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Indigo leaves

Health Conditions27
Table of contents

Other Names

African indigoAmariAnilAnila tinctoriaAnila tinctoria (L.) KuntzeAnila tinctoria var. normalis KuntzeAnjanikaAsidaiAsitaAttipurashadamAveriAviriAvuriBaphicacanthus cusiaBaphicacanthus cusia (Nees) Bremek.BasmaBengal indigoBlack hennaCommercial indigoCommon indigoDà Qīng YèDa Qing YeDyer's indigoDyer's knotweedDyer's woadEast Asian indigo plantFrank indigoFrench indigoGaliGandhapushpaGariGraminaGramyaGuatemalan indigoHabb-ul-NeelIndian indigoIndigo des teinturiersIndigo naturalisIndigo plantIndigoboomIndigofera anil L. var. orthocarpa DC.Indigofera argentea L.Indigofera bergii VatkeIndigofera cinerascens DC.Indigofera diffusa Desv.Indigofera emarginata Perr.Indigofera houer Forssk.Indigofera indica Lam.Indigofera oligophylla BakerIndigofera ornithopodioides Schumach.Indigofera orthocarpa (DC.) O. BergIndigofera suffruticosaIndigofera suffruticosa Mill.Indigofera sumatrana Gaertn.Indigofera tinctoriaIndigofera tinctoria L.IndigogewassenIndigopflanzeIndigoplantenIndigostrauchIndigotierIsatis indigoticaIsatis indigotica Fort.Isatis tinctoriaJapanese indigoKaalakeshiKaliLilMadhuparnikaMaharasaMochaMu lanNeelNeel (Hindi/Bengali/Assamese/Rajasthani)NeelaNeelamNeelayamariNeeliNilNila (Malaysia)Nila (Odia)NilaaNilakaNilamNilapushpaNilayamariNiliNili (Sanskrit)Nili (Tamil)NilichettuNilikaNilikaaNilimandu chettuNiliniNilini (Sanskrit)Persicaria tinctoriaPersicaria tinctoria (Aiton) Spach.Polygonum tinctoriumPolygonum tinctorium AitonQing DaiQingdaiRangapatriRangapushpiRanjaniRyukyu-aiShaaradiShyamalikaSmall-leaved indigoStrobilanthes cusiaStrobilanthes cusia (Nees) KuntzeSukumoTarumTrue indigoTutthaaVishodhiniWest Indian indigoWoad

Synopsis

Indigo Leaves (Indigofera tinctoria and Related Species): A Comprehensive Reference

1. Identity, Botanical Classification, and Natural Sources

The term indigo leaves refers primarily to the leaves — and in some preparations, the aerial parts — of plants in the genus Indigofera (family Fabaceae), most notably Indigofera tinctoria L. (true indigo or Indian indigo), but the term is also applied in the context of the processed herbal product indigo naturalis (Chinese: Qing Dai), which may be derived from the leaves and stems of several related plant species.

The scientific names associated with the indigo naturalis product include Baphicacanthus cusia Brem. (Thailand), Indigofera anil L., Indigofera arrecta (Bengal, Natal), Indigofera tinctoria (France), Isatis indigotica Fortune ex Lindl., Isatis tinctoria L. subspecies villarsii, Persicaria tinctoria (Japan), Polygonum tinctorium, Strobilanthes cusia (Neess) Kuntze, and Indigofera suffruticosa Mill. (Guatemala). The variety of source plants used across regions reflects indigo naturalis's status as a processed herbal product rather than a single-species botanical ingredient.

Indigofera is the third-largest genus in the Fabaceae family and consists of approximately 750 species distributed across all tropical and subtropical regions. Some 75% of these species are restricted to Africa and Madagascar, with many also found in the Sino-Himalayan region, Australia, and Central and South America.

I. tinctoria is a shrub of 1–2 metres in height, biennial or perennial depending on climate, with dark green leaves and pinkish-violet flowers. It is known as Indigo in English, Neeli chetu in Telugu, Neelam in Tamil, and Neel in Hindi.

Common Names and Synonyms

  • Common names include common indigo, Indian indigo, indigo naturalis, and Qing dai in traditional Chinese medicine.
  • In Ayurveda, the plant is known as Nili or Neelini.
  • Indigofera tinctoria has historically been called "true indigo" to distinguish it from related dye-producing species.

