Ingredient Processed / Derived product (加工品 jiā gōng pǐn)

Qing Dai

Natural indigo · 青黛

Baphicacanthus cusia (Nees) Bremek. · Indigo Naturalis

Also known as: Indigo Naturalis, Natural Indigo, Dian Hua (靛花),

Images shown are for educational purposes only

Qing Dai (natural indigo) is a deep blue powder extracted from the leaves of several indigo-producing plants. It is a potent Heat-clearing herb used for inflammatory skin conditions, bleeding caused by Blood Heat, coughs with blood-streaked phlegm, and childhood febrile convulsions. In modern clinical research, it has attracted considerable attention for ulcerative colitis and psoriasis treatment.

TCM Properties

Temperature

Cold

Taste

Salty (咸 xián)

Channels entered

Liver, Lungs

Parts used

Processed / Derived product (加工品 jiā gōng pǐn)

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Educational content Consult qualified TCM practitioners for diagnosis and treatment

What This Ingredient Does

Every ingredient has a specific set of actions — here's what Qing Dai does in the body, explained in both everyday and TCM terms

Therapeutic focus

In practical terms, Qing Dai is primarily used to support these areas of health:

TCM Actions

In TCM terminology, these are the specific therapeutic actions that Qing Dai performs to restore balance in the body:

How these actions work

'Clears Heat and resolves toxins' means Qing Dai has a strong ability to neutralize Heat-toxins in the body. In practice this applies to febrile diseases with high fever and skin eruptions (macules and papules), as well as sore throats, mouth ulcers, and toxic sores on the skin. It can be taken internally or applied topically to affected areas.

'Cools Blood and disperses macules' means Qing Dai enters the Blood level and calms reckless movement of Blood caused by Heat. When excessive Heat forces Blood out of the vessels, it produces rashes, purple-red spots on the skin, vomiting of blood, or nosebleeds. Qing Dai's cold, salty nature allows it to penetrate the Blood level and cool it down, which is why it is a key herb for fever-related skin eruptions and bleeding due to Blood Heat.

'Drains Liver Fire' is one of Qing Dai's most distinctive actions. It enters the Liver channel specifically and is used when the Liver harbors excess Fire. Liver Fire can rise upward and attack the Lungs, causing a dry cough with chest pain and blood-streaked phlegm, a condition known as 'Liver Fire invading the Lungs.' Qing Dai addresses this by clearing the Fire at its source in the Liver while also cooling the Lungs.

'Calms fright and stops convulsions' refers to Qing Dai's ability to address childhood seizures and convulsions caused by high fever. In TCM, extreme Heat can stir internal Wind, leading to convulsions and tremors, especially in children. By draining Liver Fire (the Liver governs sinews and tendons), Qing Dai indirectly reduces spasms and convulsions.

Patterns Addressed

In TCM, symptoms cluster into recognizable patterns of disharmony. Qing Dai is used to help correct these specific patterns.

Why Qing Dai addresses this pattern

Qing Dai is cold in temperature and salty in taste, giving it the ability to enter the Blood level and cool it. When Heat invades the Blood, it forces Blood out of the vessels, producing rashes, macules, nosebleeds, and vomiting of blood. Qing Dai directly clears the Heat driving this reckless Blood movement, while its toxin-resolving action addresses the underlying pathogenic Heat. It is often combined with raw Rehmannia (Sheng Di Huang), Moutan bark (Mu Dan Pi), or Imperata root (Bai Mao Gen) for Blood Heat bleeding.

A practitioner would look for one or more of these signs

Nosebleeds

Nosebleed from Blood Heat

Vomiting Blood

Vomiting blood due to Heat in the Blood

Skin Rashes

Purple-red macules and rashes from febrile illness

Cough Of Blood

Blood-streaked sputum

Commonly Used For

These are conditions where Qing Dai is frequently used — but only when they arise from the specific patterns it addresses, not in all cases

Arises from: Blood Heat Heat Toxin

TCM Interpretation

TCM understands ulcerative colitis primarily as Damp-Heat or Heat-toxin lodged in the Large Intestine, often with Blood Heat involvement. The hallmark symptoms of bloody mucous stool, urgency, and abdominal pain correspond to Heat-toxin damaging the intestinal lining and forcing Blood out of the vessels. In many patients, Liver Qi stagnation (from emotional stress) generates Fire that further aggravates the condition. The Liver's relationship with the digestive system means that unresolved Liver Fire can pour downward into the intestines, worsening inflammation.

