1. The anti-TH17 polarization effect of Indigo naturalis and tryptanthrin by differentially inhibiting cytokine expression.
- Author
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Cheng HM, Kuo YZ, Chang CY, Chang CH, Fang WY, Chang CN, Pan SC, Lin JY, and Wu LW
- Subjects
- Animals, Cell Proliferation drug effects, Disease Models, Animal, Endothelial Cells drug effects, Endothelial Cells immunology, Endothelial Cells metabolism, Humans, I-kappa B Kinase deficiency, I-kappa B Kinase genetics, Jurkat Cells, Keratinocytes drug effects, Keratinocytes immunology, Keratinocytes metabolism, Mice, Knockout, Nuclear Receptor Subfamily 1, Group F, Member 3 genetics, Nuclear Receptor Subfamily 1, Group F, Member 3 metabolism, Phenotype, Psoriasis genetics, Psoriasis immunology, Psoriasis metabolism, Skin immunology, Skin metabolism, Th17 Cells immunology, Th17 Cells metabolism, U937 Cells, Cytokines metabolism, Drugs, Chinese Herbal pharmacology, Immunosuppressive Agents pharmacology, Inflammation Mediators metabolism, Psoriasis prevention & control, Quinazolines pharmacology, Skin drug effects, Th17 Cells drug effects
- Abstract
Ethnopharmacological Relevance: The Chinese herbal medicine Qing-Dai (also known as Indigo naturalis) extracted from indigo-bearing plants including Baphicacanthus cusia (Ness) Bremek was previously reported to exhibit anti-psoriatic effects in topical treatment. TH17 was later established as a key player in the pathogenesis of psoriasis. We investigated the anti-TH17 effect of Indigo naturalis and its active compounds. The aim of this study is to evaluate the toxicity of Indigo naturalis (IN) and its derivatives on five cell types involved in psoriasis, and to study the anti-inflammatory mechanism for the toxicity., Materials and Methods: Following the fingerprint and quantity analysis of indirubin, indigo, and tryptanthrin in IN extract, we used MTS kits to measure the anti-proliferative effect of IN and three active compounds on five different cell types identified in psoriatic lesions. Quantitative RT-PCR analysis was used to measure the expression of various genes identified in the activated keratinocytes and TH17 polarized gene expression in RORγt-expressing T cells., Results: We showed that IN differentially inhibited the proliferation of keratinocytes and endothelial cells but not monocytes, fibroblasts nor Jurkat T cells. Among three active compounds identified in IN, tryptanthrin was the most potent compound to reduce their proliferation. In addition to differentially reducing IL6 and IL8 expression, both IN and tryptanthrin also potently decreased the expression of anti-microbial S100A9 peptide, CCL20 chemokine, IL1B and TNFA cytokines, independent of NF-κB-p65-activation. Their attenuating effect was also detected on the expression of signature cytokines or chemokines induced during RORγT-induced TH17 polarization., Conclusions: We were the first to confirm a direct anti-TH17 effect of both IN herbal extract and tryptanthrin., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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