Common Forms and Preparations

Indigo naturalis (IN, Qingdai) is a processed product of the leaves and stems. It takes the form of a deep blue or blue-black powder produced by fermenting the leaves in water and precipitating the pigment. In contemporary medicinal and research contexts, it appears in several forms:

  • Crude powder (Qing Dai): The traditional processed powder, administered orally or used topically in ointments.
  • Oil extract (Lindioilâ„¢): An extract of indigo naturalis in oil, developed specifically for topical application to the skin and nails in psoriasis research.
  • Capsules: Standardised capsule formulations used in clinical trials for gastrointestinal conditions.
  • Ointment/paste: Topical preparations mixed with excipients such as petroleum jelly or sesame oil, used in dermatology studies.
  • Decoction/leaf juice: Traditional preparations for oral or topical use in Ayurvedic and Siddha practice.

2. Traditional and Historical Use

Geographic and Cultural Reach

Indigofera tinctoria, commonly known as true indigo, has a long-standing historical significance bridging traditional and modern applications. Traditionally, it was highly valued for its role in textile dyeing, especially in regions like India, Southeast Asia, and Africa, where it created the iconic blue hues integral to cultural and ceremonial garments. Its use dates back thousands of years, making it a cornerstone of ancient dyeing practices.

The oldest Sanskrit texts from India mention the use of Indigofera and the dye extracted from it. According to Egyptian scriptures and texts, the blue dye from Indigofera was used for textiles of Egyptian mummies. Archaeological findings from the 11th and 12th centuries in West Africa reveal indigo-dyed textiles, highlighting its historical importance in global trade.

Indigofera tinctoria (Avuri) has been practiced as a traditional medicinal plant in India, Africa, and China for the treatment of nervous disorders, epilepsy, bronchitis, and liver diseases.

Ayurveda and the Siddha Tradition (India)

In Ayurveda, known as Neelini, Indigofera tinctoria is used for the treatment of fever, liver and spleen disorders, rheumatoid arthritis, gout, and grey hair. In Ayurvedic theory, the plant is characterised as light to digest (Laghu), drying (Rooksha), bitter in taste (Tikta), and hot in potency (Ushna), balancing Kapha and Vata doshas. Documented applications include use as a purgative, a hair-strengthening agent (Keshya), an anti-toxic (Vishahara), and for conditions including splenomegaly, ascites, gout, and toxicological emergencies.

In South India's Siddha tradition, Indigofera leaves were mixed with other herbs such as neem (Azadirachta indica) to create cooling poultices. Preparations such as Neelibhringadi Oil were used in Ayurveda for improving the quality of hair, treating split hairs, premature greying, and baldness.

Traditional Chinese Medicine (TCM)

Qing Dai, commonly known as indigo naturalis, is a traditional Chinese medicine extracted from the leaves and stems of plants such as Indigofera tinctoria, Strobilanthes cusia, and Polygonum tinctorium. It was first mentioned in a foundational 10th-century Chinese medicine textbook and has been used for centuries.

Indigo naturalis is used in traditional Chinese medicine for its hemostatic, antipyretic, anti-inflammatory, sedative, antibacterial, and antiviral properties. Due to indigo's heat-clearing, detoxifying, and blood-cooling properties, TCM practitioners have prescribed Qing Dai for a wide range of inflammatory conditions, including psoriasis, eczema, and inflammatory bowel diseases including ulcerative colitis.

Chronic myelocytic leukaemia has historically been treated with the traditional Chinese recipe Danggui Longhui Wan, a mixture of 11 herbal medicines. In 1966, the Institute of Haematology of the Chinese Academy of Medical Sciences undertook investigation of the active factor of this complex mixture. The activity was traced to one ingredient, Qing Dai — a dark blue powder prepared from leaves of Baphicacanthus cusia, Polygonum tinctorium, Isatis indigotica, Indigofera suffruticosa, and Indigofera tinctoria. Although this powder contained a high level of the blue dye indigo, the antileukaemic activity was attributed to indirubin, a red-coloured isomer and minor constituent of the mixture.

Medieval Islamic World and Africa

Lev and Amar (2008) reported that I. tinctoria seeds were used by people in medieval Cairo (10th century) to treat skin diseases, swellings, and wounds. Indigo cultivation and its applications in traditional healing spread across West Africa alongside textile traditions, with documented use by indigenous healers for skin conditions and infections.

Colonial-Era Documentation

By the 18th century, colonial botanical studies resurrected interest in the plant's constituents. British East India Company botanists documented pharmacological uses including digestive aid, fever reduction, and skin therapy.

3. Key Constituents and Active Compounds

A total of sixty-three compounds — including indole alkaloids, terpenoids, organic acids, steroids, and nucleosides — have been isolated from indigo naturalis, of which indole alkaloids are the most important.