Why Qing Dai Helps

Qing Dai's cold nature and ability to clear Heat-toxin directly addresses the inflammatory Heat lodged in the intestinal lining. Its Blood-cooling action helps stop bloody stools by calming reckless Blood movement. Its Liver Fire-draining effect is particularly relevant for patients whose flares are triggered by emotional stress. Modern research has identified Qing Dai's active components (indirubin, tryptanthrin) as potent activators of the AhR (aryl hydrocarbon receptor) pathway, which suppresses pro-inflammatory cytokines and promotes mucosal healing. Multiple clinical trials, including a multicenter randomized controlled trial, have shown clinical response rates exceeding 70-80% in ulcerative colitis patients treated with Qing Dai.

Also commonly used for

Mouth Ulcers

Applied topically, often with Borneol (Bing Pian)

Nosebleeds

Due to Blood Heat

Cough Of Blood

Liver Fire invading Lungs pattern

Bronchitis

With yellow, thick phlegm from Lung Heat

Tonsillitis

Heat-toxin in the throat

Eczema

Topical application for inflamed skin

Leukaemia

Chronic myelogenous leukemia; contains indirubin, a recognized anti-leukemic compound

Lumps

Applied topically and taken internally

Febrile Seizures

In children with high fever and convulsions

Ingredient Properties

Every ingredient has an inherent temperature, taste, and affinity for specific channels — these properties determine how it interacts with the body

Temperature

Cold

Taste

Salty (咸 xián)

Channels Entered

Liver Lungs

Parts Used

Processed / Derived product (加工品 jiā gōng pǐn)

Dosage & Preparation

These are general dosage guidelines for Qing Dai — always follow your practitioner's recommendation, as dosages vary based on the formula and your individual condition

Standard dosage

1.5–3g

Maximum dosage

Up to 6g daily under practitioner supervision for short courses in acute conditions. Do not use at high doses for extended periods due to risk of liver dysfunction and pulmonary arterial hypertension.

Dosage notes

Qing Dai is insoluble in water and should not be decocted as a standard decoction, as the active compounds will not dissolve. The standard method is to take it as a powder (散剂) stirred into warm water, or incorporated into pills (丸剂). For oral use, 1.5–3g is the standard range. Lower doses (1–1.5g) are appropriate for mild conditions or pediatric use. For external application (mouth sores, skin conditions, abscesses), the amount used is adjusted as needed and is not limited by the internal dosage range. When prescribed alongside a decoction of other herbs, Qing Dai should be stirred into the strained liquid just before drinking, not boiled with the other herbs.

Preparation

Qing Dai must NOT be decocted in the normal manner. It is insoluble in water and its active compounds would be lost. For oral use, it should be taken as a fine powder (散剂) stirred into warm water or incorporated into pills (丸剂). When combined with other herbs in a decoction, add the Qing Dai powder to the strained liquid after cooking and stir in before drinking (冲服). For improved purity, use the water-levigated form (飞青黛, Fei Qing Dai), which removes residual lime and impurities. For external use, mix the powder with sesame oil, honey, or water to form a paste for application to affected areas.

Processing Methods

In TCM, the same ingredient can be prepared in different ways to change its effects — here's how processing alters what Qing Dai does

Processing method

Water-levigation (水飞 shuǐ fēi): the raw Qing Dai powder is placed in a mortar, mixed with water, and ground finely. Fresh water is added and stirred gently so the fine particles suspend while heavier impurities sink. The suspended fine powder is poured off, allowed to settle, then dried and re-ground.

How it changes properties

The thermal nature and taste remain unchanged. Water-levigation removes residual lime (calcium hydroxide) and other heavy impurities introduced during the original extraction process. This produces a purer, finer powder that is safer for internal use, as excess lime can irritate the digestive tract and has opposite thermal properties to Qing Dai.

