Isatis

Isatis indigotica yields three Chinese medicines. The root is Ban Lan Gen (Isatidis Radix), and the leaf is Da Qing Ye (Isatidis Folium). The third, Qing Dai (indigo naturalis), is a powder prepared from isatis and other indigo plants, including Baphicacanthus cusia and Polygonum tinctorium ^{23Reference 23Xu et al. · 2024ReviewThe double-edged sword effect of indigo naturalis — reviewView study →}.

Root and leaf are both classified as bitter and cold, entering the Heart and Stomach channels, and both clear heat and resolve fire toxicity. They are used for viral febrile illness, sore throat and tonsillitis, mumps, and epidemic respiratory infection. Ban Lan Gen is also taken as a household preventive during outbreaks of influenza. Both are decocted, the root at roughly 9–15 g a day.

Because it is strongly cold, classical practice avoids prolonged use, and avoids it altogether in spleen and stomach deficiency.

Qing Dai has been used in China for coughing and vomiting blood, nosebleeds, chest pain, mouth ulcers and childhood convulsions ^{24Reference 24Sun et al. · 2021ReviewA comprehensive review of the chemistry, pharmacokinetics, pharmacology, clinical applications, adverse events, and quality control of indigo naturalis — reviewView study →}.

In a multicentre, double-blind trial (INDIGO study, 86 patients, 8 weeks), oral indigo naturalis produced a dose-dependent clinical response in active ulcerative colitis. Response rates were 69.6%, 75.0% and 81.0% at 0.5, 1.0 and 2.0 g/day, against 13.6% on placebo. Clinical remission was 55.0% at 1.0 g and 38.1% at 2.0 g, against 4.5% ^{1Reference 1Naganuma et al. · 2018RCTEfficacy of indigo naturalis in a multicenter randomized controlled trial of patients with ulcerative colitis — randomised, double-blind, placebo-controlled trialView study →}.

The trial was stopped early after pulmonary arterial hypertension was reported in a patient who had taken self-purchased indigo naturalis for six months. Mild liver dysfunction occurred in 10 treated patients, and there were no serious adverse events in the trial ^{1Reference 1Naganuma et al. · 2018RCTEfficacy of indigo naturalis in a multicenter randomized controlled trial of patients with ulcerative colitis — randomised, double-blind, placebo-controlled trialView study →}.

Two meta-analyses found clinical response about 3.7–3.8 times more likely than on placebo ^{2,3Reference 2Kakdiya et al. · 2024Meta-analysisIndigo naturalis (Qing dai) for inflammatory bowel disease — systematic review and meta-analysisView study →Reference 3Iyengar et al. · 2024Meta-analysisHerbal medicines for the treatment of active ulcerative colitis — systematic review and meta-analysis of randomised controlled trialsView study →}. Across nine studies, the pooled clinical remission rate in ulcerative colitis was 66.8% ^{2Reference 2Kakdiya et al. · 2024Meta-analysisIndigo naturalis (Qing dai) for inflammatory bowel disease — systematic review and meta-analysisView study →}. In an uncontrolled one-year study of 33 patients taking 2 g/day, 73% were in remission at 52 weeks, while 12.1% had severe adverse events ^{4Reference 4Matsuno et al. · 2022ObservationalOne-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis — prospective observational cohort studyView study →}.

In psoriasis, topical indigo naturalis ointment gave 56.3% of patients a PASI 75 response at 8 weeks, against 0% on placebo, in a trial of 24 patients. It turned down the IL-17 pathway in the skin ^{5Reference 5Cheng et al. · 2017RCTClinical efficacy and IL-17 targeting mechanism of indigo naturalis as a topical agent in moderate psoriasis — randomised, double-blind, placebo-controlled trialView study →}. In an earlier study of 14 patients, each treated one plaque with indigo naturalis and another with a plain ointment, and the treated plaques improved clinically and on biopsy ^{6Reference 6Lin et al. · 2007RCTThe efficacy and safety of topically applied indigo naturalis ointment in patients with plaque-type psoriasis — randomised controlled trialView study →}. An oil extract, Lindioil, reduced nail-psoriasis scores more than olive oil over 12 weeks ^{7Reference 7Lin et al. · 2014RCTEfficacy and safety of indigo naturalis extract in oil (Lindioil) in treating nail psoriasis — randomised, observer-blind, vehicle-controlled trialView study →}.