Indirubin, indigo (indigotin), isatin, tryptanthrin, and β-sitosterol are considered the key components in the treatment of ulcerative colitis (UC) with indigo naturalis. The broader phytochemical profile of Indigofera tinctoria leaves includes:

  • Indican (indoxyl-β-D-glucoside): The glycoside precursor to indigotin — hydrolyzed by enzymes during the fermentation and vat process to yield the famed blue dye.
  • Indigotin (indigo): The principal blue pigment and one of the two major bis-indole alkaloids in the processed product.
  • Indirubin: A red isomer with anti-inflammatory and anti-leukaemic properties, shown in laboratory studies to inhibit cyclin-dependent kinases. Isolated from indigo naturalis, indirubin was used as a new agent to treat leukaemia in China in the 1970s and is also an active ingredient in the treatment of psoriasis.
  • Tryptanthrin: Exhibits antimicrobial and anti-protozoal activity, particularly against Staphylococcus aureus and Leishmania species.
  • Isatin: A minor alkaloid identified as a component contributing to indigo naturalis's pharmacological activity in preclinical IBD research.
  • Isorhamnetin: A flavonoid constituent with anti-leukaemia effects validated in cell viability and apoptosis assays.
  • Flavonoids (kaempferol, quercetin, apigenin): Offer free radical scavenging and vascular support. Apigenin and kaempferol are among the flavonoids identified from various parts of the plant.
  • Tannins: Contribute astringent and antioxidant effects helpful in topical formulations for minor wounds.
  • β-Sitosterol: A phytosterol present in indigo naturalis with anti-inflammatory properties.

4. Mechanisms of Action

Aryl Hydrocarbon Receptor (AhR) Pathway

Indigo naturalis contains ligands for the aryl hydrocarbon receptor (AhR) and promotes regeneration of the mucosa by inducing production of interleukin-22 (IL-22), suggesting a mechanism by which it may induce mucosal healing in ulcerative colitis. Indirubin regulates various inflammatory pathways by activating the AhR pathway through expression of genes such as CYP1A1.

NF-κB and Cytokine Signalling

Anti-inflammatory mechanisms of indigo naturalis include AhR pathway activation, NF-κB/NLRP3/IL-1β inhibition, and modulation of the TLR4/MYD88/NF-κB and MAPK signalling pathways. In addition, inhibition of the MAPK pathway and NF-κB inhibition were observed by reducing expression of proteins related to the TLR4/MYD88/NF-κB pathway.

Th17/Treg Axis

In mouse colitis models, administration of Qing Dai significantly suppressed colonic myeloperoxidase activity, increased the activities of antioxidant enzymes (T-SOD, CAT, GSH-Px), and upregulated p-AMPK and Nrf-2 expression. Additionally, it reduced Th1 and Th17 cell cytokines, the frequencies of Th1 and Th17 cells, and the phosphorylation of p-STAT1 and p-STAT3 in the mesenteric lymph nodes of colitic mice.

Cyclin-Dependent Kinase (CDK) Inhibition

Indirubin was detected as a novel lead structure with potent inhibitory potential towards cyclin-dependent kinases (CDKs), resulting from high-affinity binding into the enzymes' ATP binding site. Indirubin has been reported to inhibit cyclin-dependent kinase and signal transducer and activator of transcription-3 (STAT3) activities, as well as keratinocyte proliferation in vitro.

IL-17 Pathway Modulation in Psoriasis

Indigo naturalis, and particularly indirubin and tryptanthrin, have anti-proliferative, anti-inflammatory, and anti-angiogenic effects through regulation of the TAK1, JAK3/STAT3, Wnt/β-catenin, Akt/PKB, FAK, and AP-1/c-Jun pathways. The main active components of indigo naturalis have anti-inflammatory properties. Tryptanthrin was reported to inhibit interferon-γ production by lymphocytes from Peyer's patches, and nitric oxide and prostaglandin E2 synthesis by murine macrophages.

Antimicrobial Activity

Research has demonstrated extensive antimicrobial activity of the plant against clinically significant bacteria such as Staphylococcus aureus, Escherichia coli, and Candida albicans.

5. Scientific Evidence by Area of Use

5.1 Ulcerative Colitis (UC)

Ulcerative colitis is the area in which indigo naturalis has received the most rigorous clinical investigation, including at least one multicenter randomised controlled trial (RCT) published in a major peer-reviewed journal.