When to use this form

Preferred whenever Qing Dai is taken internally, especially in pills or powders. The purified form reduces gastrointestinal irritation and ensures consistent dosing of the active pigment.

Common Ingredient Pairs

These ingredients are traditionally combined with Qing Dai for enhanced therapeutic effect

Ha
Hai Ge Ke Qing Dai 1 : Hai Ge Ke 10 (as in Dai Ge San)

Qing Dai drains Liver Fire and cools Blood, while Hai Ge Ke (clam shell) clears Lung Heat and transforms thick phlegm. Together they address both the root (Liver Fire) and the branch (Lung Heat with phlegm) when Liver Fire invades the Lungs, creating a synergy that neither herb achieves alone.

When to use: Liver Fire invading the Lungs pattern: persistent cough with chest and rib-side pain, blood-streaked or yellow sticky phlegm, irritability, dizziness, and a red tongue with yellow coating.

Shu Di Huang
Shu Di Huang Qing Dai 1.5g : Sheng Di Huang 30-60g

Qing Dai clears Heat-toxin and cools Blood from the outside, while Sheng Di Huang (raw Rehmannia) nourishes Yin and cools Blood from the inside, protecting body fluids. Together they provide powerful Blood-level Heat clearing with simultaneous Yin protection, preventing the cold herbs from depleting fluids.

When to use: Febrile disease with macules or papules on the skin, Blood Heat causing vomiting of blood or nosebleeds, especially in Yin-deficient patients where Heat has begun to damage fluids.

Bing Pian
Bing Pian Qing Dai 3 : Bing Pian 1

Qing Dai clears Heat-toxin and reduces swelling, while Bing Pian (borneol) opens blocked orifices and relieves pain with its penetrating aromatic nature. Together they are applied topically for oral and throat inflammation, with Bing Pian enhancing local pain relief and Qing Dai providing the anti-inflammatory action.

When to use: Mouth ulcers, oral sores, swollen gums, and throat inflammation. The two are typically mixed as a powder and applied directly to the affected area.

Tian Zhu Huang

Qing Dai drains Liver Fire and calms fright, while Tian Zhu Huang (bamboo silica) clears Phlegm-Heat and settles convulsions. Together they address the dual pathomechanism of Heat-generated Wind with Phlegm obstruction that underlies childhood febrile convulsions.

When to use: Childhood convulsions with high fever, flushed face, red lips, spasms, yellow urine, and signs of both Liver Fire and Phlegm-Heat.

Key Formulas

These well-known formulas feature Qing Dai in a prominent role

Dang Gui Long Hui Wan 當歸龍薈丸 Assistant

A major formula for draining excess Liver and Gallbladder Fire. Qing Dai serves as an Assistant, contributing its specific Liver Fire-clearing and Blood-cooling properties alongside multiple bitter-cold herbs. This formula showcases Qing Dai's role in intense, multi-organ Fire patterns with constipation and restlessness.

Comparable Ingredients

These ingredients have overlapping uses — here's how to tell them apart

Da Qing Ye
Qing Dai vs Da Qing Ye

Both come from the same family of indigo-producing plants and share Heat-clearing, toxin-resolving, and Blood-cooling actions. However, Da Qing Ye (Isatis leaf) is stronger for clearing Heat at the Qi and Nutritive levels in febrile disease and is primarily used in decoction, while Qing Dai excels at draining Liver Fire, treating coughs from Liver Fire invading the Lungs, and is better suited for topical application due to its powdered form.

Ban Lan Gen
Qing Dai vs Ban Lan Gen

Ban Lan Gen (Isatis root) shares the same source plant as Qing Dai and also clears Heat and resolves toxins, but it is best known for benefiting the throat and is the go-to herb for sore throat and prevention of epidemic febrile diseases. Qing Dai has stronger Blood-cooling and Liver Fire-draining actions and is more specific for skin conditions, coughs with bloody phlegm, and topical use.

Huang Qin
Qing Dai vs Huang Qin

Both clear Heat from the Lungs, but Huang Qin (Scutellaria root) clears Lung Heat more broadly and also dries Dampness, making it the better choice when Damp-Heat is prominent. Qing Dai specifically targets Liver Fire that has invaded the Lungs and has the added ability to cool Blood and stop bleeding, making it preferred when cough is accompanied by blood-streaked sputum from a Liver Fire origin.

