Clinical efficacy of topical Indigo naturalis in psoriasis

Relation

Cheng HM, Wu YC, Wang Q, et al. Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis.BMC Complement Aging Med. 2017;17(1):439.

Goals

• Um die Wirkung von zu bewerten Indigo naturalis Salbe als Monotherapie bei mittelschwerer Plaque-Psoriasis
• Etablierung einer molekularen Signatur einer mittelschweren Psoriasis mit globaler Genexpressionsanalyse
• Komponenten zu bewerten Indigo naturalis für Anti-Interleukin (IL)-17-induzierte Zytokinfreisetzung in kultivierten Keratinozyten.

Draft

Randomized, double-blind, placebo-controlled clinical trial

Participant

Twenty-four Taiwanese patients, 17 men and 6 women, mean age 40 ± 10 years, with approximately 9% body surface area (BSA) involvement of psoriasis. Participants had an average Psoriasis Area and Severity Index (PASI) of about 10 and an average Physician's Global Assessment (PGA) of about 3, corresponding to moderate psoriasis.

Study parameters assessed

Assessment of adverse events and tolerability using weekly PASI, BSA, PGA and Overall Target Plaque Severity Scores (OTPSS); Punch biopsy of lesional and non-lesional skin at week 0 and lesional skin at week 8 for gene expression microarray.

Normal human adult keratinocyte cultures stimulated with IL-17A were treated with different concentrations of the 3 main componentsIndigo naturalisIngredients: isatin, tryptanthrin and indirubin and a control IL-17 inhibitor. Tissue cultures were analyzed for the pro-inflammatory cytokines IL-6 and IL-8 using the MesoScale Discovery V-plex assay.

Primary outcome measures

Changes in weekly PASI, BSA, PGA, and OTPSS scores from baseline to week 9; Changes in gene expression Microarray of skin biopsy samples before and after treatment; and tissue culture cytokine analysis of IL-6 and IL-8.

Key insights

Psoriasis Area and Severity Index Score was significantly improved (P=0.02) inchesIndigo naturalis-treated patients versus controls by week 2 and by week 8 PASI had significantly improved from baseline (P=0.01) and differed significantly from placebo (P=0.01). FromIndigo naturalis-treated patients, 56.3% achieved an improvement of at least 75% (PASI 75) at week 8 compared to none of the placebo patients (P=0.02). One week after discontinuation of treatment, the mean PASI score of treated patients decreased, indicating reduced efficacy after discontinuation of treatment. The mean PGA score was also significantly different inIndigo naturalispatients compared to the placebo group (P<0.003).Indigo naturalisOintment was well tolerated.

treatment withIndigo naturalissuccessfully targets the IL-17 signaling pathway, similar to other systemic therapies that are much more expensive and carry significant risk of harm.

Gene expression showed that the top 15 signaling pathways included the IL-17 pathway and that it was upregulated in psoriasis lesions and downregulated thereafterIndigo naturalisTreatment. Interleukin-17A stimulation of cultured human keratinocytes resulted in a 4.5-fold increase in IL-6 and a 5.5-fold increase in IL-8; IL-17A stimulation was not affected by the presence of isatin and indirubin, but tryptanthrin showed a significant inhibition of IL-6 and a moderate reduction of IL-8 at the highest concentration tested. Tryptanthrin did not show any influence on cell viability at any of the concentrations tested.

The disease signatures of the Taiwanese study population were compared to those of a predominantly Caucasian population and were found to largely overlap.

Practice implications

The characteristic squamous plaques of psoriasis and the increased levels of T helper cells (Th) 1 and Th17 in psoriatic lesions were found to benefit from neutralization of tumor necrosis factor alpha (TNF-alpha), IL-12/23 and IL-1. 17A. Thus, Th1/Th17 cells were found to underpin the pathogenesis of psoriasis.^1.2Traditional treatments for psoriasis, although palliative, do not address the role of Th1/Th17. Newer biological therapies are more effective but are costly and carry significant risks of side effects.

Studies by Lin et al. have previously demonstrated the effectiveness of topical applicationIndigo naturalisOintment in the treatment of psoriasis.³ Indigo naturalisis a traditional Chinese medicine known as Qing Dai and consists of a dried pigment extracted from a number of plants includingBaphicacanthus cusia. This study is the first randomized, double-blind, placebo-controlled clinical trial to be evaluatedIndigo naturalisOintment as monotherapy for moderate plaque psoriasis in a Taiwanese population. It is a joint venture between a Taiwan-based group of investigators and Janssen Research and Development, LLC, a subsidiary of Johnson & Johnson. Despite the fact that the researchers were Janssen employees and 6 of them owned Johnson & Johnson stock, this was a very well-designed, thorough study.

The researchers published new findings on the profile of molecular changes associated with moderate plaque psoriasis. They also found this treatment withIndigo naturalissuccessfully targets the IL-17 signaling pathway, similar to other systemic therapies that are much more expensive and carry significant risk of harm. The discovery that tryptanthin has IL-17 activity and that the disease signatures of Taiwanese psoriasis patients largely overlap with those of Caucasians suggests thisIndigo naturalisshould also be effective in a broader population of people with psoriasis.

The authors state that the short duration of benefit is topicalIndigo naturalisThe treatment could be due to the lack of deeper penetration into the skin and lower systemic absorption or a short half-life of the active ingredients. Although these suggestions could be true, perhaps it is more currentIndigo naturaliscannot effectively counteract the chronic inflammatory systemic nature of psoriasis and that other approaches, including contributing lifestyle factors, also need to be effectively addressed to downregulate the phenotypic expression of the underlying genetic susceptibility to psoriasis.

Author Disclosure: I advise Kamedis, Ltd, a skin care company that has developed and commercialized an indigo-based topical psoriasis formulation.