Key Clinical Studies

Naganuma et al., 2018 (INDIGO Study Group, Gastroenterology): A multicenter, double-blind trial evaluated the safety of 86 patients in Japan with active UC (Mayo scores of 6 or more), enrolled from March 30 through December 27, 2016. Patients were randomly assigned to groups and given a daily dose of 0.5, 1.0, or 2.0 g indigo naturalis, or placebo (1:1:1:1 ratio) for 8 weeks. In this multicenter, randomised, double-blind, placebo-controlled study, the rates of clinical efficacy, remission, and mucosal healing observed in all three IN-treated groups were significantly higher than the rates observed in the placebo group. However, the authors found 8 weeks of IN (0.5–2.0 g per day) to be effective in inducing a clinical response in patients with UC, but concluded that IN should not yet be used because of the potential for adverse effects, including pulmonary arterial hypertension.

Short-term multicenter double-blind trial (PLoS ONE, 2020): Forty-six patients with mild to moderate active UC (Lichtiger index 5–10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks.

Systematic review and meta-analysis (ScienceDirect, 2023): Indigo naturalis is a traditional therapy reported to be useful in IBD, especially UC. A systematic review of its efficacy and safety in IBD was conducted, concluding that indigo naturalis is useful in the treatment of ulcerative colitis and provides clinicians with one more relatively cheap option.

Mechanism of AhR/IL-22 pathway (Springer Nature, 2024 RCT): A randomised controlled trial compared Qing Dai to Adisa, followed by UPLC-Q-TOF/MS and network pharmacology analyses to identify core components and targets. In vivo experiments on a UC mouse model explored QD's impact on the AhR-Th17/Treg pathway. Results showed QD's efficacy in UC treatment, with mucosal healing and remission comparable to Adisa.

Evidence Summary for UC

Indigo naturalis appears to be a very effective induction therapy for patients with IBD, particularly UC, though the likelihood of adverse events is significant and seems to increase with treatment length. It has been reported that 8 weeks of oral administration of IN is effective in patients with mild to moderate active UC; however, serious adverse events including pulmonary arterial hypertension (PAH) or intussusception were reported in patients treated with IN for long periods. The evidence for short-term induction is moderately strong (level: controlled trials with consistent direction), but the safety profile for extended use substantially limits its clinical applicability.

5.2 Psoriasis (Plaque-Type, Topical Use)

Topical indigo naturalis for plaque psoriasis has been studied in multiple small randomised or controlled trials, primarily from Taiwan.

Lin et al., 2008 (Archives of Dermatology): Forty-two outpatients with chronic plaque psoriasis were enrolled. Patients applied either indigo naturalis ointment or vehicle ointment topically to each of 2 bilaterally symmetrical psoriatic plaque lesions for 12 weeks. Significant reductions in the sum of scaling, erythema, and induration scores (P <.001) — mean score 6.3 after indigo naturalis treatment vs. 12.8 in controls — and plaque area percentage (P <.001) — mean 38.5% after treatment vs. 90% in controls — were achieved. Approximately 31 of 42 patients (74%) experienced clearance or near clearance of psoriasis in the indigo ointment-treated lesion.

Double-blind, placebo-controlled trial (BMC Complementary Medicine, 2017): A randomised, double-blind, placebo-controlled clinical study was conducted using indigo naturalis as topical monotherapy to treat moderate plaque psoriasis in a Chinese cohort (n = 24). At week 8, significant improvements in Psoriasis Area and Severity Index (PASI) scores from baseline were observed in indigo naturalis-treated patients (56.3% had 75% improvement [PASI 75] response) compared with placebo (0.0%). A gene expression signature of moderate psoriasis was established from baseline skin biopsies, including up-regulation of the IL-17 pathway as a key component; indigo naturalis treatment resulted in most of these signature genes returning toward normal, including down-regulation of the IL-17 pathway.

Nail psoriasis (Lindioilâ„¢, Phytomedicine, 2014): Lin et al. conducted a 24-week, randomised, intra-subject trial involving 31 patients with nail psoriasis. Participants applied IN extract (Lindioilâ„¢) twice daily to the nails of one hand and olive oil to the contralateral nails for 12 weeks, followed by IN extract treatment to both hands for another 12 weeks. Compared to olive oil, IN extract ointment produced significantly greater improvements in Nail Psoriasis Severity Index (NAPSI) scores, with the formulation reported as comparable to other routine topical agents and with no reported adverse events.