Common Substitutes & Adulterants

Related species and common adulterations to be aware of when sourcing Qing Dai

Qing Dai is one of the most commonly adulterated herbs in the Chinese materia medica due to its extremely low natural yield and high production cost. Common adulterants include inert powders (starch, flour, talc) added to increase weight, as well as synthetic indigo dye (which lacks the full spectrum of active compounds found in natural Qing Dai). Excess lime (calcium oxide) from the manufacturing process is another common impurity. Lan Dian (蓝靛, crude indigo sediment) is sometimes substituted for true Qing Dai. While both come from the same manufacturing process, Lan Dian is the heavier sediment that sinks to the bottom rather than the fine surface foam, and it contains significantly more lime and fewer active pigments. Authentic Qing Dai can be distinguished by its light weight, ability to float on water, fine powder texture, and purple-red flame when burned. Pharmacopoeia-grade testing for indigo and indirubin content is the most reliable way to verify authenticity.

Educational content — always consult a qualified healthcare provider or TCM practitioner before using any ingredient.

Toxicity Classification

Classical Chinese pharmacopoeia toxicity rating for Qing Dai

Non-toxic

Qing Dai is classified as non-toxic in the Chinese Pharmacopoeia and has a long history of safe use at standard doses (1.5–3g). However, modern research, primarily from Japanese clinical studies on ulcerative colitis patients, has identified several potential adverse effects with prolonged oral use: mild and usually reversible liver dysfunction (elevated transaminases), gastrointestinal symptoms (nausea, abdominal pain), headache, and rarely, pulmonary arterial hypertension (PAH). The PAH risk appears linked to indigo and indirubin acting as aryl hydrocarbon receptor (AhR) ligands, which may promote pulmonary vascular remodeling with long-term exposure. Reported PAH cases have generally been reversible upon discontinuation. The processing of Qing Dai involves lime (calcium oxide), and improperly purified products may contain excess lime residue, which can irritate the gastrointestinal tract. Using the water-levigated form (飞青黛, Fei Qing Dai) helps remove lime and other impurities. Quality and purity of the commercial product are major safety concerns, as adulteration with non-medicinal powders is common.

Contraindications

Situations where Qing Dai should not be used or requires extra caution

Caution

Spleen and Stomach deficiency Cold (脾胃虚寒). As a cold and salty herb, Qing Dai can further damage the Spleen and Stomach Yang in people with pre-existing cold deficiency patterns, potentially causing nausea, diarrhea, or abdominal pain. The Ben Cao Cong Xin (《本草从新》) specifically warns: 'Those with internal cold should not use it' (中寒者勿使).

Caution

Bleeding due to Yin deficiency with internal Heat rather than excess Heat. The Ben Cao Jing Shu (《本草经疏》) warns that in cases of bleeding arising from Yin deficiency with deficiency fire, rather than true excess Heat in the Blood, Qing Dai's cold nature may cause Blood to congeal, worsening the condition with chest and diaphragm pain.

Caution

Long-term oral use at higher doses. Modern clinical reports from Japan have documented cases of pulmonary arterial hypertension (PAH), liver dysfunction, and colitis associated with prolonged oral Qing Dai consumption (particularly over several months). Short courses at standard doses are considered safer.

Caution

Pre-existing liver disease. Mild liver dysfunction (elevated transaminases) has been reported in clinical studies of oral Qing Dai, though most cases resolved without discontinuation. Patients with compromised liver function should use with extra caution.

Avoid

Pre-existing pulmonary hypertension or significant cardiovascular disease. Given the documented association between prolonged Qing Dai use and pulmonary arterial hypertension, patients with existing pulmonary vascular disease should not take this herb orally.

