Indigo naturalis is an Old-World plant with multiple uses. Used in China for centuries as a traditional medicine, current clinical studies are proving its effectiveness as well as identifying mechanisms of action.
This year’s AAD Annual meeting took place in San Francisco, home of Levi Strauss, the jeans manufacturer. How appropriate, as the jeans were originally dyed with indigo.1
A well-known group of Old World plants are the source for the blue powder2 the Chinese call qing dai (éé»), including Baphicacavthus cusia, Polygonum tinctorium, Isatis indigotica and Indigofera tinctoria. Known best as a dye in the Western world, indigo naturalis has been used in China for the treatment of many ailments.3 This “indigo” should not be confused with Wrightia tinctoria, also known as Sweet Indrajao, Pala indigo plant, or Dyers's oleander, which is also used medicinally, more so in the Ayurvedic approach to health.4 Commercial preparations of W. tinctoria are available in the U.S.5
Over the past few years, indigo naturalis has been finding a role in the treatment of psoriasis. A Medline search for “indigo psoria*” reveals 26 articles with all but one having been published in this century and over two thirds published since 2009, the earliest being in 1982.6 Dr. Lin and colleagues have been the movers and shakers in this field, publishing about the use of indigo for treating plaque psoriasis in both children7 and adults.8
In addition to clinical observations, Dr. Lin’s team performed studies that might point to a mechanism of action: The expression of proliferating marker Ki-67 and inflammatory marker CD3 were decreased, while the differentiation marker filaggrin was increased in the epidermis after topical application of indigo naturalis ointment. Further studies on indigo extract looked at the anti-inflammatory effects of an extract of indigo naturalis and its main components indirubin, indigo, and tryptanthrin in human neutrophils. Superoxide anion generation and elastase release were inhibited in a concentration dependent fashion in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-activated human neutrophils. The extract attenuated the FMLP-induced phosphorylation of extracellular regulated kinase, p38 MAPK, and c-Jun N-terminal kinase, and also inhibited calcium mobilization caused by FMLP. The indigo extract did not affect cellular cAMP levels. The main components alone (indirubin, indigo, and tryptanthrin) did not produce similar changes in human neutrophils.9
Not only neutrophils are responsive to indigo: primary cultured human umbilical vein endothelial cells (HUVECs) pretreated with an indigo naturalis extract attenuated TNF-α-induced increases in T cell adhesion to HUVECs as well as decreased the protein and messenger (m)RNA expression levels of vascular cell adhesion molecule-1 (VCAM-1) in these cells.
Indigo naturalis extract also inhibited the protein expression of activator protein-1 (AP-1)/c-Jun, a critical transcription factor for the activation of VCAM-1 gene expression. The authors believe that the reduction of lymphocyte adhesion to vascular cells by indigo naturalis extract could reduce the inflammatory reactions caused by lymphocyte infiltration in the epidermal layer and help to improve psoriasis.10
Many other small studies have been performed on this plant extract and a meta-analysis in 2013 reported limited support for clinical efficacy but no significant side effects.11 The most recent addition to the clinical literature showed that a decolorized indigo in an oil vehicle was efficacious in treating nail psoriasis,12 likely adding a useful new treatment to our armamentarium for a disease that is difficult to manage.
Commercially, there are a number of indigo containing products on the market. One group I find especially intriguing is a line produced by Kamedis, an Israeli company that uses sustainably grown and harvested plants from China. Their Pso Medis line uses indigo naturalis as one of its active ingredients and the clinical results they report are impressive.13
Why should you, the practicing dermatologist care? Very simple. Your patients are learning about alternative treatments on the internet and you can stay credible by knowing these novel options. As indigo naturalis is very safe and not at all painful like an injection into the nail matrix, it might even be a first line treatment for patients for whom local as opposed to systemic therapy would be a good option.
Disclosures: Dr. Seigel has a consulting agreement with Kamedis.
2. Lin YK, Leu YL, Yang SH, Chen HW, Wang CT, Pang JH. Anti-psoriatic effects of indigo naturalis on the proliferation and differentiation of keratinocytes with indirubin as the active component. J Dermatol Sci. 2009;54(3):168-74.
6. Yuan ZZ, Yuan X, Xu ZX. Studies on tabellae indigo naturalis in treatment of psoriasis. J Tradit Chin Med. 1982;2(4):306.
7. Lin YK, Yen HR, Wong WR, Yang SH, Pang JH. Successful treatment of pediatric psoriasis with Indigo naturalis composite ointment. Pediatr Dermatol. 2006;23(5):507-10.
8. Lin YK, Wong WR, Chang YC, et al. The efficacy and safety of topically applied indigo naturalis ointment in patients with plaque-type psoriasis. Dermatology (Basel). 2007;214(2):155-61.
9. Lin YK, Leu YL, Huang TH, et al. Anti-inflammatory effects of the extract of indigo naturalis in human neutrophils. J Ethnopharmacol. 2009;125(1):51-8.
10. Chang HN, Pang JH, Yang SH, et al. Inhibitory effect of indigo naturalis on tumor necrosis factor-α-induced vascular cell adhesion molecule-1 expression in human umbilical vein endothelial cells. Molecules. 2010;15(9):6423-35.
11. Deng S, May BH, Zhang AL, Lu C, Xue CC. Plant extracts for the topical management of psoriasis: a systematic review and meta-analysis. Br J Dermatol. 2013;169(4):769-82.
12. Lin YK, Chang YC, Hui RC, et al. A Chinese Herb, Indigo Naturalis, Extracted in Oil (Lindioil) Used Topically to Treat Psoriatic Nails: A Randomized Clinical Trial. JAMA Dermatol. 2015; doi: 10.1001/jamadermatol.2014.5460 [Epub ahead of print].