Tryptanthrin inhibits IL-17 in keratinocytes and TH17 polarisation in cell studies ^{5,8Reference 5Cheng et al. · 2017RCTClinical efficacy and IL-17 targeting mechanism of indigo naturalis as a topical agent in moderate psoriasis — randomised, double-blind, placebo-controlled trialView study →Reference 8Cheng et al. · 2020In vitroThe anti-Th17 polarization effect of indigo naturalis and tryptanthrin by differentially inhibiting cytokine expression — in vitroView study →}. The root polysaccharide suppresses TLR-3 signalling ^{9Reference 9Li et al. · 2017In vitroRadix isatidis polysaccharides inhibit influenza A virus and influenza A virus-induced inflammation via suppression of host TLR-3 signalling — in vitroView study →}. The colitis benefit is attributed to aryl-hydrocarbon-receptor activation, which drives IL-22 and mucosal healing ^{1Reference 1Naganuma et al. · 2018RCTEfficacy of indigo naturalis in a multicenter randomized controlled trial of patients with ulcerative colitis — randomised, double-blind, placebo-controlled trialView study →}.

Gap: all of this is indigo naturalis or an isolated constituent — a processed, indigo-concentrated preparation frequently made from other plants rather than Isatis, and a different medicine from the Ban Lan Gen root decoction; no trial has tested the whole isatis root for inflammation.

Indirubin, the active constituent of the classical Chinese anti-leukaemia formula Danggui Longhui Wan, inhibits cyclin-dependent kinases, as a crystal structure with CDK2 confirms. Its derivative indirubin-3’-monoxime arrests cells at the G2/M phase ^{10Reference 10Hoessel et al. · 1999In vitroIndirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases — in vitroView study →}.

Indirubins also inhibit GSK-3β, with IC₅₀ values of 5–50 nM ^{11Reference 11Leclerc et al. · 2001In vitroIndirubins inhibit glycogen synthase kinase-3β and CDK5/p25 — in vitroView study →}. Analogues of natural 6-bromoindirubin killed imatinib-resistant T315I-mutant chronic myeloid leukaemia (CML) cells at submicromolar concentrations by inhibiting c-Src and Abl kinases ^{12Reference 12Gaboriaud-Kolar et al. · 2016In vitroNatural-based indirubins display potent cytotoxicity toward wild-type and T315I-resistant leukemia cell lines — in vitroView study →}. The derivative E804 triggered apoptosis in resistant CML cell lines and in primary patient cells by blocking Stat5 signalling ^{13Reference 13Nam et al. · 2012In vitroIndirubin derivatives induce apoptosis of chronic myelogenous leukemia cells involving inhibition of Stat5 signaling — in vitroView study →}.

Indirubin was used to treat leukaemia in China in the 1970s ^{24Reference 24Sun et al. · 2021ReviewA comprehensive review of the chemistry, pharmacokinetics, pharmacology, clinical applications, adverse events, and quality control of indigo naturalis — reviewView study →}. The semi-synthetic derivative meisoindigo has been used clinically for CML in China, and the arsenic-containing Realgar-Indigo Naturalis Formula is in registered trials for acute promyelocytic leukaemia. Both are derivative or combination products.

Gap: the isatis herb itself has never been trialled for cancer.

In an in silico screen with laboratory follow-up, six compounds from Banlangen, including tryptanthrin, indirubin and several flavonoids, inhibited H1N1 and H3N2, including drug-resistant strains. That study used Isatis tinctoria ^{14Reference 14Cai et al. · 2021In vitroIn silico prediction and bioactivity evaluation of chemical ingredients against influenza A virus from Isatis tinctoria — in silico and in vitroView study →}.

The root lignan clemastanin B inhibited human and avian influenza A and B viruses in cell culture (IC₅₀ 0.087–0.72 mg/mL). It appears to act on viral entry, uncoating or the export of viral RNP from the nucleus, and it was inactive against other respiratory viruses ^{15Reference 15Yang et al. · 2013In vitroAntiviral activity of Isatis indigotica root-derived clemastanin B against human and avian influenza A and B viruses in vitroView study →}.