Special Populations

Important considerations for pregnancy, breastfeeding, and pediatric use

Pregnancy

Use with caution during pregnancy. Qing Dai is cold in nature and enters the Blood level, which could theoretically disrupt fetal development or promote uterine cooling. Classical formulas such as Qing Dai Shi Gao Tang (from Chong Ding Tong Su Shang Han Lun) were specifically designed for treating Heat rashes during pregnancy, suggesting historical practitioners considered it acceptable in acute Heat conditions even during pregnancy when carefully prescribed. However, modern safety data in pregnant populations is lacking, and the potential for liver dysfunction and other adverse effects with oral use warrants extra caution. The herb should only be used during pregnancy under close supervision by an experienced practitioner and only when a clear Heat-toxin pattern is present.

Breastfeeding

Safety during breastfeeding has not been specifically studied. As a cold-natured herb, Qing Dai could theoretically affect the quality of breast milk by introducing a cold influence, which in TCM terms could contribute to digestive disturbance in the nursing infant. The active compounds indigo and indirubin are small molecules that may pass into breast milk, though this has not been confirmed. Topical use is generally considered lower risk than oral use. Oral use should be avoided or minimized during breastfeeding unless specifically indicated by a qualified practitioner.

Children

Qing Dai has a long history of pediatric use, particularly for childhood convulsions (惊痫) and Heat-toxin conditions. Classical texts recommend adjusting the dose according to the child's age and size. For young children, typical doses are 0.3–1g. The herb is usually given as a powder mixed into water or formula, or incorporated into pills. Because the fine powder can cause choking if inhaled, special care should be taken with the delivery method in small children. Topical application (for conditions like mumps, eczema, or chickenpox) is generally safe in children at standard external doses.

Drug Interactions

If you are taking pharmaceutical medications, be aware of these potential interactions with Qing Dai

Anticoagulant and antiplatelet medications: Qing Dai has Blood-cooling and Blood-moving properties. While no direct pharmacological interaction studies exist, theoretical caution is warranted when combining with warfarin, heparin, or antiplatelet drugs, as the herb's hemostatic or blood-affecting actions may complicate dosing.

Hepatotoxic drugs: Clinical studies have documented mild, usually reversible liver dysfunction (elevated ALT/AST) in patients taking oral Qing Dai. Concurrent use with other hepatotoxic medications (acetaminophen at high doses, statins, methotrexate, certain antifungals) may increase the risk of liver injury.

Pulmonary vasoconstrictors and drugs affecting pulmonary circulation: Given the association between prolonged Qing Dai use and pulmonary arterial hypertension via aryl hydrocarbon receptor activation, caution is advised in patients taking medications that affect pulmonary vascular tone.

Immunosuppressants: Qing Dai's active components (indirubin, tryptanthrin) have immunomodulatory effects. Concurrent use with immunosuppressive drugs (used in autoimmune conditions) may have additive or unpredictable effects on immune function.

Dietary Advice

Foods and dietary considerations when taking Qing Dai

While taking Qing Dai internally, avoid cold, raw, and greasy foods that could further burden the Spleen and Stomach, as the herb's cold nature already poses a risk to digestive function. Avoid spicy, pungent, or heating foods if taking Qing Dai for Heat-toxin or Blood-Heat conditions, as these could counteract the herb's cooling therapeutic effect. Light, easily digestible foods are recommended during treatment. Alcohol should be avoided as it may compound the risk of liver irritation associated with oral Qing Dai use.

Botanical Description

Physical characteristics and morphology of the Qing Dai source source material

Qing Dai (Indigo Naturalis) is not derived from a single plant but is a processed pigment extracted from the leaves and stems of several indigo-producing species. The three primary source plants recognized by the Chinese Pharmacopoeia are:

  • Ma Lan (马蓝, Baphicacanthus cusia): A perennial herb of the Acanthaceae family, growing 30–70 cm tall. The stems become slightly woody at the base and are somewhat square in cross-section, with swollen nodes. Leaves are opposite, obovate-elliptical to ovate-elliptical, 6–15 cm long, with shallow serrated or wavy edges. Flowers are pale purple, funnel-shaped, appearing in loose terminal or axillary spikes from June to October. It prefers moist, shaded habitats at forest margins and mountain slopes in southern China.
  • Liao Lan (蓼蓝, Polygonum tinctorium): An annual herb of the Polygonaceae (buckwheat) family, historically the most important blue dye plant in China. It grows upright with oval leaves and produces small pink-red flower spikes.
  • Song Lan (菘蓝, Isatis indigotica): A biennial cruciferous plant (the same species that yields Ban Lan Gen from its root and Da Qing Ye from its leaves), with small yellow flowers and winged seed pods.