Systematic review and meta-analysis (PMC, 2024): Findings from a systematic review across seven databases demonstrated a higher response rate in the Chinese herbal medicine (CHM) formula groups than in the control group for PASI60 (rate difference [RD] = 0.22, p < .0001). Among all adverse events, only the incidence of gastrointestinal adverse reactions was higher in the CHM formula group than in the control group (RD = 0.09, p < .0001).

Evidence Summary for Psoriasis

The evidence for topical indigo naturalis in plaque and nail psoriasis is among the strongest for this ingredient — multiple small RCTs showing clinically meaningful PASI score reductions. However, heterogeneity in formulation, extraction methods, and concentrations complicates direct comparison across studies and presents challenges in standardisation for clinical practice. As a botanical therapy, indigo naturalis is subject to variability in sourcing, processing, and quality control, which may impact the consistency of formulation. Larger multicenter trials are needed before strong clinical recommendations can be made.

5.3 Leukaemia

Indirubin, in particular, has been identified as a major active ingredient in a traditional Chinese medicinal recipe containing Indigofera tinctoria L. and Isatis tinctoria L., which have been used for the treatment of chronic myelocytic leukaemia (CML) for many years.

In clinical trials on 314 patients suffering from chronic myelocytic and chronic granulocytic leukaemia, indirubin was given orally at a dosage of 150–450 mg per day. Indirubin and meisoindigo induced haematologic remission in patients with chronic phase CML as effectively as hydroxyurea and busulfan; in addition, there were no significant differences in median duration of chronic phase, median survival, and blast crisis at 60 months from diagnosis among indirubin-, meisoindigo-, hydroxyurea-, and busulfan-treated groups.

These clinical studies were conducted in China in the context of CML treatment and represent moderate-quality historical evidence. Indirubin as an isolated compound — rather than the whole leaf preparation — is the subject of ongoing anticancer drug development research. Indirubin presents issues such as limited natural resources, poor solubility, and potential toxicity, which impede its clinical application.

5.4 Antimicrobial Effects

The antimicrobial, cytotoxic, antioxidant, and anti-inflammatory activities are the most studied for the genus Indigofera, with I. tinctoria the most investigated species. Most of the studies have been performed on extracts of leaves and aerial parts, and some isolated compounds have also been tested. Evidence remains predominantly preclinical (in vitro) with no robust human clinical trials for infectious disease indications.

5.5 Hepatoprotective Effects

Researchers from the Department of Zoology, Annamalai University, Tamil Nadu, investigated the antihepatotoxic effects of Indigofera tinctoria. These studies are at a preclinical stage; importantly, as discussed in the safety section, the clinical evidence points to a paradoxical hepatotoxicity risk with oral indigo naturalis use. No confirmed human hepatoprotective benefit has been established.

6. Body Systems and Health Areas Associated With Indigo Leaves

  • Gastrointestinal system: Ulcerative colitis, mucosal healing, inflammatory bowel disease (multiple clinical trials).
  • Dermatological system: Plaque psoriasis, nail psoriasis, eczema, wound healing (clinical trials and case series for psoriasis; traditional use and preclinical evidence for others).
  • Haematological system: Chronic myelocytic leukaemia — historical clinical use of indirubin in China.
  • Immune system: Modulation of Th17/Treg balance, IL-17, IL-22, and AhR signalling (preclinical and mechanistic human data).
  • Antimicrobial: Antibacterial activity against S. aureus, E. coli, and Candida albicans (in vitro).
  • Hair and scalp: Traditional use for hair growth promotion, greying, and dandruff in Ayurveda and Siddha medicine.
  • Neurological/antipyretic: Traditional use for fever and nervous system conditions in Ayurvedic and Chinese medicine.

7. Dosage Forms and Reported Dosages

There is no well-established, evidence-based human oral dose for Indigofera tinctoria suitable for general self-treatment. The following dosages are drawn directly from published clinical studies and traditional references:

  • Oral indigo naturalis — UC (INDIGO RCT, 2018): Patients were randomly assigned to groups and given a daily dose of 0.5, 1.0, or 2.0 g indigo naturalis, or placebo (1:1:1:1 ratio) for 8 weeks.
  • Oral capsules — short-term UC (2020 multicenter trial): Forty-six patients received 5 capsules (500 mg) twice a day (total 2.5 g per day of capsule content) for 2 weeks.
  • Indirubin — oral, CML: In clinical trials on 314 patients with chronic myelocytic and chronic granulocytic leukaemia, indirubin was given orally at a dosage of 150–450 mg per day.
  • Topical ointment — plaque psoriasis: Applied once or twice daily to affected skin lesions in studies of 8–12 weeks' duration; specific concentration varied by study formulation.
  • Topical oil extract (Lindioilâ„¢) — nail psoriasis: Participants applied IN extract twice daily to the nails of one hand for 12 weeks.
  • Ayurvedic oral powder: Traditional dosage in Ayurveda is cited as powder 3–5 g; decoction 50–100 mL.

