About Herbs, Botanicals & Other Products

Scientific Name
Indigofera tinctoria
Top
Clinical Summary

Indirubin is extracted from the Indigo plant (Isatis Root, Isatis Leaf). It is a constituent of a traditional Chinese herbal formula, Dang Gui Long Hui Wan used in the treatment of chronic myelogenous leukemia (CML). Indirubin has also been used in Asia as a systemic treatment for psoriasis.

In vitro and animal studies indicate anti-inflammatory (2), antitumor (14) (15) and neuroprotective (16) effects. Indirubin also inhibits cyclin-dependent kinases in tumor cells (5) (6). A derivate of indirubin was shown to enhance the cytotoxic effects of adriamycin (17).
A small clinical study of indirubin in patients with head and neck cancer found a reduction in mucosal damage from radiation therapy (3). Meisoindigo, a metabolite of Indirubin has also been shown to have similar properties (4). A few cases of positive effects following long term use of indirubin for the treatment of CML (7) have been reported. However further clinical trials are needed to confirm its role.

Top
Purported Uses
  • Cancer treatment
  • Inflammation
Top
Mechanism of Action

Indirubin inhibits DNA synthesis in rats. Indirubin inhibits cell proliferation in the late-G1 and G2/M phase by selectively inhibiting cyclin-dependent kinases (CDK) (4) through the interaction with the kinase’s ATP-binding site (6). It was also found that indirubin-3-oxime inhibits the growth of human laryngeal cancer cells through the induction of Cdk inhibitor p21, inhibition of cyclin D1 and activation of caspase-3 (1). Indirubin may also play a role in inhibiting the assembly of microtubules, further reducing the rate of cell reproduction (11). Indirubin’ s anti-inflammatory effects appear to come from an inhibition of interferon-gamma (2). Indirubin is a minor constituent of Indigofera tinctoria, however a synthetic form of the substance was shown to have similar effectiveness against CML (12) (13).One study investigated the inhibitory effect of six indirubin derivatives against HL-60 human promyelocytic leukemia cells (8). One of these derivatives strongly inhibited the growth of HL-60 cancer cells, whereas the others showed only weak cytotoxic activity. Another study found that Indirubin-3-oxime was also found to induce cell cycle arrest and apoptosis in human laryngeal cancer cells (1). An additional study found that four indirubin derivatives exhibited an antiproliferative activity against human HT-29 colorectal cancer cells in a solid tumor model (9). An in vitro study showed that indirubin modulates the proliferation and differentiation of keratinocytes in skin samples taken from psoriasis patients (10).

Top
Adverse Reactions

Reported (Oral): Mild to severe nausea, vomiting, abdominal pain, diarrhea, headache and edema. A few patients were found to have pulmonary arterial hypertension and cardiac insufficiency following long-term treatment (4). Long term oral ingestion has also occasionally been associated with hepatitis (10).

Top
Literature Summary and Critique

You WC, et al. Effect of extracts from indigowood root (Isatis indigotica Fort.) on immune responses in radiation-induced mucositis. J Altern Complement Med. 2009 Jul;15(7):771-8.

This study investigated the effect of indirubin (taken as indigowood root powder) on acute radiation induced mucositis. Twenty patients who were receiving radiation therapy for head and neck cancer were enrolled and randomized into a control or treatment group. The treatment group gargled with a solution made from indigowood root powder dissolved in double-distilled water for three minutes, and then swallowed it, before meals daily for seven weeks. The results of the clinical trial indicated that indigo wood root significantly reduced the severity of radiation mucositis (p=0.01), anorexia (p=0.002), and swallowing difficulty (p=0.002) in treated patients compared to the control group. The authors concluded that indirubin may play a therapeutic role in improving radiation mucositis, anorexia, and difficulty swallowing, but that the exact mechanism and pathways should be further studied.

