A Comprehensive Review of the Chemistry, Pharmacokinetics, Pharmacology, Clinical Applications, Adverse Events, and Quality Control of Indigo Naturalis

Abstract

Indigo naturalis (IN), which is derived from indigo plants such as Strobilanthes cusia (Nees) Kuntze, Persicaria tinctoria (Aiton) Spach, and Isatis tinctoria L., has been traditionally used in the treatment of hemoptysis, epistaxis, chest pain, aphtha, and infantile convulsion in China for thousands of years. Clinical trials have shown that the curative effect of IN for psoriasis and ulcerative colitis (UC) is remarkable. A total of sixty-three compounds, including indole alkaloids, terpenoids, organic acids, steroids, and nucleosides, have been isolated from IN, of which indole alkaloids are the most important. Indirubin, isolated from IN, was used as a new agent to treat leukemia in China in the 1970s. Indirubin is also an active ingredient in the treatment of psoriasis. Pharmacological studies have confirmed that IN has inhibitory effects on inflammation, tumors, bacteria, and psoriasis. Indigo, indirubin, tryptanthrin, isorhamnetin, indigodole A, and indigodole C are responsible for these activities. This review provides up-to-date and comprehensive information on IN with regard to its chemistry, pharmacokinetics, pharmacology, clinical applications, adverse events, and quality control. This review may also serve a reference for further research on IN.

Treatment-refractory ulcerative colitis responsive to indigo naturalis

“…40 41 Activation of AhR has been suggested as a possible mechanism in the pathobiology of IN-induced PAH. [42][43][44] As a natural product, the composition of IN varies widely among sources, 45 making batch-to-batch consistency difficult to control. To mitigate these risks, a single molecule AhR agonist that achieves the same therapeutic effect as IN could improve quality control.…”

Immunomodulatory drug discovery from herbal medicines: Insights from organ-specific activity and xenobiotic defenses

“…The plant Indigo naturalis is best known as a source of blue dye, but it also has traditional medicinal uses in China. Its main bioactive components are the bis-indoles indigo and indirubin, which are formed by non-biological reactions during processing ( Sun et al, 2021 ). Therapeutic benefit of Indigo naturalis in ulcerative colitis (UC, a common inflammatory disease of the colon) was proven by recent clinical trials ( Naganuma et al, 2018 ; Naganuma et al, 2020 ; Uchiyama et al, 2020 ).…”

“…Response rates for the herbal medicine were comparable to the most effective western drugs, including biologics that target TNFα, and patients whose disease was not well-managed by western drugs responded well to the herbal preparation ( Naganuma et al, 2020 ). The active ingredients in Indigo Naturalis , Indigo and indirubin, are almost insoluble in water and have very poor oral bioavailability ( Sun et al, 2021 ). They are thought to act directly in the gut, where their concentration is locally high following ingestion of Indigo naturalis powder.…”

“…Once ingested, active molecule slowly leaches from the phagocytosed particle to activate AHR. Limited clinical evidence suggests that the beneficial effects of Indigo naturalis power can extend systemically ( Sun et al, 2021 ). This is unlikely to occur by systemic distribution of indigo itself, again due to its insolubility.…”

Indigo Pulverata Levis (Chung-Dae, Persicaria tinctoria) Alleviates Atopic Dermatitis-like Inflammatory Responses In Vivo and In Vitro

“…Previously, studies have reported that CHD has antipyretic, anti-inflammatory, and detoxifying properties. Recently, it has been demonstrated to have excellent clinical efficacy in treating gastrointestinal diseases and AD [ 19 , 20 , 21 ]. Furthermore, CHD contains indigo and indirubin that are effective in treating various diseases, such as bacterial infections, cancer, and inflammation, by affecting the immune system [ 22 , 23 ].…”