →}.

Gap: a single trial of 60 patients that missed its main measure. The positive findings are secondary and need to be repeated.

Andrographolide and its derivatives inhibit several viruses in vitro, including influenza, by interfering with viral entry and replication ^{12Reference 12Adiguna et al. · 2021ReviewAntiviral activities of andrographolide and its derivatives: mechanism of action and delivery system — reviewView study →}. Its poor solubility and bioavailability limit how much reaches the body ^{12Reference 12Adiguna et al. · 2021ReviewAntiviral activities of andrographolide and its derivatives: mechanism of action and delivery system — reviewView study →}.

These findings led to COVID-19 trials during the pandemic. Registered studies have returned inconclusive or unreported results and do not establish an antiviral effect in people.

In a mouse model of Parkinson’s disease, andrographolide improved movement and protected dopamine neurons. It bound the protein DRP1 and blocked excessive mitochondrial fission ^{11Reference 11Geng et al. · 2019In vitroAndrographolide alleviates Parkinsonism in MPTP-PD mice via targeting mitochondrial fission mediated by dynamin-related protein 1 — animal model (mouse) / in vitroView study →}. Animal work also reports anti-inflammatory and anti-fibrotic effects in nerve models ^{9,13Reference 9Bertoglio et al. · 2016RCTAndrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study — randomised controlled trialView study →Reference 13Dai et al. · 2019ReviewOverview of pharmacological activities of Andrographis paniculata and its major compound andrographolide — reviewView study →}.

In a randomised, double-blind, placebo-controlled 12-month trial, patients with relapsing-remitting multiple sclerosis on interferon beta took 170 mg of dried andrographis extract twice a day. Fatigue scores fell by 44% compared with placebo ^{9Reference 9Bertoglio et al. · 2016RCTAndrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study — randomised controlled trialView study →}.

Relapse rate, disability scores and inflammatory markers did not differ. One patient on andrographis had a mild, passing skin rash ^{9Reference 9Bertoglio et al. · 2016RCTAndrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study — randomised controlled trialView study →}.

Gap: 25 patients enrolled and 22 were analysed. It is a pilot trial, and the result needs a larger one.

Pharmacology reviews summarise andrographolide’s blood-sugar-lowering and anti-obesity activity in rodents, with proposed effects on insulin signalling and glucose uptake ^{13,14Reference 13Dai et al. · 2019ReviewOverview of pharmacological activities of Andrographis paniculata and its major compound andrographolide — reviewView study →Reference 14Zeng et al. · 2022Clinical trialAndrographolide: a review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches — reviewView study →}. A small registered human study looked at GLP-1, fasting insulin and insulin resistance, but human efficacy data are lacking.

Andrographolide induces cell death and cell-cycle arrest and alters NF-κB and other cancer-related signalling in many cancer cell lines ^{13,14Reference 13Dai et al. · 2019ReviewOverview of pharmacological activities of Andrographis paniculata and its major compound andrographolide — reviewView study →Reference 14Zeng et al. · 2022Clinical trialAndrographolide: a review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches — reviewView study →}.

One registered palliative-care trial in oesophageal cancer exists, and it does not establish a treatment effect.

Gap: the evidence is in cell lines and a few animal models of the isolated compound. No trial has shown benefit from the herb in cancer, and andrographolide is poorly absorbed.

Tolerability. A meta-analysis of randomised trials found serious adverse events very rare, at about 0.02 per 1,000 patients. Non-serious effects were common, at about 103 per 1,000 patients, mostly digestive and skin reactions ^{15Reference 15Worakunphanich et al. · 2021Meta-analysisSafety of Andrographis paniculata: a systematic review and meta-analysis — systematic reviewView study →}.

Injected derivatives. A separate review found herbal preparations of andrographis essentially safe. Injectable andrographolide-derivative drugs had a higher reaction rate and have caused anaphylactic shock ^{16Reference 16Shang et al. · 2022Systematic reviewAdverse effects of andrographolide derivative medications compared to the safe use of herbal preparations of Andrographis paniculata — systematic reviewView study →}. These are not the oral herb.

Allergy. A phase 1 trial of andrographolide in escalating doses in people with HIV was stopped at 6 weeks after adverse events, including an anaphylactic reaction in one patient ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}.

Immune activity. Andrographis alters immune activity, so care is warranted in autoimmune disease and alongside immunosuppressants ^{13,14Reference 13Dai et al. · 2019ReviewOverview of pharmacological activities of Andrographis paniculata and its major compound andrographolide — reviewView study →Reference 14Zeng et al. · 2022Clinical trialAndrographolide: a review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches — reviewView study →}.

Blood thinners. Andrographolide inhibits platelet aggregation in vitro ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}, so it may add to the effect of warfarin and antiplatelet drugs.

Liver enzymes. Leaf extracts inhibit CYP3A4 and CYP2C9 in human liver microsomes, which could raise levels of drugs cleared by those enzymes ^{18Reference 18European Medicines Agency · 2014Clinical trialAssessment report on Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012 Corr1) — constituents, traditional and pharmacopoeial uses, posology, clinical trials, interactions and reproductive toxicity — regulatory review. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-andrographis-paniculata-nees-folium-first-version_en.pdfView study →}. No human drug-interaction trial has been done.

Long-term use. The safety record comes from short trials in acute illness. Long-term safety has not been assessed in people.