8. Safety Considerations and Known Adverse Events

Pulmonary Arterial Hypertension (PAH) — Serious and Well-Documented

The use of indigo naturalis in treating inflammatory diseases is clinically restricted by severe adverse events, including pulmonary arterial hypertension and hepatotoxicity.

In a randomised controlled trial of indigo naturalis for UC in Japan, the clinical and mucosal healing efficacy was confirmed, but the trial was terminated partly due to a report of pulmonary arterial hypertension (PAH) in a patient who self-medicated with indigo naturalis. A reported case involved a 45-year-old Japanese female diagnosed with PAH (pulmonary artery pressure 58/25 mmHg, mean 36 mmHg by right-sided cardiac catheterisation); clinical symptoms and examination data had completely improved at 4 months after indigo naturalis discontinuation, with BNP levels normalising and transthoracic echocardiography confirming improvement; bosentan was gradually discontinued at 6 months, with no recurrence detected over the subsequent 2 years.

Across 337 participating institutions in Japan's nationwide survey, 49,320 patients with UC were identified, with IN used in 877 (1.8%). Adverse events were reported in 91 patients (107 events), including liver dysfunction and PAH. PAH was reversible in all patients who underwent long-term (>8 weeks) treatment with IN; however, some required treatment. Intussusception occurred within 2 months of IN treatment, and surgery was required in 4 of the 10 cases.

Hepatotoxicity

Of the 40 cases of elevated liver enzymes in the nationwide survey, approximately half occurred within 2 months of initiation of IN therapy, but levels improved in all patients upon IN discontinuation. Long-term intake of IN increases the risk of adverse events; therefore, the use of IN as maintenance therapy is not recommended.

Indirubin, the main component of indigo naturalis with poor aqueous solubility, predisposes mice with chronic colitis to hepatic injury in a manner that closely mimics the hepatic damage commonly observed in ulcerative colitis patients treated with indigo naturalis. These toxic effects are believed to originate from other chemical constituents such as indigo and indirubin, rather than from tryptanthrin itself.

Gastrointestinal and Other Adverse Events

Indigo naturalis has been reported to cause mild liver dysfunction, abdominal pain, and headache. It may also cause colitis and pulmonary arterial hypertension. Topical indigo naturalis may cause pruritus, rash, erythema, and nasopharyngitis. One case report describes development of pancreatitis with use of oral indigo naturalis; another describes colitis and pulmonary hypertension with a supplement containing Qing Dai.

Toxicity in Specific Populations

Several species of Indigofera, including I. spicata, I. linnaei, I. suffruticosa, I. mysorensis, and I. tinctoria, are reported to be toxic for animals, and sometimes for humans. This toxicity is mainly due to the presence of two kinds of compounds: non-proteinogenic amino acids and nitrocompounds.

Case literature includes severe poisoning after therapeutic administration of indigo to a child. That kind of report does not prove that every form is highly toxic, but it is strong enough to rule out the casual assumption that oral indigo is harmless because it is "just a plant."

Topical Safety

In the psoriasis nail trial, the IN formulation was reported comparable to other routine topical agents, such as steroids, with no reported adverse events. In the psoriasis systematic review meta-analysis, the incidence of gastrointestinal adverse reactions was higher in the oral CHM formula group than in the control group (RD = 0.09, p < .0001).

Regulatory Responses

The Japanese Ministry of Health, Labour and Welfare issued a pharmaceutical safety notification in 2016 following reports of PAH associated with indigo naturalis use, reflecting the seriousness with which this adverse event signal was treated by regulatory authorities.

9. Evidence Strength: An Overall Assessment

The overall state of clinical evidence for indigo leaves and their processed preparations is best summarised as follows:

  • Topical psoriasis (plaque and nail): Multiple small RCTs with consistent outcomes; evidence is moderately strong but limited by small sample sizes, short durations, and formulation variability.
  • UC induction therapy (oral indigo naturalis): One multicenter RCT (Naganuma 2018) and several smaller trials showing robust efficacy signals; evidence is moderate in strength for induction, but serious adverse events (PAH, intussusception, hepatotoxicity) preclude routine clinical recommendation based on current data.
  • CML (indirubin oral): Historical Chinese clinical trials showed haematologic remission comparable to standard chemotherapy, but these predate modern trial standards and were conducted specifically with purified indirubin rather than whole-leaf preparations.
  • Antimicrobial, hepatoprotective, antioxidant: Predominantly in vitro and preclinical animal evidence; no confirmed human efficacy for these indications.
  • Ayurvedic/traditional applications (hair, fever, liver, spleen): Based on historical traditional use and limited pharmacological plausibility data; no controlled human clinical trials.