Four glucosinolate isomers from the root and their breakdown products (progoitrin, goitrin, epigoitrin and epiprogoitrin) inhibited H1N1 in a dose-dependent way, in that order of potency. They attach to the viral envelope without affecting viral adsorption or budding ^{16Reference 16Nie et al. · 2020In vitroAntiviral activity of Isatidis Radix-derived glucosinolate isomers and their breakdown products against influenza A in vitro / in ovoView study →}.

Clemastanin B, epigoitrin and fractions of Ban Lan Gen protected cells against the FM1 influenza strain ^{17Reference 17Xiao et al. · 2016In vitroAntiviral activities against influenza virus (FM1) of bioactive fractions and representative compounds extracted from Banlangen (Radix Isatidis) — in vitroView study →}.

A root polysaccharide extract inhibited several human and avian influenza strains in cell culture and reduced the inflammatory cytokines they induced. It reduced the production of new virus only at a high dose ^{9Reference 9Li et al. · 2017In vitroRadix isatidis polysaccharides inhibit influenza A virus and influenza A virus-induced inflammation via suppression of host TLR-3 signalling — in vitroView study →}.

Gap: all isolated-constituent, fraction or in silico work in cell culture; no whole-herb or human antiviral data.

An isatis methanol extract, indigo and indirubin blocked Japanese encephalitis virus from attaching to cells, and indirubin strongly protected mice against a lethal challenge ^{18Reference 18Chang et al. · 2012AnimalAntiviral activity of Isatis indigotica extract and its derived indirubin against Japanese encephalitis virus — mouse model / in vivoView study →}.

A purified root polysaccharide lowered hepatitis B virus antigens and DNA in HepG2.2.15 cells. It acted indirectly, by raising IFN-α and activating JAK/STAT signalling ^{19Reference 19Wang et al. · 2020In vitroAntiviral activity of a polysaccharide from Radix Isatidis against hepatitis B virus in vitro via activation of the JAK/STAT pathwayView study →}.

Each virus rests on a single study, and there is no human antiviral data.

Resolving “heat toxicity” in Chinese medicine covers bacterial as well as viral infection. Indigo naturalis has shown antibacterial activity in laboratory studies ^{24Reference 24Sun et al. · 2021ReviewA comprehensive review of the chemistry, pharmacokinetics, pharmacology, clinical applications, adverse events, and quality control of indigo naturalis — reviewView study →}.

There are no antibacterial data for the root or leaf on their own, and no clinical data.

Clearing heat, which includes bringing down fever, is central to the traditional use of isatis. No study has tested the root or leaf for fever.

In cell studies, indigo naturalis and tryptanthrin lower the inflammatory cytokines IL-1β and TNF-α ^{8Reference 8Cheng et al. · 2020In vitroThe anti-Th17 polarization effect of indigo naturalis and tryptanthrin by differentially inhibiting cytokine expression — in vitroView study →}.

The root. Ban Lan Gen is one of the most widely used over-the-counter herbal cold remedies in China. As a strongly cold herb it is traditionally avoided by people with digestive cold or deficiency, and it is not meant for prolonged high-dose use. Occasional reports describe digestive upset and, rarely, haemolytic reactions with heavy or extended use. There are no human safety trials and no herb–drug interaction studies.

Indigo naturalis. A Japanese nationwide survey found indigo naturalis used by 877 patients with ulcerative colitis. Adverse events were reported in 91 of them, including liver dysfunction (40), pulmonary arterial hypertension (11) and intussusception (10), and 4 of the 10 intussusception cases needed surgery. The pulmonary hypertension resolved when the powder was stopped, and no deaths were reported ^{20Reference 20Naganuma et al. · 2019Clinical trialAdverse events in patients with ulcerative colitis treated with indigo naturalis — Japanese nationwide observational surveyView study →}.

Pulmonary arterial hypertension. In one case, a woman who had taken Qing Dai for 8 months developed severe pulmonary arterial hypertension. Her mean pulmonary artery pressure fell from 72 to 18 mmHg after she stopped it and received treatment ^{21Reference 21Kubota et al. · 2023ObservationalDramatically improved severe pulmonary arterial hypertension caused by Qing-Dai for ulcerative colitis — observational case reportView study →}.

Ischaemic colitis. In a Chinese series, 15 of 1,157 patients taking patent medicines containing indigo naturalis developed ischaemic injury of the colon. All recovered after stopping ^{22Reference 22Ke et al. · 2025ObservationalIndigo naturalis-associated ischemic injury of colorectal mucosa — observational case seriesView study →}.