The medicinal product is obtained by soaking the harvested stems and leaves in water for 2–3 days until fermented, then adding slaked lime and vigorously stirring. The blue foam that rises to the surface is skimmed off and dried to yield the deep blue powder known as Qing Dai.

Sourcing & Harvesting

Where Qing Dai is sourced, when it's harvested or collected, and how to assess quality

Harvesting season

Summer and autumn, when the leaves are most lush and contain the highest pigment levels.

Primary growing regions

The highest quality Qing Dai is traditionally produced in Fujian province (福建), known as Jian Qing Dai (建青黛), which is its recognized dao di (道地) terroir. The primary source plant in Fujian is Ma Lan (Baphicacanthus cusia). Other significant producing regions include Yunnan, Jiangsu, Anhui, Jiangxi, Henan, Sichuan, Zhejiang, Guangdong, and Hebei provinces. Different regions tend to use different source plants: Ma Lan predominates in the south (Fujian, Yunnan, Guangdong), while Song Lan (Isatis indigotica) and Liao Lan (Polygonum tinctorium) are more common in northern and eastern regions.

Quality indicators

Good quality Qing Dai is a very fine, deep blue powder that is extremely light and easily dispersed by air. It should stick readily to hands and paper when touched. There should be a faint grassy or herbaceous smell and a bland to slightly acidic taste. The definitive quality test is that when a small amount of good Qing Dai is sprinkled on water, it should float on the surface rather than sink. When ignited with a small flame, it should produce a distinctive purple-red flame or smoke. Inferior quality material is heavy, dense, clumped into hard blocks with visible white specks (indicating excess lime), and sinks in water as granules. Due to the low natural yield of Qing Dai, adulteration with weight-increasing powders is common. The Chinese Pharmacopoeia requires a minimum of 2.0% indigo and 0.13% indirubin content.

Classical Texts

Key passages from the classical Chinese medical texts that describe Qing Dai and its therapeutic uses

Kai Bao Ben Cao (《开宝本草》, Song Dynasty)

Chinese: 主解诸药毒,小儿诸热,惊痫发热,天行头痛寒热,煎水研服之。亦摩敷热疮、恶肿、金疮、下血、蛇犬等毒。

English: It resolves various drug toxins, childhood fevers, convulsions with fever, epidemic headaches with alternating chills and fever. Take it decocted and ground in water. It can also be rubbed onto hot sores, malignant swellings, traumatic wounds, bleeding, and snake or dog bites.

Ben Cao Gang Mu (《本草纲目》, Li Shizhen, Ming Dynasty)

Chinese: 去热烦,吐血,咯血,斑疮,阴疮,杀恶虫。

English: It clears Heat and irritability, treats vomiting of blood, coughing blood, eruptive sores, genital sores, and kills pathogenic parasites.

Ben Jing Feng Yuan (《本经逢原》, Qing Dynasty)

Chinese: 泻肝胆,散郁火,治温毒发斑及产后热痢下重。

English: It drains the Liver and Gallbladder, disperses constrained fire, and treats warm-toxin eruptions with macules, as well as postpartum hot dysentery with tenesmus.

Ben Cao Qiu Zhen (《本草求真》, Qing Dynasty)

Chinese: 大泻肝经实火及散肝经火郁。

English: It powerfully drains excess fire from the Liver channel and disperses fire constraint in the Liver channel.

Historical Context

The history and evolution of Qing Dai's use in Chinese medicine over the centuries

The name 'Qing Dai' (青黛) literally means 'blue-black pigment' (黛 originally referred to a dark cosmetic used for painting eyebrows). The earliest recorded medicinal use appears in the Tang Dynasty work Yao Xing Lun (《药性论》) by Zhen Quan. The Kai Bao Ben Cao (Song Dynasty) noted that Qing Dai originally came from Persia and was later found to be equivalent to the indigo foam (靛花) produced domestically during textile dyeing. Li Shizhen's Ben Cao Gang Mu (Ming Dynasty) formally confirmed that the indigo foam from dye vats was identical to Qing Dai in medicinal properties.

