Isatis Root

• How It Works

  Isatis root has not been adequately studied in clinical trials, so it is not known if it works in humans.

  Isatis root extract is derived from the same plant from which indigo dye is made. It has been used in combination with other botanicals in traditional Chinese medicine and Ayurveda for a variety of conditions. In animal tests, it reduced inflammation and fever. Other lab experiments show that isatis extract can kill certain viruses and counteract some symptoms and tissue damage from bacterial infections, but it remains uncertain whether these same effects occur in the human body.

  Laboratory studies suggest that indirubin, an active compound in isatis, stops cell duplication and therefore may be useful in cancer treatment. A small study in humans indicates that an isatis root extract solution may help reduce radiation-induced mucositis in head and neck cancer patients, but more studies are needed.

  Isatis leaf has both similar and different properties from isatis root.

• Purported Uses
  • To treat bronchitis and relieve chest congestion
    Laboratory research suggests that isatis root has anti-inflammatory and immune-stimulating activity, but there is no proof from clinical trials that it can relieve bronchitis and chest congestion.
  • To treat infections
    Although antiviral and immune-stimulating activity has been shown in lab studies, there is no proof from clinical trials that isatis root can effectively treat the common cold, reduce fever, or fight viral infections. In addition, no human studies have been done to verify anecdotal reports that isatis may help ward off severe acute respiratory syndrome (SARS).
  • To prevent or treat cancer
    Lab studies show that an active compound in isatis stops cell duplication, but there is no evidence from clinical trials that it can prevent or treat cancer. In China, isatis is used in combination with other botanicals to treat chronic myelogenous leukemia.
  • To reduce severity of radiation-induced mucositis
    A small study in head and neck cancer patients suggested that a specific isatis root extract solution could reduce severity of mucositis, anorexia, and difficulty swallowing in treated patients compared with a control group.
• Patient Warnings
  • Some compounds in isatis root could have activity against SARS, but these are only lab experiments. These compounds would need to be further developed and tested because many compounds in isatis root have been found to occur at low levels. Relying solely on herbal supplements to prevent or treat SARS may induce a false sense of security from this deadly disease. Patients with suspected SARS should limit interactions outside the home. The Centers for Disease Control (CDC) recommends proper hygiene such as frequent hand washing and wearing a surgical mask to help prevent the spread of SARS.
• Side Effects

  Oral: None reported.

  Eyedrops:  Feeling a foreign substance or irritation in the eyes (one report each). Symptoms resolved after the patients closed their eyes and rested for 3 minutes.

• Brand Name

  Ban Lan Gen Chong Ji

• Scientific Name

  Radix isatidis baphicacanthi, Isatis tinctoria, Isatis indigotica

• Clinical Summary

  Isatis root is derived from the isatis plant and is a source of indigo dye. In both traditional Chinese medicine (TCM) and Ayurveda, it is used in combination with isatis leaf and other herbs to treat the common cold, sore throat, mumps, respiratory ailments, other febrile diseases, hepatitis, and malignant tumors ^(1) (2). One such formula, Danggui Longhui Wan, is used in China to treat chronic myelocytic leukemia (CML) ⁽³⁾. Isatis root has also been promoted to ward off severe acute respiratory syndrome (SARS).

  In vitro assays have identified specific compounds in isatis root with potential anti-SARS ⁽⁴⁾ and anti-influenza activity ⁽⁵⁾, as well as cytotoxic activity against human liver cancer and leukemia cell lines ⁽⁶⁾. Several in vitro and animal studies also demonstrate antimicrobial ⁽⁷⁾, antiviral ^{(8) (9) (22) (23)}, anti-endotoxic ⁽¹⁰⁾, immunostimulatory ^(3) (11), chemotherapeutic ⁽¹²⁾, and radioprotective effects ⁽¹³⁾. Animal models indicate anti-inflammatory, antipyretic, and antinociceptive effects ^(13) (14).

  A small randomized study demonstrated the utility of an isatis root extract solution for significantly reducing severity of radiation mucositis, anorexia, and swallowing difficulty in head and neck cancer patients ⁽¹⁵⁾.

  Isatis leaf has both overlapping and different properties from isatis root.

• Purported Uses
  • Bronchitis
  • Cold, fever
  • Infections
  • Cancer
  • Mucositis
• Mechanism of Action

  Isatis root exerts immunostimulatory effects by enhancing reticuloendothelial system function ⁽¹¹⁾. Sinigrin and indigo have been identified as the compounds responsible for potential SARS inhibition ⁽⁴⁾. Clemastanin B, a major lignan compound in isatis, targets viral endocytosis, uncoating, and nuclear export of viral ribonucleoproteins ⁽⁵⁾. A crude extract of isatis root prevented influenza virus attachment to cells and therefore viral replication, but was inactive against respiratory syncytial virus, adenovirus, parainfluenza virus and enterovirus ⁽¹⁹⁾. Another component of isatis root demonstrates dose-dependent anti-endotoxic effects on lipopolysaccharide-induced expression of membrane-organizing extension spike protein, a main endotoxin receptor ⁽¹⁰⁾. Alkaloids isolated from isatis can inhibit leukocyte function and reduce inflammatory response ⁽²⁰⁾. One animal study found that indigo root extract reduced tissue injury, enhanced hematopoietic system recovery, modulated serum inflammatory cytokines, and improved severe enteropathy in whole body irradiated mice ⁽¹³⁾.

  An in vitro study also found that an ethanol extract of isatis root had a dose-dependent cytotoxic effect against human leukemia HL-60 cells ⁽⁹⁾. Indirubin, an active component of isatis, inhibits cyclin-dependent kinases (CDKs) and prevents proliferation by arresting cells in the G2/M phase ⁽³⁾.