References

Health Conditions

Health conditions that Indigo leaves may help support.

  • Indigofera tinctoria leaf extracts demonstrate potent antioxidant activity in multiple in vitro assays, attributable to flavonoids, tannins, and phenolic constituents. DPPH radical scavenging activity comparable to reference antioxidants has been demonstrated, and in vivo animal studies confirm modulation of antioxidant enzymes including SOD, CAT, and GSH.

  • Multiple preclinical studies and systematic reviews demonstrate that indigo naturalis (derived from indigo plant leaves) and its active components—indirubin, indigo, and tryptanthrin—exert significant anti-inflammatory effects via multiple pathways including NF-κB, JAK/STAT, and Th17 suppression. These mechanisms have been confirmed in human disease contexts including psoriasis and ulcerative colitis.

  • ColitisScientific

    Indigo naturalis (derived from indigo plant leaves) has the strongest clinical evidence base in ulcerative colitis of any traditional herbal medicine. Multiple RCTs and a comprehensive PMC systematic review confirm efficacy in inducing clinical response and mucosal healing in active UC. The mechanism involves aryl hydrocarbon receptor (AhR) activation and IL-22 induction.

  • In vitro studies demonstrate antifungal activity of Indigofera species extracts against Candida albicans and other fungi. The EBSCO Research Starters source cites a test-tube trial showing 'significant activity against certain bacteria and fungi.' This is preclinical scientific evidence; no human trials exist.

  • Indigo naturalis (IN) has the strongest evidence base among herbal remedies for IBD, with multiple published RCTs in ulcerative colitis and extensive animal-model data. A 2025 Frontiers in Pharmacology meta-analysis of 15 animal studies and multiple human RCTs confirm clinically meaningful effects. Mechanism involves AhR activation, IL-22 induction, and gut microbiota modulation.

  • Liver DetoxScientific

    Animal studies from Annamalai University and others demonstrate hepatoprotective activity of I. tinctoria leaf extracts against chemically induced liver injury, with significant restoration of liver enzymes (AST, ALT, ALP) and antioxidant parameters. This use is also well-rooted in traditional Ayurvedic and TCM practice.

  • PsoriasisScientific

    Indigo leaves are the traditional plant material used to prepare indigo naturalis, a clinically validated topical treatment for plaque psoriasis in Traditional Chinese Medicine. Multiple RCTs show significant PASI reductions with indigo naturalis preparations applied topically.

  • Wound HealingScientific

    A PubMed-indexed animal study (2023) demonstrated that topical indigo plant leaf extract (5%) applied twice daily significantly accelerated excision wound healing in rats, supporting traditional use. The leaves have documented traditional wound-healing use across Ayurvedic, Siddha, and folk medicine systems.

  • AbscessesTraditional

    Indigo leaves (Indigofera tinctoria) have a documented traditional use in India and China for skin boils and abscesses, applied topically as a paste. The antimicrobial and anti-inflammatory properties of the leaf extract provide a plausible basis for this use. No controlled human trials exist specifically for abscesses.

  • ArthritisTraditional

    Indigo (I. tinctoria) is listed in Ayurvedic materia medica for arthritis and lumbago, and anti-arthritic activity has been demonstrated in animal studies of the Indigofera genus. The anti-inflammatory alkaloids indirubin and tryptanthrin provide mechanistic plausibility. No human clinical trials exist for arthritis per se.

  • AsthmaTraditional

    In traditional Indian medicine, including Ayurveda and folk medicine from Kerala and Tamil Nadu, indigo leaves and roots are used for asthma via decoctions and root-pepper preparations. The anti-inflammatory properties of the plant constituents are mechanistically relevant. No human clinical trials exist.

  • Bites and StingsTraditional

    Indigo leaves have a longstanding traditional use across Indian subcontinent traditions as a topical application for the bites and stings of venomous creatures. A decoction or paste was applied to the wound to relieve pain and aid healing. No human clinical evidence exists.