Top
References
  1. Kameswaran TR, Ramanibai R. Indirubin-3-monooxime induced cell cycle arrest and apoptosis in Hep-2 human laryngeal carcinoma cells. Biomed Pharmacother. 2009 Feb;63(2):146-54. PMID: 18450412
  2. Kunikata T, Tatefuji T, Aga H, Iwaki K, Ikeda M, Kurimoto M. Indirubin inhibits inflammatory reactions in delayed-type hypersensitivity. Eur.J Pharmacol. 2000;410:93-100.
  3. You WC, Hsieh CC, Huang JT. Effect of extracts from indigowood root (Isatis indigotica Fort.) on immune responses in radiation-induced mucositis. J Altern Complement Med. 2009 Jul;15(7):771-8. PMID: 19534614
  4. Xiao Z, Hao Y, Liu B, Qian L. Indirubin and meisoindigo in the treatment of chronic myelogenous leukemia in China. Leuk.Lymphoma 2002;43:1763-8.
  5. Marko D, Schatzle S, Friedel A, Genzlinger A, Zankl H, Meijer L et al. Inhibition of cyclin-dependent kinase 1 (CDK1) by indirubin derivatives in human tumour cells. Br.J Cancer 2001;84:283-9.
  6. Hoessel R, Leclerc S, Endicott JA, Nobel ME, Lawrie A, Tunnah P et al. Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat.Cell Biol. 1999;1:60-7.
  7. Chen F, Li L, Ma D, et al. Imatinib achieved complete cytogenetic response in a CML patient received 32-year indirubin and its derivative treatment. Leuk Res. 2010 Feb;34(2):e75-7.
  8. Cuong NM, Tai BH, Hoan DH, et al. Inhibitory effects of indirubin derivatives on the growth of HL-60 leukemia cells. Nat Prod Commun. 2010 Jan;5(1):103-6.
  9. Kim SH, Choi SJ, Kim YC, Kuh HJ. Anti-tumor activity of noble indirubin derivatives in human solid tumor models in vitro. Arch Pharm Res. 2009 Jun;32(6):915-22.
  10. Lin YK, Leu YL, Yang SH, et al. Anti-psoriatic effects of indigo naturalis on the proliferation and differentiation of keratinocytes with indirubin as the active component. J Dermatol Sci. 2009 Jun;54(3):168-74.
  11. Steriti R. Nutritional support for chronic myelogenous and other leukemias: a review of the scientific literature. Altern.Med Rev. 2002;7:404-9.
  12. Han R. Highlight on the studies of anticancer drugs derived from plants in China. Stem Cells 1994;12:53-63.
  13. Zhang JT. New drugs derived from medicinal plants. Therapie 2002;57:137-50.
  14. Kim SA, Kwon SM, Kim JA, et al. 5’-Nitro-indirubinoxime, an indirubin derivative, suppresses metastatic ability of human head and neck cancer cells through the inhibition of Integrin â1/FAK/Akt signaling. Cancer Lett. 2011 Jul 28;306(2):197-204.
  15. Williams SP, Nowicki MO, Liu F, et al. Indirubins decrease glioma invasion by blocking migratory phenotypes in both the tumor and stromal endothelial cell compartments. Cancer Res. 2011 Aug 15;71(16):5374-80.
  16. Martin L, Magnaudeix A, Wilson CM, Yardin C, Terro F. The new indirubin derivative inhibitors of glycogen synthase kinase-3, 6-BIDECO and 6-BIMYEO, prevent tau phosphorylation and apoptosis induced by the inhibition of protein phosphatase-2A by okadaic acid in cultured neurons. J Neurosci Res. 2011 Nov;89(11):1802-11.
  17. Shi R, Li W, Zhang X, et al. A novel indirubin derivative PHII-7 potentiates adriamycin cytotoxicity via inhibiting P-glycoprotein expression in human breast cancer MCF-7/ADR cells. Eur J Pharmacol. 2011 Nov 1;669(1-3):38-44.
Top
How It Works

Bottom Line: Laboratory studies demonstrate anticancer effects of indirubin. But Randomized clinical trials have yet to be conducted.

Indirubin is derived from the Indigo Plant (Isatis Root, Isatis Leaf). It is used as part of a traditional Chinese herbal prescription called Dang Gui Long Hui Wan, used to treat chronic myelogenous leukemia (CML). Studies have shown that the substance can help keep cancer cells from reproducing in rats. Indirubin also appears to reduce inflammation by inhibiting part of the immune response. In addition to being extracted from the plant, Indirubin may also be created synthetically in the laboratory.

Top
Purported Uses
  • To treat chronic myelogenous leukemia
    Laboratory and animal studies support this use. Clinical trials have not yet been conducted.
  • To reduce inflammation
    The results of a small study in patients with head and neck cancer suggest that the anti-inflammatory properties of indirubin (taken as indigowood root powder) reduce mucosal damage from radiation therapy. However further clinical studies are needed to confirm this effect.
Top
Research Evidence

Reduce mucosal inflammation from radiation therapy
A small clinical study enrolled 20 patients with head and neck cancer. Ten of these patients received indirubin (taken as indigowood root powder) for seven weeks during radiation therapy. The results of the study indicated that patients receiving this treatment had significantly less radiation mucositis, anorexia, and difficulty swallowing compared to the untreated patients.

Top
Side Effects
  • Mild to severe nausea
  • Vomiting
  • Abdominal pain
  • Diarrhea
  • Headache
  • Edema
  • In patients treated over a long time, blood flow to the heart and lungs may be affected.
Top
Special Point
  • Meisoindigo, which is derived from Indirubin, has been shown to have similar properties.
  • This product is currently not sold as a dietary supplement. It is only available for preclinical and clinical studies.
Top
Dosage (Inside MSKCC Only)
This field is only visible to only Inside MSKCC users.
Top
Aliases
Dang Gui Long Hui Wan
Indigo
Meisoindigo
Top
E-mail your questions and comments to aboutherbs@mskcc.org.
Last updated: October 14, 2011