• Warnings

  Although some compounds have been identified as exhibiting potential for SARS inhibition, they would need to be developed and tested for efficacy. Many compounds in isatis root occur at low levels ⁽¹⁶⁾. In addition, as SARS is a deadly disease, reliance on herbal supplements as prevention or treatment may induce a false sense of security. Patients with suspected SARS should limit interactions outside the home. The Centers for Disease Control (CDC) recommends proper hygiene such as frequent hand washing and wearing a surgical mask to help prevent the spread of SARS ⁽²¹⁾.

• Adverse Reactions

  Oral: None reported.

  Eyedrops: One report each of feeling a foreign substance and another of irritating pain in the eyes. Symptoms resolved after the patients closed their eyes and rested for 3 minutes ⁽⁷⁾.

• References

  1. Zou P, Koh HL. Determination of indican, isatin, indirubin and indigotin in Isatis indigotica by liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 2007;21(7):1239-1246.

  2. Bensky D, Gamble A. Chinese Herbal Medicine: Materia Medica Revised ed. Seattle, WA: Eastland Press; 1993.

  3. Hoessel R, Leclerc S, Endicott JA, et al. Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat Cell Biol. May 1999;1(1):60-67.

  4. Lin CW, Tsai FJ, Tsai CH, et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Res. Oct 2005;68(1):36-42.

  5. Yang Z, Wang Y, Zheng Z, et al. Antiviral activity of Isatis indigotica root-derived clemastanin B against human and avian influenza A and B viruses in vitro. Int J Mol Med. Apr 2013;31(4):867-873.

  6. Wu Y, Zhang ZX, Hu H, et al. Novel indole C-glycosides from Isatis indigotica and their potential cytotoxic activity. Fitoterapia. Mar 2011;82(2):288-292.

  7. Qi CX, Wu XM, Wang XL. [Clinical research of isatis root eyedrops on the acute bacterial conjunctivitis]. Zhong Yao Cai. Jan 2007;30(1):120-122.

  8. Wang Y, Qiao CZ, Liu S, et al. [Evaluation on antiendotoxic action and antiviral action in vitro of tetraploid Isatis indigotica]. Zhongguo Zhong Yao Za Zhi. Jun 2000;25(6):327-329.

  9. Hsuan SL, Chang SC, Wang SY, et al. The cytotoxicity to leukemia cells and antiviral effects of Isatis indigotica extracts on pseudorabies virus. J Ethnopharmacol. May 4 2009;123(1):61-67.

  10. Li J, Liu Y, Fang J, et al. Effect of Radix Isatidis on the expression of moesin mRNA induced by LPS in the tissues of mice. J Huazhong Univ Sci Technolog Med Sci. Apr 2007;27(2):135-137.

  11. Xu YM, Lu PC. [Experimental studies on immunostimulatory effects of the Isatis indigotica polysaccharide]. Zhong Xi Yi Jie He Za Zhi. Jun 1991;11(6):357-359, 325-356.

  12. Chung YC, Tang FY, Liao JW, et al. Isatis indigotica induces hepatocellular cancer cell death via caspase-independent apoptosis-inducing factor translocation apoptotic pathway in vitro and in vivo. Integr Cancer Ther. Jun 2011;10(2):201-214.

  13. You WC, Lin WC, Huang JT, et al. Indigowood root extract protects hematopoietic cells, reduces tissue damage and modulates inflammatory cytokines after total-body irradiation: does Indirubin play a role in radioprotection? Phytomedicine. Dec 2009;16(12):1105-1111.

  14. Ho YL, Chang YS. Studies on the antinociceptive, anti-inflammatory and anti pyretic effects of Isatis indigotica root. Phytomedicine. Jul 2002;9(5):419-424.

  15. 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. Jul 2009;15(7):771-778.

  16. Chen J, Dong X, Li Q, et al. Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling. BMC Genomics. 2013;14:857.

  17. Zhang CE, Xiong Y, Dong Q, et al. Comparison of reversed-phase liquid chromatography and hydrophilic interaction chromatography for the fingerprint analysis of Radix Isatidis. J Sep Sci. Mar 4 2014.

  18. Shi YH, Xie ZY, Wang R, et al. Quantitative and Chemical Fingerprint Analysis for the Quality Evaluation of Isatis indigotica based on Ultra-Performance Liquid Chromatography with Photodiode Array Detector Combined with Chemometric Methods. Int J Mol Sci. 2012;13(7):9035-9050.

  19. Yang Z, Wang Y, Zhong S, et al. In vitro inhibition of influenza virus infection by a crude extract from Isatis indigotica root resulting in the prevention of viral attachment. Mol Med Rep. Mar 2012;5(3):793-799.

  20. Molina P, Tarraga A, Gonzalez-Tejero A, et al. Inhibition of leukocyte functions by the alkaloid isaindigotone from Isatis indigotica and some new synthetic derivatives. J Nat Prod. Oct 2001;64(10):1297-1300.

  21. Centers for Disease Control and Prevention. Public Health Guidance for Community-Level Preparedness and Response to Severe Acute Respiratory Syndrome (SARS) Version 2/3. 2014; http://www.cdc.gov/sars/guidance/. Accessed March 11, 2014.

  22. Li Z, Li L, Zhou H, et al. Radix isatidis Polysaccharides Inhibit Influenza a Virus and Influenza A Virus-Induced Inflammation via Suppression of Host TLR3 Signaling In Vitro. Molecules. Jan 11 2017;22(1).

  23. Xu H, He L, Chen J, et al. Different types of effective fractions from Radix Isatidis revealed a multiple-target synergy effect against respiratory syncytial virus through RIG-I and MDA5 signaling pathways, a pilot study to testify the theory of superposition of traditional Chinese Medicine efficacy. J Ethnopharmacol. Jul 15 2019;239:111901.