  • BronchitisTraditional

    Indigo leaves are documented in traditional Indian (Ayurvedic, Siddha, folk) and traditional Chinese medicine for the treatment of bronchitis. Leaves are specifically mentioned as used for 'cough, bronchitis, and fever' in multiple ethnobotanical records. No clinical human trial data exist.

  • Burns and ScaldsTraditional

    Indigo leaves have a traditional use in Indian herbal medicine applied topically for burns and scalds to promote healing and reduce pain. This is documented in ethnobotanical records. No clinical trials exist for this specific application.

  • Crohn's DiseaseTraditional

    Crohn's disease is listed as a traditional use of indigo in the EBSCO Research Starters monograph and is included in recent IBD animal-model meta-analyses of indigo naturalis. Human clinical evidence is, however, derived from UC studies; no dedicated Crohn's disease clinical trials exist.

  • DandruffTraditional

    Indigo leaves have a well-documented traditional use in Ayurvedic and folk medicine for dandruff control, applied to the scalp as oil or paste. Antimicrobial and anti-inflammatory properties provide a plausible mechanism. No clinical trials exist for this specific application.

  • DiarrheaTraditional

    Indigo leaves are traditionally used in Ayurveda and folk medicine as a treatment for diarrhea, attributed to mild antimicrobial activity against gut pathogens and astringent tannin content. Animal studies on Indigofera species support antidiarrheal properties. No human trials exist for this indication.

  • EczemaTraditional

    In Ayurveda and Siddha medicine, indigo leaves are topically applied for eczema to reduce itching, inflammation, and redness. The anti-inflammatory and antimicrobial properties of the leaf constituents are consistent with this use. The related compound indigo naturalis has shown clinical efficacy in psoriasis, but clinical data specifically for eczema are lacking.

  • EpilepsyTraditional

    Indigo (I. tinctoria) has an extensive documented history in Ayurvedic, Siddha, TCM, and homeopathic traditions for epilepsy and seizure disorders, and animal studies confirm anticonvulsant activity via GABA modulation. No human clinical trials have been conducted.

  • FeverTraditional

    Indigo leaves have a centuries-old use as a febrifuge (fever reducer) in Ayurvedic, Siddha, and traditional Chinese medicine, documented from the Tang Dynasty onward. Multiple traditional pharmacopoeias list this indication. No human clinical trials on this specific use exist.

  • GastritisTraditional

    Indigo leaves are used in traditional Indian medicine for stomach complaints and gastrointestinal inflammation. Related Indigofera species (I. truxillensis) have shown gastroprotective activity in animal models. No human trial data exist specifically for gastritis from I. tinctoria leaves.

  • In Ayurvedic and Siddha medicine, indigo (I. tinctoria) is listed for gout, traditionally attributed to its Virechana (purgative) and anti-inflammatory properties. Ayurvedic texts and encyclopaedias of Indian medicinal plants document this use. No clinical trials exist.

  • Indigo leaves are one of the most classically documented Ayurvedic remedies for promoting hair growth and strengthening hair follicles. Preparations such as Neelibhringadi oil are formally recognized in the Ayurvedic Pharmacopoeia. No controlled clinical trials exist specifically for hair growth.

  • Hair LossTraditional

    Indigo leaves are documented in Ayurveda for preventing hair loss and promoting hair regrowth, with formal recognition in Ayurvedic Pharmacopoeia formulations. The antimicrobial and anti-inflammatory properties address scalp conditions that contribute to hair loss. No controlled clinical trials exist.

  • Rheumatoid arthritis is listed as a specific indication for I. tinctoria in Ayurvedic texts and databases. Anti-arthritic activity has been demonstrated in animal models for the Indigofera genus, and anti-inflammatory mechanisms involving JAK/STAT3 and Th17 suppression are directly relevant to RA pathophysiology.

  • Sore ThroatTraditional

    Indigo naturalis has been used in traditional Chinese and Indian medicine for sore throat and oral inflammation since at least the Tang Dynasty. It was blown as a powder into the infected region in classical TCM practice. No human clinical trials exist specifically for sore throat.

  • UlcersTraditional

    Indigo leaves are used in Ayurveda and traditional Chinese medicine for oral and gastric ulcers. Related Indigofera species show gastroprotective activity in animal models. Oral ulcers are specifically mentioned in both TCM and Ayurvedic texts, and the plant has well-documented antimicrobial and anti-inflammatory properties.

Body Systems

Body systems that Indigo leaves may help support.

  • No body systems available.
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Indigo leaves | Caring Sunshine