Qing Dai has a remarkable dual history as both a medicine and one of the world's oldest textile dyes. China has cultivated indigo plants since at least the Xia Dynasty (c. 2000 BCE), as recorded in the Xia Xiao Zheng agricultural calendar. The famous idiom '青出于蓝而胜于蓝' ('blue comes from the indigo plant yet surpasses it,' from Xunzi) derives from this dyeing tradition. In the 1970s, indirubin, an active component isolated from Qing Dai, was developed in China as a novel treatment for chronic myelogenous leukemia, representing one of the early successes in deriving modern pharmaceuticals from traditional Chinese medicine.

Modern Research

4 published studies investigating the pharmacological effects or clinical outcomes of Qing Dai

1

Multicenter Randomized Controlled Trial of Indigo Naturalis in Ulcerative Colitis (INDIGO Study, 2018)

Naganuma M, Sugimoto S, Mitsuyama K, et al. Gastroenterology. 2018;154(4):935-947.

This landmark double-blind RCT in Japan enrolled 86 patients with moderately active ulcerative colitis. Patients received 0.5g, 1.0g, or 2.0g of Qing Dai daily or placebo for 8 weeks. Clinical response rates were dramatically higher in all Qing Dai groups (69.6%, 75.0%, and 81.0% respectively) compared to placebo (13.6%), with a clear dose-dependent trend. Mucosal healing rates were also significantly higher. However, the trial was terminated early due to an external report of pulmonary arterial hypertension in a patient self-medicating with Qing Dai. Mild liver dysfunction was observed in 10 patients receiving Qing Dai.

PubMed
2

Systematic Review and Meta-Analysis: Indigo Naturalis for Inflammatory Bowel Disease (2023)

Banerjee R, et al. Journal of Gastroenterology and Hepatology. 2024;39(1):50-61.

This systematic review analyzed 9 studies involving 299 patients. The pooled clinical response rate for ulcerative colitis was 79.6%, and clinical remission rate was 66.8%. The relative risk of clinical response was 3.82 times higher with Qing Dai than placebo across two randomized trials. Except for one reversible case of pulmonary arterial hypertension, most reported adverse effects were mild. The authors concluded that Qing Dai is effective for ulcerative colitis but noted limitations including small sample sizes and studies being limited to East Asian populations.

PubMed
3

Japanese Nationwide Survey of Adverse Events with Indigo Naturalis in Ulcerative Colitis (2019)

Naganuma M, Sugimoto S, Suzuki H, et al. Journal of Gastroenterology. 2019;54(10):891-896.

This large-scale survey across 337 institutions in Japan identified 877 ulcerative colitis patients (out of 49,320) using Qing Dai. Adverse events included liver dysfunction, gastrointestinal symptoms, headache, pulmonary arterial hypertension, and intussusception. Eleven patients with PAH who had regularly taken Qing Dai were reported. The survey found no clear dose-effect relationship between Qing Dai dosage and adverse events. Following these findings, the Japanese Ministry of Health issued a public health warning, and Qing Dai was added to the international list of drugs possibly associated with PAH.

4

Comprehensive Review: Chemistry, Pharmacology, Clinical Applications, Adverse Events, and Quality Control of Indigo Naturalis (2021)

Sun Q, Leng J, Tang L, Wang L, Fu C. Frontiers in Pharmacology. 2021;12:664022.

This extensive review catalogued 63 compounds isolated from Qing Dai, with indole alkaloids (including indigo, indirubin, and tryptanthrin) as the most pharmacologically important. Indirubin was highlighted for its use as a leukemia treatment in China since the 1970s and as an active ingredient against psoriasis. The review noted confirmed pharmacological effects including anti-inflammatory, anti-tumor, antibacterial, and anti-psoriatic activities. Adverse events from oral use were categorized as mild (liver/renal dysfunction, headache, GI symptoms) or severe (colitis, intussusception, pulmonary arterial hypertension).

Research on individual TCM herbs is growing but still limited by Western clinical trial standards. These studies provide emerging evidence and should be considered alongside practitioner expertise.